BMC Infectious Diseases 2014, Volume 14 Suppl 2 http://www.biomedcentral.com/bmcinfectdis/supplements/14/S2/

MEETING ABSTRACTS Open Access Abstracts from the International Symposium HIV & Emerging Infectious Diseases 2014 Marseille, France. 21-23 May 2014

Published: 23 May 2014

These abstracts are available online at http://www.biomedcentral.com/bmcinfectdis/supplements/14/S2/

Conclusion: UDS was more sensitive than the standard Sanger ORAL PRESENTATIONS sequencing. A combination of UDS and DeepChek® software for the interpretation of DR results saved a considerable amount of time and would help clinicians provide suitable treatments. A cut-off of 1% allowed MANAGING ANTIRETROVIRAL THERAPY, a better characterization of the viral population by identifying additional PART 1 resistance mutations and improving the DR interpretation.

O1 Clinical impact of ultra deep versus Sanger sequencing detection of O2 minority mutations on HIV-1 drug resistance genotype interpretation First-line therapy with LPV/r vs NVP and 2 NRTIs in a developing after virological failure country: W144 of a randomized trial Sofiane Mohamed1,4*, Guillaume Penaranda1, Dimitri Gonzalez2, Claire Camus1, Nathan Clumeck*, Claude Mwamba, Kabamba Kabeya, Vincent Calvez, Hacène Khiri1, Ronan Boulmé2, Chalom Sayada2, Patrick Philibert3, Serge Matanda, Dolorès Vaira, Gilles Peytavin, Coca Necsoi, Marc Delforge, Daniel Olive4, Philippe Halfon1 David Kadiebwe, Chantal Milolo, Joe Ilunga, Liévin Kapend 1Alphabio Laboratory, Marseille, France; 2Advanced Biological Laboratories Saint Pierre University Hospital, Brussels, Belgium (ABL), Luxembourg, Luxembourg; 3European Hospital, Marseille, France; BMC Infectious Diseases 2014, 14(Suppl 2):O2 4Paoli Calmettes Institute, Tumor Immunology Laboratory and INSERM Center of Cancer Research, Marseille, France Aim: In resource-limited countries, NNRTI-based regimen may result in BMC Infectious Diseases 2014, 14(Suppl 2):O1 emergence of more HIV drug resistance because of a low genetic barrier. We compare the efficacy and tolerance of LPV/r and NVP-based regimens Aim: Drug resistance mutations are routinely detected using standard and 2 WHO nucleoside backbones in naive HIV infected patients (p.). Sanger sequencing, which does not detect minor variants with a frequency Materials and methods: Naive p. from 5 clinics in Lubumbashi (Congo- below 20%. The impact of detecting minor variants generated by ultra- DRC) were randomized to receive LPV/r versus NVP combined with TDF/ deep sequencing (UDS) on HIV drug-resistance (DR) interpretations has not FTC or ZDV/3TC. VL and CD4 were performed at baseline (BL) and every yet been studied. 24 weeks (W). The primary endpoint was the % of p. with therapeutic Methods: Fifty HIV-1 patients who experienced virological failure were failure defined as clinical and virologic failures (VL>1000 c/ml)(missing included in this retrospective study. The HIV-1 UDS protocol was data=failure), assessed at W48 and 96. We present here the results of 144 performed using the GS Junior (Roche 454 Life Sciences Branford, CT). This W of follow-up. UDS protocol allowed the detection and quantification of minor and major Results: 425 Black African p. (72% female; median (md) age 38 years, md HIV-1 protease and reverse transcriptase variants related to genotypes A, B, CD4 165/μL; md VL 5.2 log c/ml) were randomized (216 in LPV/r, 209 in C, E, F and G. DeepChek®-HIV (ABL, SA and TherapyEdgeTM, USA) NVP). BL characteristics were comparable. In the ITT analysis, previous simplified drug resistance (DR) interpretation software was used to results showed no difference between LPV/r and NVP treatment arms at compareSangersequencingandUDSattwodifferentthresholds(≥1% W96 except a higher proportion of virologic failure (VF) in p. on NVP-based and ≥20%). DeepChek®-HIV utilizes the ANRS, HIVdb and Rega algorithms. regimens. W144 ITT analysis showed a significant difference on endpoints Results: The total time required for the UDS protocol was found to be between LPV/r (94/216) and NVP (111/209)(p=0.0479) and persistence of a approximately three times longer than Sanger sequencing with equivalent significant difference in VF rate (20/216 vs 37/209 for LPV/r and NVP, reagent costs. UDS detected all of the mutations found by population respectively)(p= 0.015). BL genotypes showed NNRTI mutations (mt) in sequencing and identified additional resistance variants in all patients, 3/31 NVP-failing p. and no PI mt in LPV/r-failing patients. At time of failure, primarily by using 1% sensitivity. An analysis of DR revealed a total of 643 NNRTI mt were seen in 23/26 NVP-failing p. and 0/13 primary PI mt in LPV/ and 224 clinically relevant mutations by UDS and Sanger sequencing, r failing patients. NRTI mt were seen in 19/26 p. in NVP arm (including respectively. Three resistance mutations with >20% prevalence were K65R in 7p. and M184V in 18p.) vs 3/13p. in LPV/r arm (M184V in 3p.). detected solely by UDS: A98S (23%), E138A (21%) and V179I (25%). A Md CD4 change from BL was significant higher in LPV/r arm (251 cells/μL significant difference in the DR interpretations for 19 antiretroviral drugs was [interquartile range (IQR) 153;384]) compared with NVP arm (174 cells/μL observed between the UDS and Sanger sequencing methods. Y181C and [IQR 102-330])(p= 0.0093). Percentage of p. with adherence >95% was T215Y were the most frequent mutations associated with interpretation similar (73.6 vs 74.4 for LPV/r vs NVP). differences. The major discrepancies between Sanger and UDS were Conclusions: In a resource-limited setting after 144 weeks of follow-up primarily found at the 1% threshold in the three algorithms. NNRTI-NRTI first-line regimen is associated with more virologic failure,

© 2014 Mohamed et al; licensee BioMed Central Ltd. All articles published in this supplement are distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. BMC Infectious Diseases 2014, Volume 14 Suppl 2 Page 2 of 45 http://www.biomedcentral.com/bmcinfectdis/supplements/14/S2/

more drug resistance mutations and a lower immunologic response than combinations of 1 PI or 1 NNRTI + 2 NRTIs (for 4, 3 , 2 d/wk Rx); novel a PI-based regimen. quadruple antiviral compositions of 1 NNRTI + 3 NRTIs (for 4, 3 , 2, 1 d/wk Rx). Results: Intermittent treatment fully controlled patients’ HIV over 20 592 treatment-weeks. Of the 92 patients at entry, 88, 66 and 51 had sustained ENDING THE HIV PANDEMIC 52weekswith3,4or5weeklydaysoff-treatmentperiodsrespectively. Lymphocyte surface activation markers or cell-bound HIV DNA levels O4 remained stable or declined further; CD4/CD8 ratios rose to ≥1in37%of Epithelial stem cells as mucosal antigen-delivering cells: a novel patients – versus 7% patients before discontinuous treatment. preventive approach Viral failures: 13 viral escapes (plasma HIV RNA >50 copies 4 weeks apart; Marie-Claire Gauduin*, Robert White, Nicole Chenciner, Kathleen Vincent, overall failures 3.3 per 100 discontinuous treatment-years) were countered by Patrice Frost, Philippe Blancou prompt re-adjustments with 7 day-a-week effective combinations. In Texas Biomedical Research Institute, San Antonio, Texas, USA retrospect 10 failures were ascribable to physician’sorpatients’ errors or BMC Infectious Diseases 2014, 14(Suppl 2):O4 blunders: base-drug prescribed at sub (½) optimal daily dosage (3 pts); overlooked archival resistant HIVs from antecedent treatment failures (5 pts); Introduction: HIV transmission occurs predominantly across mucosal acute erratic observance (2 pts); HIV inadvertently resurged while on a 5 day surfaces. An ideal preventive strategy would be to target HIV at mucosal off (2 pts) or 6 days off-treatment period, all 3 under one quadruple entry sites to prevent infection. We developed a novel epithelial stem cells- combination, setting the antiviral power limit of the ultra-short treatment based AIDS preventive approach in female macaques. This approach is modality with that combination at 1.4 failures per 100 proper treatment-years. based on the ability of therapeutic lentiviral vectors integrated in mucosal Conclusion: discontinuous maintenance therapy in 92 patients on ARV 4 epithelial stem cells to induce virus-specific cellular immune responses at days a week and less over an average 219 treatment-weeks (median 131) mucosal sites of viral entry. We first intended to expose the cervicovaginal offered 40 to 85 % medicinal cuts. tract to conditions used for intravaginal vaccine delivery and non-invasively image local tissues to determine the vaccination effects on epithelial integrity and generation of antigen-specific mucosal immune responses. O6 Methods: Experimental cervicovaginal vaccinations were carried out on Synthetic HIV-1 matrix protein p17-based AT20-KLH therapeutic 12 uninfected female macaques, in conjunction with deliberate abrasion of immunization in HIV-1-infected patients receiving antiretroviral epithelium using Depo-Provera, 4% nonoxynol-9 treatments, or gentle treatment: A phase I safety and immunogenicity study abrasions to reduce vaginal epithelial height and cell layers number. Arnaldo Caruso*, Marialuisa Iaria, Francesca Caccuri, Cinzia Giagulli, Longitudinal study was performed for baseline levels of hormones, Simona Fiorentini antibodies, cytokine profiles during normal cycling with/without vaccination. University of Brescia, Brescia, Italy Endoscopic colposcopy followed by optical coherence tomography (OCT) BMC Infectious Diseases 2014, 14(Suppl 2):O6 helped monitor macaque cervical-vaginal epithelium pre-, post-, without treatment to measure epithelial thickness changes. Colposcopy help Introduction: Therapeutic vaccination is a promising approach to treat visualizing the vagina and cervix. Blood samples and biopsies were collected HIV-1+ people by boosting or redirecting immune system to neutralize at various time-points to evaluate immune responses to vaccination. HIV-1 antigens whose effects are relevant to viral pathogenesis. HIV-1 Results: OCT imaging provided quantitative measurements of epithelial matrix protein p17 is a structural protein that, through the interaction of changes and detected minute changes in epithelial thickness and its NH2-residing epitope AT20 with specific receptor(s), acts extracellularly morphology. Colposcopy and OCT imaging correlated with hormone as a viral toxin. In fact, p17 is able to deregulate biological activities of levels and biopsies imaging. Depo-Provera gave better results in different cells involved in AIDS pathogenesis. epithelium thinning but naturally cycling macaques showed clearer To induce neutralizing antibodies (Abs) to p17 we developed a peptide- thickness differences. All collected secretions, biopsies and blood samples based immunogen (AT20-KLH) and evaluated its safety and immunogenicity. gave a better understanding of the correlation between menstrual cycle, Methods: 24 asymptomatic HAART-treated HIV-1+ patients were enrolled in hormonal level, epithelial thickness changes. Optimal conditions for a phase I clinical study and were randomized to 3 groups: 2 groups treated vaccine delivery were determined and revealed virus-specific T cell with five IM injection (Arm A: 25 μg/inoculation; Arm B: 100 μg/inoculation) at response in all vaccinated animals. day 0, 28, 56, 84 and 112; the control group (Arm C), not injected. Safety was Conclusions: OCT is well suited for the examination of superficial mucosal assessed by monitoring local and systemic adverse events (AEs), recorded layers and close underlying stromal structures of tissues. In this study, we till day 168. Evaluation of immunogenicity was by titering Abs using ELISA. demonstrated the feasibility of using epithelial stem cells as mucosal Results: In all, 105 AEs were reported across the groups. Most were mild antigen-presenting cells to induce viral specific immune responses at and resolved without sequelae. No significant changes in the routine mucosal sites, and improved our knowledge of the role of mucosal surfaces. laboratory parameters, CD4 T-cell count or HIV-1 viremia were found. Despite the absence of anti-AT20 preimmunization Abs, 100% of treated subjects developed high titers of anti-AT20 Abs (GM 9775) in response to both AT20-KLH doses. These Abs were also capable of recognizing AT20 MANAGING ANTIRETROVIRAL THERAPY, within the p17 framework and to neutralize its binding to cell receptors. PART 2 Furthermore, we were able to recruit several participants two years after the first injection to evaluate longevity of anti-AT20 elicited Abs. 100% of O5 these subjects still showed anti-AT20 Abs with titers that were about half Four days a week and less on appropriate antiviral combinations the ones detected at the end of immunization protocol. provided long-term optimal control over HIV-1 in 92 patients Conclusion: The AT20 peptide-based approach has allowed to redirect Jacques Leibowitch*, Dominique Mathez, Pierre de Truchis, Damien Ledu, HAART-treated patients’ humoral responses toward a previously Jean Claude melchior, Guislaine Carcelain, Jacques Izopet, John David, untargeted hotspot of functional activity. Overall, the tested AT20-KLH Christian Perronne doses were safe and well tolerated, supporting further exploration of Raymond Poincaré Hospital, Infectiology Department, Garches, France AT20-KLH as an HIV-1 therapeutic vaccine candidate. BMC Infectious Diseases 2014, 14(Suppl 2):O5

Patients and treatments: 92 volunteer patients on optimally SHORT ORAL COMMUNICATIONS suppressive antiviral combinations for 5 months or more consented to step wisely reduce their weekly treatment from 7 to 5 to 4 days/wk, or directly O7 from 7 to 4 d/wk after bi-monthly checks on HIV plasma levels at < 50 copies. Long-term protection of hepatitis B vaccine in HIV-infected patients Weekly treatment was further reduced to 3, 2, and 1 d/wk for respectively 72, RBiekre*, N Ben Lasfar, N Viget, M Valette, V Baclet, T Huleux, E Senneville, F Ajana 59 and 12 pts. Antiviral combinations included : one integrase inhibitor-base Gustave Dron Hospital, Infectious Diseases Department, Tourcoing, France + 2 or 3 NRTIs, or 1 NNRTI and 1 PI (for 4 d/wk regimens, (Rx); standard triple BMC Infectious Diseases 2014, 14(Suppl 2):O7 BMC Infectious Diseases 2014, Volume 14 Suppl 2 Page 3 of 45 http://www.biomedcentral.com/bmcinfectdis/supplements/14/S2/

Aim: Many studies reported in HIV-positive patients 50% of hepatitis B question of the molecular mechanisms involved in the generation of vaccine response with a duration of protection between 24 and 36 Interferon-producing Killer pDCs (IKpDCs), and the consequences on viral months. The aim of our study is to determine the long term protection in control. our HIV patients who responded to a standard immunization schedule. Materials and methods: pDCs and NK cells were negatively sorted from Materials and methods: Our database NADIS allows us to collect the blood of healthy donors with specificmagneticbeads.NKcellswere information from March 1986 to October 2013 (gender, age, CD4 count, kept either in a resting state or activated with PMA/ionomycine for 2 hrs. HIVRNA and Hepatitis B surface antibody titers = HBs Ab > 10 IU / L.) pDCs were stimulated with ODB 2006, ODN 2216, or were infected with Patients were included gradually after 3 Engerix B 20 hepatitis B vaccines at R5-HIV-1 at various concentrations. In some experiments, pDCs were day 1, one month and 6 months later, conferring a rate of HBs ab > 10 IU /L. cocultured with NK cells for 24 hrs at NK:DC ratio of 1:5. Phagocytosis Then we observed the duration of protection from the initial response. experiments were performed with fluorescent microsphere beads. The Results: Among 403 HIV patients who responded to HBV, 298 were men mutual influence of NK-pDC interaction was analyzed by multiparametric (74%) vs 105 women (26%). The median age was 36 years. We observed flow cytometry, combining maturation and cell death/survival markers a progressive decline in HBs ab titer until <10 IU/ L. At 24 months 74.7% with cytokine detection, and released cytokines in cultures supernatants (n=223) men remained protected vs 79.2% (n=83) women. At 60 months. were quantified with the MAP luminex technology. 33.1% (n=99) men lost their HB protection vs 27.7% (n=29) women (LR = Results: We report that high concentrations of HIV-1 induced both 0,11 NS). survival and maturation of pDCs. ThesepDCswerecharacterizedby At 84 months and over 120 months, 34.7% (n=103) and 39.1% (n=117) increased size and the expression of HLA-DR, CD40, CD86, CCR7 and men lost their HB protection vs 35.8% (n=38) and 38.2% women (n=40). CD83 molecules. This phenotypic maturation was coupled to a functional Conclusions: Long term HBV protection was observed in the majority of maturation since HIV-1-infected pDCs exhibited higher phagocytic our HIV patients. One third had lost their HBs ab after 2 years, and activity, expressed mTRAIL and released high levels of pro-inflammatory require HB boost injections. We are thinking of using an adjuvanted HB cytokines and chemokines (IL-6, IL-8, TNF-a,IP-10,MIP-1a and MIP1-b). vaccine as a booster to provide a sustained protection. We will also study The release of these mediators was dependent on both IFN-a and factors associated with the loss of HBV protection. HMGB1. Finally, pDC activation by HIV-1 triggered the expression of mTRAIL on NK cells. Interestingly, both IFN-a and HMGB1 were required to induce killer NK cells. O8 Conclusion: We report for the first time the critical role of both HMGB1 Innate sensing of viral infection by pDCs and regulation by IFN-a and and INF-a on the expression of TRAIL at the surface of both infected- HMGB1 of TRAIL expression on pDCs and NK cells pDCs and NK cells during their interaction, and also on the triggering of Héla Saïdi*, Marlène Bras, Pauline Formaglio, Bruno Charbit, beta-chemokines synthesis by pDCs. These data suggest that the cross- Jean-Philippe Herbeuval, Marie-Lise Gougeon talk of HIV-infected pDCs with NK cells favors the emergence of both Pasteur Institute, Paris, France killer pDC and cytotoxic NK cells that is essential for the control of viral BMC Infectious Diseases 2014, 14(Suppl 2):O8 replication at the early stage of the infection.

Introduction: At an early stage of HIV-1 transmission, plasmacytoid dendritic cells (pDCs) and natural killer (NK) cells are recruited into mucosal O9 tissues. pDCs are the major source of type I interferon (IFN-a), a powerful Structural and functional studies of HIV-1 pre-integration complexes innate antiviral cytokine, and a strong pDC response is associated with Marc Ruff1*, Nicolas Levy1, Sylvia Eiler1, Karine Pradeau1, Corinne Crucifix1, spontaneous virus control. The contribution of pDCs to licensing NK cells Aurélie Schaetzel1, Robert Drillien1, Vincent Parissi2, Stéphane Emiliani3, and inducing antiviral immunity make them a key player in the early phase Yves Mely4, Patrick Schultz1 of HIV-1 infection. In contrast, the chronic expression of IFN-a was found 1Institute of Genetics and Molecular and Cellular Biology, Illkirch, France; to be a key mediator for HIV pathogenesis. We addressed herein the 2University of Bordeaux, Laboratory of basic microbiology and pathogenicity,

Figure 1(abstract O7) Duration of HBV protection (months) BMC Infectious Diseases 2014, Volume 14 Suppl 2 Page 4 of 45 http://www.biomedcentral.com/bmcinfectdis/supplements/14/S2/

Bordeaux, France; 3Cochin Institute, Paris Descartes University, Paris, France; over time and transient Perforin productions that peak at day 56. Mtb- 4Faculty of Pharmacy, Laboratory of biophotonics and pharmacology, specific T cells responses were also detected and increased IL-12 and Illkirch, France MIP-1b production in PBMC, Spleen and LN collected day 84. BMC Infectious Diseases 2014, 14(Suppl 2):O9 Conclusions: Overall, we successfully developed/optimized an aerosol neonatal macaque model that mimics clinical and bacteriological HIV-1 integrase (IN) is a key component of the pre-integration complex (PIC) characteristics of early Mtb-infection as seen in human newborns/infants. and is involved in several steps of retrovirus replication. IN cannot perform This model represents a unique opportunity to characterize neonatal these functions on its own and need to recruit host cell proteins to efficiently Mtb infection and, further understand all interactions between TB and HIV co- carry out the different processes. Retroviral INs are flexible proteins showing infection in pediatric AIDS and develop appropriate therapeutic interventions. high inter-domain flexibility. This intrinsic flexibility accounts for IN ability to interact with multiple partners, which in turn chaperones PIC formation and its multiple functions. Biochemical and structural studies have long been hampered due to the PIC dynamics and intrinsic flexibility. We demonstrated O12 that the low solubility and inter-domain flexibility can be circumvented by Persistent production of an integrase-deleted HIV-1 variant with no forming stable and specific complexes with DNA or protein co-factors and by resistance mutation and wild-type proviral DNA in a treated patient post-translational modifications. MA Trabaud*, L Cotte, J Saison, C Ramiere, C Ronfort, JC Tardy, P Andre Hundreds of milligrams of stable complexes are needed for in vitro Hospices Civils of Lyon, Lyon, France functional and structural studies. For this, we develop new technologies BMC Infectious Diseases 2014, 14(Suppl 2):O12 for high molecular weight transient complexes production as well as for functional and structural analysis (mammalian cell system for protein Introduction: An HIV-1-infected patient with suppressed viremia for production, in vitro functional analysis and complexes characterization). several years, in whom a variant carrying a deleted integrase (IN) gene, Structures have been solved by Cryo-EM and X-ray crystallography. without reverse transcriptase (RT) or protease (PR) resistance mutations, We reconstruct in vitro stable and soluble complexes around IN. We emerged in the plasma and persisted is described. solved the cryo-EM structures of the IN/LEDGF/DNA (Michel et al. 2009) Materials and methods: Viral load (VL) was tested by routine assays and IN/LEDGF/INI1/DNA (Maillot et al. 2013) complexes. Structures following manufacturer’s instructions. RT, PR and IN genes were together with functional assays gave important hints on the functional sequenced with the ANRS consensus techniques. role of LEDGF and INI1. Other sub-complexes of the PIC have been Nested PCRs with patient virus IN-specific primers and probes were characterized. One of them is the IN/transportin-SR2/VBP1 complex developed to detect the deleted variant from plasma, blood lymphocytes, (structure in progress). Our results suggest that the function of INI1 (core rectal biopsies, and sperm. protein of the swi/snf chromatin remodeling complex) in HIV-1 replication Results: VL remained undetectable for more than two years under is to stabilize the PIC in the host cell, by maintaining integrase in a stable therapy, excepted for 1 observed blip. Thereafter HIV RNA increased constrained conformation which prevents non-specific interactions and slightly but persistently, fluctuating from 56 to 466 copies/ml during autointegrationontheroutetoitsintegrationsitewithinnucleosomes, more than five years. By population sequencing a 38 nucleotides deletion while LEDGF (a transcriptional co-activator) organizes and stabilizes an was observed in the IN C-terminal domain (CTD) encoding sequence active integrase tetramer suitable for specific vDNA integration. (residues 215 to 227 of the WT IN). In plasma, the variant progressively emerged during therapy-induced virosuppression, HIV RNA being undetectable by routine viral load assay, O11 and then persisted during detectable viremia. The WT IN, not detected by Neonatal macaque model to study Mycobacterium tuberculosis infection bulk sequencing, was present but at stable low level. in pediatric AIDS HIV DNA and RNA with WT IN were amplified from each cell extract. Marie-Claire Gauduin*, Magdalena Cepeda, Mary Salas, Robert White, Detection of the deleted IN was a very rare event in blood and rectal cells. Melissa de la Garza, Edward J Dick, Michael Owston, Lisa Y Armitige Conclusions: Although the reservoir of this virus is yet unknown it is Texas Biomedical Research Institute, San Antonio, Texas, USA likely in a tissue compartment and not predominantly in cells migrating BMC Infectious Diseases 2014, 14(Suppl 2):O11 through blood. Questions arising from this case are how and why this certainly defective Introduction: Tuberculosis (TB) is the leading cause of death in AIDS variant emerged during efficient virosuppression, and how it could be patients worldwide; the earliest opportunistic infection occurring in preferentially and stably produced. conjunction with HIV; an accelerant of HIV replication and immune As for interpretation of residual viremia found in long-term treated system deterioration. Co-infection with Mycobacterium tuberculosis (Mtb) patients with undetectable viral load, virus production can originate from and HIV is an increasing global emergency. Little is known regarding the on-going replication, but the cells had to be continuously co-infected early events of Mtb infection in humans especially infants. There is an with the two viral forms, or synthesis by chronically infected cells. urgent need for a clinically relevant animal model that mimics TB disease However, the defective virus production at detectable level suggests inhumanchildrentobetterunderstand early immune responses, unusual circumstances. pathogenicity and disease progression in newborn/infants. Anyway, this case raises concern about the possible long term synthesis Methods: Aerosolized Mtb transmission was performed in neonatal of defective viruses. macaques to mimic mother-to-child transmission and to: i. Characterize early TB-specific immune responses during acute Mtb-infection, ii. Investigate the dynamics of Mtb-specific T cell responses following early infection in infants; and, iii. Characterize the distribution and frequency of O13 Mtb-specific responses in various host tissues. Six newborn macaques (6 Competition between HIV-1-encoded RRE RNA and miRNA-TRBP weeks old) were infected via broncho or aerosol routes of infection with interactions alters RNA interference activity and gene expression various Mtb doses (Erdman or Rh37rv strains). All clinical, immunologic, A Gatignol1*, SM Daniels1, L Sinck1, NJ Ward1, CE Melendez-Peña1, microbiologic, and pathologic events were assessed for 84 days post- RJ Scarborough1, I Azar1, A Daher1, KM Pang2, JJ Rossi2 infection. 1McGill University, Lady Davis Institute for Medical Research, Montreal, Canada; Results: Gross pathological abnormalities were observed as early as 35 et 2Beckman Research Institute of the City of Hope, Duarte, California, USA 42 days post infection including Ghon complex formation and BMC Infectious Diseases 2014, 14(Suppl 2):O13 granulomas in the lung. Caseous granulomas were also observed in the lungs at these early time-points, reflecting strong initial responses. Using Aim: RNA interference (RNAi) is a mechanism by which small double- ELISPOT assays, we found that IL-12 production correlated with early Mtb stranded RNAs called micro(mi) or small interfering(si) RNAs bind messenger infection lesions seen by routine thoracic radiographs. Flow cytometry RNAs (mRNAs) to inhibit their expression. The mechanism involves the RNA- revealed robust granzyme B productions by NK8/NK cells that increased induced silencing complex (RISC) composed of Dicer, TRBP and Ago2 BMC Infectious Diseases 2014, Volume 14 Suppl 2 Page 5 of 45 http://www.biomedcentral.com/bmcinfectdis/supplements/14/S2/

Figure 1(abstract O12)

proteins in which TRBP loads miRNAs into the active complex [1]. Several Montreal, Department of microbiology and immunology, Montreal, Canada; mammalian viruses interfere with RNAi activity. Changes in miRNA and 5CHUM Research Center, Montreal, Canada mRNA expression have been observed in patients infected by HIV-1, but the BMC Infectious Diseases 2014, 14(Suppl 2):O14 mechanisms are not understood. To explain part of the relationship between RNAi and HIV-1, we investigated the ability and the mechanism of Background: We showed in cross-sectional studies that tryptophan (Trp) the HIV-1-encoded RNA Rev-Response Element (RRE) to suppress RNAi. catabolism into kynurenine (Kyn) by IDO enzyme expressed by dendritic Methods: We used a model based on miRNA Let7 activity on a reporter cells (DC) contributes to regulatory T-cells (Tregs) expansion and immune gene (RL or EGFP) linked to a complementary sequence (cLet7) to measure suppression in chronic HIV infection. We prospectively assessed Trp RNAi activity or its suppression. We used RNA-immunoprecipitation (IP) and catabolism and anti-inflammatory response following primary HIV gel mobility shift assays to compare TRBP binding to RRE or siRNAs. We infection (PHI). studied RRE activity on RNAi in the context of the entire HIV-1, a lentiviral or Methods: Plasma and Peripheral blood mononuclear cells (PBMCs) were an adenoviral vector. longitudinally collected in 41 PHI patients (infection <90 days), 24 Results: We observed that RRE, acts as an RNAi suppressor with no remained untreated (ART-naive) and 17 were ART-treated one year later. In modification of the endogenous RISC (Daniels et al., submitted). In contrast, addition, samples from elite controllers (EC, n=12) and healthy subjects RRERNAdisplacessiARNsfromTRBP,whichsuggestsachangeinmiRNA (HS, n=12) were also assessed. IDO enzymatic activity marker (Kyn/Trp incorporation into the RISC. RNAi remains functional in HIV-1 infected cells, ratio) was measured by isotope dilution tandem mass spectrometry. IL-6, whereas a lentiviral vector expressing RRE has a suppressive activity. The IL-18, TNF-a and IP-10 plasma levels were assessed by Luminex. Frequency suppression is alleviated when Rev or GagPol is expressed. Adenovirus is of Tregs (CD4+CD25highCD127lowFOXP3high), CD11c+ myeloid DC (mDC) known to be suppressed by RNAi and RRE reverses this inhibition as seen by and CD123+ plasmacytoid DC (pDC) as well as HLA-DR/CD38 co-expression increased viral replication. of on T-cells were assessed. Conclusions: RRE is a new RNAi suppressor, which acts by competition with Results: PHI patients had elevated Kyn/Trp ratio compared to HS and EC siRNA and miRNA for binding to TRBP and therefore incorporation into the and further increased during the chronic phase, while normalized RISC. This could explain in part the alteration of certain gene expression and following ART. Accordingly, an increase of Treg frequency was observed modifications of the cell metabolism in patients with long-term HIV-1 at the baseline and continues to increase in the chronic phase only for infection. those remaining untreated, when compared to HS and EC. Conversely, Reference the frequency of mDC and pDC decreases over time only for those who 1. Daniels SM, Gatignol A: The Multiple Functions of TRBP, at the Hub of remained untreated. Higher Kyn/Trp ratios were inversely correlated with Cell Responses to Viruses, Stress, and Cancer. Microbiol Mol Biol Rev 2012, the frequency of mDC and pDC at PHI and for those untreated. 76:652-666. Importantly, the highest level of immune activation (HLA-DR+CD38+ CD8 T-cells) was observed during PHI followed by a decrease in chronic phase in ART-naïve and became comparable to EC and HS when receiving ART. O14 Importantly, Kyn/Trp ratio was correlated with level of CD8 T-cell IDO-induced immunosuppressive tryptophan catabolism following activation during PHI and for those who remained untreated. In line with primary HIV infection this, positive correlations were observed between Kyn/Trp ratio and levels Mohammad-Ali Jenabian1*, Kishanda Vyboh1, Ido Kema3, of IL-18 and TNF-a as well as markers of HIV disease progression IL-6 and Cynthia Kanagaratham2, Danuta Radzioch2, Norbert Gilmore1,2, IP-10. Petronela Ancuta4,5, Cécile Tremblay4,5, Jean-Pierre Routy1,2 Conclusion: The progressive increase of Kyn/Trp ratio observed in the 1Chronic Viral Illnesses Service of the McGill University Health Center, chronic phase of HIV infection in contrast to decreased viral load and T-cell Montreal, Canada; 2Research Institute of the McGill University Health Center, activation, support the contribution of tissue damage and/or myeloid Montreal, Canada; 3Department of Laboratory Medicine, University Medical inflammatory syndrome in addition to viral replication for the development Center, Groningen, University of Groningen, The Netherlands; 4University of of immunosuppression. BMC Infectious Diseases 2014, Volume 14 Suppl 2 Page 6 of 45 http://www.biomedcentral.com/bmcinfectdis/supplements/14/S2/

THE HCV REVOLUTION response (SVR). IDO and TDO enzymatic activity (Kyn/Trp ratio) was measured by isotope dilution tandem mass spectrometry. Statistical analyses O15 were performed using Anova, unpaired or paired t-tests and Spearman Carcinovic cohort: prognostic factors of death in HIV/HCV coinfected correlation tests. patients with hepatocellular carcinoma (HCC) Results: Among HCV/HIV patients, those having fibrosis compared with M Gelu-Simeon*, M Lewin, R Sobesky, M Ostos, T Bayan, F Boufassa, L Meyer, non-fibrosis had higher APRI scores (2.48±0.23 vs 0.36±0.018, p<0.0001) A Persoz, E Teicher, H Fontaine, D Salmon-Céron, O Seror, J-C Trinchet, and elevated Kyn levels (2.6±0.24 vs. 1.97±0.15 μmol/L, p=0.038). For J-C Duclos-Vallée HBV/HIV co-infected, Kyn level was also elevated (2.1±0.16 μmol/L). The Paul Brousse Hospital, Villejuif, France Kyn/Trp ratio was equally elevated in all HCV and HBV co-infected BMC Infectious Diseases 2014, 14(Suppl 2):O15 groups, similar to the untreated mono-infected HIV group. Importantly, HCV/HIV fibrotic and HBV/HIV groups but not the non-fibrotic group had Background and aim: We have previously reported a more advanced higher Kyn/Trp ratios compared to the ART-treated and HS groups. Unlike radiological presentation in HIV+/HCV+ than HIV-/HCV+ patients (pts). The HIV viremia, HCV viremia was not correlated with the Kyn/Trp ratio. aim of our study was to define prognostic factors of death in HIV+/HCV+ However, in all HCV/HIV co-infected patients, Kyn/Trp ratio was correlated pts with HCC. with the APRI score (p=0.027). Successful HCV treatment improved APRI Methods: Cases of HCC in HIV+/HCV+ pts were obtained from the 3 score (0.89±0.13 vs. 0.4±0.04, p=0.001), contrasting with unchanged ANRS Prethevic, HepaVih and CirVir cohorts. Imaging was reviewed elevated Kyn/Trp ratios six months after SVR. according to EASL criteria. Conclusion: ART-treated HCV/HIV and HBV/HIV co-infected patients Results: Fifty HIV+/HCV+ coinfected pts (n=44 men (88%), median age 50 presented with elevated immunosuppressive Kyn/Trp ratios when years [40-74], median CD4 cell count 334/mm3 [58-1621], n=28 Child A compared to mono-infected HIV-treated patients and reached a ratio cirrhosis (60%)) developed HCC. Thirty-one (63%) pts presented cirrhosis similar to the untreated HIV mono-infected patients. In ART-treated decompensation before HCC diagnosis. At HCC diagnosis, median serum patients, liver fibrosis on its own, but not HCV viremia, was associated aFP was 20.4 [1.9-198,900] ng/ml, 38 (76%) pts had a nodular tumor (median with an enhanced level of immunosuppressive Tryptophan catabolism. main diameter 23.5 [11-70] cm) and 12 (24%) pts an infiltrating form (62.5 Thesefindingssuggestthatanecrotico-inflammatoryliversyndrome [10-130] cm), p=0.007. Tumor portal thrombosis was diagnosed in 14 (28%) persists even after SVR, and subsequently induces a systemic immune pts. A curative or a palliative procedure was further performed in 22 (44%) activation by increasing tryptophan catabolism. pts and 20 (40%) pts, respectively. The 2-years and 4-years overall survival rates were 51% and 28%, respectively. Age (p=0.0005), infiltrating or nodular tumor (p= 0.0009) and tumor portal thrombosis (p=0.004) were associated ACUREFORHIV? to survival. In a Cox model, two prognosticfactorsofdeathswerefound: prior episode of cirrhosis decompensation (aRR 11.43 [3.01-43.34], p=0.0003) O17 and tumor portal thrombosis (aRR 4.66 [1.19-18.27], p=0.03), adjusted on Impact of the level of pre-ART CD4+ T cells in blood on the rectal HIV age, CD4 cell count and the therapeutic strategy for HCC. reservoir in long-term treated men (VIRECT study) Delphine Vergnon-Miszczycha1*, Alexandre Girard1, Anne Depincé1, Conclusions: Cirrhosis decompensation and tumor portal thrombosis 1,3 3 2 2 significantly impact the survival of HIV+/HCV+ pts with HCC. Our results Xavier Roblin , Emilie Del Tedesco , Anne Frésard , Claire Guglielminotti , Claude Lambert4, Bruno Pozzetto1,5, Frédéric Lucht1,2, Stéphane Paul1,4, suggest new rules of screening HCC in HIV+/HCV+ pts with advanced 1,5 liver disorders. Thomas Bourlet 1University Hospital of Saint-Etienne, Groupe Immunity of the Mucous Membranous and Pathogen Group (GIMAP), EA 3064, Saint-Etienne, France; 2University Hospital of Saint-Etienne, Infectious Diseases Department, Saint- O16 Etienne, France; 3University Hospital of Saint-Etienne, Gastroenterology Liver fibrosis is strongly associated with an enhanced level of Department, Saint-Etienne, France; 4University Hospital of Saint-Etienne, immunosuppressive tryptophan catabolism independently of HCV Immunology Unit, Saint-Etienne, France; 5University Hospital of Saint-Etienne, viremia in ART-treated HIV/HCV co-infected patients Virology Unit, Saint-Etienne, France Mohammad-Ali Jenabian1,2*, Ido Kema3, Robert Paulino Ramirez4, BMC Infectious Diseases 2014, 14(Suppl 2):O17 Sahar Saeed5, Kathleen Rollet1, Kishanda Vyboh1, Jean-Carlos Tejada6, Norbert Gilmore1,2, Marina B Klein1,2, Jean-Pierre Routy1,2 Gut associated lymphoid tissue (GALT) represents the largest reservoir of 1Chronic Viral Illnesses Service of the McGill University Health Center, HIV-1. The aim of the study is: 1) to establish the viral and cellular Montreal, Quebec, Canada; 2Research Institute of the McGill University Health characteristics of the HIV-1 rectal reservoir from chronically infected men Center, Montreal, Quebec, Canada; 3Department of Laboratory Medicine, under antiretroviral therapy (ART) for more than one year and less than University Medical Center, Groningen, University of Groningen, The five years, and, 2) to correlate the size of the rectal reservoir and the Netherlands; 4School of Medicine, Research Department, Universidad cellular composition of rectal mucosa to the level of CD4+ T cells in Iberoamericana, Santo Domingo, Dominican Republic; 5Clinical Research blood at the start of ART. Solutions, Montreal, Quebec, Canada Division of Hematology, McGill For each patient, whole blood and six rectal biopsies were collected. Total University Health Center, Montreal, Quebec, Canada; 6Instituto Dominicano HIV DNA and cell-associated HIV RNA were quantified in PBMCs and in de Estudios Virologicos, Santo Domingo, Dominican Republic rectal samples by rtPCR assays. The cellular composition of blood and BMC Infectious Diseases 2014, 14(Suppl 2):O16 rectal samples in CD4+ and CD8+ T cells, Th17 lymphocytes, regulatory T cells (Treg), CD4+/p24+ and CD8+/ PD-1+ T cells was established by flow Background: HCV infection induces hepatic and extra-hepatic damage cytometry. that includes kidney and neurocognitive dysfunction. Tryptophan (Trp) is Up to now, 12 patients were enrolled: 4 with pre-ART CD4+ T cell count catabolized into immunosuppressive kynurenine (Kyn) by indoleamine above 350/mm3, 3 between 200 and 350/mm3 and 5 under 200/mm3. The 2,3-dioxygenase (IDO) and tryptophan 2,3 dioxegenase (TDO). Increased mean HIV DNA level in rectal cells was lower in patients who initiated ART Trp catabolism measured by Kyn/Trp ratio has been associated with with a blood CD4+ T cell count > 350/mm3, compared to those who neurocognitive impairment and immune dysfunction in HIV mono- started ART with a blood CD4+ T cell count < 200/mm3 (3.49 vs 3.74 log10 infection. Here, we assessed the contribution of Trp catabolism in HCV/ copies/106 cells). Moreover, the rate of rectal CD8+ T cells exhibiting an HIV co-infected patients. exhausted phenotype (CD8+/ PD-1+ T cells) tended to be negatively Methods: Plasma samples were collected from ART-treated (HIV RNA <40 correlated to the pre-ART blood CD4+ T cell count (p = 0.06, rho = -0.61) copies/ml) HCV/HIV co-infected patients with or without liver fibrosis (n=20 and to the rectal [Th17/Treg] ratio (p = 0.058, rho = -0.66). per group), HBV/HIV co-infected patients (n=25), ART-treated and untreated These preliminary results suggest that initiating ART with a high blood CD4+ HIV-mono-infected patients and 30 healthy subjects (HS), (n=30 per group). T cells (> 350/mm3) limits the size of the HIV rectal reservoir and preserve Furthermore, 17 additional HCV/HIV INF-a/ribavirin treated patients were local immunity, even after long-term therapy. This could participate to longitudinally assessed before and 6 months after sustained virological decrease local inflammation and viral replication. The study is still ongoing BMC Infectious Diseases 2014, Volume 14 Suppl 2 Page 7 of 45 http://www.biomedcentral.com/bmcinfectdis/supplements/14/S2/

to increase the size of the effective and to complete these results by RNAs targeting the same sequence. The shRNA was very active against detecting viral integrated and 2LTR DNA forms, investigating co-infections HIV-1 clades B, C and A/G. Neither the Rz, nor the shRNA disturbs the agents and studying the inflammatory environment. cellular transcriptome, suggesting no toxicity. In lymphocytic cell lines, both the Rz and the shRNA inhibit long-term HIV-1 replication [2]. Conclusions: We identified new SOFA-HDV-Rz, siRNA and shRNA O18 targeting HIV-1 Gag RNA. The shRNA is as active as the only shRNA that Next-generation LTR-specific Tre-recombinase targets a majority of HIV- has advanced to clinical trials and targets more strains. Long-term 1 isolates inhibitory activity of these molecules shows that this site is particularly Joachim Hauber1*, Janet Karpinski2, Ilona Hauber1, Jan Chemnitz1, accessible to other antisense molecules. These molecules have a high Helga Hofmann-Sieber1, Claus-Henning Nagel1, Niklas Beschorner1, potential to be used in combination gene therapy or as drugs with Carola Schäfer1, Frank Buchholz2 appropriate delivery methods. 1Heinrich Pette Institute, Leibniz Institute for Experimental Virology, References Hamburg, Germany; 2University of Technology Dresden, University Hospital 1. Lainé S, et al: RNA Biol. 2011, 8:343. and Medical Faculty Carl Gustav Carus, Department of Medical Systems 2. Scarborough RJ, et al: Methods Mol Biol. 2014, 1103:31. Biology, Dresden, Germany BMC Infectious Diseases 2014, 14(Suppl 2):O18 EMERGING INFECTIOUS DISEASES Introduction: HIV-1 integrates into the host chromosome and persists as a provirus flanked by long terminal repeats (LTR). To date, treatment O20 regimens primarily target the virus enzymes, virus attachment or virus-cell Clinical spectrum of post-chikungunya rheumatic musculoskeletal fusion, but not the integrated provirus. Thus, current antiretroviral disorders and use of disease-modifying antirheumatic drugs to treat the therapies (i.e. cART) cannot eradicate HIV-1, a fact that highlights the chronic inflammatory entities: 6-year experience from Reunion Island urgency of pursuing new strategies to find a cure for HIV/AIDS. Emilie Javelle1*, Anne Ribera2,3, Isabelle Degasne3, Catherine Marimoutou4, Previously, we engineered an experimental LTR-specific recombinase (Tre- Fabrice Simon1 recombinase) that can effectively excise integrated HIV-1 proviral DNA from 1Department of Infectious Diseases and Tropical Medicine, Laveran Military infected human cell cultures (Sarkar et al. 2007 Science 316:1912). Teaching Hospital, Marseille, France; 2Rheumatology Office, Saint Denis, La Subsequently, we demonstrated highly significant antiviral activity of this Réunion, France; 3Rheumatology Unit, University Hospital Félix Guyon, Saint HIV-1 subtype A-specific Tre in humanized mice (Hauber et al. 2013 PLOS Denis, La Réunion, France; 4Army Center for Epidemiology and Public Health, pathogens 9:e1003587). Broad clinical application, however, requires Marseille, France availability of a tre-recombinase that recognizes a majority of clinical HIV-1 BMC Infectious Diseases 2014, 14(Suppl 2):O20 isolates. Materials and methods: Here we report LTR target site identification as Aim: The re-emerging invalidating chikungunya (CHIK) disease has well as the engineering and functional analysis of a next-generation recently extended to temperate areas. Following the acute febrile Tre-recombinase that recognizes the vast majority (e.g. >93% clade B polyarthritis, miscellaneous long-lasting rheumatic musculoskeletal and >80% clade A) of clinical HIV-1 isolates. disorders (RMSKD) are reported, consistent with chronic inflammatory Results: It is shown that the HIV-1 LTR harbours a conserved region that rheumatisms (CIR) notably rheumatoid arthritis (RA). The post CHIK- may serve as a universal tre recognition site for provirus excision. In fact, infection stage remains a challenge to treat, while the early use of targeting this site by next-generation tre-recombinase demonstrates disease-modifying antirheumatic drugs (DMARDs) is recommended in RA. pronounced antiviral activity in the absence of cellular toxicity. After the 2005-2006 CHIK outbreak in Reunion Island, we retrospectively Conclusion: The presented data suggest that next-generation Tre categorizedCHIK-relatedRSMKDandanalyzedtheempiricaluseof technology may be a valuable component of future antiretroviral DMARDs starting with methotrexate (MTX) to treat the CIR forms. therapies to reverse infection and thereby providing a cure for HIV/AIDS. Materials and methods: We reviewed medical files of patients referred to rheumatologists in Saint Denis between 12/2005-05/2012 for persisting rheumatic disorders (>4 months) after a proven CHIK infection. We O19 distinguished de novo post-CHIK RMSKD from exacerbation of pre- Towards gene therapy against HIV-1: new therapeutic target in gag existing disorders. CIR included: 1) RA defined according 2010 ACR/EULAR RNA accessible to ribozymes and RNA interference molecules criteria, 2) spondylarthropathy (SA) defined according ESSG classification, A Gatignol1*, RJ Scarborough1, MV Lévesque2, E Boudrias-Dalle1, IC Chute3, and 3) undifferentiated polyarthritis (UP) defined as at least three swelling SM Daniels1, RJ Ouellette3, J-P Perreault2 joints. Response to MTX was efficacy versus failure (defined as a need for 1Lady Davis Institute for Medical Research, McGill University, Montreal, MTX switch or escalation). Determinants for efficacy were identified using Canada; 2Department of Biochemistry, University of Sherbrooke, Sherbrooke, Fisher exact test. Canada; 3Atlantic Institute for research on cancer, Moncton, Canada Results: Among 159 patients included, 122 suffered from de novo RSMKD BMC Infectious Diseases 2014, 14(Suppl 2):O19 with 28 presenting chronic pains and 94 fulfilling CIR criteria. RA accounted for 40/92 (12 positive for anti-CCP antibodies); SA for 33/94 (15 with Aim: Antisense molecules targeting HIV-1 RNA have the potential to be psoriasis); and distal UP for 21/94. 72 of them (including the 31 CIR with used as part of combination gene or drug therapy to treat HIV-1 infection joint damages) were treated with MTX (40 RA, 26 SA), reaching efficacy in 54 to reach a functional or complete cure. Only a small number of extremely cases (30 RA, 19 SA, 5 UP) versus failure in 18 cases (10 RA, 7 SA, 1 UP). No active molecules currently exist and a treatment option has not yet been severe side event was observed. The group efficacy did not differ with age, identified in clinical trials. We have previously developed new hepatitis sex or type of CIR, but was significantly associated with the early delta virus (HDV)-derived ribozymes (Rzs) called “switch on-off adaptor” introduction of MTX within the first year of CIR progression (p =0,034). (SOFA) to target HIV-1 RNA [1]. Our aim is to develop highly active RNA- Conclusions: Among the wide spectrum of post CHIK RMSKD, CIR should based molecules with complementary mechanisms, which are able to benefit from the early use of MTX. DMARD’s efficacy could bring some reach a large number of HIV-1 variants. clues to investigate the underlying post CHIK-infection disorders. Methods: We screened HIV-1 RNA to identify conserved target sites for new HDV-Rzs [2]. We designed new SOFA-HDV-Rzs against the Gag RNA and developed a rapid test to evaluate the inhibition of HIV-1 production. O21 We designed small interfering (si) RNAs targeting the same region and Chikungunya infection: six years after, rheumatic morbidity and tested their activity on HIV-1 replication. impaired quality of life persist! Results: We identified 13 conserved regions in the gag RNA and F Simon1*, J Ferraro1, E Javelle1, C Marimoutou2 constructed the corresponding Rzs. We transfected HEK293T cells with 1Laveran Military Teaching Hospital, French Military Health Service, Marseille, these Rzs and HIV-1 molecular clones. We identified one Rz that was France; 2Army Center for Epidemiology and Public Health, Marseille, France particularly efficacious. We then constructed siRNAs and short hairpin (sh) BMC Infectious Diseases 2014, 14(Suppl 2):O21 BMC Infectious Diseases 2014, Volume 14 Suppl 2 Page 8 of 45 http://www.biomedcentral.com/bmcinfectdis/supplements/14/S2/

Background and objective: In 2006, all the military policemen deployed other antiretroviral drugs is ongoing with the aim of developing a device in Reunion Island during the chikungunya outbreak were enquired, 25% able to protect efficiently against the viral loads observed in semen. At self-declared chikungunya infection (CHIK+) and 19% had positive term, this system could be rendered more complex by the addition of serology. In 2008, a self-questionnaire was sent to the same persons, 403 antiviral compounds directed against other viruses and/or of anti- responded, 101 were CHIK+. The latter presented higher frequency of inflammatory drugs or hormones. rheumatic disorders and significantly lower quality of life (QoL) than non- infected (CHIK-) responders, 30 months after the outbreak. The purpose of this study is to understand if the difference persisted at six years. P2 Method: The 646 participants to the 2006 enquiry were sent self- In vivo analysis of GenePro, a lentivral therapeutic vaccine questionnaires by postmail with informed consent to the present study Mariel Selbovitz*, David Miller and proposal of new biological testing. Only 609 could be reached, and Cornell AIDS Clinical Trials Group, New York, USA 252 fulfilled the questionnaire: 81 CHIK+ (32%) and 171 CHIK-. The results BMC Infectious Diseases 2014, 14(Suppl 2):P2 are based on their declaration. QoL was estimated with the SF-36 scale. Results: CHIK+ patients declared higher health care consumption Introduction: Despite advances in HIV commercial therapies, including between 2008 and 2012 (more frequent general practitioners consultation fixed-dose combinations, unprecedented proportions of HIV patients and use of paracetamol). They complained of more frequent and intense remain without therapeutic options due to lack of access to treatment joint pain (40% versus 22% at least once a week, 64% versus 38% and epidemiologically significant proportions of multi-class drug moderate to intense pain), stiffness and swelling during the same period. resistance that are driving morbidity levels in both developed and They also report more frequent fatigue, headache and depress mood resource-poor settings. The need to emphasize the development of (respectively 60% versus 32%, 42% vs29% and 21vs 6%, p<0.001). Finally therapeutic options with the potential to abrogate these correlating all dimension of SF36-QoL were significantly impaired in CHIK+ patients, trends are receiving insufficient dedication of resources, as new clinical reflecting social, physical and mental impact of the disease. strategies do not address these enduring disparities. GenePro, a Conclusion: Despite a possible selection bias of the most symptomatic CHIK therapeutic vaccine candidate, has shown preclinical efficacy via publicly + patients increasing the observed differences, the large differences observed sponsored research that demonstrates the potential to address a current in rheumatic morbidity, fatigue, and QoL lead to the conclusion that CHIK therapeutic issue. infection has very long term impact on health, social life and QoL with a very Materials and methods: The GenePro therapeutic construct includes low proportion of patients returning to their previous health status. strong lentiviral promoter and 7 out of 9 HIV genes: Gag, pol, tat, rev, vpu, env and nef. In a preclinical study, kinetic analyses on splenocytes of BALB/c mice that were immunized by a single injection with a GenePro POSTER PRESENTATIONS were performed. IFN-gamma-ELISPOT and multiparametric FACS analysis were conducted to characterize the induced CMI response. Animals immunized with a single high dose of GenePro were monitored HIV EPIDEMIOLOGY AND PREVENTION longitudinally for vaccine-induced IR using multiparametric flow cytometry-based assays. P1 Results: Comprehensive analysis demonstrated the capacity of a single Kinetics of release of antiretroviral drugs through a silicone intravaginal high dose of HIV DNA vaccine alone to induce long-lasting and ring polyfunctional T-cell responses in the nonhuman primate model. In Bruno Pozzetto1*, Meriam Memmi1, Marlène Desloir2, Blaise Figuereo1, preclinical studies, GenePro has been found to generate the HIV-specific Thomas Bourlet1, Christian Carrot2 memory cells found in elite controllers and reconstitution of the immune 1University Hospital of Saint-Etienne, Groupe Immunity of the Mucous system. The TriGrid delivery system increases DNA delivery efficiency by Membranous and Pathogen Group (GIMAP), EA 3064, Saint-Etienne, France; up to 1,000 fold. This approach has less toxicity and no drug resistance 2University Hospital of Saint-Etienne, Engineering of polymer materials, Saint- and may allow for STIs from ART. Etienne, France Conclusion: Data from initial investigations of GenePro indicate BMC Infectious Diseases 2014, 14(Suppl 2):P1 improvements in immune response and generation of HIV-specific memory cells that induced immune responses by altered HIV DNA Aim: The propagation of HIV-1 infection represents a major problem of constructs, which synthetically mimic virologic responses of elite public health, notably in sub-Saharan Africa where about six out of ten controllers. Advancement of GenePro into human studies will serve as a infected adults are women. Among the new options of preventive hallmark in continuing commercial efforts to discover a universal address therapy, antiretroviral drugs used as microbicides distributed via an for the global AIDS crisis. intravaginal ring (IVR) constitutes an original solution. IVR is an interesting mode of drug delivery because it is a coit-independent device that can be left in the vagina for several months and can release regular amounts P3 of microbicides. The aim of this work was to set up a silicone IVR able to Prevalence of HIV, HBV and chlamydia infections in Cameroonian deliver simultaneously several drugs with the precise objective of University context: case of the University of Dschang, in the Western determining if the release of each drug is possible with the used silicones region and of choosing the best formulation. Martin Sanou Sobze*, Jean Hubert Donfack, James-Francis Onohiol, Materials and methods: IVRs were made manually with siloxanes Joseph Fokam, Ghislaine Bruna Djeunang Dongho, combining two elastomers from Blue Star Silicone before and after Patrick Stephane Nkamedjie Pete, Vittorio Colizzi, Gianluca Russo reticulation, and were loaded with different concentrations of tenofovir. Department of Biomedical Sciences, Faculty of Sciences, University of The rings were then placed under conditions mimicking closely the Dschang, Dschang, Cameroon physiological environment of the vagina. The amounts of released BMC Infectious Diseases 2014, 14(Suppl 2):P3 tenofovir were measured by UV spectrophotometry. Results: The manual mode of fabrication of IVR is described with details. Introduction: In sub-Saharan Africa HIV infection remains largely Different combinations of siloxanes were used. Only some of them were epidemic, whereas HBV infection is highly endemic (>8%). In Cameroon, shown to release amounts of tenofovir that can be considered as efficient the prevalence of HIV is 4.3%. Concerning HBV and chlamydia infections, for protecting from a heterosexual HIV-1 infection. We present rheological their prevalence are both ≥10%. Teenagers and young adults, including analyses that sustain these differences. university students, are the population groups mostly affected by STDs. Conclusions: We propose a model that was shown able to test the Epidemiological data on these infections, among university students release of antiretroviral drugs by a silicone multi-reservoir IVR under could be helpful to implement specific prevention strategies. various experimental conditions. The release of tenofovir by silicone Methods: A descriptive study was performed in May 2013 among 624 obeys to physico-chemical rules that we tried to elucidate. The study of students from the University of Dschang, Cameroon. Participants were BMC Infectious Diseases 2014, Volume 14 Suppl 2 Page 9 of 45 http://www.biomedcentral.com/bmcinfectdis/supplements/14/S2/

screened for HIV, HBV and Chlamydia infections. Data was collected by a Aim: According to New York State law, HIV testing must be offered to standard questionnaire and analyzed by Epi Info. every patient aged 13-64. However, acute mental health hospitalizations Results: The average age of participants was 23.3 years (s =3.2)witha can be difficult settings in which to conduct HIV screening. Because female predominance (58.7%). The observed prevalence of HIV, HBV and individuals with mental illness have higher rates of HIV infection, routine Chlamydia infection was 1.1% (7/624), 2.8% (5/176) and 2.0% (2/100) testing of stabilized patients in psychiatric inpatient wards could be respectively. 83.2% of participants were sexually active. Concerning sexual beneficial. This study describes the implementation of a rapid HIV testing risky behaviors, participants reported having multi partners (14.8%), using program in this nontraditional setting. condom regularly (36.4%), occasionally (58.6%) or never (5.0%). 100%, Methods: This prospective, descriptive study was conducted in a 62.6% and 52.2% reported to be aware on HIV, HBV and Chlamydia psychiatric inpatient ward over 22 days. A convenience sample of patients infections respectively. In addition, only 5.5% and 21.3% of the participants deemed to have capacity to consent by a team of physicians were were aware of their HBV and Chlamydia status respectively, versus 64.4% recruited by Public Health Advocates (PHAs). PHAs collected demographic for HIV. The excessive cost of HBV and Chlamydia tests has been identified characteristics and risk factors during targeted counseling sessions. Chart as the major barrier to testing (87.6%). reviews were conducted to assess psychiatric diagnoses and sexual/drug Conclusion: Among college Cameroonian students the prevalence of HIV, abuse history. Rates of test acceptances were tracked during the last HBV and Chlamydia infections seems to be relatively low if compared to 8 days of the study. general population. However, having multiple sexual partners in addition Results: 346 patients were tested for HIV. Demographic characteristics of to non-systematic use of condoms during sexual intercourse represents the participants were: 60.1% male, 43.4% Hispanic, and 40.5% Black. Mean risky behaviors among students. Awareness campaigns and screening age was 37.7 ± 12.8. 36.7% do not engage in regular medical care. As per facilitation on HBV and chlamydia infections among students need to be CDC criterion, 27.7% of participants were high-risk for acquiring HIV. Risk strengthened. factors were: multiple sex partners (21.7%), injection drug use (5.8%), sex for commodities (4.9%), sex with an injection drug user (3.5%), or sex with an HIV-positive partner (1.5%). Psychiatric diagnoses were: Schizophrenic/ P4 Psychotic/Affective (64.5%), Depression (15.0%), and Bipolar (14.2%). Drug Evaluation of pharmacy-based HIV testing in a high-risk New York City abuse was noted in 31.2% of cases, and 7.5% reported sexual abuse history. community One patient was confirmed HIV positive and linked to outpatient HIV care. In S Amesty*, N Crawford, V Nandi, A Rivera, C Fuller last 8 days of study, 240 of 322 consentable patients were offered the HIV Columbia University, New York, USA test (74.5%), of which 149 accepted (62.1%). BMC Infectious Diseases 2014, 14(Suppl 2):P4 Conclusion: A rapid HIV testing program with multidisciplinary staff buy-in can test a large number of patients in a psychiatric inpatient ward. Introduction: Injection drug users (IDUs) face limited access to HIV Expansion of HIV screening initiatives to nontraditional settings can testing and experience delayed HIV diagnoses. New York City (NYC) increase access to testing for high-risk populations that may not otherwise pharmacies play an important role in HIV prevention among IDUs engage in primary care. through the Expanded Syringe Access Program (ESAP), which provides access to sterile syringes without a prescription. We examined in- pharmacy HIV testing among syringe/non-syringe customers in ESAP P7 pharmacies in NYC. A randomized, controlled study exploring factors associated with Materials and Methods: Syringe/non-syringe pharmacy customers were decision to undergo HIV screening recruited in two ESAP community pharmacies in high HIV prevalence Gerard O’Connor*, Ailbhe Ni Flaitheartaigh, Aoife Lacey, Jane O’Halloran, neighborhoods to complete a 30-minute survey. In-pharmacy HIV testing Eamon Brazil, Yvette Calderon, Patrick WG Mallon was offered to all HIV-negative participants. Descriptive statistics, chi-square HIV Molecular Research Group, School of Medicine and Medical Science, and Fisher’s exact tests were performed for categorical outcomes and t-tests University College of Dublin, Dublin, Ireland for continuous outcomes to determine significant differences in individual BMC Infectious Diseases 2014, 14(Suppl 2):P7 characteristics between patrons who accepted in-pharmacy HIV testing compared with those who declined. Stepwise multivariable logistic Introduction: Little is known of the factors associated with a decision to regression was used to assess the relationship between receiving in- test for HIV, particularly among varied gender and cultural groups. The pharmacy HIV testing and customer characteristics identified from bivariate Mater-Bronx Rapid HIV Testing (M-BRiHT) project explored if choice of analyses. pre-test counselor affected the decision to undergo HIV testing and Results: Of 327 participants, most were male (57%), black (80%), had ever hypothesized that offering expanded choice of counselor would lead to used hard drugs (88%); 217 (66.4%) were HIV-negative, and 39.6% received higher testing completion rates. in-pharmacy HIV testing. After adjustment, being female (AOR 2.71; 95% CI Materials and methods: The M-BRiHT project is a single-site, prospective 1.44-5.10), having multiple sex partners (AOR 1.31; 95% CI 1.08-1.59), randomized study of adult Emergency Department attendees offered having an HIV test more than 12 months ago (AOR 2.90; 95% CI 1.30-6.47), automated video-based pre-and post-test counseling combined with injecting drugs (AOR 2.26; 95% CI 1.04-4.91), and seeing the same regular rapid HIV testing (buccal swab). Subjects were randomly assigned to medical provider (AOR 0.33; 95% CI 0.17-0.67) were associated with receive identical, standardized video-based pre- and post-test counseling receiving in-pharmacy HIV test. from a single pre-assigned counselor (Caucasian female) or to choose one Conclusions: This study presents evidence for a potential new venue for of four counselors (male or female from Caucasian or African origin). HIV testing that could provide access for hard-to-reach populations that Primary endpoint was the proportion of subjects completing HIV testing have limited access to HIV testing. The approach we used was feasible to in each randomization group. pharmacists. Given that pharmacies are located everywhere in NYC and Results: Of 6,000 subjects recruited from September 2012 to 2013, 2950 have access to new point-of-care and home-based HIV testing (49.1%) were randomized to choice of counselor. Mean (SD) age was 40.9 technologies, the provision of HIV testing in pharmacies could provide (16.4) yrs, 48.8% were female and 91.0%, 2.5% and 3.1% were of Caucasian, easy access to HIV testing for IDUs as well as other populations. African or Asian ethnicity respectively. 4,919 (82.0%) completed HIV testing, with significantly higher completion rates in those randomized to choice of counselor (83.1 versus 80.9%, P6 P<0.001). Other factors associated with higher HIV test completion rates Implementation of a rapid HIV testing program in psychiatric inpatient included younger age (median 36 (SD 15.6) versus 46 (SD 18.6) yrs, wards P<0.001); and male gender (84.1 % v 79.8%, P< 0.001). Maryann J Popiel*, Vikram Duvvi, Albert Turkieh, Ethan Cowan, Fourteen subjects tested HIV positive (prevalence 2.8/1000), with 10 new Yvette Calderon, Kelly M Chacón, Sara Rahman, John Y Rhee, Adam Kornmehl HIV diagnoses and four re-confirmed HIV positive and re-linked to care. , Jason Leider None had symptomatic HIV. Median (IQR) CD4+ T-cell count of new Albert Einstein College of Medicine, Bronx, USA diagnoses was 515 (332, 595) cells/mm3 and all subjects were successfully BMC Infectious Diseases 2014, 14(Suppl 2):P6 linked to care. BMC Infectious Diseases 2014, Volume 14 Suppl 2 Page 10 of 45 http://www.biomedcentral.com/bmcinfectdis/supplements/14/S2/

Conclusions: The M-BRiHT study demonstrates the feasibility of were presented at the clinic for follow up; of these, 21(0.8%) tested HIV implementing large scale HIV screening within the Emergency Department positive by DNA at an average age of 12 weeks. and highlights the importance of offering choice of counselor when Conclusion: The PMTCT success rate of 99% achieved is comparable to automated systems are employed to optimize HIV testing rates. that in developed countries. In low income countries where it is not possible to implement full PMTCT protocol, a strategy where a public institution is the center and provides services for other smaller institutions is recommended. P8 Occupational exposure, knowledge of standard precautions and behavior among health workers in Southern Nigeria P10 Samuel Ereh Characteristics of men who have sex with men (MSM) who tested for Eku Baptist Hospital, Department of Family Medicine, Eku, Nigeria HIV while donating blood in Latvia BMC Infectious Diseases 2014, 14(Suppl 2):P8 A Mozalevskis1*, A Karnite2 1National Center of Epidemiology (CNE), Salud Carlos III Institute, Madrid, Background: Developing countries account for the highest prevalence of Spain; 2Riga Stradins University, Department of Public Health and HIV-infected patients in the world and also record the highest needlestick Epidemiology, Riga, Latvia injuries. The objective of this study was to assess the exposure, BMC Infectious Diseases 2014, 14(Suppl 2):P10 knowledge and practices of standard precautions among Health care workers (HCWs) in Southern Nigeria. Background: In 2005, Latvia lifted the ban on blood donation for men Methods: We surveyed 212 HCWs in 4 state-owned hospitals and 25 who have sex with men (MSM). The prevalence of HIV infection in blood local government primary health centers. Structured questionnaires were donations since then has been stable (around 0.02%), though it is higher utilized. Descriptive statistics and multivariate analysis using logistic than the European average (0.009% in 2006). We aim at describing the regression were done. MSM who report that their last HIV test was done while donating blood Results: 57.7% of respondents were aware of the term Standard (WDB) to approach the role of MSM in the donor blood safety. Precautions (SPs) overall. Doctors (94.4%) and nurses (84.2%) had the Methods: We used the Latvian dataset from the European MSM Internet highest levels of awareness compared to 3.0% of health assistants. There Survey (EMIS, 2010). We compared the MSM who had their last HIV test WDB was a significant relationship between the respondents’ level of with those who had their last HIV test elsewhere in terms of socio- education and a correct knowledge of SPs. (Fisher’s Exact= 125.745, df = demographic and behavioral factors using Chi-square and Fisher’sexacttests. 4, p = 0.000) and duration of employment was not significantly Results: Of 708 EMIS respondents in Latvia, 346 (49.8%) ever tested for associated with the awareness of SPs. (x2 = 5.676, df =3, p =0.128). Life HIV and of these, 46 (13.3%) received their last HIV test WDB. Reactive time risks of needle stick (39.8%; 95% CI 36.4-44.6%) and sharps injuries HIV test were lower among MSM who reported having last test WDB than (25.7%; 95% CI 21.8-29.6%) were high. 77 .8% washed their hands at the elsewhere (4% vs. 8% p=0.292). Respondents below 25 years, MSM self- close of work. Over half (56.6%) always used gloves and two-thirds identified as bisexual rather than gay and MSM who were less open (62.3%) had never worn goggles during contact with blood and body about their sexual orientation were more likely to have their last HIV test fluids. Only 46.2% of HCWs reported washing their hands before each WDB (25% vs. 11%, p=0.003; 22% vs. 11%, p=0.066; 15% vs. 5.5% patient contact. Overall compliance with non-recapping of used needles p=0.061, respectively). There was no difference in terms of reported risk was generally poor (14.6%) and about half (48.1%) of the respondents behavior. Only one respondent who received last HIV test WDB (2%) recapped used needles before disposal. The one year prevalence of reported having the opportunity to discuss sexual practices before the needle stick and sharps injury were 29.3% (95% CI 26.7-32.8%) and 22.9% test while they were 48 (16%) among those tested elsewhere (p=0.047). (95% CI 19.8-25.2%) respectively. Conclusion: MSM donate blood and the prevalence of HIV infection in Conclusions: The poor knowledge and non-compliance with SPs among blood donation from MSM might be higher than from general population. the HCWs placed them at significant health risks. Adequate supply of MSM who donate blood are younger, self-identified as bisexual and not protective equipment with regular training programs should therefore be open about their sexual orientation. More attention is needed to evaluate put in place to promote appropriate use by the HCWs at all times. their sexual risk behaviors in a sensitive and acceptable way during the pre-donation interview.

P9 Success rate of an outreach PMTCT program in Nigeria P11 EC Herbertson*, AGI Ohihoin, TA Gbajabiamila, AN David, O Odubela, HIV risk behaviors and condom use in west region of Cameroon: need SO Ekama, CV Gab-Okafor, H Owhodo, OC Ezechi, IAO Ujah for HIV prevention strategies shifted towards HIV seropositive Nigerian Medical Institute of Research, Lagos, Nigeria individuals BMC Infectious Diseases 2014, 14(Suppl 2):P9 Celine Nkenfou*, Japhette T Kembou, Irenee Domkam, Appolinaire Djikeng, Timoleon Tchuinkam Introduction: Prevention of mother-to child transmission (PMTCT) of HIV Chantal Biya International Research Center, Yaoundé, Cameroon is an important strategy to achieving zero new HIV infection and has BMC Infectious Diseases 2014, 14(Suppl 2):P11 been an important strategy in preventing the upsurge of HIV infection in Nigeria. Introduction: Implementation of HIV/AIDS control programs in Cameroon Method: This study is an 8 year (2004 – 2012) review to evaluate the has not completely limited the spreading of the disease. Few studies outcome of PMTCT outreach services offered by the Nigerian Institute of conducted in West region of Cameroon determined factors favoring disease Medical Research (NIMR). It is a retrospective review of PMTCT and infant propagation; thus the need of an assessment so as to design strategies follow-up databases. PMTCT enrollees (from the NIMR adult antiretroviral which will optimally limit the rate of transmission of HIV in this area. clinic and referrals from public and private antenatal clinics) were placed on Materials and methods: Participants attending voluntary counseling routine PMTCT care and subsequent infant prophylaxis, based on the WHO/ during a screening campaign were recruited for a cross-sectional study after National PMTCT guidelines. While ANC services are provided at the clinic, informed consent. Interview-administered questionnaires were used for data labor and delivery services are provided by partner institutions. The women collection. HIV sero-status was assessed following the national algorithm and are referred out at 36 weeks with delivery protocol. They are referred back by oral fluid rapid test. Analyses of data were carried out using Microsoft after delivery with complete delivery summary form. Infants were followed Excel 2010 and the statistical package for social sciences (SPSS) at a level of up for 18 months and had HIV DNA PCR done at 6 weeks and 6 months. significance of 5%. Results: There were a total of 4139 records for PMTCT uptake. 257 of these Results: 66.7% of men and 61.1% of women declared scarification had incomplete data and were excluded from analysis. The delivery exposures. Poor knowledge of the disease was reported by 62.5% of men outcomes include: miscarriage -107 (2.8%); still birth- 134 (3.5%); live births and 54.7% of women. They were less likely to use condoms (OR= 0.9; 95% -3641 (94%), neonatal deaths-68 (1.8%).Only 2623(73%) of the live births CI: 0.6- 1.3). Multiple sexual partners were noted for 34.7% of men and BMC Infectious Diseases 2014, Volume 14 Suppl 2 Page 11 of 45 http://www.biomedcentral.com/bmcinfectdis/supplements/14/S2/

24.5% of women, who were found significantly less likely to use condoms Introduction: Internal migrants have been repeatedly characterized as (OR= 0.5; 95% CI: 0.3-0.7). 43.3% of patients declared occasional usage of “the tipping point” for HIV epidemic in China. Despite increasing condoms with women less likely to use them (OR= 0.8; 95% CI: 0.5-1.1). awareness that condom use of the internal migrants is essential in the Unawareness on the serologic status of the sexual partner was also battle for reducing the spread of HIV/AIDS in China, little is known as to observed in 31.4% of men and 43.3% of women (95% CI: 0.5-1.2). HIV what factors influencing actual condom use in the population. This study seropositive study participants used condoms occasionally (in 71.4% of aims to explore cognitive and socio-environmental correlates of condom cases) even though aware of their sero-status. They were not aware of the use comprehensively, and test a model for illustrating condom use sero-status of their sexual partners in 57.1% of cases. Moreover 50% of among internal migrants in Shenzhen, China. them had more than one sexual partner. All these should be incorporated Materials and methods: A cross-sectional survey was conducted among when designing prevention strategies to reduce disease impact. a purposive sample of 400 migrants between April 2013 and June 2013. Conclusions: Ratesofriskybehaviorsnoted among HIV positive Participants were asked by a questionnaire about their socioeconomic individuals should raise our attention on implementation of prevention status, HIV-related knowledge, sexual behavior, cognition of condom use, strategies shifted towards this particular group of people. and socio-environmental conditions. A hypothesized model was expanded from constructs of the theory of planned behavior and protection motivation theory to environmental conditions. We performed P12 multivariate analyses and structural equation modeling using SPSS 21.0 A quantitative exploration of health care workers opinions and and Amos 22.0 to assess the model on explaining condom use. attitudes towards HIV-infected co-workers and patients in Beijing, Results: Of 268 sexual active participants, 66.8% reported use condom(s) China inconsistently in the preceding year, and 51.1% reported did not use Xiaona Liu*, Xinying Sun, Lenneke van Genugten, Yuhui Shi, Yanling Wang, condom in their last intercourse. Both measurements of condom use Wenyi Niu, Jan Hendrik Richardus correlated with education, knowledge, cognition (severity, susceptibility, Erasmus MC, University Medical Center of Rotterdam, Rotterdam, the fear, response efficacy, self-efficacy, barriers to action, and subjective Netherlands norms), environmental conditions (living with a committed partner, living BMC Infectious Diseases 2014, 14(Suppl 2):P12 in a community where condoms are easily available, involving in HIV prevention program, discussion on condom with partner) (P<0.05). The Introduction: Health care workers (HCWs) face moral and practice-related hypothesized model used in this study was well fit in illustrating condom dilemmas when working with co-workers and patients with HIV. This use (P=0.035, GFI=0.952, AGFI=0.962, CFI=0.983, NFI=0.997, RMSEA=0.068). study aims to understand the underlying stigmatizing opinions and Barriers to action were the strongest correlates of consistent condom use attitudes of HCWs that may drive discrimination towards HIV-infected co- (coefficient=0.38, P=0.002), while discussing condom with sexual partner workers and patients in the workplace. was the strongest correlates of condom use in the latest intercourse Materials and methods: A cross-section survey was conducted among (coefficient=0.26, P<0.001). 392 HCWs (113 doctors, 236 nurses and 43 technicians) in two tertiary Conclusions: Our findings confirmed the model integrating cognitive and hospitals in Beijing between May and July 2010. Participants were asked socio-environmental factors as a suitable model for Chinese internal by a self-administered anonymous written questionnaire about their migrants regarding condom use. HIV prevention programs may benefit socio-demographic characteristics; experience on HIV-related training, by focusing on barriers to behavior change and environmental conditions testing, and percutaneous injury; and the extent of their agreement with for internal migrants in China. 9 rigid opinions regarding managing HIV-infected co-workers, and with 10 negative attitudes regarding working with HIV-infected patients on a 5-point Likert scale. Pearson correlations and multivariate regression P14 analyses were performed using SPSS 20.0 to study possible correlates of Epidemiological and clinical aspects of paediatric HIV infections in Setif the general opinion and attitude. (Algeria) Results: Participants perceived a high risk of HIV transmission in both co- A Ouyahia*, M Rais, A Gasmi, S Mechakra, A Lacheheb worker and HCW-patient relationships (86% and 87% respectively). Half of Ferhat Abbes University, faculty of medicine, Setif, Algeria participants agreed that HCWs should routinely and mandatorily receive BMC Infectious Diseases 2014, 14(Suppl 2):P14 HIV-tests, HCWs with HIV should disclose their diagnosis to relevant parties, and should be restricted from performing invasive procedures. Participants Background: Algeria has a low HIV prevalence and data on the risk had a negative feeling towards patients infected through sexual contact factors and clinical presentation of HIV-infected children are lacking. (80%), and believed that HCWs have the right to refuse to care for infected Objective: To describe the epidemiological, clinical characteristics and patients (51.8%), and that those patients should be treated only in outcome of HIV-infected children in Setif. designated hospitals (87.0%). Almost all HCWs intended more or less to Methods: A retrospective review was undertaken of the medical records avoid performing invasive clinical procedures or nursing services for HIV- of all patients admitted to the HIV unit of the teaching hospital of Setif infected patients (91.0%). After corrected by other factors (e.g., age, gender), which serves a population from a wide geographic catchment area, nurses retain significantly more stigmatizing attitudes towards HIV-infected between January 2002 and November 2013. patients than doctors (b = -0.19, 95%CI: -0.32, -0.05) and technicians (b = Results: Of 286HIV-infected patients, 12 were children (4.1%), 8 (66.7%) of -0.15, 95%CI: -0.32, 0.02). whom were male. Ages at diagnosis ranged from 6 months to 12 years Conclusions: The identified rigid opinions on managing HIV-infected co- (median 5). workers, together with stigmatizing attitudes towards HIV-infected patients, Of the 10 (83.3%) children who acquired the infection by vertical underscores an urgent need to decrease stigmatizing attitudes and prevent transmission, median age at diagnosis was 3 years. Only one woman was discriminatory practices in health care settings. Rectifying gaps in ethics, offered PMTCT interventions with HAART started lately at 38 weeks of legislation, and practice is critical to reach the balance between ensuring pregnancy, oral AZT and replacement feeding to neonate. rights of people with HIV and preventing HIV transmission in the workplace. All neonates were delivered by spontaneous vaginal delivery, 9 of them were breastfed throughout infancy. Children commonly presented with prolonged fever (25%), recurrent cough P13 (n=33.3 %), failure to thrive (n=41.66 %) and recurrent diarrhoea (n=8.3%). Cognitive and socio-environmental correlates of condom use among One case had tuberculosis associated to herpes zoster, 2 cases of moluscum internal migrants in Shenzhen, China: a structural equation model contagiosum, one case of anal condyloma and one case of visceral approach leishmaniosis. All cases received highly active antiretroviral. Of those 91.6% Xiaona Liu*, Tan Jingguang, Vicki Erasmus, Lenneke van Genugten, were compliant with treatment and had a sustained virologic response Xinying Sun, Jan Hendrik Richardus below the detectable levels. One child died at age of 6 months. Erasmus MC, University Medical Center of Rotterdam, Rotterdam, the Conclusion: The majority of HIV-infected children presenting to our Netherlands hospital acquired HIV through vertical transmission. A strong prima facie BMC Infectious Diseases 2014, 14(Suppl 2):P13 case for the introduction of mandatory HIV testing of pregnant women BMC Infectious Diseases 2014, Volume 14 Suppl 2 Page 12 of 45 http://www.biomedcentral.com/bmcinfectdis/supplements/14/S2/

must be made because the price paid by HIV-infected newborns for their • A regional disparity of this prevalence. mothers’ failure to undergo testing and treatment is very high. • No identification of a population at risk. • The improvement of hygiene and the use of disposable syringes in hospitals can explain this decrease of the prevalence; HVB vaccination P15 began in 1995 and didn’t affect the sample of the study. Prevalence of HIV-2 and ART treatment coverage in Northern Sierra Conclusion: Hepatitis B is still a public health problem in Tunisia. Leone Vaccination and better socio-economic condition will lead in short term Nell G Bond1*, Augustine Goba2, Danielle Levy2,3, Lina M Moses2,3, to the decrease of the HVB prevalence, started since the 90’s. Sallieu K Sesay4, Idriss Bangura4, Matthew Kemoh Gibateh4, Sheik H Khan2,5, Preston A Marx1,3,6 1Tulane University School of Public Health and Tropical Medicine, New P17 Orleans, Louisiana, USA; 2Tulane University Lassa Fever Project, Kenema, Do penile cutting practices other than full circumcision protect Sierra Leone; 3Tulane University School of Medicine, New Orleans, Louisiana, against HIV? USA; 4Kabala Government Hospital, Kabala, Sierra Leone; 5Sierra Leone John M Kaldor1*, David MacLaren2, John McBride2, Peter Siba3, Ministry of Health and Sanitation, Freetown Sierra Leone; 6Tulane University Andrew Vallely1,3 National Primate Research Center, Covington, Louisiana, USA 1Kirby Institute, University of New South Wales, New South Wales, Sydney, BMC Infectious Diseases 2014, 14(Suppl 2):P15 Australia; 2James Cook University, Townsville City, Queensland, Australia; 3Papua New Guinea Research Center, Goroka, Papua New Guinea Acquired immunodeficiency syndrome caused by HIV-1 or HIV-2, affects 35.3 BMC Infectious Diseases 2014, 14(Suppl 2):P17 million people worldwide. Nine HIV-2 subtypes originating from sooty mangabeys in West Africa have been described. Subtypes A and B are Introduction: Male circumcision provides a high level of protection epidemic while C to I are crossovers that are known in single persons. HIV-2F against sexually acquired HIV infection and is a key element of prevention is an exception among non-epidemic subtypes, being pathogenic and found in countries with extensive heterosexual transmission. In some countries, in two persons, both from Northern Sierra Leone, suggesting transmissibility. penile cutting practices other than full circumcision are a part of the Very little data are published concerning the distribution and prevalence of cultural landscape, raising the question of their ability to modify the risk of HIV2 in Northern Sierra Leone despite a new pathogenic HIV2 emerging from HIV. One such country is Papua New Guinea. this region. Data on ART treatment coverage is also lacking. Methods: We reviewed information on prevalence of HIV, sexually Subjects presenting for voluntary HIV test and those referred by transmitted infection (STI), and penile cutting practices, and their possible healthcare providers were enrolled following informed consent. This relationships. represents a targeted, higher risk population than the general population. Results: Based on antenatal testing, the prevalence of HIV infection Commercial HIV1/2 rapid tests were used in the field. PCR and NGS among pregnant women in Papua New Guinea is around 0.9%. Surveys methods are being used to determine prevalence of newly emerging HIV- of STI in pregnant women have found prevalences of chlamydia, 2F. A questionnaire was administered to collect demographic information gonorrhoea and trichomonas in the range 15-25%, and infectious syphilis and treatment history in those testing positive. at 2-3%. In three studies of penile cutting around half the men have Currently the prevalence of HIV in the targeted sample population is some form of procedure; 10% had full foreskin removal with a further 30- 5.98%. Interestingly, when compared to the last published data on HIV-2 40% having dorsal slits, with lateral retraction of the foreskin and in the region, prevalence has increased by a factor of 32, from 0.021 to exposure of the glans. There is evidence of an inverse geographic 0.68%. 77% of HIV positive persons were newly identified cases. Of those correlation between HIV prevalence and partial cutting practice. previously testing HIV positive, only 41% were currently on treatment Conclusions: Levels of curable STIs in Papua New Guinea are very high compared to 61% ART coverage in HIV positive persons in low and by international levels, while HIV infection is at moderate levels compared middle-income countries globally. to the countries in which male circumcision is now being promoted. The Our data indicate the prevalence of HIV has increased in Sierra Leone since role of partial penile cutting procedures deserves further examination to the civil war. Further data are needed to conclusively show prevalence see whether it provides protection, and if so what this tells us of the changes of HIV in Northern Sierra Leone on a population level. The data biology of HIV transmission. also show that ART treatment rates in Northern Sierra Leone are significantly lower than the global average highlighting the need for improved case identification and treatment provision in this resource poor P18 setting. Sequencing of HIV positive samples to determine the subtype is in Characterizing the epidemiology and interaction between HIV-1 and process. This study provides a basis for further population based study of HBV co-infection in South Africa the HIV strains circulating in Northern Sierra Leone. Philippa C Matthews1,2*, Apostolos Beloukas3, Amna Malik4, Thumbi Ndung’u5, Philip Goulder4,5, Anna Maria Geretti3, Paul Klenerman1,2,6 1Nuffield Department of Medicine, University of Oxford, Oxford OX1 3SY, UK; P16 2Department of Infectious Diseases and Microbiology, Oxford University Epidemiology of hepatitis B in Tunisia: retrospective study in 198157 Hospitals, John Radcliffe Hospital, Headington, Oxford OX3 9DU, UK; blood donors in military environment 3Institute of Infection & Global Health, University of Liverpool, Liverpool L69 MT Khoufi*, A Mrabet, B Nsiri, MN Ebdelli, M Yedeas 7BE, UK; 4Department of Pediatrics, University of Oxford, Peter Medawar General Direction of military health, Tunis, Tunisia Building, Oxford OX1 3SY, UK; 5HIV Pathogenesis Program, Doris Duke BMC Infectious Diseases 2014, 14(Suppl 2):P16 Medical Research Institute, University of KwaZulu-Natal, Durban, South Africa; 6NIHR Biomedical Research Center, John Radcliffe Hospital, Headington, Introduction: Hepatitis B is endemic in Tunisia. His prevalence was Oxford OX3 9DU, UK evaluated at 5.5% in 1990. The aim of this study is to estimate the BMC Infectious Diseases 2014, 14(Suppl 2):P18 prevalence of this disease in the last years in Tunisia. Methods: it was a retrospective study about all the blood donors in the Introduction: Anti-Retroviral Therapy (ART) has dramatically reduced Military Center of Blood Transfusion between 2000 and 2011. morbidity and mortality associated with HIV/AIDS. However, this has left a The Ag HBs was systematic for every blood donation, by immuno- niche for the emergence of liver disease in HIV-positive individuals co- enzymatic reaction. infected with HBV. Despite the geographical overlap between highly Results: In this period, 198157 blood donors were compiled. These donors endemic HBV and HIV in Southern Africa, there is a wide range in the were, for 95%, young men, between 20 and 25 years, from all the parts of prevalence of co-infection. We therefore set out to characterize the the country. epidemiology of HIV/HBV co-infection in a Durban cohort, and to investigate This study showed: the possible impact of HBV infection on HIV disease progression. • A net decrease in prevalence of hepatitis B in 12 years: from 3.54% in Materials and methods: We investigated a cohort of 498 adult women 2000 to 0.8% in 2011. recruited via antenatal/postnatal clinics in Durban, South Africa, of whom BMC Infectious Diseases 2014, Volume 14 Suppl 2 Page 13 of 45 http://www.biomedcentral.com/bmcinfectdis/supplements/14/S2/

72 were HIV negative and 426 were chronically HIV-infected and ART- Introduction: HIV/HCV coinfection may have important implications for naïve (median CD4 count 368 cells/mm3, median HIV-1 RNA load 4.47 therapeutic and evolving plans. The Knowledge of its epidemiological, log10 copies/ml). We screened plasma for HBsAg by ELISA (Biokit). CD8 clinical features may help to anticipate needs and improve care. The aim + T cell responses to HIV peptides were quantified by IFN-gamma of the Study was to determine the epidemic profile of patients co- ELISpot assay in 325 HIV-infected individuals including 35 with HBV infected by hepatitis C virus and HIV. coinfection. Materials and methods: A retrospective study was conducted in the Results: Overall HBsAg prevalence was 46/498 (9.2%; 95%-confidence infectious department diseases between 2003 and 201 3, were included interval 7-12%); coinfection rates were 9.4% in HIV-positive and 8.3% in all patients treated for HIV and HCV with positive serology (ELISA HIV-negative individuals. CD4 counts were significantly lower in with positive). Data were collected on computer files (Nadis) and analyzed on HBV/HIV coinfection than with HIV monoinfection (302 vs. 375 cells/mm3; Epi Info. p=0.02). However, HBV status made no significant impact on HIV Results: We collected 147 patients with HIV/HCV coinfection (4% of the viral load (4.49 log10 copies/ml in coinfection vs. 4.46 log10 in total workforce). The average age was 40 ± 10 years, males predominated monoinfection). There was no difference in breadth, magnitude, or (4H/1F). Intravenous drug use was found in 29.25 % of patients. At the protein-specificity of IFN-gamma responses to HIV according to HBV moment of diagnosis of the coinfection, 64 patients (43.5%) were in status. category C (CDC) . Antiretroviral therapy was prescribed for 131 patients Conclusions: In this cohort of Durban women, 9% were coinfected with (89%). The viral RNA research by RT-PCR and the genotyping were HBV. Women with HIV/HBV co-infection had significantly lower CD4 performedin39patients(27%).TheRNAHCVPCRwaspositivein28 counts, highlighting the potential detriment of coinfection. However, in a cases (19 %). The most frequent viral genotypes were 1a and 1b with 14 small subset we did not find a difference in CD8+ T cell responses to cases (50%). The IL28B performed in 8 patients had type CC (2 cases), C/T HIV. These data contribute towards an improved understanding of the (3 cases), TT (1 case). Liver function tests were normal in 116 cases; liver scale of the HIV/HBV coinfection problem in Africa, and suggest that cytolysis was found in 31 cases. The liver ultrasound was normal adverse outcomes are mediated by factors other than CD8+ T cell (80 cases) or showed lesions of chronic liver disease (30 cases) or responses to HIV. ascites (10 cases). Ten patients undergoing treatment with pegylated interferon and ribavirin. Two patients who completed treatment were non-responders. 79 patients (54%) are being used and 27 cases P19 died (18%). Determinants of recent HIV testing among male sex workers and other Conclusion: The HIV/HCV co-morbidity is a challenge in support of PLHIV. men who have sex with men in Shenzhen, China: a cross-sectional study Currently, free access to treatment and explorations of hepatitis C in Rui Cai*, Jin Zhao, Wende Cai, Lin Chen, Jan Hendrik Richardus, Sake J de Vlas Morocco as part of a health program (RAMED) is an important step Erasmus MC, University Medical Center Rotterdam, Rotterdam, the whose impact needs to be evaluated. Netherlands BMC Infectious Diseases 2014, 14(Suppl 2):P19

Background: Men who have sex with men (MSM), including male sex P21 workers (also known as money boys, MBs), are highly vulnerable to HIV, Profile of female sex workers suffering from violence in but HIV testing rates remain unacceptably low in China. We compared Ukraine and separately evaluated determinants of recent HIV testing among MBs Anna Tokar*, Liudmyla Shulga and other MSM. International HIV/AIDS Alliance in Ukraine, Kyiv, Ukraine Methods: We recruited 510 MBs and 533 other MSM in Shenzhen by BMC Infectious Diseases 2014, 14(Suppl 2):P21 time-location sampling. We compared their HIV testing history in the last year, socio-demographics and behavioral information, and we performed Introduction (aim): Science 2008 the main rode of HIV transmission logistic regression to identify determinants of having been tested in the began to shift from parenteral toward sexual. So, female-sex workers and last year among MBs and other MSM. FSW- drug users are considered to have increased risk of HIV infection due Results: Compared to other MSM, MBs had a slightly lower rate of HIV many factors, some of which could be consequences of personal violence testing (43% versus 48%, p = 0.10). MBs having multiple anal sex partners towards females: economic pressure, stigmatized needle-borrowing, (adjusted odds ratio, AOR = 2.03, p=0.006) and having more commercial sharing of drug preparation equipment and sexual behavior (Choi, 2006; male partners (> 4 versus ≤4 commercial male partners, AOR = 1.49, p = Evans, 2003; Bennett, 2000; Montgomery, 2002). The goal of our research 0.053) reported a higher rate of HIV testing. Condom use was not was to define socio-demographic factors associated with risk of personal associated with HIV testing among MBs. Among other MSM, HIV testing violence among FSWs. was reported more often for those with homosexual orientation than for Methods: Secondary data analysis was performed on the dataset of bio- those with bisexual orientation (58% versus 37%, p = 0.003) and for those behavioral survey with 5023 respondents conducted in 2011. RDS and TLS with heterosexual orientation (58% versus 28%, p = 0.018). Other MSM sampling methodology were applied, only females were recruited. The who had only male sex partners (AOR = 1.82, p = 0.026), and those study was approved by Ethical Review Board of Ukrainian Sociological having a STI history (AOR = 2.53, p = 0.004) reported more often HIV Association and Institute of epidemiology and infectious diseases named testing. Living in Shenzhen longer was positively correlated with HIV after L. V. Gromashevskyi. testing for both MBs (p = 0.078) and other MSM (p < 0.001). To reveal relationships between ever in life experience of violence, and Conclusion: Compared to Western countries, the HIV testing rates among socio-demographic characteristics of CSWs, binary logistic regression MBs and other MSM are still low in Shenzhen, China. For MBs, testing analysis was provided in SPSS 15.0. should be advocated through education programs to provide better HIV Results: About 55% of respondents were aged 20-30 years old, 52% - and condom use knowledge. For other MSM, de-stigmatizing programs completed secondary, vocational school or obtained not full high are urgently needed to encourage those with female sex partners to go education, 64% - were unmarried and did not live together with sexual for testing services. For both MSM groups, more efforts are needed to partner. FSWs, who obtained full secondary (OR=1.6 (1.2-2.2) and not full target the new comers. secondary (OR=2.1 (1.4-3.2) education and FSWs of older age group (OR=2.8(2.2-3.6) suffered more often from violence. Those who mostly worked in unsafe environment: on a road (OR=1.2 (1.1-1.4), on a street P20 (OR=2.0 (1.7-2.4), in a hotel (OR=1.9 (1.5-2.4), at a railway station (OR=1.1 Prevalence of hepatitis C virus infection among HIV-infected people in (1.0-1.4) – had higher risk to experience violence. Alcohol use during 30 Casablanca days period (OR=3.7(3.0-4.6) and current drug use (OR=2.2(1.7-2.9) were L Badaoui*, G Dabo, R Bensghir, M Sodqi, L Marih, A Oulad Lahsen, A Chakib, positively associated with risk of violence. K El Filali Marhoum Conclusions: Older, less educated CSWs, who provide sexual services in University Hospital of Ibn rochd, Casablanca, Morocco unsafe environment and used alcohol and drugs, had greater risk to BMC Infectious Diseases 2014, 14(Suppl 2):P20 experience violence. BMC Infectious Diseases 2014, Volume 14 Suppl 2 Page 14 of 45 http://www.biomedcentral.com/bmcinfectdis/supplements/14/S2/

Results: The average time from HIV infection to date of first CD4 count was P22 5 years. The proportion of cases reported to SISCEL in the same year of HIV Rapid-2-rapid – a collaborative approach to linkage for those recently infection increased from 30%, in 2005, to 36%, in 2011.The HIV incidence infected was estimated as 38968 (95% CI 36805-41130) in 2011, or 2.67 per 10000 Eugene Martin*, Gratian Salaru, Joanne Corbo, Loretta Dutton, Linda Berezny, population. The estimated HIV incidence represents approximately 5% of Steven Saunders, Sindy Paul, Evan Cadoff the HIV prevalence. The analysis by gender showed that the HIV incidence Rutgers University - Robert Wood Johnson Medical School, Somerset, New increased among men and decreased among women in the period Jersey, USA 2005-2011. The male-female incidence ratio was 1.45 in 2005 but increased BMC Infectious Diseases 2014, 14(Suppl 2):P22 to 1.96 in 2011. Conclusions: In Brazil, where antiretroviral therapy is free and coverage is Introduction: In light of evolving, 4th generation HIV diagnostics, more high, the survival of people living with HIV/AIDS is continuously increasing, effective strategies to test, link, and retain clients in care, are needed. In and so is the HIV prevalence. Therefore, only studies that consider the HIV New Jersey, USA medical facilities are twice as effective at engaging clients incidence can provide information on recent changes in transmission into HIV care as alternative screening entities including community based patterns. The results here depicted suggest that interventions in Brazil and public health screening facilities. The goal: Complete screening, should be focused on young adult men. confirmation, linkage and entry into care within 2 business days. Methods: A facilitated, collaborative process that allows rapid engagement and treatment for all including those at highest risk of infecting others has been developed. Seven collaborations have been P24 established across the State of NJ to connect HIV screening facilities with HIV positive lactating mothers a missed opportunity in the roll out of medical partners. Entry into care is facilitated by Patient Navigators. A the eMTCT strategy in Uganda two-test, sequential rapid test algorithm (RTA) is used to expedite initial Lillian Ayebale*, Pamella Bakabulindi, Erasmus Tanga screen confirmation and linkage into care improving the percentage of Research Triangle Institute International, Kampala, Uganda positive clients linked into care. A community-based screening site BMC Infectious Diseases 2014, 14(Suppl 2):P24 performs the first test; the collaborating medical site performs a second orthogonal test. The intake facility has credible verification and Introduction: Although Uganda has embraced the strategy of EMTCT by immediate justification for laboratory intake. The Patient Navigator serves 2015, the strategy focuses mainly on HCT for first ANC visit with less as a concierge, tester, and facilitator. attention on mothers who never attend ANC, deliver in the community Results: To date, 165,317 ‘rapid-rapid’ tests have been performed in NJ. and are lactating with unknown status which creates a missed Data to be discussed includes performance data on the multi-facility opportunity. The supporting public sector work places Expand Action and orthogonal process, entry and linkage into care. Clients testing positive in Responses to HIV (SPEAR) Project with funding from USAID, has piloted rapid-rapid sites are characterized as: NEW POSITIVES, RE-ENGAGED PMTCT/HCT camps/outreaches as an intervention to bridge this gap in clients or as ALREADY IN CARE. their target population. Conclusions: Rapid screening with 4th generation HIV diagnostics Materials and methods: SPEAR supports a given Health Facility to offer coupled with rapid identification of acute HIV infection permits rapid outreach services. A two-three days wellness camp that offers HCT, ANC, initiation of treatment and the potential to reduce transmission. PNC, FP, Immunization, and general health education is organized in the Collaboration between screening facilities and medical facilities provides barracks over a weekend. Prior community mobilization in target barracks expedited entry into care and permits treatment within 2 days across a that included a film van and door to door mobilization by VHT is carried system of more than 30 facilities. out. Results: 559 mothers had HCT during the five camps held at different locations. Of these 103 were pregnant mothers and 456 were lactating P23 mothers. Of the 103, 76 were 1st ANC visits and of the 456 lactating Estimation of HIV incidence in Brazil, 2005-2011 mothers, 306 were receiving 1st HCT since pregnancy and birth of current Celia Landmann Szwarcwald*, Paulo Roberto Borges de Souza Júnior, child. 8 pregnant and 30 lactating mothers were HIV positive. Ana Roberta Pascom, Orlando Ferreira Conclusion: Most lactating mothers do not receive HCT for PMTCT and are Fundação Oswaldo Cruz, Rio de Janeiro, Brazil at a higher risk of transmitting to their babies. About half of the population BMC Infectious Diseases 2014, 14(Suppl 2):P23 of pregnant mothers do not attend ANC during pregnancy and deliver in the community unattended by a professional health worker. Introduction: The incidence of HIV is nowadays the most valuable Recommendation: There is need to roll out provider initiated HCT not indicator of epidemiologic surveillance, both to guide prevention only at the health facilities, but also at community level for pregnant and activities and to monitor ongoing interventions. This paper addresses a lactating mothers in Uganda, for Uganda to achieve virtual EMTCT by 2015. method to estimate the HIV incidence in Brazil in recent years. Methods: As the information source, we used the national lab information system (SISCEL) created to monitor CD4/CD8 count and viral load among P25 HIV infected people. The proposed method is based on a statistical model The experience of the Kiev regional AIDS center in combating the that relates the first CD4 count to time of HIV seroconversion (Lodi et al., spread of HIV infection in the Kiev and interaction with non- Clinical Infectious Diseases: 53(8): 817-825, 2011). To use the model in governmental social organization Brazil, we simulated the slope and the intercept for sex and age at first Oleksandr Yurchenko*, Tetiana Stepchenkova CD4 count. For each treatment-naïve HIV infected case reported in SISCEL Kiev regional AIDS center, Kyiv, Ukraine aged 15 years and older, we estimated the time lag between HIV infection BMC Infectious Diseases 2014, 14(Suppl 2):P25 and the date the case was reported. The HIV incidence was estimated as the sum of the cases reported in the same year of infection, one year after Since the beginning of the registration of HIV, in Kiev there were infection, and so on up to 20 years after infection. registered a total 13,500 cases of HIV, 1,5 thousands people died. Under

Table 1 (abstract P22) NEW RE- ALREADY CLIENT Denied Chanty Avg. Bus Days to Complete Linkage Appt No POS ENGAGED IN-Care REFUSED Care (ID) and Lab Intake Show YTD (Through 131 55 9 12 4 1.48 26 November, 2012) BMC Infectious Diseases 2014, Volume 14 Suppl 2 Page 15 of 45 http://www.biomedcentral.com/bmcinfectdis/supplements/14/S2/

medical supervision in Kiev there are 9697 people with HIV, including the Multiple clinical studies show the importance of genital HSV-2 infections 1790 people who are in the stage of AIDS. Among vulnerable groups in women on the sexual transmission of HIV-1 and vice versa. Therefore, particularly distinguished IDU. During 2013 the number tested for HIV it is important to develop molecules with potent dual antiviral activity to among this group is 3900 people. Infection level among them is 19.5 %. reduce sexual transmission of these life-treating pathogens. Here, we Identified by year of HIV-positive injecting drug users - 752. Enrollment describe that the polyanionic compound lignosulfonic acid (LA; MW: rate in 2013 is 64 %. The majority (70.6 %) from infected IDU’s have III – 8000), which belongs to the family of lignin-derived macromolecules, is a IV clinical stage of disease. The assistance of non-governmental social cheap byproduct that is formed during the conversion of wood pulp into organizations is critical. With the number of employees in the region of paper. LA exhibits low toxicity (CC50: >62.5 μM) and potent broad- NGOs involved in the implementation of measures to combat HIV / AIDS in spectrum anti-HIV activity (IC50s: 0.10 - 0.34 μM), irrespective of the viral the region, the 5 most productive organizations are supported by the coreceptor tropism. In addition, it inhibits the formation of giant cells administration of Kyiv regional Clinical Hospital № 5 by allocating space for between HIV-1 persistently infected cells and non-infected CD4 target T activities. Based cabinets anonymous HIV testing within the network Kyiv cells (IC50: 0.23 μM). City AIDS Center and sites of ART also established cooperation with AIDS- HSV-2 is not solely an epitheliotropic virus, as it also infects CD4 T cells, service NGOs that implement preventive work with vulnerable groups and macrophages and MDDCs. We show that LA is able to inhibit HSV-2 provide social support for persons living with HIV. Social workers allocated infection in HIV-1 susceptible T cells in the lower μM-range (IC50: 0.78- by the rooms required for their activity. Other NGOs engaged in 0.82 μM). In addition, LA blocks viral replication of dual HIV-1 and HSV-2 addressing transition to the offices of anonymous testing people, who infected cells with comparable potency (IC50: 0.71 μM). were positive in a testing in community centers, the mobile clinic or while. DC-SIGN plays an important role in the sexual transmission of HIV and of Results cooperation center and HIV service NGOs in Kiev: HSV. We could show that LA (12.5 μM) has no effect on the capture of • Of the 932 patients, who were appointed ART, 894 patients (95.9 %) HIV by Raji.DC-SIGN cells, however it inhibited further transmission to under the guidance of social workers uninfected CD4 T cells (IC50: 1.2 μM). Comparable observations were • Percentage of adults and children with HIV known to be on ART at 12 made with HSV-2 using MDDCs and MT-4 cells (IC50: 1.1 μM). We months after initiation of ART- 86.43 % investigated also its potential side-effects and stimulatory effects. PBMCs • Percentage of HIV -infected persons who received outpatient examination were exposed to high amounts of LA and the expression of CD25, CD69 at the end of the year among the total number of HIV-infected persons who and HLA-DR on CD4+ T cells was measured. No significant increased are under medical supervision 82% effects were seen for each activation marker, while the mitogenic lectin • Since 2009 increased the percentage of HIV -infected with TB who received PHA stimulated. Finally, LA did not harm the vaginal lactobacilli and treatment for TB and HIV, including through implementation of measures of synergistic activity was observed with acyclovir, PRO2000 and the social support persons with a triple problem of injecting drug users, HIV, TB. lantibiotic LabyA1. In conclusion, lignosulfonic acid has potential for a microbicidal agent.

P26 HIV risk taking and risk preventing behaviors in men who have sex P28 with men and women: a respondent-driven sampling study in A rapid assessment of Uganda police force and Uganda prisons service Shenzhen, China health facilities capacity to roll out the virtual elimination of mother to Rui Cai*, Jin Zhao, Wende Cai, Lin Chen, Jan Hendrik Richardus, Sake J de Vlas child HIV transmission (eMTCT) strategy Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands Lillian Ayebale1*, Benjamin Lutimba1, Erasmus Tanga2 BMC Infectious Diseases 2014, 14(Suppl 2):P26 1Research Triangle Institute International, SPEAR Project, Kampala, Uganda; 2World Vision Uganda, SPEAR Project, Kampala, Uganda Introduction: Men who have sex with men (MSM) has clearly become the BMC Infectious Diseases 2014, 14(Suppl 2):P28 predominant route of HIV transmission in China. Due to traditional cultures and values, many MSM have frequent sexual relationship with females. These Background: Uganda has embraced the strategy of virtual elimination of men who have sex with men and women (MSMW) may bridge and facilitate mother to child HIV transmission (eMTCT) by 2015 which has seen the roll an expansion of the HIV epidemic from MSM to the general heterosexual out of Option B + country wide. According to the Modes of Transmission population. report 2009, HIV prevalence among uniformed personnel was 18.4percent, Methods: We quantified the burden of HIV/syphilis and studied patterns a rate that is almost three times the national average. However little has of risk taking and preventing behaviors in 107 MSMW, and compared been done to reach Uganda police Force (UPF) and Uganda Prisons Service that with 542 men who have sex with men only (MSMO) in a (UPS) communities, most affected by HIV and AIDS. In October 2012, The respondent-driven sampling survey in Shenzhen, China. Supporting Public Sector workplaces Expand Action and Responses to HIV Results: The HIV risk preventing behaviors such as uptake of HIV testing (SPEAR) Project funded by USAID, planned to implement eMTCT and other services and consistent condom use with male partners were interventions in the health facilities (HF) of UPF and UPS. comparable in MSMW and MSMO. However, HIV risk taking behaviors, in Objective: This was an assessment to determine the capacity of UPFs terms of having multiple anal sex partners, using illicit drugs, using and UPS HF to roll out the eMTCT strategy. alcohol before or during sex and having group sex, were more common Methods: Thirty four Prisons and 23 police HF were listed for assessment to among MSMW than among MSMO. Moreover, HIV prevalence was as offer comprehensive Artiretroviral Therapy and roll out the eMTCT strategy. high as 6% and consistent condom use was low: 41% with wives and A standard Ministry of Health (MOH) ART accreditation assessment tool, 38% with girlfriends in MSMW. which looked at human resource, equipment and supplies, physical space, Conclusions: We conclude that there is risk of HIV transmission from and additional HF inputs was used. The assessment team, comprised of MSMW to the general heterosexual population. Special efforts targeting MOH Officials, UPF and UPS representatives, and SPEAR project staff, MSMW are needed to reduce their HIV risk taking behaviors. Outreach administered the questionnaire to HF staff, inventoried equipment, supplies, education programs implemented by their peers who are behaviorally and registers for each HF. bisexuals may be an important strategy. Results: Nineteen HFs (10 UPS, 9 UPF) met the inclusion criteria for the ART accreditation assessment; 17 HCIII, 1HCIV and 1Hospital. Only 1/10 of Prison and 1/9 of Police facilities had at least one medical doctor and had been accreditedasARTcentersbutdidnotmeettheotherminimum P27 requirements as per the national guidelines for eMTCT roll out. 9/10 prisons Lignosulfonic acid exhibits broad-spectrum anti-HIV and anti-HSV and 3/9 of police had at least one clinical officer. 60% of all the facilities activity and has potential for microbicidal applications assessed had a midwife. 7/10 prisons facilities had limited space for Geoffrey Férir*, Sandra Claes, Stephanie Gordts, Graciela Andrei, Antenatal Care Clinic and 8/9 of police facilities had no basic equipments Robert Snoeck, Dominique Schols and supplies, lacked physical space and functional laboratories. Rega Institute for Medical Research, Leuven, Belgium Conclusions and recommendations: HFs faced common challenges BMC Infectious Diseases 2014, 14(Suppl 2):P27 impeding the rollout of eMTCT including; inadequate skilled staff, lack of BMC Infectious Diseases 2014, Volume 14 Suppl 2 Page 16 of 45 http://www.biomedcentral.com/bmcinfectdis/supplements/14/S2/

usable space for a fully functional clinic, limited laboratory and medical Kalenjin, Teso, or Luo. All data were audio recorded, transcribed, translated equipment, and inadequate financial commitment for providing necessary to English, and a content analysis performed. Demographic data was only upgrades. The assessment reflected a great need for health systems available for those who participated in the FGDs. strengthening not only to roll out eMTCT but for general healthcare. Results: The mean age of participants in the FGDs was 36 years (SD=9.24). The majority (87%) were married, (62.7%) had a secondary education level and above, and (77.6%) had a source of income. Overall, there were no P29 differences in the perceived barriers across all study participants. Salient Community needs assessment of key populations-at-risk of HIV/AIDS in barriers reflected on patients’ satisfaction with HIV care. There were Nigeria’s capital territory similarities in some of the barriers cited for linkage and retention including Godwin Asuquo*, David Owolabi, Ali Onoja, Uche Okoro, Floria Durueke access to health facilities, stigma associated with health facilities, service Africa Center for Health Care Leadership Development, Abuja, Nigeria efficiency, poor provider-patient interactions, and lack of patient incentives. BMC Infectious Diseases 2014, 14(Suppl 2):P29 Barriers unique to linkage were reported as, quality of post-test counseling and poor patient reception at the clinics. Obstacles unique to retention were Introduction (aim): Nigeria currently has one of the highest HIV and frequency of clinic appointments, different appointments for mother and AIDS epidemic burden worldwide. Prevalence among key populations is child, lack of HIV care for institutionalized populations including students currently, 34.1% (brothel-based sex workers), 21.95 (non-brothel-based), and prisoners, lack of food support, and inconsistent linkage data. 37.6% (MSMs) and 9.3% for IDUs respectively. A huge gaps exists in the Conclusion: Our findings revealed that there were similarities and national response to key populations as a result of socio-cultural barriers differences between perceived barriers to linkage and retention. The cited and unfavorable political and legislative environment. This has become barriers reflected on the need for a more patient-centered approach to accentuated by the recently enacted anti-gay law. The Federal Capital HIV care. We believe that addressing health facility barriers may Administration in collaboration with UNDP and UNFPA in 2013 ultimately be easier than addressing patient related (intrapersonal and commissioned a study on key populations in the Capital territory to interpersonal) barriers. identify services available to them, the gaps and opportunities for scaling up municipal responses for MSMs, FSWs and IDUs. Materials and methods: A cross sectional study relying on the needs P31 assessment methodology which included a community social survey, Determinants of systematic condom use among students and community mapping and focus group discussions. A total of 120 (70 sex apprentices ages 15–24 in Benin workers, 30 MSMs and 20 IDUs) participated in the study. In-depth Cyprien Zinsou*, Joseph Inungu, Margaret Wilson interviews were conducted for policy makers and technical leads from Beninese Association of Social Marketing, Cotonou, Benin government agencies, NGOs and development partners. Institutional BMC Infectious Diseases 2014, 14(Suppl 2):P31 analysis of relevant NGOs preceded a desk review of the response to key populations in Nigeria and a validation workshop was conducted to Introduction: Adolescents ages 15–24, particularly young women, continue validate the findings. to bear the brunt of the HIV epidemic in sub-Saharan Africa with an Results: About 17,117 FSWs were mapped in 1004 hotspots, while, 692 estimated 50% of new infections occurring in this age group. While MSMs were located in 692 hot spots and 135 IDUs in 16 hotspots in the adolescents in Benin have many sexual partners (3,4 for women and 4,5 for FCT. About 689 non-governmental organizations were providing services men) (EDS, 2012), less than 50% used condom during the last sexual with the majority (40%) providing HCT services, 34 %, condom encounter. The Association of Social Marketing in Benin (ABMS), in programming, 20 % peer education and 16%, youth friendly services. collaboration with PSI, has been implementing a youth project funded by None of the NGOs was providing STI services while only 10% provided the DUTCH embassy to reduce HIV prevalence among youth since 2012. The lubricants. HIV/AIDS risk perception and current knowledge of prevention objective of this study is to identify the factors associated with consistent of sexual transmission was generally low (32%). Social stigma, poor condom use in this population. coordination and inadequate government support were identified as Methods: ABMS/PSI conducted a sexual behavior survey between major barriers to scaling up services. January-February 2013 in schools and vocational centers in the project Conclusion: The findings support the need for the development of a areas to assess the sexual behavior of students and apprentices ages 15- municipal action plan for key populations in the FCT based on the 24. Logistic regression was used to identify the factors associated with identified priorities and the review of the national HIV/AIDS strategy to systematic condom use in this population. be more responsive to the needs of key populations. Results: A total of 4288 youths (2678 students, 1610 apprentices) were interviewed. 59.4% of them were girls and their mean age was 17,9 years. On average 17% of them (24.6% of boys and 11.7% of girls) had more P30 than one sexual partners in the last 12 months before the survey. Of Perceived health facility barriers to HIV linkage and retention in those (N=727), 46.2% used condom consistently. western Kenya The logistic regression model showed that consistent condom use among J Wachira1*, V Naanyu1,2, B Genberg7, S Ndege1,3, AM Siika1,2, S Kimayo1,2, adolescents was associated with their ability to discuss about condoms J Mamlin1,2,4, P Braitstein1,2,4,5,6 (OR=2,8; p<0,001), to demonstrate how to wear condom correctly (0R=2,2 ; 1Academic Model Providing Access to Healthcare (AMPATHPlus) Partnership, p<0,001), their level of knowledge about the mode of HIV transmission Eldoret, Kenya; 2Moi University School of Medicine, Eldoret, Kenya; 3Moi (0R=1,5 ; p<0,05), the fact of being a woman (OR=2,1; p<0,001) or apprentice University School of Public Health, Eldoret, Kenya; 4Indiana University School (OR=2,2; p<0,001) and watching television regularly (OR=1,4; p<0,05). of Medicine, Indianapolis, USA; 5Regenstrief Institute, Inc. Indianapolis, USA; Conclusion: To improve consistent use of condoms among adolescents 6Dalla Lana School of Public Health, University of Toronto, Toronto, Canada; in Benin, the ABMS should take these determinants into account when 7Brown University, Department of Health Services, Policy & Practice, designing its behavior change communication interventions. Providence, Rhode Island, USA BMC Infectious Diseases 2014, 14(Suppl 2):P30

Introduction: HIV linkage and retention rates in sub-Saharan Africa remain P32 low. The objective of this study was to explore perceived health facility Clinico epidemiological profile of HIV - TB coinfection among PLHIV in barriers to linkage and retention in an HIV care program in western Kenya. coastal south India Methods: This qualitative study was conducted between, July 2012-August Unnikrishnan Bhaskaran 2013. A total of 150 participants including; 59 patients (HIV, TB, and Kasturba Medical College, Manipal University, Mangalore, India hypertension); 16 caregivers; 10 community leaders; and 65 healthcare BMC Infectious Diseases 2014, 14(Suppl 2):P32 workers, were purposely sampled from three Academic Model Providing access to Healthcare (AMPATHplus) sites. We conducted 16 In-depth Background: Tuberculosis is the most common opportunistic infection interviews and 16 focus group discussions (FGDs) in either, English, Swahili, diagnosed in HIV positive patients in India. HIV and Tuberculosis co-infection BMC Infectious Diseases 2014, Volume 14 Suppl 2 Page 17 of 45 http://www.biomedcentral.com/bmcinfectdis/supplements/14/S2/

is a major public health problem as well as a leading cause of death in Background: Serbia hosts some 228,000 Internally Displaced Persons developing countries. (IDPs) from Kosovo, of whom more than 2,000 live in 24 collective Aims: To study the trends and clinico epidemiological profile of HIV and centers. A large number of refugees and IDPs reside in substandard tuberculosis co-infection from January 2008 to December 2011. temporary housing or in illegal settlements lacking basic facilities. Method: A hospital based retrospective study was conducted on all The research to assess vulnerability to HIV among young IDPs in Serbia subjects having HIV and Tuberculosis co-infection from January 2008 to was carried out with the support of the UN Joint AIDS Team. The goal of December 2011. Data was collected using semi-structured proforma from the research was to: assess the level and exposure to HIV risk behavior Integrated Counselling and Testing Center (ICTC) records. All analysis was amongyoungIDPsintwocities,Belgrade and Kragujevac, where the done using SPSS version 11.5. Statistical test Chi-square was done. largest ID collective centers are placed; to inform stakeholders to tailor Results: In 2011, 17.3% HIV positive cases were co-infected with services to the needs of targeted population. tuberculosis in comparison to 6.5% in 2008, 14.9% in 2009 and 8.5% in 2010. Methods: Sampling was performed by combining methods of random HIV and Tuberculosis co-infection was more prevalent in males (69.3%) than choice of respondents using lists of registered young IDPs provided by in females (30.7%) and 90.9% of the study subjects were married. Most of UNHCR and the “snowball” method. Research instruments included the co-infected cases (89.8%) were on anti-tubercular treatment. procedure checklists and questionnaire, which consisted of 10 modules. Conclusion: HIV and Tuberculosis co-infection is under-diagnosed and The interviewers conducted filling-in of questionnaires. The sample under-treated. Thus there is a need to integrate Tuberculosis and HIV included 305 IDP youth, with 31.1% of Roma youth which is in accordance prevention programmes to face the threat of HIV associated tuberculosis. with the estimated distribution of Roma in the overall IDP population. Results: The analysis has shown that accommodation of the respondents, together with their education, represented a significant variable in P33 respect of risky behavior amongst IDP youth. The degree of knowledge A qualitative and quantitative exploration of determinants and about STI and HIV grows in parallel with better living conditions and intervention methods for increasing condom use among internal higher level of education, as well as knowledge on where condoms can migrants in China: results of a three-round Delphi study be obtained and the frequency of their use with permanent partners, Xiaona Liu*, Vicki Erasmus, Xinying Sun, Rui Cai, Yuhui Shi, while the frequency of pregnancies among young females decreases. Jan Hendrik Richardus Coverage with specific preventive programs is low (4.3%). Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands Conclusion: Amongst the IDP youth, young Roma and those who have BMC Infectious Diseases 2014, 14(Suppl 2):P33 inferior living conditions show a greater degree of vulnerability to HIV in relation to those with better living conditions. Young females, in relation Introduction: Internal migrants have been repeatedly characterized as to young males, are at higher risk due to having less influence on the “the tipping point” for HIV epidemic in China. This study is a step towards use of condoms during sexual intercourse. the development of a successful behavioral HIV prevention intervention among Chinese internal migrants. It aims to explore important and changeable determinants of condom use, and inspect effective and feasible methods to increase condom use for the target population. P35 Materials and methods: We conducted a three-round web-based Delphi Reducing mother to child HIV transmission: a successful experience study among a panel of 62 experts between October 2012 and March 2013. A Ouyahia*, M Rais, A Gasmi, S Mechakra, A Lacheheb In the first round, the panelists were asked to qualitatively identify Ferhat Abbes University, Medicine Faculty, Setif, Algeria determinants of condom use, and past and/or ongoing relevant intervention BMC Infectious Diseases 2014, 14(Suppl 2):P35 methods they considered successful. In the subsequent rounds, they were asked to rate importance and changeability for each identified determinant, Background: Mother-to-child transmission of HIV remains the main and to rate effectiveness and feasibility for each identified intervention source of pediatric HIV infection, women constituted 50% of infected method, on a 5-point Likert scale. The median and Inter Quartile Deviation people in Algeria, mostly in the reproductive age group. (IQD) were calculated for describing each item. Items with an IQD ≤ 1 were Objectives: Mandatory HIV screening in pregnancy, as part of mother-to- judged as reaching consensus among the panelists. child transmission (MTCT) prevention, is useful to increase the number of Results: Overall, 21% of our initial sample completed all three rounds of patients under follow-up. Our work aimed to describe MTCT prevention the study (13). The panelists identified 19 possible determinants of interventions and outcome of newborns during 24-months follow-up. condom use, and they considered 16 intervention methods successful. Methods: From 99 HIV women followed between 2002 and 2013 to the HIV The quantitative results were obtained from the panelists with a variety unit of the teaching hospital of Setif, 10 pregnant women were identified. of expertise across the globe, but reached strong consensus over almost Pregnancies and deliveries (over 15 days) that occurred before referral to all questions (98%). They agreed that attitude of towards using condoms our institution were excluded from the study. were important (median=5) and changeable (median=4) determinants of We used data collected in the patients’ medical files, Epi info 3.5 version condom use, while applying behavioral theory, increasing education and was used for statistical analysis. condom access, performing worksite health promotion, detecting risk Results: 10 mothers had 14 pregnancies, resulting in a total of 14 live factors, and working closely with relevant organizations and the born children. government were effective (median=5) and feasible (median=4) methods The median age was 19.5 years, 7 were married and 3 were single. The to increase condom use among internal migrants in China. most frequent transmission route was heterosexual (90 %). 3/10 fathers Conclusions: The development of a successful behavioral HIV prevention were unaware of HIV maternal status. intervention targeting Chinese internal migrants should build messages 70 % had been previously diagnosed with HIV. All had HAART as MTCT upon a behavioral theory integrating multiple determinants (e.g., cognitive prevention, with AZT+3TC+LPV/r; median viral load (VL) at delivery was factors, skills, social influence), with the priority of shaping positive attitude below 1000 cp/mL in 100% of patients. Cesaerean-section was performed towards condom use among the target population, and should take in 28.5 % of deliveries. multiple identified intervention methods (e.g., education, condom access, 3 women were diagnosed after vaginal delivery, PMTCT started in post worksite health promotion) into consideration. partum, median viral load after delivery was 7800 cp /mL. All neonates benefited of post natal antiretroviral prophylaxis (AZT during 6 weeks) and fed with formula milk. Mean newborn weight was 3030 g and HIV- P34 PCR at birth, 3 months, 6 months of age was negative in 13 infants. All Vulnerability to HIV of Internally Displaced Persons in the Republic of mother-infant pairs maintained follow-up at 24months except for one Serbia child who died at 6 months age. Miljana Grbic*, Verica Lela Ilic, Sladjana Baros, Farida Bassioni Stamenic, Conclusion: This important reduction in MTCT is a result of antenatal Rade Grbic, Milan Parlic, Svetomir Samardzic diagnosis and provision of antiretroviral prophylaxis and treatment for United Nations Development Program, Belgrade, Serbia mothers and infants. It highlights the necessity of revisiting the debate of BMC Infectious Diseases 2014, 14(Suppl 2):P34 voluntary versus mandatory HIV/AIDS testing during pregnancy. BMC Infectious Diseases 2014, Volume 14 Suppl 2 Page 18 of 45 http://www.biomedcentral.com/bmcinfectdis/supplements/14/S2/

HIV: CLINICAL ASPECTS (15.1 dB vs 8.6 dB, p=0.03). Six HIV+ children had unilateral hearing loss whereas one HIV- child had a unilateral hearing loss. Risk for hearing loss P36 was higher for HIV+ children with WHO stage IV disease compared to Personalizing humanized mice with cells obtained from an HIV post other stages, but not significant. treatment controller Conclusions: There were more middle ear infections, a higher risk of Ilona Hauber1*, Julian Schulze zur Wiesch1,2, Udo Schuhmacher2, hearing loss, and more unilateral hearing loss in HIV+ than HIV- children; Carola Schäfer1, Jan van Lunzen1,2, Joachim Hauber1 HIV+ children had a significantly higher PTA (worse hearing) in their 1Heinrich Pette Institute, Leibniz Institute for Experimental Virology, poorer ear. The risk of hearing loss was higher in those with WHO stage Eppendorf, Germany; 2University Medical Center Hamburg-Eppendorf, 20251 IV disease than those with stage II or III. Hamburg, Germany BMC Infectious Diseases 2014, 14(Suppl 2):P36

Introduction: HIV research greatly benefits from the use of immunodeficient P38 mouse systems that are susceptible to HIV target cells. Usually, High mortality among people living with HIV and AIDS accessing care immunodeficient mice are transplanted with primary human cells to develop at hospitals in Ghana. Do they report too late? a “human” immune system. Following engraftment, the animals are Thomas Agyarko-Poku1*, Shella Bawa1, Angela El-Aldas2, Helena Afriyie Siaw1, subsequently infected with HIV. Here, we applied a different approach and Yaw Adu Sarkodie3 personalized mice by directly transplanting cells from an HIV-infected patient. 1Suntreso Government Hospital, Ghana Health Services, Kumasi, Ghana; Materials and methods: CD4+ T cells were isolated from a HIV-infected 2Ghana AIDS Commission, Accra, Ghana; 3Department of Clinical post treatment controller (PTC) and transplanted into 6 week old Rag2-/- Microbiology, School of Medical Sciences, Kwame Nkrumah University of gc-/- (Rag-hu) mice in order to monitor virus replication over time. Science and Technology, Kumasi, Ghana Upon presentation to the clinic in 1998, the patient’s viral load was 52.000 BMC Infectious Diseases 2014, 14(Suppl 2):P38 HIV copies/ml with near-normal CD4+ T cell count of 491/ul and slightly reduced CD4+/CD8+ ratio of 0,4. Treatment with AZT, 3TC and effavirenz Introduction: The reported high level of mortality among patients both was initiated and the viral load was undetectable after few weeks and on clinical care and on Highly Active Antiretroviral Therapy (HAART) in undetectable for the next couple of years. In May 2004 therapy was Ghana in recent years has been blamed on an advance presentation of stopped after more then 5 years in an attempt of STI (structured treatment AIDS cases due to delay by patients accessing care at Hospitals. The study interruption). Remarkably, the viral load stayed below the level of hypothesized that HIV and AIDS patients report at the ART clinics with very detection with stable CD4+ counts since then. The patient was further low CD4 lymphocyte count and determined the CD4 lymphocytes count of analyzed for host factors but neither the HLA molecules (HLA A 01,02, B44, HIV positive patient at first presentation in the Ashanti Region of Ghana. B52) nor a deletion of the CCR5 receptor could account for the control of Materials and methods: This retrospective study reviewed clinical records the virus after treatment interruption. of 2,971 patients accessing care at 19 ART Clinics in the Ashanti region of Results: At 8 weeks after transplantation the mice were engrafted with 15- Ghana for the period January 2010 to December 2012. The date of first 30% human CD45+CD3+ and significant viral loads (from 3 - 62 x 10E6) reporting and the level of first CD4 counts were recorded. Socio were detected. Analysis of lymphoid cells of the spleen, bone marrow, liver demographic information was also recorded. Data was analyzed using SPSS and salivary gland demonstrated a fully established HIV infection. version 16. Conclusion: The direct transplantation of patient-derived cells into hemato- Results: More than half (54.9%, 1631/2971) of all HIV patients reviewed lymphoid system mice provides a novel experimental approach to analyze presented with CD4 count of less than 250 cells/mm3. Of this number, the presence of replication-competent HIV in patients with undetectable 37.7% (615/1631) reported with CD4 count less than 50 cell/mm3, 17.3 % viral loads such as, for example, post treatment controllers (PTC). (282/1631) with CD4 count of less than 100 cells/mm3, 45.2% (737/1631) with CD4 count of less than 250 cells/mm3. Almost a quarter (23.9%, 710/ 2971) presented with CD4 count between 250 and 350cells/mm3 with 21.2% (630/2971) reporting with CD4 count of 350 cells/mm3 and above of P37 which only 11.1% ( 70/630) came with CD4 greater than 500cell/mm3. In all Hearing sensitivity in perinatally HIV-infected children more than three quarter (78.8%, 2341/2971) of the patients reported with Peter Torre III*, Alyssa Cook, Hannah Martin, Haley Elliott, Gouwa Dawood, CD4 count of less than 350cell/mm3. Barbara Laughton Conclusions: The study shows that CD4 lymphocytes count of HIV San Diego State University, San Diego, USA patients accessing care at Hospitals is very low. Delay reporting might BMC Infectious Diseases 2014, 14(Suppl 2):P37 account for this development. Public education on the need to access care at the earliest possible time once tested HIV positive must be intensified. Introduction: Research on the effects of perinatal human immuno- Further study is needed to determine the causes for late presenting at the deficiency virus (HIV) exposure on hearing sensitivity is increasing. This is HIV clinic and address them, since this may account for high mortality important because hearing loss can delay language and communication among HIV positive patients. development in young children. The purpose of this project was to evaluate hearing sensitivity characteristics in HIV+ and HIV- children. Materials and methods: Children were recruited from outpatient clinics within Tygerberg Children’s Hospital in Cape Town, South Africa. Caregiver P39 report of middle ear infections was obtained through a questionnaire. Opportunistic digestive parasitic infections in adults infected with HIV: Bilateral otoscopy, tympanometry, then pure-tone testing was completed. epidemiological expression Hearing loss was defined as a pure-tone average (PTA) of 500, 1000, 2000, L Badaoui*, G Dabo, R Bensghir, I Halim, M Soussi Abdallaoui, A Chakibi, and 4000 Hz of >15 decibels of hearing level (dB HL) in the poorer ear. K El Filahi Marhoum Unilateral hearing loss was defined as one normal ear and one ear with Ibn Rochd University Hospital, Casablanca, Morocco hearing loss. Conductive hearing loss was defined as an air-bone gap of ≥15 BMC Infectious Diseases 2014, 14(Suppl 2):P39 dB at a minimum of two frequencies in either ear. The percentage of children with hearing loss and mean PTA were compared between HIV+ Introduction: In Morocco as in many African countries, AIDS and its and HIV- children. The effect of WHO status on hearing loss was examined procession of opportunistic infections are a major cause of morbidity and for HIV+ children. mortality. The purpose of study was to determine the frequency of Results: Sixty-one children: 37 HIV+, 24 unexposed uninfected (HIV-), digestive opportunistic parasitosis in patients infected with HIV. mean age 7.1 years (SD=1.6) were assessed. HIV+ children had a higher Materials and methods: A retroprospective study conducted 20 months rate of reported middle ear infections and more conductive hearing loss. in the department of infectious diseases. Were included all patients The risk for hearing loss was higher for HIV+ children (p=0.18), who also infected with HIV and opportunistic intestinal parasitosis confirmed in EPS. had a significantly higher mean PTA in the poorer ear than HIV- children Data were collected on computer files (Nadis) and analyzed on Epi Info. BMC Infectious Diseases 2014, Volume 14 Suppl 2 Page 19 of 45 http://www.biomedcentral.com/bmcinfectdis/supplements/14/S2/

Results: Among the 70 patients involved, the average age was 37 years symptoms at least a week after ART initiation. Screening and diagnosis with a slight male predominance. The median CD4 was 62cel/mm³. techniques of possible Opportunistic infections before or at ART initiation Digestive opportunistic parasitic were indicative of HIV infection in 54 cases were reviewed as well as management of IRIS. (77%) and in 16 cases (23%) they occurred at the waning of treatment Results: Five case notes of patients suspected to have IRIS were accessed. failure. All patients had diarrhea. These opportunistic parasitic agents were 3 were male patients. All the patients had low CD4+ count (< 200c/μl) and isolated only in 56 cases: the cryptosporidiosis (40%), microsporidia (31%), suspected Tuberculosis IRIS. 3 were diagnosed with TB through Gene-Xpert Isospora belli (6%) and Cyclospora (3%). They were associated in 14 cases testing (none had Rifampicin resistance TB) and 2 on radiological findings including Cryptosporidiosis+ Microsporidiosis (18.57%) and Cryptosporidiosis (chest x-ray and abdominal ultrasonography). + Isosporiasis (1.43%) in HARRT the outcome was favorable for 86% of Two had ART-associated TB IRIS and 3 had unmasking TB-IRIS. 1 new HIV- patients (n = 60) and mortality was 14% (n=10). reactive patient with CD count < 50c/μl, was negative for TB during Conclusion: Opportunistic digestive parasites remain common in our screening before ART initiation. However, she developed TB-IRIS within 2 context because of late diagnosis of HIV / AIDS. Early detection of HIV will weeks of starting ART. prevent them. Laboratory diagnosis and TB treatment were done at distant district and tertiary public hospitals due to limited resources and equipment available within and closer to the clinic. 1 died within 1 month of starting TB P40 treatment and IRIS management, due to suspected hepatic complications. Microbial infections in HIV/AIDS women with abnormal vaginal Conclusion: Predicting and diagnosing IRIS remains a challenge in discharge in Lagos, Nigeria developing countries, adversely affected by HIV/AIDS. With most patients NM Otuonye*, SI Smith, NN Odunukwe, CT Oparaugo, AA Adesesan, having late HIV diagnosis and starting ART at lower CD4+ count, there is need RN Okoye, CV Gab-Okafor, RC Chigbo to aggressively screen Opportunistic infections and manage possible IRIS. Nigerian Institute of Medical Research, Lagos, Nigeria Better, low-cost diagnostic options needs to be developed and available BMC Infectious Diseases 2014, 14(Suppl 2):P40 in limited-resource areas.

Introduction: Vaginal infections which are caused by bacterial vaginosis (BV), bacteria pathogens (BP) trichomoniasis (TV), and yeast infections are P42 common among HIV-infected women. This may be a marker for increased Aetiology of fever among under fives in Lagos, Nigeria transmissibility to sexual partners, infants at delivery, significant morbidity, VNV Enya*, N Idika, AG Mafe, KN Akinside, SI Smith, PU Agomo, IN Ibeh, underscoring their importance from a public health perspective. SNC Wemambu Methods: Three eighty seven (387) patients who presented to the HIV clinic Nigerian Institute of Medical Research, Lagos, Nigeria with symptoms of lower abdominal pain, itching and abnormal vaginal BMC Infectious Diseases 2014, 14(Suppl 2):P42 discharge were selected after obtaining written informed consent. Patients on oral or vaginal medications for vaginitis were excluded. High vaginal/cervical Introduction: Fever is a common presentation of HIV/AIDS, malaria and swabs were collected, cultured and processed using standard microbiological acute respiratory tract infections (ARIs) all of which are major causes of methods.Anti-microbial sensitivity patterns of the isolates were determined. childhood morbidity and mortality in sub-Saharan Africa. Correct The characteristics of the discharge, vaginal pH >4.5, presence of ‘clue cell’ management requires accurate diagnosis of the cause of fever. This study and Amine test with 10% KOH were used for Bacterial vaginosis (BV) was carried out to determine prevalence and pattern of in HIV, malaria and investigations. The age range of study population was between 20 – 45 years ARI in febrile children under 5 years of age. with mean of 24+. All patients complained of abnormal vaginal discharge. Materials and methods: Acrosssectionalstudyof all consenting and One hundred and twenty (38.46%) had lower abdominal pain, itching/ consecutive children 6- 59 months and their mothers / care-givers seen at the irritation 200 (64.10%) and 30 (9.61%) had sore and blisters on the genitals. out patient department of Massey Street Children’s, Hospital presenting with Vaginal pH > 5.0 was recorded in 215 (68.91%) of the patients. fever. Semi structured questionnaire was used to obtain information from the Results: A total of 80.6% of HIV/AIDS women were infected withmicrobial mothers / care-givers and laboratory investigations were done for febrile infection. Microbial agents isolated were as follows: Candida species children using 5mls of venous blood aseptically collected for blood culture, 163 (52.2%), BV 77 (24.6%), bacterial pathogens 66 (21.2%) and HIV, PCV and Malaria. Plasmids mediated antimicrobial resistance among Trichomonasvaginalis 6 (2.0%).Thirty bacterial isolates co-infected with bacteria isolates was determined. Data obtained from questionnaire, clinical Candidaspecies while 3 T. vaginalis co-infected with Candida species, 15 and laboratory diagnoses were analyzed using EPI-INFO version 3.5.1 software. BV co-infected with other bacterial pathogens. About 4 patients had Results: Among 202 patients studied, 186 (92.1%) and 16 (7.9%) were triple infection of BV, yeast and bacterial pathogens. clinically diagnosed as Malaria and ARIs respectively, but laboratory Conclusion: Most of the bacterial isolates were sensitive to Ciprofloxacin, investigations showed 47 (23.3%) positive for malaria, ARIs 31(15.3%), HIV Ofloxacin, levofloxacin and gentamicin antibiotics.Microbial infections in HIV/ 10 (5.0%) and anaemia 12(5.9%). The results revealed the prevalence of AIDS women was statistical significant (p>5.0). Treating an HIV positive HIV and ARIs co-infection as 10 (5%); HIV and Malaria 10(5%); Malaria and woman presenting with abnormal vaginal discharge would reduce ARIs 27 (13.4%). The entire Malaria positive cases 47 (100%) were due to transmission of HIV virus to her sexual partners and perinatal HIV transmission. Plasmodium falciparum. Haemophilus influenzae isolates 5 (100%) and Streptococcus pneumoniae 23 (82.1%) isolates harboured plasmids which conferred multiple antimicrobial resistant on them. P41 Conclusion: Fever in children may be as a result of Infection with HIV/AIDS, TB-IRIS among HIV patients in an urban private medical clinic, Malawi Malaria, ARI, or co-infection of any of the two diseases. Home management Sekeleghe Kayuni of fever was very high among mothers / care-givers. The commonest drugs MASM Medi Clinics Limited, Blantyre, Malawi used for treatment of childhood fever by mothers / care-givers were BMC Infectious Diseases 2014, 14(Suppl 2):P41 chloroquine and cotrimoxazole. Streptococcus pneumoniae the major organism isolated was highly resistant to cotrimoxazole. Introduction: Malawi is one of the countries in sub-Saharan Africa, adversely affected by HIV/AIDS. At least 40% of eligible people are on ART and most of them are initiated ART at very low CD4+ count. P43 Kanjedza Medi Clinic attends to over 5,000 patients monthly and runs an Factors affecting quality of life of people living with HIV/AIDS ART clinic of 1,253 clients, with 280 clients managed every month. attending a community care center in Chennai, India We looked at HIV infected patients presenting with symptoms and G Shanmugasundaram Anusuya1*, NC Appavoo1, T Mahalakshmy2, AS Valan3, conditions suggestive of Immune Reconstitution Inflammatory Syndrome PJ Parameaswari1, PM Udayshankar1, T Stephen1 (IRIS) and discuss challenges faced in diagnosis and managing them. 1Sree Balaji Medical College and Hospital, Bharath University, Chennai, India; Materials and methods: Case notes of patients who visited our clinic 2Department of Community Medicine, JIPMER, Pondicherry, India; between June 2013 and November 2013 and suspected to have IRIS were 3International Training and Education Center for Health, India accessed and reviewed. The patients presented in the clinic with worsening BMC Infectious Diseases 2014, 14(Suppl 2):P43 BMC Infectious Diseases 2014, Volume 14 Suppl 2 Page 20 of 45 http://www.biomedcentral.com/bmcinfectdis/supplements/14/S2/

Introduction: Health is defined by WHO as “complete physical, mental Background: Human Immunodeficiency Virus (HIV) reduces the ability of and social well-being”. Though the physical well-being is improved with person’s immune system to combat infection from microorganism such antiretroviral therapy, it does not guarantee mental and social well-being. as Tuberculosis, Herpes simplex, Candida, Toxoplasma. Some of these Hence we wanted to assess the Quality of Life (QOL) and to identify the microorganism are normal flora and usually do not generate a serious factors that influences QOL in People Living with HIV/AIDS (PLHA) disease in healthy people, therefore these infections are known as Materials and methods: A cross sectional study of 141 adult PLHA opportunistic infections (OIs). The OI by tuberculosis is the most common attending the out patient department of a community care center in cause of death for people infected with HIV worldwide. Since the OIs are Chennai during the period from 1st January to 31st August 2011 were not well recorded in Indonesia, in 2011 we conducted study in seven included in the study.QOL was evaluated using WHOQOL-HIV BREF provinces to identify the incidence of OIs among HIV patients. questionnaire. Analysis: Mean Scores of QOL was calculated using SPSS Method: The cross sectional study was conducted in several hospitals syntax file developed by WHO, Geneva. The One way Analysis of Variance that has voluntary counseling test (VCT) clinic. The respondents were HIV (ANOVA) was performed to find out significant difference between the patients who visited VCT clinics in seven provinces (North Sumatera, West socio-demographic variables and clinical categories on QOL domains. Sumatera, Riau Islands, South Sulawesi, North Sulawesi, Maluku, and Results: In study population 76 (53.9%) were males, 59 (41.8 %) were Papua) by purposive sampling in 2011. There were 490 respondents females and 6 (4.3 %) transgender. The overall QOL mean score on a scale included in this study. The statistical analyses were completed using of 0-20 was found to be 13.1. The mean scores of six domains of QOL in STATA 9.0 version. descending order were Spirituality/Religion/Personal beliefs (SRPB) (14.5); Results: From the study we found several OI from HIV patients. 379 out level of independence (LOI) (14.3); physical (13.3); environmental (12.5); of 490 respondents reported OIs. Among OIs patients, Tuberculosis, psychological (12.3) and social relationships domain (11.7): (p-value=0.000). Candidiasis and Diarrhea were the most common OIs with Tuberculosis QOL in physical domain was high among transgenders (17.3) when as the leading cause of OIs. There were 238 out of 490 (48.6%) infected compared with males (12.7), and females (13.7): (p=0.019). Social by Tuberculosis, 202 out of 490 (41.2%) with Candidiasis and 98 out of relationships domain scores between those who were single (11.5), married 490 (20%) with diarrhea. Moreover, we also found Dermatitis, Anemia, (12.8), and separated/widowed/divorced (10.9):(p=0.000). LOI domain was Lymphadenopathy, Hepatitis C, Herpes Zoster, Toxoplasmosis, Kaposi’s high among employed (14.5) than the unemployed (13.2): (p=0.028). sarcoma, Steven-Johnson Syndrome, Morbili, Cirrhosis Hepatis, Rheumatic Significantly better QOL scores in the LOI domain (15.2) (p=0.000) with Lupus and Cryptococcus Meningitis as OIs. We found highest number of respect to the CD4 count category. LOI domain better among patients Tuberculosis as the OI in Papua with 50 out of 70 (71.4%) respondents. without current history of tuberculosis (14.5) (p=0.008). There were 201 out of 379 (53%) cases developed more than one OI. Conclusions: In our study, QOL was associated with gender, marital Tuberculosis was reported mostly from patients with advanced stages status, employment status, CD4 counts of the patients and current history of HIV. of tuberculosis. Conclusion: In Indonesia, Tuberculosis was the leading cause of OIs and it was developed in advance stage of HIV infection.

P44 Are health care workers (HCWs) of long term care facilities (LTC) ready to take care of HIV older patients? P46 Philippe AL Henrivaux1*, Yvette RMG Fairon2 Socio-epidemiological and therapeutic profile of patients infected by 1St Joseph Hospital, Liège, Belgium; 2St Luc University Hospital, Brussels, Belgium HIV in 2011 at Tunis (Tunisia) * BMC Infectious Diseases 2014, 14(Suppl 2):P44 A Mrabet , MT Khoufi, A Yaakoubi, MR Kamoun, A Ben Hamida Faculty of Medicine of Tunis, Tunis, Tunisia Objectives: We have the feeling that the problem to find a place for elderly BMC Infectious Diseases 2014, 14(Suppl 2):P46 patients in long term facilities is even worse for those who are HIV+. This is probably due to the fact that HCWs in LTC are not sufficiently aware of the Introduction: Tunisia began, since 2004, with UNAIDS collaboration, potential presence of HIV in their professional life and that they do not have strategic planning against HIV infection and STD to figure out the enough experience of this type of care. epidemic dynamic and his determinants, reduce the risk of transmission Methods: We contacted 32 LTC with which we had never got in touch of STD/HIV among the vulnerable persons, and reduce the mortality and before. Initially, we phoned the nurses’ responsibles and asked to morbidity in people living with HIV(PLHIV) and families by improvement spontaneously comment the demand of a place for a HIV+ old patient. of whole support. Our aim was to trace the socio-epidemiological profile Thereafter, we sent a written questionnaire about their feelings of having and the treatment of persons infected by HIV in 2011 in Tunis. such a patient in their establishment. Methods: A retrospective study of 56 patients infected by HIV whose Results: All of them (32/32) said that they have no experience with HIV treatment began in 2011 in the reference medical department of HIV in patients and they want preliminary information. A quarter of them (8/32) Tunis. We included all patients whose HIV infection was confirmed by never thought about HIV in their professional life. 3/32 evoked the problem Western Blot and whose medical support began in the disease stage during as they organized the care for a HCV patient. Concerning the written the first medical consultation according to the clinical and biological criteria questionnaire, we received answers from 15/32 institutions. Based on their of CDC. responses, we tried to assign a note (mean+/-SD: 8.2+/-2.1) about their Results: Population mean age was 38.4 years. PLHIV faced unemployment feelings concerning the care of HIV patients. Two institutions got a note problems. Half of patients are destitute, 10.8% are students and 62% live above the mean+1SD, suggesting that they are more ready to take care of a lonesome. Imprisonment was found in 3.6% of patients. 79% of PLHIV have HIV patient. Tunisian nationality and benefit of free tritherapy and medical support. Conclusions: HCWs from rest homes in our region are not sufficiently 50% made at least one travel abroad. The foreign PLHIV are from sub- informed and trained to welcome HIV older patients. They want saharan African countries. Risks behaviors are multiple, as non protected preliminary information. We think also that a practical experience is the heterosexual intercourse (68%). The discovery of HIV infection occurs in best way in order to tackle this health problem. Therefore, we invite stage A (62%), C3 (21%). All eligible patients to a highly active antiretroviral them to participate to the care of HIV patients in our service. therapy (HAART) received the treatment. 12% have co-infection HIV – Hepatitis B and/or C. VHC was found in injection drug users (p<10-3). Opportunistic infections were observed in 30%. Good observance was P45 notified in 70%, in the first year of treatment. The poor observance was The cases with opportunistic infections among HIV patients in due to unavailability of HAART and to the denial of a binding treatment. Indonesia 2011 Four deaths were notified: males, singles, C3 stage in beginning of Roselinda Rusli*, Vivi Setiawaty treatment. Center for Biomedical and Basic Technology of Health, NIHRD, Jakarta, Conclusion: PLHIV are a part of the population that cumulates Indonesia vulnerability factors which increases the risks for reaching further stages of BMC Infectious Diseases 2014, 14(Suppl 2):P45 the AIDS and for poor medical support. BMC Infectious Diseases 2014, Volume 14 Suppl 2 Page 21 of 45 http://www.biomedcentral.com/bmcinfectdis/supplements/14/S2/

Conclusion: In the era of c-ART, incidence of anemia remains high P47 especially in patients above 60 years. Given the growing age of HIV Surgical treatment of perforative tubercular intestines ulcers at patients patients, physicians should be attentive to this problem in the oldest with HIV infection patients. Further prospective studies are needed to better characterize MN Reshetnikov*, MS Skopin, RV Mal’tsev, ON Zuban the mechanisms of anemia observed in this population. Moscow city scientifically practical center of fight against tuberculosis, Moscow, Russia BMC Infectious Diseases 2014, 14(Suppl 2):P47 P49 Cutaneous drug-reactions to nevirapine: study of risk factors in 268 High incidence of HIV infection leads to increase in number of HIV-infected patients tuberculosis cases. The Abdominal Tuberculosis (AT) makes 1/4 among L Badaoui*, G Dabo, H Lamdini, R Bensghir, A Oulad Lahsen, M Sodqi, L Marih other extra pulmonary localizations at patients with late stages of HIV , A Chakib, K Marhoum El Filali infection. The worst complication of AT is perforation of tubercular ulcers Ibn Rochd University Hospital, Casablanca, Morocco of intestines when the lethality reaches 80%. BMC Infectious Diseases 2014, 14(Suppl 2):P49 The clinical material is presented by 76 patients with HIV infection in 4B stage and ruptured tubercular intestines ulcers. Depending on localization of Introduction: Several studies have shown a high prevalence of rash ulcers, resection of small intestine or a right-sided hemicolectomy was made. induced by nevirapine. The aim of this study was to identify risk factors The first group included 40 patients, the second one - 36. Duration of HIV associated with the occurrence of rash during the treatment with infection was 7-8 years. The periods from the moment of perforation to nevirapine of HIV-infected patients. operation varied from 12 to 36 hours. Materials and methods: A retrospective study was conducted in the In group 1 primary anastomosis was not made, leaving the created stumps infectious department diseases between January 2007 and October 2013. of bringing and taking-away departments of intestines in an abdominal The study included all HIV-infected patients receiving HAART regimens cavity, carrying out a decompression of bringing department of intestines. that included nevirapine. The following data were collected: age, sex, Relaparotomy was carried out with an interval of 48 hours. After knocking CDC classification of HIV, CD4 and lymphocyte counts, plasma HIV RNA peritonitis two-row anastomosis was made. load, history of drug allergy, concomitant medication. In group 2 resection of a gut was finished with one-stage anastomosis, Results: During the study period, 268 HIV-infected patients were treated sanitation of an abdominal cavity was made. with HAART regimens including nevirapine. Nineteen developed cutaneous Active heavy bilateral processes prevailed among the other forms of lungs drug-reactions attributable to nevirapine (7. 09%). 16 women and 3 men; tuberculosis. The patients’ number of CD4 was noted to have decreased mean age: 38 (± 12) years old. The mean initial CD4 was 320 cell/mm3, we lower than 150, at this time at the number of CD4 of 55 (72,4%) patients observed 17 cases of maculopapular exanthema and 2 case of DRESS, the was less than 50. hepatic cytolysis retouved in 5 cases. Female gender (84%), plasma HIV RNA Tuberculosis colitis at all patients was presented by infiltrative and ulcer load > 10 000 copies/ml (100%) constituted risk factors associated with rash. form. In 25% of all the cases acid resisting mycobacterium was revealed TheniverapinehasswitchedeitherEfavirenz or IP; no allergic event was in the exudate received from an abdominal cavity by luminescent detected after changing the niverapine. microscopy method. During luminescent microscopy of ulcers edges, Conclusion: The number of HIV-infected patients who are newly exposed mycobacterium tuberculosis was always revealed. to nevirapine is increasing worldwide. To minimize toxicity, clinicians In group 1 the results of the treatment were better: the faster recover from must adhere to dosing guidelines, avoid prescribing the drug in patients peritonitis was note, and there was no insolvency anastomosis, perforation with known increased risk of toxicity, and promptly recognize toxicities, of new tubercular intestines ulcers was noted at 8 patients. 14 patients which are mainly cutaneous and hepatic. delivered in a sad plight with intense immunodeficiency died of accruing polyorgan insufficiency. Ingroup2-28patientsdied,at18ofwhichnewgutsperforationand peritonitis progressing occurred what required repeated surgeries. P50 Spectrums of opportunistic infections in HIV-Infected patients in referral hospital of Setif (Algeria) P48 A Ouyahia*, M Rais, A Gasmi, W Guenifi, S Mechakra, A Lacheheb Is anemia still a problem in cART era: a single center study? Ferhat Abbes University, faculty of medicine, Setif, Algeria P Genet*, J Gerbe, V Masse, D Chaoui, B Wifaq BMC Infectious Diseases 2014, 14(Suppl 2):P50 Victor Dupouy Hospital, Argenteuil, France BMC Infectious Diseases 2014, 14(Suppl 2):P48 Background: The clinical course of HIV/AIDS and pattern of opportunistic infections vary from patient to patient and from country to country. in Aim of the study: In the pre-cART era, anemia was a frequent this report we describe the clinical and laboratory profiles of different complication observed in HIV patients. But, recent studies showed a opportunistic infections (OIs) among 266 immunocompromised patients persistent high prevalence of anemia, integrating anemia in the premature admitted to a referral hospital in the eastern of Algeria. aging observed in HIV patients. The aim of the study was to estimate the Methods: Between January 2003 and November 2013, 266 HIV infected prevalence of anemia in our patient’scohort. patients were admitted to our center. Clinical data about patients were Materials and methods: All patients, except pregnant women, seen in our collected retrospectively from standardized HIV/AIDS forms filled at admission. unit after 2007 were included in this analysis. For each patient, last Results: Out of 266 patients, 65% were male, the mean age was 37 years hemoglobin’s concentration was collected. Incidence of anemia was and the most frequent route of transmission was heterosexual (86%). 60 calculated according WHO’s definition. % were admitted with obvious clinical signs and symptoms, whereas 40% Results: 544 patients (260 female, 284 men) with a median age of 45.9 were asymptomatic, and they were diagnosed through screens or check- years (18.9-80.8) were included. 513 patients were on ART (94.3%). Median up tests. The most frequent clinical symptoms on first admission were CD4 was 546.5 (14-2707), viral load (VL) < 50 in 75.9% of patients. oral candidiasis (66.4%), herpes zoster virus infection (18.6%), tuberculosis Anemia was present in 141 patients (25.9%): mild 18.9%, moderate 6.8%, (16.7%), Pneumocystis jirovecii pneumoniae (12%), weight loss (10%), severe 0.2%. No correlation with VL was seen: mean Hb for patients with persistent generalized lymphadenopathy (3.5%), , malignancies (3.2%), CV>50 versus <50 was respectively 13.3 and 13.4. No correlation with CD4 chronicfever(2.5%).WefoundthelowprevalenceofAIDS-defining was seen: mean CD4 for anemic and non-anemic patients was respectively illnesses in central neural system in this study, including progressive 502 and 544 (NS). However, a correlation with age was seen with an multifocal leukoencephalopathy (1.8%), cerebral toxoplasmosis (3%), incidence of anemia of 24.5% for patients under 60 y and 36.4% for cryptococcal meningitis (2.3%). patients ≥60 y (p<0.001). These impact on age was only seen in men with Median viral load was 120000cp/mL. Screening tests were conducted an incidence of anemia of 12.6% for age under 60 y vs 33.3% for age ≥60 y most frequently during blood donations (20%), before surgeries (13%) (p<0.001). For women, age has no impact on prevalence of anemia. and check-ups (6%). BMC Infectious Diseases 2014, Volume 14 Suppl 2 Page 22 of 45 http://www.biomedcentral.com/bmcinfectdis/supplements/14/S2/

Conclusion: Algeria is among low prevalence countries in the world for species most frequently isolated. 80% of patients had progressed well (n HIV/AIDS. Clinical profile of our patients is similar to the developed = 60), and we recorded 20% of deaths (n = 15). countries. More than half of the patients diagnosed at late stages of the Conclusion: The prevalence of cryptosporidiosis is higher in patients disease. It highlights the need for early screening and also the need to infected with HIV. The strengthening of preventive measures is necessary increase awareness in healthcare providers, in order to improve decisions especially as some of the identified species at risk of human transmission regarding prophylaxis for prevention and appropriate therapeutic in hospitals. The prognosis of the disease remains in the absence of intervention. effective therapy, dark in refractory cases symptomatic treatment and HAART.

P51 Cutaneous anaplastic large cell lymphoma in HIV exceptional case in P53 Algeria Epidemiological aspects of new HIV/AIDS diagnoses in south-east M Rais*, A Ouyahia, W Guenifi, A Gasmi, S Mechakra, A Lacheheb Romania Infectious diseases Hospital, Faculty of medicine of Setif, Setif, Algeria M Arbune*, C Georgescu, D Tutunaru, M Dobre, A Nechita BMC Infectious Diseases 2014, 14(Suppl 2):P51 “Dunarea de Jos” University, Galati, Romania BMC Infectious Diseases 2014, 14(Suppl 2):P53 Introduction: Anaplastic large cell lymphoma is a rare and account for 10 % of cases of cutaneous lymphoma T is characterized by the presence of Introduction: The characteristic of HIV/AIDS Romanian epidemic is the anaplastic tumor cells, pleomorphic or immunoblastic for the majority of high proportion of youth infected in 1988-1990, during their first year of them (over 75 %) antigen CD30 . It is in the form of single or multiple life, when a nosocomial epidemiological accident took place. In Galati nodules or as patches in adult patients. (South-East Romania) they were recorded 535 people with HIV/AIDS during Patient: We report a patient of 43 years old followed for HIV + 1990-2003 and 79.5% belonged to the pediatric nosocomial cohort. The hypothyroidism who presented for 8 months multiple purplish nodules mortality was 56.8% and half of the deaths were recorded during the first scattered all the body but especially in the left lower limb or there is a large year after diagnosis. The aim of the study is to identify the changes in the ulcerated a budding and painful nodule the upper part of the inner side of HIV/AIDS epidemic in the last 10 years. the left thigh associated with lymphedema of the lower limb all concerned Materials and methods: This retrospective study was based on Clinically, it measured 3-5 cm in diameter, were clear limits, an erythematous epidemiological reports of the newly diagnosed HIV/AIDS patients. The ulcerated area with serosanglant flow and was fixed with respect to deeper descriptive statistics and comparative Kaplan-Meier graphs by transmission level. We found nodular lesions on the abdominal and thoracic wall. He had way were analyzed using XL-Stat Software. no lymphadenopathy or hepato splenomegaly. We discussed the diagnosis Results: During 2004-2013, 182 new patients have been diagnosed with of cutaneous leishmaniasis, epidermoid carcinoma, cutaneous tuberculosis HIV/AIDS in Galati. Most patients are young people with the same age as the and Kaposi sarcoma. Histological examination of a fragment of skin pediatric cohort of HIV/ AIDS, but predominance of heterosexual resection was in favor of anaplastic large T-cell lymphoma / No primitive transmission marks the change of the epidemic pattern. (table 1). Late according to OMS classification 2008 (CD30 + , CD20 - , CD5 + / -, ALK- , presentation is less associated with sexual than other transmission ways CD15 - and granzyme B + / - ). Lymph node ultrasound, thoracoabdominal (p=0.026), but is most likely expected in males (p=0,003), with symptomatic computed tomography showed thoraco-abdominal polyadenopathies with context (p<0,001). Death rate is 15%. Retention in care was achieved in 95% two right pulmonary micronodules. The treatment consisted in CHOP of cases. Tuberculosis is still the leading indicator of AIDS (21.4%). chemotherapy protocol. Tuberculosis (12/26) and cancer disease (6/26) are the main causes of death. After four cycles of chemotherapy lesions disappeared completely with disappearance of lymphedema with a very good condition and weight regain. Thoracoabdominal CT scan was done showing the complete disappearance of thoraco- abdominal lymphadenopathy. Table 1 (abstract P53) Characteristics of new HIV/AIDS Conclusion: Front dragging and recurrent chronic ulcers, the diagnosis of diagnosed patients in Galati cutaneous lymphoma should be considered in the differential diagnosis and skin biopsy is needed. Median diagnostic age: 23[1;78] Sex: Male/ Female 98/84 P52 Area: Urban/ Rural 87/95 Intestinal cryptosporidiosis in HIV-infected patients in the department Transmission: of infectious diseases L Badoui*, G Dabo, H Lamdini, A Oulad Lahcen, M Sodqi, L Marih, A Chakib, Perinatally 4.4% M Soussi, K Marhoum El Filali Nozocomial 19.8% Ibn Rochd University Hospital, Casablanca, Morocco BMC Infectious Diseases 2014, 14(Suppl 2):P52 Heterosexual 56% MSM 1.6% Introduction: The Cryptosporidiosis is a gastrointestinal opportunistic parasitic disease is a major cause of diarrhea and malnutrition in patients IVDU 3.8% infected with HIV. Its prevalence is estimated at 2.76%. The aim was to Unknown 14.3% determine the prevalence of intestinal Cryptosporidium in patients infected with HIV and to identify Cryptosporidium species in question. Context of HIV testing: Materials and methods: This is a retrospective study conducted 20 HIV partner 17.6% months in the department of Infectious Diseases. Cryptosporidium research was conducted by the Ziehl-Neelsen and modified by PCR. Data Pregnancy 11.5% collection was made from computerized records. Perinatal exposure 3.6% Results: We collected 75 patients. The mean age of patients was 37 years old. The median CD4 was 62cel/mm ³. Intestinal cryptosporidiosis was Drugs users 1.6% indicative of HIV infection in 54 cases (77%) and in 16 cases (23%) they Other screening programs 8.2% occurred at the waning of treatment failure. Cryptosporidia were isolated Symptomatic: 51.2% from 52 patients (69.3%). Eight of them were gay. Consumption of raw milk and the presence of animals in the environment have been reported Clinical CDC-class: A/B/C 19/81/83 by more than two thirds of patients. Thirty five infected individuals were Immunological-class:1/2/3 27/52/103 diarrhea, 12 had febrile abdominal pain. Cryptosporidium parvum was the BMC Infectious Diseases 2014, Volume 14 Suppl 2 Page 23 of 45 http://www.biomedcentral.com/bmcinfectdis/supplements/14/S2/

Conclusions: The life expectancy of HIV/AIDS patients has obviously improved in the last decade, but the yearly number of new cases is P55 constant, with a high rate of late presenters. The strategy of future screening Support for current patients infected addicts programs should consider the trends of HIV/AIDS epidemic in our region. Karine Bartolo*, Pascal Auquier Aix-Marseille University, La Timone Faculty, Addiction Center, Marseille, France P54 BMC Infectious Diseases 2014, 14(Suppl 2):P55 Opportunistic infections in HIV positive patients in Bahrain in 4 years study 2009-2013 In 2013, the network supported 282 addict patients. 121 patients Nermin Saeed*, Eman Farid, Afaf E Jamsheer including 24 women are infected with HIV or HCV and 109 have hepatitis SMC, Pathology Department, Microbiology Section, Muharaq, Bahrain C. All have a substitution of Buprenorphine or Methadone treatment. BMC Infectious Diseases 2014, 14(Suppl 2):P54 110/121 patients have a general practitioner and 101/121 have a regular pharmacist. (figure 1) Objectives: This study aimed to examine the prevalence of opportunistic 25 patients are cured of hepatitis C out of 47 who received treatment and infections in HIV-infected patients in Bahrain and related them to the 14 patients are cured spontaneously without treatment. Among 121 absolute CD4 count, CD4% and CD4/CD8 ratio. patients, 16 have already been hospitalized in psychiatry. 45 patients have Methods: The research was a retrospective, cohort study using laboratory a psychiatric co-morbidity and 40 are treated for this disease. (figure 2) records from a major hospital in Bahrain, from January 2009 to May 2013. Very few patients have less than 200 CD4. (figure 3) Opportunistic infections (OIs) and absolute CD4 count, CD4% and CD4/ Most patients were followed up since 2008. (figure 4) CD8 ratio were recorded for every patient. Conclusion: Addict patients take subscribe to a course of complex care, Results: CD4% and absolute CD4 count in HIV patients with associated and often long term. They are often supported in a complementary infections was significantly lower than in those without associated manner by the city and the hospital. Their immune status for seropositive infections (P< 0.001) but there was no significant difference in CD4/CD8 patients of HIV are often above 200 CD4. They often have an associated Ratio between the two groups. Infection with Staphylococcus aureus was psychiatric comorbidity for which they receive treatment. When the the commonest encountered infections and present in 9.8% % of total treatment with Interferon is go on, only ½ is cured. Today, they most AIDS patients and 28.7% of AIDS patient group who had OIs; followed by often have non-treated hepatitis C. yeast infections (9.2% and 27.2% respectively). Mycobacterium tuberculosis was present in 3.6% of total AIDS patients and 10.6% of the group with OIs while Mycobacterium Other Than Tuberculosis (MOTT) was present in 2.5% and 7.5% respectively. Pneumocystis jirovecii pneumonia (PCP) was P56 observed in 5.1% and 15.1% respectively. The least bacterial infections Morphological spectrum of lymphadenopathy in AIDS patients observed were Streptococcus penumoniae, Streptococcus melleri, Kanthilatha Pai*, Ranjini Kudva Stenotrophomonas maltophilia, & Citrobacter species. Herpes simplex II Kasturba Medical College, Manipal, India (HSV-II) was the commonest OIs observed while Cytomegalovirus BMC Infectious Diseases 2014, 14(Suppl 2):P56 antigenemia was only present in 2% and 6% respectively. Conclusion: Studying the pattern of OIs in HIV-infected patients in Introduction: Lymph node biopsy is essential in the evaluation of Bahrain is of paramount importance due to scarcity of data in the Arab lymphadenopathy in patients infected with Human immunodeficiency worlds. This help to improve physician’s awareness to improve care of virus to diagnose the many complications and institute proper treatment. AIDS patients. Lymph node abnormalities in patients can be varied, showing spectrum

Figure 1(abstract P55)

Figure 2(abstract P55) BMC Infectious Diseases 2014, Volume 14 Suppl 2 Page 24 of 45 http://www.biomedcentral.com/bmcinfectdis/supplements/14/S2/

Figure 3(abstract P55)

Figure 4(abstract P55) of morphologic changes ranging from reactive lymphadenitis, opportunistic diagnosed. 2 cases included Lympho-epithelial cyst and infarction of lymph infections, Kaposi’s sarcoma, malignant lymphomas. node.CD 4 counts were available for 16 patients which was low in all Materials and methods: This is a retrospective study that analyses the patients and ranged from 21-181/cumm. morphological diagnosis of lymphadenopathy in patients with retroviral Conclusion: It is imperative to perform lymph node excision in HIV illness over a 2 year period (2012-2013). All lymph node biopsies performed patients as it can display wide variety of conditions ranging from reactive in HIV positive patients for work-up of lymphadenopathy are included and to opportunistic infections to neoplastic conditions, which require specific the following clinical information is analyzed: Age, sex, clinical symptoms, treatment. Lymph node biopsy in HIV patients will help to understand the duration of illness, retroviral treatment and CD4 counts. The morphological epidemiology and geographical prevalence of lymph node abnormalities diagnosis is classified into reactive lymphadenitis which is further divided in HIV patients. into Pattern A, B and C, opportunistic infections, lymphomas and others.CD4 levels and other parameters are analyzed in the study. Results: A total of 29 patients with retroviral illness in whom lymph node HIV: VIROLOGY biopsies were done were included in the study, of which 17 were males and 12 were females. The most common age group ranged from 31-40 years in P57 both males and females. Fever and generalized lymphadenopathy were the Serial passage of HIV-2F: a pigtail macaque model for HIV emergence most common symptoms .Reactive lymphadenitis and opportunistic Nell G Bond1*, Stephanie L Feely2, Christopher Monjure2, Michael Lauck3, infections were diagnosed in 11 patients each (42.3%) showing, Pattern A in David O’Connor3, Nick Manness2, Preston A Marx1,2 7 patients and Pattern B in 4 patients. Tuberculosis was the most frequent 1Tulane University School of Public Health and Tropical Medicine, New opportunistic infection in 9 patients, followed by Crytococcal infection in 2 Orleans, Louisiana, USA; 2Tulane National Primate Research Center, patients. 4 patients with Non-Hodgkins lymphoma and 1 patient with Covington, Louisiana, USA; 3University of Wisconsin, Madison, Wisconsin, USA polymorphous Hodgkin like B cell lymphoproliferative disorder was BMC Infectious Diseases 2014, 14(Suppl 2):P57 BMC Infectious Diseases 2014, Volume 14 Suppl 2 Page 25 of 45 http://www.biomedcentral.com/bmcinfectdis/supplements/14/S2/

The AIDS pandemic affects over 35 million people worldwide. Human contiguous sequences and successfully subtyped. Subtype B was the only immunodeficiency types 1 and 2 (HIV-1 and HIV-2), the etiologic agents non-recombinant virus characterized in this study and accounted for 60% of AIDS, originated from simian immunodeficiency viruses of chimpanzees (27/45) of samples. The remaining 40% (18/45) specimens showed various (SIVcpz) in Cameroon and SIVsm from sooty mangabeys in West Africa. patterns of subtype discordance in different regions of HIV-1 genomes While the simian origin of HIV is well established, how the virus adapted indicating 2-4 circulating recombinant subtypes derived from clades B, F to humans is poorly understood. The bulk of HIV-2 morbidity and and C. Over 50% of infection in MG and RJ harbor unique inter-subtype mortality is caused by a few strains; however, new pathogenic subtypes recombinant forms. of HIV-2 continue to emerge (HIV-2F, 2008 and HIV-2H, 2004) Conclusion: Our findings revealed a high proportion of HIV-1 recombinants underscoring the need for deeper understanding of the mechanisms among recently infected blood donors in Brazil which has implications for behind the adaption of these viruses to humans. This study aims to test future diagnosis, therapy and efficient vaccine development. the serial passage theory of HIV emergence and elucidate adaptive mechanisms to a new host using the newly emerged, pathogenic HIV-2F virus in an in vivo pigtail macaque (PTM) model. P59 We inoculated one pigtail macaque with HIV-2F isolated from the patient PMTCT of HIV-1 in Burkina Faso: evaluation of residual vertical followed by serial passage into 2 PTMs. Blood, lymph node; endoscopy transmission by PCR, molecular characterization of subtypes and and vaginal wash were collected. An HIV-2F specific quantitative PCR determination of antiretroviral drugs resistance (qPCR) assay was developed (LOQ=1.9 log VC/mL) for this experiment. T Sagna*, C Bisseye, TS Kagone, FW Djigma, D Ouermi, MTA Zeba, VJT Bazié, All three PTMs were infected; reaching peak PVLs between 6.0 and 7.2 Z Douamba, R Moret, V Pietra, A Koama, S Pignatelli, C Gnoula, JD Sia, log viral copies/milliliter. PTM KF25, passage one, cleared the virus by day JB Nikiema, J Simpore 42 post inoculation (PI) and remains qPCR negative at day 344 PI. KF26 Pietro Annigoni Biomolecular Research Center (CERBA), Ouagadougou, and KF24, passages two and three, cleared the virus following acute Burkina Faso infection by days 42 and 60 respectively. Importantly, virus rebounded in BMC Infectious Diseases 2014, 14(Suppl 2):P59 the 2nd and 3rd passage animals at day 150 and 120, respectively, and remains between 5.6 and 3.2 log VC/mL. Aim: Vertical HIV transmission is a public health problem in Burkina Faso. Following one passage in PTMs, HIV-2 F escaped host control and This study on the prevention of mother to child HIV-1 transmission had the sustained replication, showing that the virus adapted to the new host via objectives to: i) determine the residual rate of vertical HIV transmission by serial passage. Sequence analysis comparing peak and re-emergent virus PCR ii) Detect of HIV antiretroviral drugs resistance among mother-infant is ongoing and will be completed for presentation. Flow cytometry pairs and iii) Identify sub-types and Circulating recombinant form (CRF) in analysis to correlate changes in VL with cytokine markers of pathogenesis Burkina Faso. is in process. Clinical monitoring is ongoing to assess pathogenesis of Materials and methods: In this study, 3,215 samples of pregnant women passaged HIV-2F. were analyzed using rapid tests “Determine HIV1/2”. Vertical transmission was estimated by PCR in newborns from those who were HIV positive. HIV-1 Resistance to ARVs, subtypes and CRFs were determined through ViroSeq kit using the ABI PRISM 3130 sequencer. P58 Results: In this study, 12.26% (394/3215) of the pregnant women were Ultra-deep sequencing of HIV-1 near full-length and partial proviral diagnosed HIV-positive, 0.52% (2/388) overall residual rate of transmission genomes from recently infected blood donors at four blood centers in was identified with rates of 1.75% (2/114) among mothers under prophylaxis Brazil and 0.00% (0/274) for those under HAART. Genetic mutations have also Rodrigo Pessôa1*, Jaqueline Tomoko Watanabe1, Paula Loureiro2, been isolated that induce resistance to ARVs like M184V, Y115F, K103N, Maria Esther Lopes3, Anna Barbara Carneiro-Proietti4, Ester C Sabin5, Y181C, v179E, G190A, etc. And there were subtypes and circulating Michael P Busc6, Sabri S Sanabani1 recombinant forms (CRF) of HIV-1 such as: CRF06_CPX (58.8%), CRF02_AG 1Institute of Tropical Medicine, University of São Paulo, São Paulo, Brazil; (35.3%) and subtype G (5.9%). 2Pernambuco Hematology and Hemotherapy Institute - HEMOPE, Recife, PE, Conclusion: Antiretroviral drugs reduce the residual rate of HIV vertical Brazil; 3Rio de Janeiro Hematology and Hemotherapy Institute - HEMORIO, transmission. However, they cause mutations that induce resistance of Rio de Janeiro, Brazil; 4Federal University of Minas Gerais - UFMG, Belo HIV to antiretroviral therapy. Resistance to ARV therefore requires a Horizonte, MG, Brazil; 5Department of Infectious Diseases, University of São permanent dialogue between clinicians, prescribers, pharmacists, and the Paulo, São Paulo, Brazil; 6Blood Systems Research Institute, San Francisco, creation of a network of monitoring and surveillance of drug resistance in California 94117, USA Burkina Faso. BMC Infectious Diseases 2014, 14(Suppl 2):P58

Background: Monitoring the genetic diversity of HIV-1 during the early P60 stage of infection offers the best opportunity for understanding viral HIV-1 CRF08_BC mutants resistant to reverse transcriptase inhibitors transmission dynamics and evolution of transmitted/founder viruses. Hao Wu*, Xiao-Min Zhang, Bo-Jian Zheng Previous studies of HIV-infected donorsinBrazilemployingpolregion University of Hong Kong, Hong Kong, Hong Kong sequencing have shown a predominance of subtype B (~80%) followed BMC Infectious Diseases 2014, 14(Suppl 2):P60 by F and C, with rare recombinant viruses. Here, we report application of high-throughput near-full-length (NFLG) and partial HIV-1 proviral Human immunodeficiency virus type (HIV)-1 circulating recombinant form genome deep sequencing to characterize HIV in recently infected blood 08_BC (CRF08_BC), carrying recombinant reverse transcriptase (RT) gene donors at four major blood centers in Brazil. from subtype B and C, has recently become highly prevalent in Southern Methods: From 2007-2011, 341 HIV+ blood donors from 4 blood centers China. As the number of patients infected by CRF08_BC increases, it is were recruited to participate in a case control study to identify risk important to characterize the drug resistance mutations of CRF08_BC, exposure and motivation to donate. Forty-seven (17 from São Paulo [SP], 8 especially against widely used antiretrovirals. In this study, clinically isolated from Minas Gerais [MG], 11 from Pernambuco [PE] and 11 from Rio de virus was propagated in human peripheral blood mononuclear cells (PBMCs) Janeiro [RJ]) were classified as recently infected based on testing by with increasing concentrations of nevirapine (NVP), efavirenz (EFV) or less-sensitive (LS) or “detuned” enzyme immunoassay (Vironostika HIV-1 lamivudine (3TC). Three different resistance patterns led by initial mutations MicroElisa; bioMérieux, Durham, NC) or an LS chemiluminescent of Y181C, E138G and Y188C were detected after in vitro selection with NVP. immunoassay (Vitros HIV-1/2 Assay; Ortho Diagnostics, Rochester, NY). Five Virus variants with initial mutations, in combination with three other overlapping amplicons spanning the HIV genome were PCR amplified from previously reported substitutions (K20R, D67N, V90I, K101R/E, V106I/A, V108I, peripheral blood mononuclear cells (PBMCs). The amplicons were molecularly F116L, E138R, A139V, V189I, G190A, D218E, E203K, H221Y, F227L, N348I and bar-coded, pooled, and sequenced by Illumina paired-end protocol. T369I) or novel mutations (V8I, S134N, C162Y, L228I, Y232H, E396G and Results: Of the 47 recently infected donor samples studied, 39 (82.9%) D404N) developed during NVP selection. EFV-associated variations NFLGs and 6 (12.7%) partial fragments were de novo assembled into contained two initial mutations (L100I and Y188C) and three other BMC Infectious Diseases 2014, Volume 14 Suppl 2 Page 26 of 45 http://www.biomedcentral.com/bmcinfectdis/supplements/14/S2/

mutations (V106L, F116Y and T139V). Phenotypic analyses showed that understanding the genesis of HIV-1 epidemic in this particular area of E138R, Y181C and G190A contributed high level resistance to NVP, while South America and inform vaccine design and clinical trials. L100I and V106L significantly reduce virus susceptibility to EFV. Y188C resulted in a 20-fold reduction of susceptibility to both NVP and EFV. M184V was selected by 3TC as expected. This mutation, alone or with V90I or D67N, P62 decreased 3TC susceptibility by over 1000 folds. These results have brought Complete genome sequence of new unique recombinant HIV type 1 new insight into the development of drug-related mutations in patients and isolated from a child born to an HIV-infected mother provided useful information for the optimization of antiretroviral regimens. S Sasinovich*, V Eremin, E Gasich, M Thomson RRPC for Epidemiology and Microbiology, Minsk, Belorussia BMC Infectious Diseases 2014, 14(Suppl 2):P62 P61 Ultra-deep sequencing of HIV-1 near full-length and partial proviral Introduction: In our previously studies we detect a HIV recombinant genomes among chronically infected blood donors at four blood form with BgagApolAenv by isolate named Mos. This virus differs from centers in Brazil CRF02_AB with AgagBpolBenv. For more detailed studying of isolate Mos Rodrigo Pessôa1*, Jaqueline Tomoko Watanabe1, Paula Loureiro2, genome we carried out complete genome sequencing. (Figure 1) Maria Esther Lopes3, Anna Barbara Carneiro-Proietti4, Ester C Sabin5, Materials and methods: HIV-1 RNA was extracted from plasma, reverse Michael P Busc6, Sabri S Sanabani1 transcribed, and amplified using sets of primers designed to span the 1Institute of Tropical Medicine, University of São Paulo, São Paulo, Brazil; complete genome of HIV-1. Contig assembled in SeqMan®, DNAStar. 2Pernambuco Hematology and Hemotherapy Institute - HEMOPE, Recife, PE, Recombination analysis was performed using REGA HIV Subtyping Tool. Brazil; 3Rio de Janeiro Hematology and Hemotherapy Institute - HEMORIO, Phylogenetic analysis was made in MEGA4 software with Kimura-2-parametres. Rio de Janeiro, Brazil; 4Federal University of Minas Gerais - UFMG, Belo Results: Analysis of complete genome shows that recombinant Mos is a Horizonte, MG, Brazil; 5Department of Infectious Diseases, University of São new HIV-1 URF with gag/pol mosaic structure composed of parental Paulo, São Paulo, Brazil; 6Blood Systems Research Institute, San Francisco, subtypes A and B and rest genome composed of subtype A. California 94117, USA Phylogenetical analysis had shown that HIV-1 subtype A ancestor is BMC Infectious Diseases 2014, 14(Suppl 2):P61 AY500393 Russia, subtype B - DQ207943 Georgia. Conclusions: This study confirms the presence of a unique recombinant Introduction: Here, we aimed to gain a comprehensive picture of HIV-1 HIV-1 strain, emerging as a result of recombination between HIV-1 strains diversity in the north-east and south-east part of Brazil. To this end, a from Russia and Georgia. high-throughput sequencing was used to characterize the near full length (NFLG) and partial HIV-1 proviral genome in blood donors at four major blood centers in Brazil: Pro-Sangue foundation (São Paulo state (SP), n P63 48), Hemominas foundation (Minas Gerais state (MG), n 41), Hemope HIV-1 Tat promotes premature brain aging foundation (Recife state (PE), n 97) and Hemorio blood bank (Rio de Asen Bagashev*, Ruma Mukerjee, Jenny Shrestha, Maryline Santerre, Janeiro (RJ), n 90). Ying Wang, Bassel E Sawaya Material and methods: From 2007-2011, 341 HIV+ blood donors from 4 Temple University, Philadelphia, USA blood centers were recruited to participate in a case control study to BMC Infectious Diseases 2014, 14(Suppl 2):P63 identify risk exposure. Of those, 294 specimens were classified as chronically infected subjects based on reactivity and positivity on the tests Background: It is estimated that by 2015, about half of all HIV-positive for recent HIV infection. Five overlapping amplicons spanning the HIV individuals will be older than 50 due to the introduction of the HAART. genome were PCR amplified from PBMCs. The amplicons were molecularly Yet those over 50 progress to AIDS faster than adults in their 20s or 30s, bar-coded, pooled, and sequenced by Illumina protocol. and those in the younger age bracket still exhibit illnesses and clinical Results: Of the 294 samples studied, 229 (77.9%) NFLGs and 50 (17%) conditions commonly associated with older people, such as HIV- partial fragments were de novo assembled into contiguous sequences and associated neurocognitive disorders (HAND), certain cancers, liver and successfully subtyped. Of those, 200 (71.7%) were pure subtypes consisting bones diseases. For the most part, the reasons for this have remained a of clade B (n = 151, 75.5%), C (n = 11, 5.5%) F1 (n = 4, 2%) and D (n = 3, mystery. In support of the eradication failure, studies showed the 1.5%). Recombinant viruses were detected in 79 (28.3%) samples and consist persistence of HIV-1 in brain cells as well as the presence of viral proteins of BF1 (n = 67, 84.8%), BC (n = 6, 7.6%), BCF1 (n = 4, 5%), CF1 and BUA1 (n = in CSF. This notion was supported by the compelling neuropathological 1, 1.2%, each). Evidence of dual infection with the same subtype was data suggesting that the loss of Synaptic Plasticity occurs with the detected in 1 patient. Two distinct BF1 recombinant profiles based on NFLG, ongoing presence of virus and despite HAART. Clinically, these with four samples in profile I and seven in profile II were detected and neuropathological data manifest by a gradual loss of working memory constitute two novel recombinant forms circulating in PE. and learning disability that may manifest by symptoms similar to the Conclusion: Subtype B appears to be the prevalent subtype in the north- ones observed in aged brain. Anatomically, working memory and learning east and south-east part of Brazil followed by a high proportion of ability functions are assured by neurons of the hippocampus, a brain area intersubtype recombinants. These results provide insights into the known-to-be affected by HIV-1 proteins such as gp120.

Figure 1(abstract P62) BMC Infectious Diseases 2014, Volume 14 Suppl 2 Page 27 of 45 http://www.biomedcentral.com/bmcinfectdis/supplements/14/S2/

Results: Mechanistically, several laboratories, demonstrated that Tat Materials and methods: Discordant patients (n=20) with mean absolute protein performs its functions through deregulation of several molecular CD4 numbers (absCD4: 273±29) were compared with virologically pathways that can deregulate the mitochondrial bioenergy such as controlled patients on HAART (concordant, n=20) with optimal CD4 T-cell depletion of mitochondrial calcium and release of ROS and decrease of recovery (absCD4:852±51) and 10 healthy controls (HCs). cTh17 cells were ATP. Once altered, these factors cause disruption of mitochondria measured in PBMCs, as frequencies of CD4+IL-17+ cells, after PMA distribution along the axons leading to slower or loss axonal transport, +Ionomicin stimulation by flow cytometry, and correlated with markers of thus, preventing neuronal communication. Interestingly, CREB protein has IA (HLA-DR+CD38+) and IE (Tim-3, PD-1 and CTLA-4) of CD4 and CD8 been shown to play a key role in these events directly. Similar data were T-cells and frequencies of T-regs (CD4+CD25brightFoxP3+). Plasma levels obtained with tissues isolated from AD patients. of lipopolysaccharide (LPS) and soluble-CD14 (sCD14) were measured to Hypothesis: The most critical signaling pathway for the regulation of determine gut microbial translocation (MT). Results obtained for long-lasting memory formation is that containing CREB and its discordant patients were compared with concordant patients and HCs. downstream targets. CREB is often referred to as “the master of memory Results: Frequencies of cTh-17 cells were significantly higher in discordant genes.” Therefore, we will examine the impact of HIV-1 Tat protein on patients than concordant patients (P < 0.0001) and HCs (P = 0.014). cTh-17 mitochondrial functions by focusing on the role of CREB protein. cells frequency correlated inversely with CD4 T-cell percentages and Expected outcome: Identification of the molecular mechanisms used by absolute count and directly with CD4-IA and T-reg frequencies. Discordant Tat leading to the development of Premature Brain Aging. patients showed higher CD4-IA (HLA-DR+CD38+) than concordant patients which directly correlated with MT. CD4 T-cells of discordant patients showed higher expression of multiple IE markers (PD1+Tim3+) that P64 correlated with IA. Although naive CD4+ T-cells were lower, effector The potential role of HIV-specific CD38-/HLA-DR+ CD8+ T cells in viral memory cells were higher in discordant patients. suppressive activity and cytotoxicity in HIV controllers Conclusions: Persistent CD4 T-cell IA and inflammation in discordant Stéphane Hua*, Camille Lecuroux, Asier Saez-Cirion, Gianfranco Pancino, patients may favor the differentiation of activated CD4 T-cells towards Isabelle Girault, Martine Sinet, Olivier Lambotte, Alain Venet cTh-17 phenotype. cTh-17 cell frequency could be an indicator of INSERM U1012, Le Kremlin Bicêtre, France ongoing IA and inflammation in discordant patients. Analysis of the BMC Infectious Diseases 2014, 14(Suppl 2):P64 nature and function of cellular subsets associated with IA and immune regulation would assist in understanding HIV immunopathogenesis and Introduction: In HIV-1 infection, some rare patients called HIV controllers developing strategies to target disease progression. (HICs) are capable to spontaneously control viral replication in vivo. Interestingly, HICs exhibit higher frequency of a particular activated phenotype CD38-HLA-DR+ HIV-specific CD8+ T cells. The aim of this study was to characterize this profile and evaluate its role in HICs. P66 Materials and methods: To investigate the functionality of the CD38-HLA- An impact of HIV disease severity on in vitro CD4+ T cell expansion DR+ profile, we compared it with the classically activated phenotype CD38 using anti-CD3/28 coated magnetic beads for being used as an +HLA-DR+ by evaluating several qualitative parameters: (1) activation alternative treatment in HIV infected patients measured by CD69, CD25, CD71, CD40 and Ki67 expression, (2) memory Nattawat Onlamoon*, Vajee Petphong, Kasama Sukapirom, parameters measured by proliferation capacity, CD127 and Bcl-2 expression, Kovit Pattanapanyasat cytokine production measured by IL-2 production and (3) cytotoxic activity. Mahidol University, Bangkok, Thailand We also determined the mechanism responsible for this particular profile. BMC Infectious Diseases 2014, 14(Suppl 2):P66 Results: CD38-HLA-DR+ cells exhibited a more resting profile than CD38 +HLA-DR+ cells marked by a lower expression of several activation Introduction: Antiretroviral therapy (ART) could lower viral burden and markers. Although they presented similar ex vivo profile especially increase CD4+ T cell level in HIV infected patients. However, the immune concerning survival, IL-2 production, CD38-HLA-DR+ cells displayed reconstitution never completes therefore an alternative treatment is significantly higher HIV-specific cytotoxic capacity after in vitro culture required. Interestingly, an in vitro expansion of CD4+ T cells from patients compared to CD38+HLA-DR+ cells (13% [7%-23%] vs. 7% [3%-11%], through CD3/28 signaling provided intrinsic control of viral replication p=0.02). Furthermore only the frequency of CD38-HLA-DR+ HIV-specific and transfusion of autologous expanded cells in ART treated patients CD8+ T cells correlated with the capacity of CD8+ T cells to inhibit viral showed increase in CD4 count. Since functions of CD4+ T cells were replication ex vivo (r=0.32, p<0.0001). Moreover, the CD38-HLA-DR+ profile different in each stage of the disease, we determined whether disease was preferentially displayed after activation by low doses of antigen. These severity has any impact on an in vitro expansion of CD4+ T cells and results are in line with the enhanced expression of this profile in patients conducted the experiments to increase CD4 expansion level for being use which exhibit high functional sensitivity (r=0.41, p=0.01). in clinical trial. Conclusions: Collectively, these data highlight the cytotoxic role of CD38- Material and methods: Whole blood samples were collected from both HLA-DR+ expressing HIV-specific CD8+ T cells in HICs and we provide healthy subjects and different groups of ART treated HIV infected patients insights into the mechanism of its induction. Induction of this type of based on CD4 count (<200, 200-500 and > 500 cells/μl). CD4+ T cells protective cell subset could be an important goal in vaccine strategies. were isolated using immunorosette formation and purified CD4+ T cells were expanded using anti-CD3/28 coated magnetic beads for 3 weeks. Fold expansion, viability and purity of anti-CD3/28 expanded CD4+ T cells were observed. Improvements in fold expansion of CD4+ T cells collected HIV: IMMUNOLOGY from patients were tested by a scheduling IL-2 supplemented culturing method. P65 Results: The results demonstrated that purified CD4+ T cells from healthy Increase in frequencies of circulating Th-17 cells in HIV-1 infected subjects can be expanded up to 1000-fold after 3 weeks with high patients with poor CD4+ T-cell reconstitution on effective HAART viability (>90%) and high purity of CD4+ T cells (>95%). Although highly D Asthana*, D Gracia, R Valiathan purified expanded CD4+ T cells can be obtained from patients, a lower University of Miami, Miami, USA fold expansion was demonstrated when compare to normal subjects. BMC Infectious Diseases 2014, 14(Suppl 2):P65 Furthermore, patients with low CD4 count showed lower fold expansion when compare to patient with high CD4 count. Finally, the result showed Introduction: Although circulating Th-17 (cTh-17) cells are related to that a low level IL-2 supplementation after 1 week of cell expansion can inflammatory diseases, its role in HIV immunopathogenesis is not well increased the level of cell expansion for patients. known. We investigated the association of cTh-17 cells with immune Conclusions: A large scale in vitro expansion of CD4+ T cells from HIV activation (IA), immune exhaustion (IE) and regulatory T-cells (T-regs) in infected patients could support an immunotherapy using autologous HAART treated virologically controlled (<40 HIV RNA copies/ml) HIV-1 transferred of anti-CD3/28 expanded CD4+ T cells. This method could be infected patients with poor CD4 T-cell recovery (discordant). used as a new therapeutic strategy in HIV infected patients. BMC Infectious Diseases 2014, Volume 14 Suppl 2 Page 28 of 45 http://www.biomedcentral.com/bmcinfectdis/supplements/14/S2/

antibodies after PNGase F treatment was found for gp120 expressed in HEK P67 293T and CHO cell lines, common producers of recombinant proteins for Resistance to HIV-1 infection among HIV-exposed seronegative partners vaccination purposes. Conversely, the gp120 produced by T cells (Jurkat) in HIV-discordant couples is associated with higher frequency of CD8+ displayed the least increase in reactivity after partial deglycosylation. T cells expressing CD107a and b molecules Conclusion: Changes in reactivity of selected monoclonal antibodies with A Padane1*, M Camara1,2,3, M Seydi2, W Jennes3, AA Diallo1, M Fall1, PA Diaw1, native and PNGase F-treated proteins indicated that some glycans were PS Sow2, S Mboup1, L Kestens3, T Ndiaye Dieye1 resistant to deglycosylation and that this characteristic was dependent on 1Cheikh Anta Diop University, Laboratory of Immunology, CHU Le Dantec, producer cell type. Furthermore, CBA allowed more sensitive detection Dakar, Senegal; 2Cheikh Anta Diop University, Clinic of Infectious Diseases, (about 40-times) of gp120-specific antibodies compared to ELISA. CHU Fann, Senegal; 3Institute of Tropical Medicine, Laboratory of Supported by CZ.1.07/2.3.00/20.0164 European Social Fund, UAB CFAR Immunology, Department of Microbiology, Antwerp, Belgium Developmental Grant (P30AI027767) and a Pilot Grant from UAB School BMC Infectious Diseases 2014, 14(Suppl 2):P67 of Medicine.

Background: Some individuals remain persistently HIV-seronegative despite multiple high-risk exposures to the virus (HIV-exposed seronegatives or ESN). P69 Different mechanisms may influence host resistance to HIV infection. CKR-L3, a deletion version CCR6-isoform shows coreceptor-activity for HIV-specific CTL has been suggested to play a role in HIV-1 protection. limited human and simian immunodeficiency viruses Methods: Ten HIV-1 ESN in HIV-discordant couples were enrolled at the Salequl Islam*, Nobuaki Shimizu, Takahiro Ohtsuki, Atsushi Jinno-Oue, Fann University hospital, Dakar, Senegal. Thirty HIV-1 infected patients Atsushi Tanaka, Hiroo Hoshino (10 HIV-1 non transmitted partners in discordant coupes and 20 HIV-1 Johns Hopkins University, Baltimore, USA infected partners in HIV-concordant couples) and 10 HIV-negative BMC Infectious Diseases 2014, 14(Suppl 2):P69 unexposed subjects were included as controls. Levels of CD107a and b, and CD107a/b+IFN-g+ in CD8+ T cells sub-set were measured in fresh Background: Chemokine receptors (CKRs), CCR5 and CXCR4 function as PBMC by flow cytometry, in the presence or absence of stimulation with major coreceptors in human/simian immunodeficiency virus (HIV/SIV) SEB. infections. About 20 alternative G protein-coupled receptors (GPCRs) have Results: HIV-negative subjects (10 ESN subjects and 10 HIV-negative been identified as minor coreceptors for the viruses. We reported CCR6 controls) showed significantly lower percentages of CD107a/b+ expression as an alternative coreceptor. A five-amino acid shorter isoform of CCR6, on CD8+ T-cells than did HIV-1 infected patients (2.9% vs. 11.6%, P = 0.016). namely CKR-L3, was examined for its coreceptor function and described Similar conclusions were reached when expression of CD107a/b+IFN-g+ in this report. were analyzed. Interestingly, HIV-1 ESN subjects showed higher frequency of Methods: NP-2 cells transduced with CD4-receptor (NP-2/CD4) normally CD8+ T cells expressing CD107a and b compared with unexposed remain resistant to all HIV/SIV infection; however, further introduction of HIV-negative controls (11.6% vs. 1.3%, P = 0.018), concordant with functional coreceptor can make the cells susceptible to the viruses. NP-2/ production of intracellular IFN-g. CD4/CKR-L3 cells were produced to examine coreceptor activity of CKR-L3. Conclusions: Taken together, our data suggest that resistance to HIV-1 Viral antigen in infected NP-2/CD4/coreceptor cells was detected by infection among ESN partners in HIV-discordant couples may be indirect immunofluorescence assay (IFA). The results were validated by associated with HIV-specific CTL responses. detection of syncytia, proviral DNA and by measuring reverse transcriptase (RT) activities. Results: HIV-2MIR and SIVsmE660 were found to infect NP-2/CD4/CKR-L3 P68 cells. This justifies the coreceptor function of CKR-L3. Viral antigens appeared Differential glycosylation of envelope gp120 affects reactivity with HIV- faster in NP-2/CD4/CKR-L3 cells than in NP-2/CD4/CCR6, indicates that the 1 specific antibodies CKR-L3 carries more efficient coreceptor-activity. Moreover, syncytia Lydie Czernekova1*, Milan Raska1,2, Zina Moldoveanu2, Katerina Zachova1, formation was sooner, RT release was higher and earlier through CKR-L3 Stacy Hall2, Dita Badalova1, Alzbeta Krcmarska1, Hana Synkova1, compared to CCR6. Partial sequence analyses of HIV-2MIR and SIVsmE660 Michael Hoelscher3, Leonard Maboko4, Rhubell Brown2, Zdenek Novak2, replicated through CKR-L3 and CCR6 coreceptor showed some divergence Jiri Mestecky2, Jan Novak2 in envelope region compared to the parental CCR5-variant. 1Department of Immunology, Palacky University, Olomouc, Czech Republic; Conclusions: Isoform CKR-L3 exhibited coreceptor activity for limited 2University of Alabama, Birmingham, Alabama, USA; 3Clinic of the University primary HIV/SIV isolates with better efficiency than CCR6-isoform. Amino of Munich, Munich, Germany; 4NIMR-Mbeya Medical Research Program, acid substitutions in the envelope region of the viruses may confer selective Mbeya, Tanzania pressure towards CKR-L3-use. CKR-L3 with other minor coreceptors may BMC Infectious Diseases 2014, 14(Suppl 2):P68 contribute to HIV/SIV pathogenesis including dissemination, trafficking and latency. Introduction: Cellular entry of human immunodeficiency virus type 1 (HIV- 1) depends on envelope glycoprotein (gp120/gp41) interactions with host- cell receptors. Approximately one-half of molecular mass of gp120 consists P70 of N-glycans which may act as antigenic determinants as well as a shield Assessment of the ability DS-EIA-HIV-AB-TERM assay correctly identify against immune recognition. We have shown that glycosylation of subtype long-standing and recent HIV infection B HIV-1 gp120 varies according to the producing cell type and the YE Zagryadskaya1*, VF Puzyrev1, AN Burkov1, DA Neshumaev3, TI Ulanova1,2, differential glycosylation affects reactivities with serum antibodies of persons Irina Sharipova1 infected with HIV-1 subtype B. Here we studied reactivities of above proteins 1RPC “Diagnostic Systems”, Nizhny Novgorod, Russia; 2DSI S.r.l. Saronno (VA), with panel of monoclonal gp120-specific broadly neutralizing antibodies and Italy; 3Krasnoyarsk Regional Center of AIDS Prevention, Krasnoyarsk, Russia sera from persons infected with HIV-1 subtype A/C. BMC Infectious Diseases 2014, 14(Suppl 2):P70 Materials and methods: Recombinant gp120 produced in different cell lines (HEK 293T, Jurkat, RD, HepG2, and CHO) were tested as a native and Background: The assessment of newly acquired human immunodeficiency after partial removal of N-glycans by PNGase F under native conditions. virus type 1 (HIV-1) infection, or incidence, provides important information Several methods (ELISA, Cytometric Bead Array - CBA, SDS-PAGE with for public health programs and is crucial for understanding the status of the western blot, and dot blot) were used for determination and comparison epidemic and providing information regarding the impact of prevention of reactivities with monoclonal gp120-specific antibodies (268-D IV, F425 measures. The aim of this study was to evaluate the ability of the assay DS- B4e8, 257-D IV, 447-52D, 19b, 2G12, and b12) or with sera of HIV-1 EIA-HIV-AB-TERM correctly identify long-standing and recent HIV infection in subtype A/C-infected persons. samples with the preliminary defined time of HIV-1 infection. Results: After partial removal of N-glycans from gp120, the reactivity of Materials and methods: The assay DS-EIA-HIV-AB-TERM intended for the most monoclonal antibodies increased, as did the reactivities of sera from identification of recently acquired HIV-1 infection was used in the study. HIV-1-infected persons. The largest increase in binding of polyclonal Efficiency assessment of the test was carried out using serum samples BMC Infectious Diseases 2014, Volume 14 Suppl 2 Page 29 of 45 http://www.biomedcentral.com/bmcinfectdis/supplements/14/S2/

Figure 1(abstract P69)

(n=239) with the preliminary defined time of HIV-1 infection which was assay assessment was carried out using seroconversion panels (n=32) identified based on HIV algorithm testing: recent infection samples (SeraCare, ZeptoMetrix, USA). (n=150), long-standing infection (n=89, including samples with a low CD4 Results: The assay is able to define as recent infection 100% of samples + T cell count) ("Krasnoyarsk Regional center of AIDS prevention”, “Nizhny with seroconversion profile. Among samples with the preliminary defined Novgorod Regional center of AIDS prevention”,Russia).Additionallythe time of HIV infection the accuracy of testing was: 93.3% - for recent (up BMC Infectious Diseases 2014, Volume 14 Suppl 2 Page 30 of 45 http://www.biomedcentral.com/bmcinfectdis/supplements/14/S2/ to 9 months), 97.8% - for long-standing infection (9 month and more). All HIV: THERAPEUTICS ASPECTS serum samples with late-stage infection (low CD4+ T cell count) were determined correctly. P72 Conclusion: Our data demonstrated high efficiency of the kit DS-EIA-HIV- 48 week bone marker changes with Dolutegravir (DTG) plus Abacavir/ AB-TERM to identify both recently acquired and long-standing infection Lamivudine (ABC/3TC) vs. Tenofovir/Emtricitabine/Efavirenz (EFV/TDF/ among samples from HIV type 1 seropositive persons. FTC): the SINGLE trial Y Yazdanpanah*, M-A Khuong-Josses, L Hocqueloux, G Pialoux, J Durant, B Wynne, C Granier, P Tebas, K Pappa, S Min P71 Bichat Claude-Bernard Hospital - APHP, Paris, France Evaluation of the Bio-Rad Geenius HIV-1/2 test as a confirmatory assay BMC Infectious Diseases 2014, 14(Suppl 2):P72 I Montesinos*, J Eykmans, ML Delforge Erasme Hospital, Brussels, Belgium Background: DTG is a once-daily integrase inhibitor that in combination BMC Infectious Diseases 2014, 14(Suppl 2):P71 with ABC/3TC, demonstrated superior efficacy with favorable tolerability over TDF/FTC/EFV (SINGLE study) at 48 weeks. EFV is associated with Introduction: HIV testing algorithms include a supplemental assay to reduced Vitamin D levels through CYP450 enzyme induction; TDF has confirm and differentiate HIV-1 and HIV-2 on repeated reactive samples been associated with decreased bone mineral density (BMD). by a 4th generation EIA screening test (EIA). In this study we evaluate the Antiretroviral treatment (ART) initiation is characterized by initial rapid recently CE-marked Bio-Rad Geenius HIV1/2 (Geenius) confirmatory assay, decline in bone mineral density (BMD) that subsequently stabilizes. Bone a single use immunochromatographic test, in comparison with the MP turnover markers are increased during these BMD changes. Diagnostic HIV Blot 2.2 (WB). Methods: In the double-blind SINGLE study (table 1) we measured markers Methods: A total of 161 serum samples were tested by Geenius test: 72 of bone turnover (bone-specific alkaline phosphatase, C-termial telopeptide nonreactive samples by EIA (Liaison XL Murex and/or VIDAS bioMérieux), type 1 collagen, osteocalcin, and procollagen type 1 N-propeptide) & 8 indeterminate samples by WB confirmed negative after follow up, 5 low Vitamin D at baseline (BL) and at 48 weeks. ANCOVA analyses were adjusted reactive samples by EIA negative by WB and confirmed negative after for the following factors age, sex, HIV RNA, CD4+ cell count, BL biomarker follow up, 44 HIV-1 reactive samples by EIA and WB, 5 HIV-2 reactive level, BMI, smoking status, and Vitamin D supplementation. samples, 1 HIV-1/HIV-2 co-infection sample, 15 HIV-1 non-B subtype Results: 833 subjects were analyzed: 84% males; 68% whites. Mean BL samples (8 CRF02, 1 CRF01, 1 CRF11, 1 CRF15, 2 subtype G, 1 subtype F1, VL: 4.7 log10 c/mL; 32% VL>100,000 c/mL and mean BL CD4 cell count = 1subtypeC)and11confirmedHIV-1earlyseroconversionsamples.The 350 cells/mm3. Bone markers increased in both groups but the increases ’ samples were tested according to the manufacturer s guidelines. Geenius were significantly greater in subjects treated with TDF/FTC/EFV. Vitamin D cassettes were read and interpreted by an automated reader utilizing a levels decreased in both treatment groups; the differences were not proprietary algorithm. The diagnostic performance and the quality significant between groups. management of the test were analyzed. Conclusions: After 48 weeks, significantly greater changes from baseline Results: Overall sensitivity for Geenius assay was 92%. Five of 11 early were observed for all bone markers in subjects receiving TDF/FTC/EFV, seroconversion samples were tested positive, 4 negative and 2 indicating more active bone turnover when compared to changes seen in indeterminate. The overall sensitivity of WB was 88%. After excluding subjects receiving DTG + ABC/3TC. These differences may correlate with early seroconversion samples, the sensitivity reaches 100% for both known TDF-associated changes in BMD over time and further study of assays. All HIV-1 non-B subtype samples were tested positive. The ability the potential advantages of a DTG+ABC/3TC regimen appear warranted. to differentiate HIV-1 and HIV-2 was as follow: 2 out of the 5 HIV-2 reactive samples were tested positive HIV-2, 2 positive HIV-2 with HIV-1 cross reaction, and 1 HIV positive untypable. The co-infection HIV-1/HIV-2 sample was tested HIV positive untypable. The overall specificity for the P73 Geenius assay was 96%. All 5 low reactive samples by EIA, negative by Optimizing HIV treatment through point-of-care CD4 testing – ACHAP WB were tested negative by Geenius. Two out of the 8 indeterminate Botswana community-based pilot samples by WB confirmed negative were tested indeterminate and one Kenneth Mugisha1*, Frank Mwangemi1, Jerome Mafeni1, invalid, the other 6 were negative. After excluding these last 13 samples, Makadzange Panganai1, Lesego Busang1, Juliana Cuervo Rojas1, the specificity of Geenius assay reached 100%. In comparison with WB, Ntumba Kanayi2, Lesedi Tsalaile1, Madisa Mine2,3, Lucy Mpfumi2,3, the Geenius assay is markedly less time consuming (<30 minutes), allows Mulamuli Moyo2,3 full traceability, automatic reading and interpretation. 1African Comprehensive HIV/AIDS Partnerships (ACHAP), Gaborone, Conclusions: The Bio-Rad Geenius HIV1/2 confirmatory system represents Botswana; 2Ministry of Health, Gaborone, Botswana; 3Laboratory Technologist a reliable alternative to other confirmatory assays in HIV testing Botswana Harvard HIV/AIDS Institute, Botswana algorithms and provides clear improvement in quality management. BMC Infectious Diseases 2014, 14(Suppl 2):P73

Table 1 (abstract P72) DTG+ABC/3TC change from TDF/FTC/EFV change from Geometric Mean [95% CI for the baseline* (N=414) baseline* (N=419) Ratio** ratio] p-value Bone-specific alkaline 15% 60% 0.720 [0.685-0.756] <0.001 phosphatase C-terminal telopeptide for 33% 68% 0.789 [0.747-0.832] <0.001 type 1 collagen Osteocalcin 22% 48% 0.827 [0.779-0.878] <0.001 Procollagen type 1 N- 30% 66% 0.784 [0.749- 0.821] <0.001 propeptide Vitamin D (25-hydroxy- -7% -10% 1.036 [0.970-1.107] P=0.292 Vitamin D) *adjusted percent change from baseline=100 X adjusted geometric mean of (week 48/baseline)-100 **GMR= (DTG+ABC/3TC+100) / (TDF/FTC/EFV+100) BMC Infectious Diseases 2014, Volume 14 Suppl 2 Page 31 of 45 http://www.biomedcentral.com/bmcinfectdis/supplements/14/S2/

Introduction: At 17.6%, Botswana has one of the highest HIV prevalence safer than the circular pDNA, where cells having undergone unwanted rates globally. Tutume district, has a disproportionately higher HIV vector integration events into were targeted for cell death. prevalence at 20.7% (BAIS, 2008). Only 54% of the infected actually know Conclusion: We optimized a robust technology conferring one-step in their HIV status. The investigators set out to determine if increased access to vivo production of an efficient and safe DNA ministring gagV3(BCE) DNA- HIV testing and point-of-care CD4 testing can minimize delays to ART VLP vaccine gene therapeutic versus HIV. initiation. Materials and methods: Six ART-providing clinics were allocated 2 PIMA machines each. The PIMA machines were validated against the FACS Calibur P75 machine as the instrument of reference. Community mobilizers were Chitosan nanoparticles for the intracellular delivery of triphosphate identified for each village. Door-to-door HCT and CD4 testing was done. nucleotide analogues Community outreaches and HIV/CD4 testing in schools, brick laying factories Giovanna Giacalone*, Elias Fattal, Hervé Hillaireau and mines were organized. Road shows were conducted to attract youth to Galien Paris-Sud Institute, UMR 8612, Châtenay-Malabry, France test. External quality assurance was done quarterly. Data was recorded on BMC Infectious Diseases 2014, 14(Suppl 2):P75 HCT registers and Point-of-Care CD4 registers and entered into CSPro database and analyzed using STATA 10.0. Aim: Nucleotide analogues such as Azidothymidine-triphosphate (AZT-TP), Results: A total of 6274 clients were tested for HIV in 3 months. Of these, the active form of Zidovudine, display an important pharmacological 62% were new testers, while 501 clients tested HIV positive (8%). Of these, activity for the treatment of HIV. The administration of these nucleotide 157 (31.3%) were enrolled on ART. A total of 2717 CD4 tests were analogues would bypass the intracellular phosphorylation which can be a performed. Of these, 73.4% were conducted at home, or outreach sites. metabolic bottleneck. This possibility is however limited by their instability Majority (65%) of the new testers were women aged 15- 49 years. Youths in physiological conditions, and furthermore their hydrophilicity restricts preferred to test at night during moonlight testing. There were no their access to the target cells. Several nanocarriers have been proposed so statistically significant differences in the CD4+ T cell counts obtained using far for the encapsulation of these molecules, but their applications are the PIMA with capillary blood and those observed using FACS Calibur and limited due to the low drug loading achieved. Our strategy proposes the venous blood. The difference tended to be significant at CD4+ T cell counts use of chitosan, a biocompatible and hydrophilic polysaccharide which is greater than 350 cell / μl (-21.2 (95% CI -45.3, +2.9)) whereby the PIMA gave known to form nanoparticles through complexation with TPP; in contrast slightly lower values than the FACS Calibur. Time from HIV testing to with previous methods, in our case the drug itself will be the driving force ART-initiation was reduced from 6 to 3 weeks. for the formation of nanoparticles [1]. Conclusions: Point-of-care CD 4 testing has the potential to reduce the Material and methods: Different molar ratios between chitosan and AZT- time to ART initiation; thereby contributing to reduction in morbidity and TP (or ATP, used here as a model drug) have been tested in order to study mortality. Youth-friendly services can contribute to increased HCT uptake the formation of nanoparticles; some selected ratios have been then in this age group. evaluated for their size, surface properties, drug encapsulation and loading. In vitro cell uptake experiments were performed on a cell line of macrophages, using the free molecule as a negative control. The intracellular distribution of the delivered molecules was further investigated P74 using confocal laser microscopy. Optimized production of a safe and efficient gene therapeutic vaccine Results: Colloidal suspensions have been obtained from chitosan and versus HIV via a linear covalently closed DNA minivector AZT-TP; nanoparticles present a minimal size about 200 nm with a zeta Roderick Slavcev*, Chi Hong Sum, Nafiseh Nafissi potential above +20 mV. An encapsulation efficiency of 70% can be School of Pharmacy, University of Waterloo, Waterloo, Canada reached, allowing loading rates as high as 44%. A cell viability of 80% has BMC Infectious Diseases 2014, 14(Suppl 2):P74 been found for particle concentrations up to 0.6 mg/mL. The cellular uptake is at least 2-fold higher when molecules are delivered as Introduction: Conventional plasmid vectors (pDNA) possess unwanted nanoparticles, compared to the free molecules. prokaryotic DNA that when delivered to the mammalian cells can reduce Conclusions: An original method is proposed to design nanoparticles, transgene expression and integrate into the human genome, potentiating which allows high loading rates; this lowers the amounts of excipients oncogenesis. Bacterial sequence-free, linear covalently closed (LCC) DNA needed, thus limiting the toxicity concerns. These nanosystems allow an minivectors have shown improved safety and efficacy both in vitro and in efficient in vitro intracellular delivery of nucleotide analogues. Further in vivo. We previously constructed and characterized an in vivo LCC DNA vivo studies will investigate the potential of these nanocarriers. minivector (ministring) system that can convert pDNA into DNA ministrings. Reference Here we sought to optimize this system and apply ministrings to encode a 1. Giacalone G, Bochot A, Fattal E, Hillaireau H: Drug-Induced Nanocarrier gene to generate HIV virus-like particles (VLPs) in targeted cells. The DNA- Assembly as a Strategy for the Cellular Delivery of Nucleotides and VLP expresses gagV3(BCE) gene in target cells to simultaneously yield GagV3 Nucleotide Analogues Biomacromolecules. Biomacromolecules 2013, (BCE) VLP assembly and presentation of immunodominant HIV antigens, 14(3):737-742. eliciting production of neutralizing antibodies and cytotoxic T-cell responses against HIV. Methods: A one-step invivo linear covalently closed (LCC) mini-plasmid production system that conditionally expresses the tel protelomerase was P76 constructed in Ecoli (R-cells) to enable efficient production of DNA Viral suppression among young adults in a US outpatient clinic ministrings from a specialized pDNA.LCCgagV3(BCE)DNAministrings Enbal Shacham*, Amy Estlund, Rachel Presti were produced from the constructed precursor pGagV3(BCE) parent Saint Louis University, Saint Louis, USA plasmid (from Dr. Chil-Yong Kang) when passaged through R-cells. BMC Infectious Diseases 2014, 14(Suppl 2):P76 Protease gene deletions were introduced into R-cells to sustain protelomerase expression while limiting the detrimental effects of heat Introduction: HIV infection has become a chronic disease for populations shock-induced recombinant protein degradation upon prolonged heat with access to medical care and treatment. Regardless of medical induction. Plasmid and DNA ministring derivatives were lipoplexed with a advancements, new infections persist. With young adults being those that RGD-complexed gemini surfactant and transfected into immortalized are most often newly infected, research needs to be conducted to assess leukemia K562 cells with induced surface expression of CD51/CD61, and medication adherence barriers, specific to young adults with HIV. assessed for cell trafficking, transfection efficiency and viability. Materials and methods: As standard of care, patients presenting for care Results: R-cells with a hflX protease-associated gene deletion significantly completed behavioral and psychological distress assessments annually. Data imcreased DNA gagV3(BCE) DNA ministring yields to greater than 90%, were abstracted from medical charts to include both the self-reported data compared to ~70% in wildtype cells. DNA ministrings indicated and HIV parameters in 2013 among patients aged 18 and 30 years. remarkably improved cellular trafficking and nuclear translocation of the Descriptive and regression analyses were conducted to identify factors vector, significantly higher transfection rates and LCC DNA proved far related to viral suppression (< 20 copies/mL). BMC Infectious Diseases 2014, Volume 14 Suppl 2 Page 32 of 45 http://www.biomedcentral.com/bmcinfectdis/supplements/14/S2/

Results: A total of 335 individuals presented for care during the 12 Introduction: Loss to follow up (LTFU) is a challenge in care and month period. The majority were African American (84%, n=281), and had treatment programs in Sub Saharan Africa, Tanzania included. We a mean age of 25.1 (SD = 2.8). Nearly all (n = 305; 91%) had current analyzed risk factors LTFU among HIV+ patients receiving care and prescriptions antiretroviral therapy (ART); among those receiving ARTs, treatment in Dar es Salaam, Tanzania in order to inform strategies to 72.8% were virally suppressed. Sexually transmitted infection tests are retain patients in care and treatment services. conducted annually and by assessed need; 30% of this sample had at Materials and methods: We conducted prospective cohort study of least 1 STI diagnosis (gonorrhea, chlamydia, syphilis, trichomoniasis) patients enrolled in care and treatment facilities in Dar es Salaam from within the last year. Nearly 60% reported condom use at last sex, which October 2004 to September 2011. LTFU was defined as missing clinic visit was not associated with viral load suppression. Women more often had for 90 and 180 consecutive days after the last scheduled appointment date unsuppressed viral loads (p< 0.001). Significant proportions of the sample among patients on ART and care and monitoring respectively. For expressed moderate to severe depressive and anxiety-type symptoms; univariate and multivariate analysis, Cox proportional hazard regression which was more common among individuals who were not virally model was employed to identify the risk factors. suppressed (n = 230; p< 0.001). Additionally, 13% endorsed suicidal Results: Among 85,608 patients followed, 77% were on antiretroviral ideation within the past 2 weeks; which was also associated with viral therapy (ART). The median age of participants was 34 (interquartile range, suppression (p< 0.001). Further, 3% reported injecting drugs, this IQR: 29- 41 years) and their median CD4+ cell count was 206 cells/ L (IQR: suggests new trends in HIV infection regionally. 84-378 cells/μL). For those on ART, it was found that patients aged ≥50 Conclusions: These findings related to how young adults are managing years and those with CD4+ cell count <100 cells/ L had an independent their HIV care suggest increased efforts to preventing additional STIs, significantly increased risk of loss to follow up (RR: 1.11, 95% CI 1.03 – 1.19, managing psychological distress, and improving opportunities for female p< 0.0001 and RR: 1.22, 95% CI 1.10 – 1.24, p=0.01 respectively). Among patients. Applying lessons from global settings to U.S. settings may patients on care and monitoring male patients, patients with advanced provide great insight to improving engagement in HIV care, as has been disease and lower CD4 cell count were found to have significantly increased done successfully in many international settings. risk with (RR: 1.06, 95% CI 1.01 – 1.14, p< 0.04), (RR: 1.26, 95% CI 1.14 – 1.39, p< 0.0001) and (RR: 2.10, 95% CI 2.07 – 2.22, p< 0.0001) respectively. Patients on care and monitoring were significantly more likely to be LTFU P77 (45%) compared to patients on ART(21%). Novel MDR-reversing inhibitors of MRP subtypes related to Conclusions: Determining risk of LTFU at enrollment and initiation of antiretroviral drug resistance and CD4 cell counts ART and focused tracking are crucial to improve retention rates for Andreas Hilgeroth*, Paul Naujoks, Sebastian Neuber, Marc Hemmer, patients on ART and care and monitoring. Strengthening access and Hermann Lage, Joséf Molnar immediate tracking of patients on care and monitoring is recommended Institute of Pharmacy, Martin Luther University Halle-Wittenberg, Halle, Germany to improve patient outcomes, detection and documenting deaths. BMC Infectious Diseases 2014, 14(Suppl 2):P77

Introduction: Transmembrane efflux pumps play an increasing role in the P79 success of ART. The occurrence of increasing mRNA levels of the efflux Dual anti-HSV and anti-HIV activity of the lantibiotic Labyrinthopeptin pump proteins P-gp and MRP subtypes has been associated with ART A1 therapeutics like PIs and NNRTIs. Moreover, a relation has been suggested Geoffrey Férir1*, Mariya I Petrova2, Graciela Andrei1, Robert Snoeck1, of MRP subtypes and CD4 cell counts.Sothereisachallengetofind Mark Brönstrup3, Roderich D Süssmuth4, Dominique Schols1 selective MRP inhibitors which may reduce MRP-induced drug resistances 1Rega Institute for Medical Research, University of Leuven, Leuven, Belgium; as well as discussed effects on CD4 cells. We developed novel nonpeptidic 2Center of Microbial and Plant Genetics, University of Leuven, Leuven, inhibitors of important MRP subtypes related to both MRP-mediated Belgium; 3Helmholtz Center for Infection Research, Braunschweig, Germany; resistances as well as reduced cell counts. 4Technische Universität Berlin, Fakultät II – Institut für Chemie, Berlin, Germany Materials and methods: The molecular structures of the various efflux BMC Infectious Diseases 2014, 14(Suppl 2):P79 pumps guided the development of both symmetric and nonsymmetric inhibitors dedicated to selectively inhibit the relevant MRP-subtypes. Background: It has been shown that genital lesions and altered innate Inhibiting properties were evaluated in exclusively P-gp as well as MRP- mucosal immunity caused by HSV-2 are important cofactors to increase overexpressing cell lines in comparison to nonexpressing parental cell the rate of HIV transmission and infection. Therefore, a product that lines with fluorescent substrates using flow cytometry. inhibitsHIVandHSVwouldhavepotentialbenefitsintheprophylaxis Results: Our inhibitors with allover symmetric substitution patterns are against these sexually transmitted viruses. The labyrinthopeptin A1 excellent P-gp inhibitors, while a reduction of those symmetric elements (LabyA1) is a prototype peptide of a novel class of carbacyclic lantibiotics. concerning their number and exact positioning significantly lowers the Here, we extensively evaluated LabyA1 for its broad-spectrum activity P-gp inhibition whereas the MRP1 inhibition is found mainly increased. against HIV and HSV. So selective inhibitors are demonstrated to influence the efflux pump Methods: Replication of HIV-1, HIV-2 and drug (e.g. tenofovir, maraviroc, type-related antiretroviral drug resistance. raltegravir, saquinavir)-resistant viruses were evaluated in CD4+ T cell Conclusions: The success of ART may be mainly increased by selective MRP lines and in PBMCs. LabyA1 was also tested against HSV-1 and HSV-2 and inhibitors which reduce the MRP-related effects on drug resistance as well as HSV-resistant viruses (such as acyclovir). It was tested also in combination on discussed cell counts. Structure-guided studies of the efflux pump with other classes of anti-HIV/HSV drugs. EC50 values and potential inhibition helped to design novel selective inhibitors with structure- synergy levels were calculated using CalcuSyn software. Potential cellular reasoned effects of the nonsymmetric substitution patterns. So far only side-effects, cytokine induction, toxicity and growth inhibitions were also nonselective inhibitors have been used in ART with undesired effects on investigated. transporter-related pharmacokinetics. Selective inhibitors will mean a Results: LabyA1 exhibited a consistent and broad anti-HIV activity (EC50: progress in ART especially with less limiting side effects. 0.70-3.3 μM) and anti-HSV activity (EC50: 0.29-2.8 μM). LabyA1 also inhibited viral cell-cell transmission between persistently HIV-infected T cells and uninfected CD4+ T cells (EC50: 2.5 μM) and inhibited the P78 transmission of HIV captured on DC-SIGN to CD4+ T cells (EC50: 4.1 μM). Who are they? Identifying risk factors of loss to follow up among HIV+ LabyA1 behaves as a novel type of viral entry inhibitor. LabyA1 also patients on care and treatment in Dar es Salaam demonstrated additive to synergistic effects in its anti-HIV-1 and anti-HSV- Lameck C Machumi*, Expeditho Mtisi, Irene Andrew, David Sando, 2 activity with anti(retro)viral drugs in dual combinations such as Humphrey Mkali, Enju Liu, Ellen Hertzmark, Donna Spiegelman, Wafaie Fawzi, tenofovir, acyclovir, saquinavir, raltegravir and enfuvirtide. LabyA1 was Guerino Chalamilla equally active against all drug-resistant HIV and HSV strains. It did not Management and Development for Health, Dar es Salaam, Tanzania induce any inflammatory cytokines/chemokines and did not affect the BMC Infectious Diseases 2014, 14(Suppl 2):P78 growth of vaginal Lactobacilli. BMC Infectious Diseases 2014, Volume 14 Suppl 2 Page 33 of 45 http://www.biomedcentral.com/bmcinfectdis/supplements/14/S2/

Conclusions: LabyA1 has profound dual antiviral activity. Based on the Preclinical studies demonstrated i)the generation of a strong, specific and lack of toxicity on the vaginal Lactobacillus strains and its synergistic/ very long lasting T-cell immune response (up to 2 years in murine animal additive profile in combination with all approved anti(retro)virals, it models), ii) the restricted diffusion of the vaccine candidates after deserves further attention as a potential microbicide candidate in the injection and iii)their fast disappearance within few weeks, correlated prevention of sexually transmitted (HIV/HSV) diseases. with an absence of macroscopic and microscopic toxicity. These data allowed the settlement of the anti-HIV therapeutic Phase I/II clinical trial that is held in France and Belgium and that has ended the P80 enrollment of the 36 HIV-1 infected patients. THERAVECTYS’ anti-HIV Too bad! Fixed dose combination antiretroviral drugs vaccine treatment is assessed at three doses and safety, tolerability and Thomas Agyarko-Poku1*, Yaw Adu Sarkodie2, Linda Atakorah-Yeboah3 immunogenicity compared to a placebo group. Furthermore, vaccine 1Suntreso Government Hospital, Ghana Health Services, Kumasi, Ghana; efficiency is be evaluated by the interruption of the HAART treatment in 2Department of Clinical Microbiology, School of Medical Sciences, University all patients, including placebo. Final results are expected by 2014 with of Science and Technology, Kumasi, Ghana; 3Manhyia Government Hospital, intermediary analysis in April 2014. Ghana Health Services, Kumasi, Ghana BMC Infectious Diseases 2014, 14(Suppl 2):P80 P82 Introduction: Pill burden is a factor for non-adherence to Antiretroviral Outcomes of HIV pregnant women on Option B+ treatment in an urban drugs (ARVs). The introduction of Fixed Dose Combination ARVs regime is Malawian private medical clinic, between July 2011 and November seen as an antidote to pill burden among HIV patients on treatment. The 2013 study hypothesized that not all HIV patients will accept this new regime, Sekeleghe Kayuni and was conducted to determine their perception on the new treatment MASM Medi Clinics Limited, Blantyre, Malawi regime. BMC Infectious Diseases 2014, 14(Suppl 2):P82 Materials and methods: 1681 HIV positive patients accessing care at Suntreso STI/HIV Clinic in Kumasi, who have been on treatment for more Background: Malawi is one of the sub-Saharan African countries than 12 months and consented to participate were recruited for this cross adversely affected by HIV/AIDS. Option B+ was adopted by Malawi from sectional study. They were interviewed using semi-structured pre-texted 1st July 2011 as an effective way of managing HIV through lifelong ART questionnaire prior to the commencement of the new fixed dose in pregnancy. Poor ART outcomes such as high default rates have been combination ARVs treatment regime. Data was entered and analyzed using reported, raising concerns of setbacks on PMTCT progress. We assessed SPSS version 16. the outcomes of HIV infected pregnant clients on Option B+ at ART clinic Results: Whereas, 60.9% (1023/1681) find the present dose regime at an urban Private medical facility in Malawi. cumbersome, 39.1% (657/1681) of the patients prefer the multiple dose Materials and methods: This retrospective survey was conducted in regime. 42.2% (709) of respondents have some reservations about fixed December 2013 at Kanjedza Medi Clinic. All records of Option B+ clients dose combination regime whilst 24.6% (413) prefer it, with 33.3 % (559) between July 2011 and November 2013 were reviewed. Information on being in different. Reasons for the reservation included; ‘Side effect may age, HIV test, ART initiation and duration, adverse reactions, ART outcome be too serious’ (48.3%, 342/709), ‘Virus too powerful for a single molecule’ (alive on ART, defaulted, dead, stopped, transfer out), delivery status and (30.2%, 214/709), ‘Attempt to deprive us of drugs and facilitate our death’ baby HIV test were analyzed. (13.8%, 92/709) and ‘Cost of drugs will be expensive in future for a Results: There were 1,253 clients registered in the ART clinic and 711 alive, combine drugs therapy’ (7.7%, 55/709). taking ART as of 30th November 2013. Fifty-one clients (pregnant women) Conclusions: Although, majority of patients find the multiple dose tested HIV positive and registered on Option B+ after adherence counseling. regimes cumbersome, they are skeptical about the use of the fixed dose 9 clients transferred out, remaining with 42 clients in the clinic register. combination treatment regime. The new regime may result in overdosing Forty clients (78.4% of all Option B+ clients and 95.2% of remaining if they find it inadequate to provide the needed protection. The fear of clients) were alive and on ART. Their age range was 23 to 55 years old, serious adverse reaction from combination of ARVs compared with with mean of 31.6 years (confidence interval CI; 24.4-39.4). ART duration separate drugs may scare them from taking the treatment. Intensive ranged from 33 days to 794 days, with mean of 428 days. No adverse adherence counseling taking care of the above concerns is essential reactions were reported. Two clients (3.9%) defaulted ART after 182 days before patients are switched onto the fixed dose ARV regime. and 183 days respectively. 27 clients delivered during the period with 1 baby dying within an hour of birth. 18 babies were tested at 6 months of age and all were HIV P81 negative. One client who defaulted delivered a baby who tested negative Lentiviral-based anti-HIV therapeutic vaccine: design, preclinical studies at age of 6 months. and phaseI/II clinical trial preliminary results Conclusion: We noted better ART outcomes including lower default rate Cécile Bauche*, Marie Rodriguez, Emeline Sarry, Ana Bejanariu, in our Option B+ clients. Babies were tested HIV non-reactive, depicting Emmanuelle Sabbah-Petrover the success of Option B+ treatment. High default rates can be addressed THERAVECTYS, Villejuif, France through Option B+ program strengthening, adherence counseling and BMC Infectious Diseases 2014, 14(Suppl 2):P81 continued follow-up of clients.

THERAVECTYS, a spin off the Pasteur Institute, develops a new generation of prophylactic and therapeutic vaccines using optimized lentiviral VIRAL HEPATITIS vectors. It’s most advanced product, a therapeutic anti-HIV vaccine treatment, has entered clinical Phase I/II end of 2012. This vaccination P83 should allow seropositive patientstogainanimmunologicalstatus Boceprevir (BOC) and Telaprevir (TPV) therapeutic drug monitoring in identical to the so-called “Functional Cured” patients who develop an HCV and HIV-HCV infected patients treated with triple therapy efficient immunological response capable of controlling the infection Ribavirine/Peg-interferon/Boceprevir or Telaprevir: impact of the without therapy. antiretroviral (ARV) treatment Vaccine candidates are integrative and self-inactivated live-recombinant AS Chantry1*, M Tching-Sin1, C Dhiver2, T Allegre3, JM Ruiz4, A Assi5, lentiviral vectors. They encode an HIV antigen, under the regulation of a D Botta-Fridlund6, P Halfon7,8, O Faucher-Zaegel9, C Solas1,10 patented promoter that is preferentially induced in APC (generating the 1Timone Hospital, Pharmacokinetics and toxicology department, Marseille, specific immune response), and showing a basal level expression in all France; 2AP-HM Conception Hospital, Infectious Diseases department, cells (allowing their elimination by the settled immune response).These Marseille, France; 3Pays d’Aix Hospital, Hematology and Internal Medicine vaccine candidates are classified as “Live recombinant vectored vaccines” Department, Aix-en-Provence, France; 4AP-HM, Hôpitaux Sud, Medicine in (EMA, 2011). prison department, Marseille, France; 5Sainte Musse Hospital, Infectiology BMC Infectious Diseases 2014, Volume 14 Suppl 2 Page 34 of 45 http://www.biomedcentral.com/bmcinfectdis/supplements/14/S2/

department, Toulon, France; 6AP-HM Conception Hospital, Digestive surgery (DRV/r),6% lopinavir, efavirenz and rilpivirine. Tenofovir in 72%. Genotype 1a department, Marseille, France; 7European Hospital, Marseille, France; (n=20) or 1b (n=10) or 4 (n=1), METAVIR fibrosis stage was F3F4 in 55%, F2 8Alphabio Laboratory, Marseille, France; 9AP-HM Sainte-Marguerite Hospital, in 32% and F0F1 in 13% of cases. HVC was treated with PR+ BOC (33%) or Immuno-Hematology department, Marseille, France; 10University of Aix- TLV (67%). 25 patients reached W72. PCRVHC- was observed in 54% of Marseille, INSERM UMR 911 - CRO2, Faculty of Pharmacy, Marseille, France patients at W4, 67% at W12, 58% at W24 and 58% at W48. SVR was BMC Infectious Diseases 2014, 14(Suppl 2):P83 obtained for 58% (50% on PR+BOC, 64% on PR+TLV) and in 51% of cirrhotic patients. Six patients discontinued therapy for VF (n=1) or AE (n=5). Introduction: BOC and TPV are potent NS3/4A protease inhibitors for the Conclusion: Despite SVR increased with DAA-PI based therapy, treatment treatment of chronic hepatitis C (HCV) genotype 1 infection. BOC and TPV of HCV in HIV remains complex with multiple challenges, including high are both substrates and strong inhibitors of the CYP3A, therefore presenting pill burden, higher rates of adverse events (AEs) and difficult drug-drug- a wide interindividual pharmacokinetic variability and multiple drug interactions. interactions especially with ARV such as lopinavir/r, darunavir/r or efavirenz, thus restricting options for concomitant ARV therapy. We evaluated plasma concentrations of coinfected and monoinfected patients treated with BOC P85 and TPV and the PK data of patients treated with non recommended ARV. Evaluation of diagnostic efficiency of the new enzyme immunoassay for Method: Data from patients whose BOC and TPV trough concentration had detection of IgM antibodies to Hepatitis B core antigen been assessed during treatment were retrospectively analyzed. Plasma OF Fedorova1*, NM Khodak1, NA Bugrova1, VF Puzyrev1, AN Burkov1,2, concentrations were determined using a LC-MS/MS method. Mann-Whitney TI Ulanova1,2 U test was used for statistics (PASW Statistics 17). 1RPC «Diagnostic Systems», Nizhny Novgorod, Russia; 2DSI S.R.L. Saronno, Italy Results: Overall, 58 patients were included (84% male, median age: 51 years BMC Infectious Diseases 2014, 14(Suppl 2):P85 (34-70)), treated with BOC (25) or TPV (33). Thirty-two (55%) patients are coinfected (14 BOC, 18 TPV) and 26 (45%) are monoinfected (11 BOC, Introduction: Recently, many studies are available about the detection of 15 TPV). Median (range, CV) TPV and BOC trough concentrations were viral DNA in sera containing IgM to HBcAg in the absence of HBsAg, respectively, 1928 ng/mL (92-3204, 47%) and 111 ng/mL (33-903, 112%) in which lead to increase the risk of transmission of HBV, what is especially coinfected patients versus 2787 ng/mL (252-5551, 54%) and 153 ng/mL important for blood transfusion and the use of blood products. In this (25-2658, 150%) in monoinfected patients, which is statistically different only regard, it is important to use highly sensitive ELISA test for detection of for TPV (p<0.05). Six patients received non recommended ARV: 4 were IgM against HBcAg which could help to eliminate the risk of transmission treated with darunavir/r (2 BOC, 2 TPV), 1 with efavirenz and BOC and 1 with of HBV, especially during the «serological window». lopinavir/r and TPV. Median (range) TPV and BOC concentrations were Aim: To assess the diagnostic efficiency of the new high sensitive test for respectively, 1967 ng/mL (580-3204) and 103 ng/ml (33-903) with the IgM to the core antigen of HBV detection with the aim to use it for recommended ARV versus 1304 ng/mL (92-2565) and 146 ng/ml (65-304) early diagnostic Hepatitis B virus. with non recommended ARV. Materials and methods: Analytical sensitivity of the kit was evaluated Conclusion: This study highlights a strong interindividual variability in using standard of Paul-Ehrlich Institut - HBc-Referenzserum-IgM 84 (IgM BOC and TPV trough concentrations. Lower concentrations were observed anti-HBc). Diagnostic sensitivity of the kit was evaluated using samples of in coinfected patients but remaining within the expected range, which Anti-HBc IgM Performance Panel PHE203 (BBI), four seroconversion panels may be explained by drug interactions with some ARV. Hence, produced by ZeptoMetrix and BBI (USA) and 264 positive samples from therapeutic drug monitoring is useful to manage these interactions and patients with HBV at various stages. Diagnostic specificity was evaluated evaluate the risk-benefit balance of using non recommended ARV in by testing different categories of the population: primary donors coinfected patients with advanced hepatic disease. (n=1056), clinical patients (n=386), potentially cross-reacting samples (n=509). Diagnostic efficiency of the kit was evaluated in comparison with the reference kits with the analytical sensitivity of 25-50 U/ml PEI. P84 Results: Analytical sensitivity of the new test is ≤10 U/ml PEI. The Efficacy and safety of hepatitis C direct-acting protease inhibitors seroconversion panels study has found that the kit detects 56 positive (DAA-PI ) in real life in HIV-HCV coinfected patients samples out of 92 seroconversion samples, compared with commercial A Ménard1*, C Dhiver1, I Ravaux1, J Moreau2, S Mokhtari2, P Colson3, reference assays, which detect 46 samples. The diagnostic sensitivity of L Meddeb1, P Brouqui2, A Stein1 the developed assay is 100% (264/264) compare to the 41% (108/264) of 1SMIT, La Conception University Hospital, Marseille, France; 2SMIT, North the reference test that may be caused by higher sensitivity level of the University Hospital, Marseille, France; 3Microbiology federation, Aix Marseille new test in comparison with the reference test. Diagnostic specificity of University, URMITE, UM63, CNRS 7278, IRD 198, Inserm 1095, Timone the kit is 99.6%. University Hospital, Marseille, France Conclusion: High sensitivity and specificity of the new test provide more BMC Infectious Diseases 2014, 14(Suppl 2):P84 effective anti-IgM detection which is important for the diagnostic of the current or past infection of HBV. Background: HCV Triple therapy opens new perspectives for HCV cure in HIV-HCV patients but data concerning the use of HVC DAA-PI in this patients in a real life setting are scarce. Our objective was to evaluate P86 efficacy and safety of Telaprevir (TLV) and Boceprevir ( BOC) based- Prevalence and molecular characterization of Hepatitis B in HIV infected therapy in our cohort. individuals in Botswana Materials and methods: We included HIV-HCV patients treated with Peg Motswedi Anderson1*, Simani Gaseitsiwe1, Sikhulile Moyo1, Interferon RIB (PR) plus TLV/BOC between 2011-2013 in a multicenter Terence Mohammed1, Theresa K Sebunya2, Jason Blackard3, retrospective cohort. Demographic, clinical and imunologic characteristics Joseph Makhema1, Max Essex1,4, Rosemary Musonda1 were obtained, as well as adverse events and discontinuations. Treatment 1Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana; efficacy and safety data were collected at week (W) 4, 8, 12, 24 and 48. 2University of Botswana, Department of Biological Sciences, Gaborone, Success if HCV-RNA became undetectable (PCRHVC-)72 weeks after the Botswana; 3University of Cincinnati College of Medicine, Cincinnati, USA; end of treatment (SVR). Failure if treatment was discontinued due to 4Harvard School of Public Health, Department of Immunology and Infectious virologic failure (VF), adverse events (AE). Diseases, Boston, USA Results: 31 patients were analyzed, 5 Naives and 26 re-treatments (21% BMC Infectious Diseases 2014, 14(Suppl 2):P86 relapsers, 53% non responders and 26% intolerance discontinuation). All were Caucasian, 86% were male with a 49 years old’s mean age. Mode of Introduction: Hepatitis B Virus (HBV) is a major coinfection in HIV infected transmission of HIV& HCV was IUDV for 24 patients, MSM for1. Median patients and it has emerged as an important cause of morbidity and CD4 counts 692. All were on HAART with undetectable Viral Load in 92%. mortality in this group since the start of Highly Active Antiretroviral Background HIV therapy contained in 51% raltegravir (RAL), 20% Therapy (HAART).HIV/HBV coinfection prevalence varies by geographic ritonavir-boosted atazanavir (ATV/r), 12% etravirine (ETV) 9% darunavir region even within the same country. In Botswana the coinfection prevalence BMC Infectious Diseases 2014, Volume 14 Suppl 2 Page 35 of 45 http://www.biomedcentral.com/bmcinfectdis/supplements/14/S2/

data is very sparse and what is reported varies. Ten HBV genotypes with (AOR= 7.1; 95% CI: 1.37- 36.97), razor sharing (AOR= 4.81; 95% CI: 1.84- some subgenotypes have been described differing by geographic 12.55), sex (AOR= 8.83; 95% CI: 3.16- 24.87), and condom use in sexual distribution, course of disease, response to treatment and development of activity with main partner (AOR= 0.15; 95% CI: 0.02- 0.44) were associated mutations. Even though data have shown that genotypes are predictive of with actor HCV positivity. disease outcome, the circulating HBV genotypes in Botswana remains Conclusion: Health care providers need to pay special attention to sexual unknown. Therefore this study aims at determining the HIV\HBV coinfection transmission of HCV among HIV-infected individuals and the control/ prevalence rate and the circulating HBV genotypes in Botswana. preventive measures for HCV sexual transmission should be recommended. Materials and methods: This is a retrospective cross sectional study of HIV individuals initiating HAART. Hepatitis B surface antigen (HBsAg) was screened for in 300 baseline samples and those which were positive were P88 also screened for HBeAg. For the HbsAg positive a 415 bp fragment of the Hepatitis C diagnosics: clinical evaluation of the HCV-core antigen HBV polymerase gene was sequenced using Big Dye sequencing chemistry determination and the sequences were analyzed for genotypes and mutations. Josef van Helden Results: Of the 300 participants, 28(9.3%) were HBsAg positive and 5(17.9%) MVZ Dr. Stein und Kollegen, Moenchengladbach, Germany were HBeAg positive. Of the 27 samples that were successfully genotyped, BMC Infectious Diseases 2014, 14(Suppl 2):P88 genotype A was found in 23 (85.2%), 22 subgenotype A1 and 1 subgenotypeA2, genotype D subgenotype D3 made up the remaining 4 Background: The aim of the evaluation was to investigate the relevance of (14.8%). Known escape mutations were found in 12(44.4%) with the most the HCV-core antigen testing for the diagnosis and monitoring of HCV common one being N131N found in 8(29.6%) of the participants. The other infections in the daily routine. Up to now, most of the serological escape mutations were R122K, T123A, Q129R, G130N, M133T and F134V.No diagnosticswasperformedasdetermination of antibodies while the drug resistance mutations were detected. determination of activity and the monitoring of antiviral therapy were Conclusion: The HIV/HBV prevalence is consistent with what has been checked by HCV RNA PCR. reported in the country. The predominant genotype in this cohort is A1 Methods: The routine requests for HCV-core antigen of a private laboratory and its consistent with findings from the region. Escape mutations were analyzed for a period of two years. previously associated with failure of HBsAg detection and vaccine or Results: The determination of HCV antigen highly correlates with the immunogloblin therapy were found in a significant number of participants. quantitative measurement of HCV RNA (r=0.73), p=0.0003). The diagnostic No known drug resistance mutations were found in the cohort. window is comparable with that of the HCV PCR (27.1 ± 12.8 d vs. 23.9 ± 9.2 d, p=0.11). The sensitivity of the HCV antigen assay was 99.0 % with a specificity of 99.2 %. 54.3 % of the confirmed antibody positive samples P87 were also antigen positive. Only in 3 of 560 HCV-RNA positive samples HCV Sexual transmission of Hepatitis C virus between HIV infected subjects and antigen was not detectable, but 3 samples without HCV antibodies were their main heterosexual partners; Actor Partner Interdependent Modelling confirmed positive for HCV antigen. Abbas Alipour1*, Abbas Rezaianzadeh2, Jafar Hasanzadeh2, Conclusions: The HCV antigen assay is a suitable tool for the detection of Abdorreza Rajaeefard2, Mohammad Ali Davarpanah3 chronic active HCV infections, for the early diagnosis of acute infections 1Social medicine department, Medical school, Mazandaran university of and for testing of HCV in patient with immunodeficiency. The HCV antigen medical sciences, Sari, Iran; 2Epidemiology department, Health and Nutrition assay valuable completion of serological testing for HCV. School, Shiraz university of medical sciences, Sari, Iran; 3HIV Research center, Shiraz University of medical Sciences, Sari, Iran BMC Infectious Diseases 2014, 14(Suppl 2):P87 P90 Antiviral treatment in severe acute hepatitis B Introduction: Overall, 60-70% of the hepatitis C virus’ (HCV) transmission Anca Streinu-Cercel1,2*, Oana Streinu-Cercel1,2, Alina Cristina Negut1,2, routes is parenteral and in 30-40% of the cases was unknown (e.g. sexual Marius Stefan3, Adrian Streinu-Cercel1,2 route). Knowing of these routes in HIV infected dyads very important due 1Department of Infectious Diseases, Carol Davila University of Medicine and to clinical and methodological reasons. Whether HCV transmits through Pharmacy, Bucharest, Romania; 2National Institute for Infectious Diseases, sexual route in these dyads is controversy. Bucharest, Romania; 3Polytechnic University of Bucharest, Romania Materials and methods: Of the 1338 dyads enrolled in Behavioural BMC Infectious Diseases 2014, 14(Suppl 2):P90 Consultation Center in Shiraz, Iran in 2011, 984 couples (HIV infected subjects and their main heterosexual partners) have eligibility criteria. Random Introduction: We aimed to evaluate the clinical, biological and virological samples, 168 of 984 couples, were chosen through random generated impact of antiviral therapy in severe acute hepatitis B. [1] numbers using a computer program. We used actor partner independent Materials and methods: We performed a study in the National Institute for model (APIM) and multilevel analysis to assess multiple risk factors for HCV Infectious Diseases “Prof. Dr. Matei Bals”, Bucharest, Romania, randomizing while partitioning the source of risk at the individual and couple level. patients between two groups initially: therapy with lamivudine 100 mg/day Results: Age of the index samples was 38.71± 7 years and 33.2± 6.3 vs. standard of care (no antiviral therapy) and subsequently between three years for their main heterosexual partners; the mean duration of sexual groups: lamivudine, standard of care and entecavir 0.5 mg/day, when this relationship for couples was 11.9 (median= 8.5) years. Multivariate new analogue became available in Romania. analysis showed that actor risk factor of intravenous drug using (IDU) Results: HBs antigen to antibody seroconversion was recorded by 24 weeks (AOR= 13.03; 95% CI: 3.9- 43.82) and actor cofactors of HIV positivity in 10.1% of the patients in the lamivudine group (p=0.032 compared to

Table 1 (abstract P87) Multilevel logistic regression estimation of individual and couple level risk factors for actor anti-HCV positivity, final model, Shiraz (southern of Iran), 2011 Effects† b SE AOR (95% CI) Actor IDU 2.57 0.62 13.03 (3.9- 43.82) Actor Razor sharing 1.57 0.49 4.81 (1.84- 12.55) Actor HIV positive 1.96 0.84 7.1 (1.37- 36.97) Actor male 2.18 0.52 8.83 (3.16- 24.78) No condom use in sexual activity with main heterosexual partner 1.89 0.92 6.6 (1.1- 39.6)

† -19 Random effect (level 2 variance component), su= 3.98 BMC Infectious Diseases 2014, Volume 14 Suppl 2 Page 36 of 45 http://www.biomedcentral.com/bmcinfectdis/supplements/14/S2/

control), 42.9% of those in the entecavir group (p=0.053 compared to University of Edinburgh, Easter Bush, Edinburgh, EH25 9RG, UK; 4Department control), and 22.7% in the control (standard of care) group. of Pediatrics, University of Oxford, Oxford, OX1 3SY, UK; 5Paediatric Conclusions: If antiviral therapy is to be considered in severe acute Department, University of Free State, Kimberley Hospital, Kimberley, Northern hepatitis B, entecavir could be regarded as an option, as it might increase Cape, South Africa; 6NIHR Biomedical Research Center, John Radcliffe the chance of HBs antigen to antibody seroconversion when Hospital, Oxford OX3 9DU, UK administered in the first 24 weeks of infection. [2,3] However, further BMC Infectious Diseases 2014, 14(Suppl 2):P92 studies are required to ascertain this, and to eventually determine the magnitude of the effect. Introduction: First identified in 2005, PARV4 is best characterized in References Western cohorts where it is strongly associated with other blood borne 1. Streinu-Cercel A: Hepatitis B in the spotlight. GERMS 2011, 1(1):5. viruses and occurs only in individuals with risk factors for parenteral 2. De Socio GV, Sgrelli A, Tosti A, Baldelli F: Severe acute hepatitis B treated infection (in particular, injecting drug users). However, studies in Africa have with entecavir. Mediterr J Hematol Infect Dis 2011, 3(1):e2011010. shown evidence of PARV4 in subjects with no clear risk factors for 3. Streinu-Cercel O, Streinu-Cercel A, Preotescu LL, Streinu-Cercel A: Entecavir acquisition of blood borne viruses. The clinical significance of PARV4 as specific antiviral therapy in selected cases of severe acute hepatitis B. remains uncertain, but there is growing interest in the role of coinfecting GERMS 2012, 2(1):18-22. pathogens in shaping outcomes of HIV, and in chronic viral infections as determinants of immunological development in childhood. Materials and methods: We studied a cohort of HIV-infected mothers EMERGING INFECTIOUS DISEASES (n=32) and children (n=40; median age 28 months), and HIV-negative pediatric controls (n=24, median age 86 months) in Kimberley, South P91 Africa. PARV4 serostatus was determined by ELISA for IgG to the PARV4 Hantaviruses: seroprevalence and risk factors among humans in Achaia VP2 protein. HIV viral load was determined using the Abbott m2000 prefecture, Greece assay, and CD4 T cell count by flow cytometry. George Panos1*, Maria Sargianou1, Anna Papa2, Charalambos Gogos1 Results: In this cohort, 45/96 individuals (46.9%) were positive for PARV4 1Division of Infectious Diseases, Department of Internal Medicine, Patras IgG, including 19/32 adults (59.4%) and 26/64 children (40.6%). The University General Hospital, Patras, Greece; 2Department of Microbiology, seroprevalence of PARV4 IgG increased with age, demonstrating acquisition Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece throughout childhood, plateauing by age 6-10 years (Fig. 1; R2=0.75 by BMC Infectious Diseases 2014, 14(Suppl 2):P91 logistic regression). There was strong concordance between maternal and child infection, with the mother’s PARV4 status being a clear predictor of IgG Introduction: Inhalation of hantavirus-contaminated aerosol of rodents’ in her offspring (p=0.006). HIV-negative individuals were more likely than excreta can cause in humans hemorrhagic fever with renal syndrome HIV-positive subjects to be PARV4 IgG positive (p=0.03), although this (HFRS) in Eurasia and Hantavirus pulmonary syndrome in the Americas. In relationship may be confounded by age. There was no relationship between Greece, 1-5 cases are being diagnosed annually, mainly in the northern PARV4 status and HIV viral load or CD4 T cell count in HIV-infected adults or and western part. After the recent diagnosis of a hantavirus infection in children. Achaia prefecture (Peloponesse), a seroepidemiological study was Conclusions: The epidemiology of PARV4 in this cohort contrasts strikingly designed to determine seroprevalence in the local population and to with that in Western countries: the prevalence of PARV4 IgG approached assess factors playing a role in the acquisition of hantavirus infection. 50%, with evidence for ongoing transmission throughout the early years of Materials and methods: Between March-July 2012, 207 serum samples life. The observed concordance within families is suggestive of maternal to were prospectively collected. The participants were randomly selected child transmission. Future studies are planned, to investigate further the among apparently healthy individuals, referred for routine blood testing or relationship between PARV4 status and outcomes of HIV infection. for blood donation to Patras University General Hospital and to healthcare centers of the 5 munipalities of Achaia. Sampling was performed and a questionnaire regarding demographics and potential risk factors was P93 completed after a written consent had been obtained. HPV vaccination in HIV+ adolescents and young adults induces strong Serum samples were tested for hantavirus IgG antibodies by ELISA (Anti- HPV-specific immune responses Hanta Virus Pool 1 “Eurasia” ELISA IgG, Euroimmun, Lübeck, Germany), V Rainone*, D Trabattoni, F Penagini, V Fabiano, F Calascibetta, V Giacomet, according to the manufacturer’s instructions. The data were statistically A Vigano, M Clerici, GV Zuccotti analyzed using SPSS 20.0 (IBM, Chicago, Illinois, USA). University of Milan, Chair of Immunology, Milan, Italy Results: In total, 20/207 (9.66%) serum samples tested IgG positive for BMC Infectious Diseases 2014, 14(Suppl 2):P93 hantavirus, with seropositivity rates ranging from 0-18.5% among municipalities; a local seroprevalence maximum was encountered in one of Background: HPV-associated ano-genital infections represent the most the municipalities (5/27, 18.5%). Univariate analysis showed that age (OR common sexually-transmitted disease in the general population. The 1.036, 95%CI 1.011-1.062), peridomestic sighting of rodents (<200m radius incidence of HPV-associated cancers has been increasing in HIV-infected from residence, OR 4.538, 95% CI 1.019-20.219) and ownership of a storing patients. HPV vaccination may be an approach to reduce the risk of HPV- shed (OR 2.892, 95%CI 1.004-8.327) were statistically significant risk factors. associated cancers in HIV-infected patients and a combined strategy of Conclusions: An unexpectedly high hantavirus seroprevalence was screening and vaccination may guarantee an adequate prevention of HPV- observed in Achaia, indicating the presence of CCHFV in the region and associated lesions. Immunogenicity of HPV vaccines in HIV-infected patients the possible exposure of the habitants to hantaviruses. Studies in rodents is still not adequately evaluated. We analyzed immunogenicity of a are needed to identify the circulating strain(s), which could lead to a better quadrivalent HPV vaccine in HIV-infected patients without molecular understanding of the epidemiology of hantaviruses in southwestern evidence of vaccine-type HPV infection focusing on HPV-specific cell Greece. Clinicians should include hantavirus infections in the differential mediated immunity (CMI). diagnosis of acute febrile cases accompanied by renal impairment and/or Methodology: 31 ARV-treated HIV-infected adolescents (age range 28-14 hemorrhagic manifestations. years, with undetectable viremia and effective CD4 recovery) and 25 sex- and age-matched HIV-seronegative healthy controls were enrolled in the study. HPV-16/18/6/11 VLP vaccine (Gardasil®) was administered 3 times P92 (baseline, 2 and 6 months). Immune activation (CD4/CD25/HLADRII, CD8/ Paediatric PARV4 infection in South Africa: relationship to age, CD25/HLADRII), T-cell patterns and HPV-specific immune responses (CD4/ maternal PARV4 status, and HIV infection IFN-g/IL-2, CD8/IFN-g/TNF-a, CD8/Perforin/GranzymeB) were evaluated. Philippa Matthews1,2*, Colin Sharp3, Amna Malik4, Emily Adland4, Results: HIV-infected individuals showed: 1) no changes in CD4 counts, Pieter Jooste5, Philip Goulder4, Peter Simmonds3, Paul Klenerman1,2,6 percentage of CD4 cells and HIV viral load; 2) a significant increase in naїve 1Nuffield Department of Medicine, University of Oxford, Oxford, OX1 3SY, UK; CD8 T-cells, activated CD8 T-cells and in central memory CD4 and CD8 2Department of Infectious Diseases and Microbiology, Oxford University T-cells; 3) a significant reduction in terminally differentiated CD8 T-cells; 4) Hospitals, John Radcliffe Hospital, Oxford, OX3 9DU, UK; 3Roslin Institute, a significant increase in unstimulated and in HPV-specific IL2+/CD4+, IFN-g BMC Infectious Diseases 2014, Volume 14 Suppl 2 Page 37 of 45 http://www.biomedcentral.com/bmcinfectdis/supplements/14/S2/

+/CD4+, IFN-g+/CD8+ and TNF-a+/CD8+ T-cells; and 5) a significant Methods: It was a prospective study conducted over a six month period increase in HPV-specific Perforin- and Granzyme B-secreting CD8 T-cells. (2012, January to June). 665 women were screened by an examination of Results obtained in HIV-infected patients were comparable to those seen the cervix, a cervical screening test and a detection of the HPV DNA by in HC. PCR. This detection of the high oncogenic risk HPV was made from the Conclusions: HPV-16/18/6/11 VLP vaccine induces strong HPV-specific cytobrush that was used for the spreading of the cervix cells. cell-mediated immunity in ARV-treated HIV-infected individuals that are Results: The mean age was 41.5 ±9.1 years (20-71 y). The mean age of comparable to those observed in HIV-seronegative controls. HPV-specific themarriagewas24.8±5years(16-50y).Theageofthefirstpregnancy CMI is likely an important component of the protective effect of this was 24.8±5.7 years (14-48 y). Six percent reported history of genital lesion vaccine, data herein indicating that this arm of immunity is not impaired in in their partner. 37% used or are still using Intra Uterine Device and 48% ARV-treated HIV infected individuals. used or are still using contraceptive pills. 58% had never had a routine CST and 27% had one CST. 65% of the women reported a history of vaginal discharge, 25% a genital ulceration and 4.5% condylomas. The P94 cervix examination showed 51% of normal cervix, without any clinical Emerging virus coinfections of the CNS: HTLV I/II as a common macroscopic anomaly. 41% had a cervix inflammation, 18% had denominator leucorrhea, 7% had polypus and 3% had condylomas. HPV prevalence George Panos1*, Maria Sargianou1, Dionysios Watson1, Nikolaos Dimisianos1, was 3%. Paraskevi Chra2, Marina Andreou1, Christina Sklavou1, John Ellul1 Conclusion: Our results showed lower HPV prevalence, probably due to 1Patras University General Hospital, Patras, Greece; 2Athens General Hospital later onset of sexual practice and fewer sexual partners. “Korgialenio-Benakio”, Greece BMC Infectious Diseases 2014, 14(Suppl 2):P94 P96 Introduction: HTLV I is a retrovirus that can result in decreased Use and acceptance of long lasting insecticidal net screens for dengue effectiveness of immune response and an increased incidence of prevention in Acapulco, Guerrero, Mexico coinfections. HTLV I CNS coinfections with rare clinical manifestations that Catrin Huws Jones1*, David Benítez-Valladares6, Mario Barrera-Pérez5, may relate to impaired cellular immunity are presented. Felipe Dzul Manzanilla4, Azael Che-Mendoza3, Guillermo Guillermo-May2, Materials and methods: Case1: a 15-year-old patient presented with Johannes Sommerfeld6, Axel Kroeger6, Timothy O’Dempsey1, difficulty in standing up and walking on her own (following a fall), with Pablo Manrique-Saide2 visual disturbances, and refractory epileptic seizures; travel history 1Liverpool School of Tropical Medicine, Liverpool, UK; 2University of Yucatán, included trips to the Caribbean (Isla Margarita). Mérida, México; 3Medical services of Yucatán, Yucatán, México; 4Servicios Case2: a 24-year-old patient presented with difficulty in standing up and Estatales de Salud de Guerrero, Chilpancingo, México; 5Special Program for walking without support, with sudden hearing loss, peripheral paresthesia, Research and Training in Tropical Diseases, México; 6World Health and generalized weakness, after having experienced grand mal seizures Organization, Geneva, Switzerland several days before; travel history included trips to the Caribbean (her BMC Infectious Diseases 2014, 14(Suppl 2):P96 fiancé was captain of a cruise ship), the Amazon rainforest and Antarctica. Results: Case1: brain MRI imaging revealed localized, non-Gadolinium Introduction: Dengue, recognized by the WHO as the most globally enhancing lesions in the right thalamus and occipital lobe and cortex important mosquito-borne viral disease, is a growing problem. Currently, edema. EBV DNA and HTLV I/II RNA were detected in the CSF and EBV the only effective way of preventing dengue is vector control. Standard VCA IgG antibodies in the serum. Following administration of supportive methods have failed, and there have been calls to develop new integrated treatment and gancyclovir IV for EBV encephalitis, the patient was vector management approaches. One novel tool, insecticide-treated discharged with residual mobility impairment. window screens, is being trialed in a cluster randomized controlled trial by Case2: brain MRI imaging revealed several medium sized, non-Gadolinium a joint UADY/WHO TDR study in Acapulco, Mexico, districts of which have enhancing lesions in the white matter of both hemispheres (especially in exceptionally high levels of crime and insecurity. This study investigated the temporal lobe). India ink examination and latex agglutination for the community’s perspectives of insecticide-treated window screens, in Cryptococcus spp. were positive in the CSF. Cryptococcus gattii was homes and in schools, in order to ascertain their acceptability, identify consequently isolated from CSF cultures. HTLV I/II antibodies and HTLV I/II challenges to further implementation and opportunities for future RNA were both detected in the serum only. Following a 4-month improvements. hospitalization, the patient was discharged with clinical improvement, but Methods: This was a sequential mixed-methods study. The quantitative with relative speech and mobility impairment. arm contained two descriptive questionnaire surveys: a household survey Conclusions: Neurologic manifestations can be encountered in HTLV I/II administered to 2000 households prior to the intervention investigating monoinfected and coinfected patients, regardless of HAM/TSP. In CNS dengue knowledge and attitudes, and a satisfaction survey administered coinfections, the definite diagnosis for HAM/TSP cannot be established by to 288 houses that had received the intervention examining their current diagnostic criteria, reflecting the need for further criteria to also perspectives of both the intervention and dengue prevention in general. include coinfections. Quantitation of HTLV I/II proviral load and The qualitative arm consisted of Focus Group Discussions (FGDs) with investigation of factors related to cellular immunity might augment those who had accepted the intervention to discuss their perspectives in diagnosis and prognosis. greater depth; and key informant interviews with: school teachers to discuss the use of the screens in schools, program staff to discuss their perspectives and experiences of implementing the project, and community members who had refused the intervention. P95 Results: Overall satisfaction and acceptance of the screens was very high, Prevalence of Human Papilloma Virus in Tunisia with only some operational and technical complaints relating to screen Ali Mrabet*, MT Khoufi, C Tounsi, R Dhaoui, M Chibani, N Doss fragility and the installation process. However, the wider social context of Tunisian Military Health General Directorate, Tunis, Tunisia urban violence and insecurity was a major barrier to screen acceptance. BMC Infectious Diseases 2014, 14(Suppl 2):P95 Lack of information dissemination and community collaboration were identified as project weaknesses. Introduction: Cervical cancer is still a major health problem in Tunisia and Conclusion: Thescreensarewidelyacceptedbythepopulation,and over the world. HPV infection may induce malignant transformation of could be a major new dengue prevention tool suitable for widespread lesions, especially in case of colonization by oncogenic HPV genotypes. Early use. The project implementation could be improved by reassuring the detection of viral genome by molecular biology in women with normal community of its legitimacy in the context of insecurity. More community cytology in cervical screening test (CST) can be a part of a screening policy engagement and better information sharing structures are needed. to improve cancer prevention. Our aim was to evaluate HPV prevalence and Further research is needed looking at the impact of insecurity on dengue genotype distribution in routine CST. prevention programs. BMC Infectious Diseases 2014, Volume 14 Suppl 2 Page 38 of 45 http://www.biomedcentral.com/bmcinfectdis/supplements/14/S2/

Conclusion: Thus, carried-out sequencing and phylogenetic analysis have P97 showed that on the territory of Belarus circulation as “old” HPV-16 variants Current clinico-mycological trends of onychopathies in Casablanca takes place, and there is a penetration of new types HPV because of L Badaoui*, G Dabo, R Bensghir, I Halim, S Belyamani, M Soussi Abdallaoui, borders of Belarus, generally from the countries of South East Asia. S Chiheb, K El Filali Marhoum Ibn Rochd University Hospital, Casablanca, Morocco BMC Infectious Diseases 2014, 14(Suppl 2):P97 P99 Molecular diagnosis of cytomegalovirus, Epstein-Barr virus and Herpes Background: Onychopathies in patients infected with HIV are dominated virus 6 among blood donors in Ouagadougou, Burkina Faso by onychomycosis. It is one of the early manifestations of HIV infection . Lassina Traore*, Issoufou Tao, Cyrille Bisseye, Florencia Djigma, the purpose was to study the epidemiology, clinical manifestations and Djénéba Ouermi, Theodora Zohoncon, Tegwindé Rebecca Compaoré, mycological profile of onychomycosis in HIV-infected individuals and to Birama Diarra, Maleki Asshi, Jacques Simpore identify the other causes of onychopathies in this population. Labiogene, Ouagadougou, Burkina Faso Methods: A total of 88 HIV infected patients, monitoring at Department BMC Infectious Diseases 2014, 14(Suppl 2):P99 of Infectious Diseases, were screened for nail involvement over a period of 3 months. Inclusion criteria: Patient who had do not receive any Introduction: This study focuses on three herpes viruses, including EBV, antifungal treatment were included. CMV and HHV -6. Our study aims to determine the prevalence of these Results: A total of 88 subjects were examined (45men and 43 women); the viruses in blood donors in Ouagadougou. average age were 41 years old. Abnormal appearing nails were present in Material and methods: The study included 198 blood donors. We 48 cases. Mycologic evidence of onychomycosis were present in 42 cases. extracted DNA, using DNA extraction kit -Sorb -B. For amplification, we The clinical presentation of onychomycosis was: distal and lateral subungual used PCR Real -96 SaCycler of V.7.3 “Sacace Biotechnology” and kit As onychomycosis (47%); white superficial onychomycosis (5%); proximal CMV/EBV/HHV-6 TM Real - Time apparatus. The results were analyzed subungual onychomycosis (21%); total dystrophic onychomycosis (26%). using the standard software SPSS -17 for Windows and EpiInfo-6 -6. Toenail involvement was seen in 26 patients, fingernail in 11 patients while Results: Of the 198 samples tested, 18 (9.09%) were positive to at least one 5 patients had involvement of both fingernail and toenail. The various of the three viruses, 10 (5.10%) were positive for EBV, 10 (5.10%) positive for aspects noted were: Xanthonychia (19 cases), pachonychia (17 cases), CMV and 12 (6.10%) positive for HHV -6. According to age, we found that onycholysis (7 cases), leuconychia (6 cases) and melanonychia (4 cases). The only those who had a less than or equal to 30 years old were infected. culture has allowed the confirmation of onychomycosis in 73.3%. Among Infection with EBV, CMV and HHV-6 in women accounted for 8.57%, 8.57% the 16 positive dermatophytes cultures, Trichophyton rubrum was isolated and 11.43% respectively. Against by men, infection rates were low were in 12 cultures, Trichophyton interdigitale in 3 cultures, and Trichophyton 4.29%, 3.68% and 4.90 % for EBV, CMV and HHV -6. Based on HIV status we Mentagrophyte in one case. Of the 12 non-dermatophytic cultures, Candida found that HIV-positive were more infected than HIV-negative, EBV (12.5 % albicans and Candida dubliensis were isolated in 4, Candida parapilosis in versus 4.74), CMV (12.5 % versus 4.74) , HHV-6 (12.5% versus 5.79) . Seven (7) 2 while Trichosporon spp., and Penicillium spp. in each one. samples were co- infected EBV/CMV/HHV-6, or 38.89 % of positive samples. Conclusion: The prevalence of onychomycosis was 48%. It seems that Conclusion: The prevalence that we recorded is low compared to those the incidence of NMD is higher in the HIV patients compared with reported by previous studies in the sub-region among blood donors. This immunocompetent population. difference can be explained by the fact that previous studies have used serological techniques.

P98 High risk HPV genotypes in Belarus VF Eremin1*, GI Viarheichyk2, EL Gasich1, EA Shishkin1, MV Domnich1, P100 EI Nesterovskaja1 Hepatitis E virus seroprevalence in patients with HIV in Nizhny 1Republican research and practical center of epidemiology and Novgorod, Russia microbiology, Minsk, Belarus; 2Gomel state medical University, Gomel, Belarus IN Sharipova1*, AV Berezhnaya1, VF Puzyrev1, AN Burkov1, TI Ulanova1,2 BMC Infectious Diseases 2014, 14(Suppl 2):P98 1RPC “Diagnostic Systems”, Ltd., Nizhny Novgorod, Russia; 2DSI S.R.L. Saronno, Italy Introduction: 897 cases of cervical cancer and 358 women death are BMC Infectious Diseases 2014, 14(Suppl 2):P100 registered in Belarus for 2008. Materials and methods: 764 PCR positive vaginal and cervical specimens. Introduction: More than 20 million cases of infection with Hepatitis E (HEV) PCR,products were purified and sequenced on the genetic analyzer ABI are registered every year all over the world. By now it is known that chronic Prism 3100 Avant. Software programs Sequencing Analysis 5.1.1., SeqScape Hepatitis E develops in immunosuppressed individuals, including individuals v2.6, BioEdit were used. Phylogenetic analysis was performed using the infected with HIV. Studies regarding coinfection of HIV and HEV are limited. MEGA4.1 software with the Neighbour-Joining and Kimura 2-parameter Some studies have suggested that patients with HIV may acquire HEV method. infection more frequently than individuals without HIV. Other studies have Results: Of764PCRpositivesamplesthereweresequenced77and10 not shown differences in HEV prevalence between HIV-infected and non- DNAs on genes L1 (296 bp) and E6/E7 (620 bp) HPV-16 regions, infected individuals. respectively. The phylogenetic analysis of gene L1 region established that Aim: The aim of this study was to define the degree of prevalence of generally all samples from Belarus clustered round reference-sequences Hepatitis E markers in the group of HIV infected patients in Nizhny from South East Asia and Europe, only 15 and 9 samples formed Novgorod. Donor blood serum samples were studies as the control group. independent groups with each other. p-distances between the Belarusian Materials and methods: 505 donor sera provided by Nizhny Novgorod samples fluctuated from 0.000 to 0.024 that points as to new virus regional blood transfusion station and 500 sera from HIV infected patients penetration to the country, and on circulation of our “old” HPV-16 types provided by Regional Center for prevention and control of AIDS and which formed independent groups of samples on a phylogenetic tree. infection diseases, Nizhny Novgorod, were studied for presence of Separately the sample 63 from Gomel settled down, it didn’tenteroneof antibodies to Hepatitis E virus. The levels of IgM or IgG antibodies against groups. Most likely, it is our “domestic” HPV-16 variant. Three viruses, two HEV were determined with the CE-marked EIA kits (RPC “Diagnostic from Minsk and one from the Grodno region settled down in one group Systems”,Russia). “Africa” with African reference - sequences, but separately from each other Results: 19 (3.8%) of 500 sera from HIV infected patients examined for that points to a different origin of a virus at these patients. Sequencing on markers of viral hepatitis E were seropositive. 4 patients out of 500 had both gene of E6 and E6/E7 region also divided viruses into groups. Also as well anti-IgM and anti-IgG (0.80%), 5 patients (1.0%) had only anti-IgM and as on L1 gene on gene E6/E7 region virus formed, generally the general 10 patients had only anti-IgG (2.0%). Detection rate of Hepatitis E antibodies groups with Asian HPV-16 variants. In too time part of isolates settled in healthy population of Nizhny Novgorod was 7.3% (37 individuals). down separately and formed independent groups. FrequencyonlyofIgMmarkeroccurrence was 1.78% (9 individuals); only BMC Infectious Diseases 2014, Volume 14 Suppl 2 Page 39 of 45 http://www.biomedcentral.com/bmcinfectdis/supplements/14/S2/

IgG marker occurred with the frequency 4.75% (24 individuals). Simultaneous 8. Do PrEP and Intermittent PrEP Have a Chance? Certainly, these are presence of IgM and IgG marker in donor sera was 0.79% (4 out of 505 strategies that should be effective when used together with counselling. donors). 9. What if HIV Failed to Develop Resistance to a New Drug in First-Line Conclusions: According to the results of the study described above, Therapy? If this were ever to happen, it would change our thinking on frequency of occurrence of Hepatitis E markers in control group of blood how to prevent HIV transmission in a dramatic way. For example, the use donors was higher than in HIV infected patients. Lower percentage of of such a drug should potentially eliminate future new HIV transmissions. detection of Hepatitis E markers in HIV-positive patients may be caused How significant is it that no-one who has received Dolutegravir in first- by interactive effect of viruses in case of HIV/HEV coinfection. line therapy has yet developed resistance against it or is this only a matter of time? 10. What is the Impact of Global Warming on Infectious Diseases and Will P101 Future Dengue Epidemics Surpass the HIV Pandemic in Incidence, Morbidity, Functional properties of the novel PA-X endonuclease of human and Mortality? The range of the mosquitos that transmit West Nile virus has influenza virus already expanded to significant extent. Can Dengue be far behind? Laura Bavagnoli*, Giovanni Maga Institute of Molecular Genetics CNR, National Research Council, Pavia, Italy BMC Infectious Diseases 2014, 14(Suppl 2):P101 SESSION: MANAGING ANTIRETROVIRAL

The PA subunit of the RNA dependent RNA polymerase of influenza virus is THERAPY, PART 1 an endonuclease required for the cap-snatching mechanism leading to the S2 synthesis of viral mRNA. Recently, the PA-X protein has been discovered in New ARV drugs human influenza, which is translated from an alternative open reading Roy Gulick frame within the PA gene coding sequence, resulting from a ribosomal Weill Cornell Medical College, Division of Infectious Diseases, New York, USA frameshifting. The PA-X retains the N-terminal endonucleolytic domain of BMC Infectious Diseases 2014, 14(Suppl 2):S2 PA, but has a different and shorter C-terminal part. Two isoforms of PA-X are present in circulating human infuenza A strains. It has been proposed There are 28 approved antiretroviral drugs for the treatment of HIV infection; that PA-X degrades cellular mRNA, contributing to the attenuation of viral combinations of these drugs clearly change the natural history of HIV, pathogenesis in the host. Here we express the diferent recombinant PA-X dramatically decreasing HIV-related morbidity and mortality and promoting proteins from human seasonal influenza virus and show that their and prolonging healthy survival. Despite the benefits of HIV treatment, endonucleolytic activities have distinct substrate specificities, which some antiretroviral regimens may be inconvenient, toxic, and/or have depend on the structure of the RNA to be cleaved. Collectively, our results suboptimal antiretroviral activity, particularly against drug-resistant viral support distinct roles of PA and PA-X in the viral life cycle. strains. Thus, newer compounds are needed that continue to improve convenience and tolerability, reduce toxicity, and improve antiretroviral activity, particularly against drug-resistant viruses. Additionally, newer drugs SPEAKER PRESENTATIONS may better penetrate tissue reservoirs (e.g. genital tract, central nervous system) and/or exploit new viral or cellular targets with new mechanisms of action. In addition to the direct antiretroviral action, some investigational THIRTY YEARS OF DISCOVERIES IN HIV agents may target inflammation and/or immune responses. Finally, newer formulations of antiretroviral agents may allow additional options for one- S1 pill, once-daily dosing or allow less frequent dosing than once-daily, perhaps Ten big challenges ahead as infrequently as once-monthly or once-quarterly parenteral dosing. Mark Wainberg There are a number of investigational antiretroviral agents currently in McGill AIDS Center, Montreal, Quebec, Canada development. These include newer antiretroviral agents in existing classes, BMC Infectious Diseases 2014, 14(Suppl 2):S1 including new nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, integrase inhibitors, and entry inhibitors. Of 1. Can We Cure AIDS? This is an intense area of investigation at the those in the pipeline, a few compounds are in advanced stages of current time with much focus on the activation of latently infected cells development: Tenofovir alafenamide fumarate (TAF) is a nucleoside within reservoirs by such agents as histone deacetylase inhibitors. analogue reverse transcriptase inhibitor currently in phase 3 that is potent However, there is concern about some of these approaches due to and potentially less toxic than the current TDF formulation. Doravirine considerations of possible long-term toxicities involving the activating (formerly MK-1439) is a non-nucleoside analogue reverse transcriptase agents as well as questions about whetheritwillbepossibletoactivate inhibitor currently in phase 2 that demonstrates activity against NNRTI- all latently infected cells or not. resistant viral strains. GSK ‘744 is an integrase inhibitor currently in phase 2, 2. Can We Provide High Quality HIV Drugs to All People at Need Regardless being developed in a long-acting preparation. In addition there are of Ability to Pay? At present, people living in developing countries often investigational drugs with new mechanisms of action in development: BMS- receive sub-standard therapy, with drugs such as Raltegravir being 663,068, is a small molecule CD4 attachment inhibitor that completed phase available only for second-line therapy. So, when will our best new drug, ie 1 testing. Cenicriviroc is a novel CCR5/CCR2 antagonist currently in phase 3 Dolutegravir, become available in resource-limited settings? that offers both antiretroviral activity and the potential for an anti- 3. How Will We Pay? There is a real risk that worldwide assistance inflammatory effect (through CCR2 antagonism). A number of other programmes will run out of funds. compounds are in earlier stages of pre-clinical and clinical development. 4. Will Treatment as Prevention Work in the Real World? Hopefully, the The clinical use of these newer agents and formulations will depend on answer to this question will be Yes, but we have already seen that other the results of clinical trials, and the timeline for development and prevention strategies have experienced difficulties when employed availability. Continued progress in HIV drug development will allow outside the context of a controlled clinical trial. improvements in the clinical care of patients living with HIV infection. 5. Will Drug Resistance Compromise All Prevention Strategies? Perhaps it is too early for HIV drug resistance virologists to retire. The answer to this question will be key and only time will provide an answer. 6. When Will We Have a HIV Vaccine? There is a very limited rate of S3 success in the development of vaccines to all forms of sexually First Line Therapy in 2014 transmitted disease, with the obvious exception being Human papilloma Mark Nelson virus. We should be more honest about this. Chelsea and Westminster Hospital, Department of HIV and Genitourinary 7. Are Microbicides Still in the Game? Clearly, they would probably never Medicine, London, UK be as popular as PREP, if it worked, or as Treatment as Prevention. BMC Infectious Diseases 2014, 14(Suppl 2):S3 BMC Infectious Diseases 2014, Volume 14 Suppl 2 Page 40 of 45 http://www.biomedcentral.com/bmcinfectdis/supplements/14/S2/

The choice of antiretroviral therapy for those naïve to therapy is vast, of PI/r monotherapy is accepted in EACS Guidelines for selected with over 30 drugs available for the treatment of HIV disease. Although virologically suppressed patients and may be an option for patients with international and national guidelines often give recommended preferred previous nucleoside analogue toxicities, such as tenofovir-related choices for commencement of therapy, it is important that treatment is nephrotoxicity. Raltegravir may be switched to once-daily regimens to always individualised. Therefore for the individual patient, it may be improve adherence or it may replace other drugs to avoid interactions in necessary to utilise treatments outside of the guidelines which too often medically complex patients. Unboosted atazanavir is a PI-containing refer to the near perfect patient. option for patients who do not tolerate ritonavir. Two drug regimens Choice of antiretroviral therapy must be based on several factors. These have been assessed in randomized clinical trials and cohort studies with would include comparative trials on efficacy. However the toxicity of the different results because of negative drug interactions leading to agents both singly and in combination may be the most important in unexpected toxicities or low efficacy in some cases. individualisation of therapy, due to patient wishes and associated co- In summary, many switching options are currently available for morbidities. The ability for the patient to comply with therapy may be virologically suppressed patients. However, although switching strategies made easier with once daily therapy although the role of single tablet may be useful for improving ART, not all regimens used in clinical regimens remains controversial. Together efficacy, toxicity and adherence practice are based on data from randomized clinical trials and not all contribute to the potency of the antiretroviral regimen, where potency is regimens are suitable for everyone. It is therefore important to defined as the ability to succeed. individualize treatment, taking into consideration not only patient and Other factors have become increasingly important. There are increasing drug characteristics but also the best evidence available. reports of primary resistance in several European areas, which clearly may impact on the choice of therapy, particularly within the non-nucleoside class. In addition, with an ageing HIV population including those newly SESSION: KEYNOTE LECTURE diagnosed, potential drug interactions will become an increasingly important factor. In several countries the issue of cost has now become S5 an essential driver towards choice of therapy, particularly with the advent Managing HCV infection: present and future of generic drugs. Jürgen K Rockstroh The majority of individuals will receive two nucleoside reverse transcriptase Department of Medicine I, Bonn University Hospital, Bonn, Germany inhibitors in combination with either a ritonavir boosted protease inhibitor, BMC Infectious Diseases 2014, 14(Suppl 2):S5 a non-nucleoside reverse transcriptase inhibitor most commonly efavirenz, or an integrase inhibitor. The development of direct acting antiviral agents against the hepatitis C A recent large scale study performed by the ACTG, suggested that overall virus has revolutionized treatment paradigms for hepatitis C. In 2011 the success may be higher with an integrase inhibitor, when compared with first HCV protease inhibitors boceprevir and telaprevir were approved, a ritonavir boosted protease inhibitor, but closer examination of these which still needed to be combined with pegylated interferon and results shows that this was mostly driven by toxicities associated with the ribavirin and were only usable in patients with genotype 1. However, the protease inhibitors and a switch from these drugs was not associated new triple therapy achieved successful cure rates of hepatitis C in almost with a lower rate of long-term success. 70% of treatment naïve patients and immediately became the new gold Several studies have examined novel treatments include nucleoside standard of HCV therapy. With the development of further agents, in sparing regimens. A recent study from the NEAT Network suggested that a particular the recent licensing of sofosbuvir and simeprevir, two further combination of raltegravir, ritonavir and darunavir performed as well as a DAA’s have become available. Thereby, for the first time Interferon free combination of truvada, ritonavir and darunavir. Again closer inspection of regimens are already available for genotype 2 and 3 patients allowing these results would suggest that the nucleoside sparing regimen did not cure rates approaching 90% after 12 weeks of sofosbuvir and ribavirin for perform as well when stressed both at high viral load and low CD4 count. genotype 2 treatment naïve as well as treatment-experienced patients The initial choice of antiretroviral therapy is perhaps one of the most and 24 weeks of all oral therapy for patients with genotype 3 (again important choices for the patient to make. This should never be rushed, treatment-naïve or experienced). For genotype 1 the combination of should be performed within a partnership of patient and physician, and sofosbuvir with pegylated interferon and ribavirin allows curing over 90% should always reflect the needs of the individual patient not the of patients after 12 weeks of triple therapy and therefore has become the prescribing physician. preferred HCV therapy for this particular patient group. Also combination of sofosbuvir with other agents have been presented in particular simeprevir or daclatasvir leading to high success rates above 90% even in S4 patients who failed previous triple therapy with one of the first HCV Switch strategies in 2014 protease inhibitors. Therefore, where available, 2 DAA combinations ± Daniel Podzamczer ribavirin are rapidly becoming the new HCV treatment standard for more HIV Unit, Infectious Disease Service, Hospital Universitari de Bellvitge, difficult to treat patient groups. In the near future combinations of L’Hospitalet, 08907, Barcelona, Spain antiviral agents with no cross resistance and improved safety profile will BMC Infectious Diseases 2014, 14(Suppl 2):S4 further reduce treatment durations and will become the new recommended HCV regimens making HCV the first viral infection to be Despite great advances in antiretroviral therapy (ART) in the last decade, possibly eradicated worldwide. several limitations remain regarding adverse effects, poor adherence, and drug-drug interactions. Switching ART in stable, virologically suppressed patients with the aim of improving tolerability and convenience is a widely SESSION: ENDING THE HIV PANDEMIC used strategy in clinical practice. Several factors need to be considered when switching from a successful antiretroviral regimen, including previous S6 virologic failure and duration of virologic suppression, genetic barriers to Improving prevention and early diagnosis resistance of the new regimen and expected level of adherence. Reductions Virginie Supervie in the number of pills, drugs, or doses are the most common switching Sorbonne University, Pierre Louis Institute of Epidemiology and Public strategies. Health, Paris, France Triple therapy regimens including ritonavir-boosted protease inhibitors BMC Infectious Diseases 2014, 14(Suppl 2):S6 (PI/r) are the most frequently switched regimens. Thymidine analogues, which are now uncommon in developed countries, have been successfully More than thirty years after the discovery of HIV, the HIV/AIDS epidemic replaced with non-thymidine analogues in recent years. The main aim of continues to expand worldwide. Undiagnosed HIV infections and late this switch is to prevent or improve abnormal fat redistribution. diagnoses remain major public health challenges in all HIV-affected Simple one-pill triple regimens such as tenofovir/emtricitabine (TDF/FTC) countries. According to recent estimates, the proportion of persons living plus efavirenz (EFV), rilpivirine (RPV) or Elvitegravir/Cobicistat (ELVI/Cobi) with HIV unaware of their infection varies from >50% in sub-Saharan may help to improve adherence and reduce some PI/r toxicities. The use Africa to 20-50% in European countries and 20-30% in North America. In BMC Infectious Diseases 2014, Volume 14 Suppl 2 Page 41 of 45 http://www.biomedcentral.com/bmcinfectdis/supplements/14/S2/

high-income countries, around 50% of new HIV diagnoses are made late Treatment as prevention (TasP) not only stands for prevention of HIV (i.e., when CD4 count is <350 cells per μL); mean CD4 cell count at first transmission by treating HIV-positives, but also for prevention of morbidity presentation to medical care in high-income countries was slightly above and mortality in those positives. Mathematical models have shown that it 300 cells per μL in 2011, and has not increased significantly over the past should be possible to “eradicate” HIV at the population level, or at least 20 years. In low- and middle-income countries, most patients start HIV come close to it, if this approach were rigorously applied. treatment with CD4 counts well below the recommended thresholds; the But these optimistic models are based on assumptions which are not main reason for late initiation of HIV treatment is late diagnosis. realistic: Undiagnosed HIV infections and late diagnoses have serious implications for both the individual and public health. Patients diagnosed late cannot • That it is possible to test the whole adult population every year; benefit fully from timely initiation of HIV treatment and are more likely to • That every individual found to be HIV positive will accept experience HIV-related morbidity and premature mortality. Undiagnosed immediate antiretroviral treatment; HIV-infected individuals have a higher risk of transmitting HIV than • That those accepting antiretroviral treatment will all be therapy individuals aware of their HIV infection, because they are not engaged in adherent; HIV treatment (which greatly reduces the risk of transmission) and cannot • That there will be no drug stock-outs; make informed decisions about their sexual behavior. As a consequence, • That there will be no development of antiretroviral drug resistance. the majority of new HIV transmissions may originate from individuals who are unaware of their HIV infection. We should realize, however, that early treatment is good for an individual’s Improving prevention and early diagnosis are thus key objectives to own benefit, and that this is the overriding reason to test as many people reduce mortality and turning the tide on HIV transmission. In this as possible and offer them antiretrovirals. presentation, we will describe the non-biomedical HIV prevention Early treatment prolongs life expectancy, prevents co-morbidities, and methods, including early diagnosis, review and summarize the evidence allows for task shifting from doctors to nurses and community workers. supporting (or not) their effectiveness and discuss how these methods Moreover it will reduce TB incidence, which is not a trivial fact in resource could be improved. poor settings. Early treatment thus presents an enormous opportunity to save lives, reduce HIV transmission and tackle the dual epidemic of HIV and TB. The world must be willing, however, to surmount the enormous S7 hurdles (financial, logistical) that stand in the way of realization of this ART for prevention: opportunities, challenges and predictions opportunity. Myron S Cohen University of North Carolina, Chapel Hill, North Carolina, 28443, USA BMC Infectious Diseases 2014, 14(Suppl 2):S7 SESSION: MANAGING ANTIRETROVIRAL Many antiretroviral agents (ARVs) concentrate in genital secretions. When THERAPY, PART 2 provided to people with HIV these agents stop the transmission of the virus, presumably by i) reducing the concentration of virus and ii) bathing S9 vulnerable tissues with ARVs during the potential transmission. In 11/13 ARV regimen choice and co-morbidities observational studies ART reduced HIV transmission. In one observational Barry Peters study that included gay couples, treatment of the infected partner stopped Infectious Diseases Department, King’s College, London, SE1 1UL, United transmission. In one randomized controlled trial (HPTN 052) of 17623 Kingdom couples at 13 sites in 9 countries, documented suppression of viremia BMC Infectious Diseases 2014, 14(Suppl 2):S9 appears to have been 100% effective in prevention of HIV transmission. The maximal potential of ARVs for prevention of HIV requires universal early or The main HIV co-morbidities include coronary heart disease (CHD), immediate treatment, with good adherence to therapy. Currently only a few metabolic syndrome and lipodystrophy, renal impairment, fragility countries (including the US and Brazil) have guidelines leading to immediate fractures, neurocognitive disease, and the emerging complications of treatment of infection. In addition, wider testing is required to identify HIV insulin resistance and fragility fractures. The evidence base for toxicities infected people who do not know their status. And new tests must be seen with ART is gained mainly from comparative efficacy studies of ART developed to detect acute HIV infection, a short stage of disease that regimens, where toxicity is not the primary endpoint, or cohort studies, contributes disproportionately to the spread of HIV. Earlier ART benefits the with their inherent limitations. health of the HIV infected person: CD4 cells are restored to a high level, ART choice to mitigate co-morbidities: Coronary Heart Disease: Most tuberculosis is averted, subtle changes in mentation are avoided, and HIV cohorts show an increase in CHD, thought due to a direct pro- normal lifespan is restored. While the biomedical benefits of early treatment inflammatory consequence of HIV infection and increased risk factors. Some of HIV have been established, logistical challenges of treatment-including drugs, notably the protease inhibitors, and to some extent others including early treatment-are considerable; and such logistical challenges compromise efavirenz, increase lipids with a detrimental total cholesterol (TC) HDL ratio; more immediate utilization of ARVs. It can be anticipated that universal by increasing HDL, neviripine improves the ratio. However, cardiac risk is immediate ART will become the standard of care in the near future. more important in selection of drugs than lipid levels alone. The evidence of Commitment to simplifying treatment regimens and improving from DAD and other cohort for increased CHD with abacavir probably infrastructure is essential. In addition, HIV infected patients must be inspired represents a channelling bias, and most other cohorts have not found this to protect their own health through treatment. Ongoing confusion about association. The integrase inhibitors, CCR5 inhibitors, eg maraviroc, and the when to start ART among patients and providers convinces asymptomatic newer PIs, including Atazanavir and Darunavir, have less lipid effects. people with HIV infection that delay of treatment has no adverse Metabolic effects, including lipodystrophy, metabolic syndrome, IR: consequence, which does not appear to be the case in either short or long The cessation of thymidine analogue use has markedly reduced lipoatrophy time frames. While treatment can be difficult, people who are not offered and several other metabolic effects. Again the integrase inhibitors, ARVs are often lost to follow-up. ARVs represent the cornerstone of maraviroc, and for insulin resistance the newer PIs, are “clean” in these combination HIV prevention; optimizing the clinical and public health respects. benefit(s) of these agents is of the greatest priority. Renal impairment: Tenofovir is unlikely to be a problem if renal function, incl urine protein: creatinine ratio, is monitored. Fragility fractures: The marked increase in osteoporosis, and reduced S8 bone mineral density (BMD) is likelytoheraldacommensuraterisein Implementation of TasP: challenges and opportunities fragility fractures as our patients age and may justify avoiding drugs Joep Lange associated with accelerated BMD loss, the protease inhibitors and Department of Global Health, Academic Medical Center, University of tenofovir, in the elderly and those with greatest fracture risk. Statins Amsterdam, Amsterdam, 1012WX, The Netherlands reduce CHD risk, may improve BMD, but are associated with increased IR BMC Infectious Diseases 2014, 14(Suppl 2):S8 and diabetes. BMC Infectious Diseases 2014, Volume 14 Suppl 2 Page 42 of 45 http://www.biomedcentral.com/bmcinfectdis/supplements/14/S2/

Neurocognitive disease: As well as issues of tolerability, there is data 5. Hsue PY, Hunt PW, Schnell A, et al: Role of viral replication, antiretroviral suggesting that efavirenz might have long-term neurological effects. therapy, and immunodeficiency in HIV-associated atherosclerosis. AIDS Conclusions: The wide and increasing choice of ART means that 2009, 23:1059-1067. considerations of avoidance of short and long term co-morbidities can be 6. Aslangul E, Assoumou , Bittar R, et al: Rosuvastatin versus pravastatin in fully addressed without compromising efficacy. Thymidine analogues are dyslipidemic HIV-1-infected patients receiving protease inhibitors: a rarely justified. ART co-morbidities are best mitigated by screening for risk randomized trial. AIDS 2010, 24:77-83. of co-morbidities, and use of use of those drugs that are least likely to 7. Dube MP, Stein JH, Aberg JA, Fichtenbaum CJ, et al: Guidelines for the exacerbate these risks. evaluation and management of dyslipidemia in human The integrase inhibitors, CCR5 blockers, non-thymidine NRTIs, neviripine immunodeficiency virus (HIV)-infected adults receiving antiretroviral appear to be preferential to some other agents, but for good access, therapy: recommendations of the HIV Medical Association of the pricing and a tiered tariff for developing countries will be important Infectious Disease Society of America and the Adult AIDS Clinical Trials determinants. Group. Clin Infect Dis 2003, 37:613-627. 8. Sattar N, Preiss D, Murray HM, et al: Statins and risk of incident diabetes: a collaborative metaanalysis of randomized statin trials. Lancet 2010, 375(9716):735-742. S10 9. Ridker PM, Danielson E, Fonseca F, et al: Cardiovascular benefits and Statin use in setting of HIV infection diabetes risks of statin therapy in primary prevention: An analysis from Kenneth Lichtenstein the JUPITER Trial. N Engl J Med 2008, 359:2195-2207. National Jewish Health, Denver, Colorado, 80206, USA 10. Sukhija R, Prayaga S, Maashdeh M, et al: Effect of statins on fasting plasma BMC Infectious Diseases 2014, 14(Suppl 2):S10 glucose in diabetic and nondiabetic patients. J Investig Med 2009, 57:495-499. 11. Culver AL, Ockene IS, Balasubramanian R, et al: Statin use and risk of As HIV-infected individuals age due to improved antiretroviral therapy, diabetes mellitus in postmenopausal women in the Women’s Health they may be at increased risk for age-related co-morbidities such as Initiative. Arch Intern Med 2012. cardiovascular disease (CVD). Increasing numbers of these individuals are 12. Goldstein MR, Mascitelli L: Do statins cause diabetes mellitus? Curr Diab initiating statins by meeting criteria for primary cardiovascular disease Rep 2013, 13(3):381-90. prevention [1]. 13. Carter AA, Gomes T, Camacho X, et al: Risk of incident diabetes among Previous guidelines for the general population had recommended statin patients treated with statins: population based study. BMJ 2013, 346:f2610. therapy based on 10-year cardiovascular risk (CV risk) with goal LDL- 14. Lichtenstein KA, Debes R, Wood K, Bozzette S, the HIV Outpatient Study cholesterol (LDL-C) levels depending on the risk score. The latest guidelines investigators: 20th CROI. 2013, Abstract 767. have changed to identify four statin-requiring risk groups. They include: 1. Patients with known atherosclerotic cardiovascular disease. 2. Individuals with LDL-C ≥ 190 mg/dL (≥ 4.91 mmol/L). 3. Anyone age 40 to 75 with Type S11 1 or 2 diabetes mellitus (DM). 4. Individuals with a 10-year CV risk ≥ 7.5%. Development of long-acting ARV’s Statin therapy is then considered moderate intensity or high intensity when Marta Boffito achieving a 30-50% reduction or > 50% reduction in LDL-C, respectively. The Chelsea and Westminster Hospital, Saint Stephen’s Center, London, UK guidelines define the intensity of therapy that applies [2]. BMC Infectious Diseases 2014, 14(Suppl 2):S11 In HIV infection, incident cardiovascular events are higher than that of the general population [3-5]. Clinical judgment must be brought into play Research on improved treatment of HIV infection and pre-exposure when deciding whether to follow the general population guidelines for prophylaxis (PrEP) continues. Poor adherence to treatment is the critical calculation of 10-year CV risk and whether to select a lower risk value at risk factor for virologic failure and resistance development, and long-acting which to start therapy. Also, there arethreecalculators: 1. Framingham formulations of anti-HIV medications that need only infrequent dosing may risk calculation. 2. Pooled cohort risk calculation. 3. D*A*D risk calculation. facilitate long-term therapeutic responses. However, such formulations and To date, management guidelines in HIV-infection are lacking. long-term persistence of drug are associated with challenges, such as Providers must also be cognizant of the interactions of statins with safety and selective pressure of the drug in case of resistance. protease-inhibitors and other drugs metabolized by the cytochrome CYP Furthermore, to prevent transmission of HIV, long-acting injectable 3A enzyme and adjust the doses accordingly [6,7]. formulations of ARV agents with infrequent dosing may be advantageous Finally, statins have recently been found to be associated with incident over daily oral drug intake. However, the knowledge on protective drug (DM). In the general population the benefits of statin therapy outweigh concentrations and frequency of dosing is poor to date and the risks of incident DM [8-13]. A study in an HIV-infected population implementation globally is challenging. demonstrated similar incidence of DM as compared to studies in the general population [14]. Statin therapy reduces CVD events in all at risk patients. Initiation of statin SESSION: THREE HOT DEBATES IN HIV therapy in HIV-infection requires additional clinical judgment due to the increase risk of CVD events and drug interactions. The cardiovascular S12 disease benefits of statins outweigh the risks of incident DM. Should we avoid protease inhibitors in first lines due to their lipid side References effects? - cons 1. Grundy SM, Cleeman JI, Merz CN, et al: National Heart, Lung, and Blood Hans-Jürgen Stellbrink Institute; American College of Cardiology Foundation American Heart Hospital of Hamburg, Infectious Diseases Department, Hamburg, Germany Association. Implications of recent clinical trials for the National BMC Infectious Diseases 2014, 14(Suppl 2):S12 Cholesterol Education Program Adult Treatment Panel III guidelines. Circulation 2004, 110(2):227-239. Treatment is medical risk management. In treatment decisions, the relative 2. Stone NJ, Robinson J, Lichtenstein AH, et al: Guideline on the treatment of risks of interventions have to be weighed against each other, with long- blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: A term irreversible untoward events being most important to avoid. report of the American College of Cardiology/American Heart Association Resistance development is such a deleterious long-term effect, especially Task Force on practice guidelines. Circulation 2013, Published on line. with lower adherence, as it reduces the numbers of options for successful 3. Law MG, Friis-Moller N, El-Sadr WM, et al: The use of Framingham equation long-term viral suppression. It is less frequent with PIs, even with lower to predict myocardial infarctions in HIV-infected patient: comparison with levels of adherence. Therefore, PIs are often used to in order to prevent observed events in the D:A:D Study. HIV Med 2006, 7:218-230. resistance development in settings in which it may otherwise arise. They 4. Triant VA, Lee H, Hadigan C, Grinspoon SK: Increased acute myocardial represent an attractive option for avoiding exposure to other drug classes infarction rates and cardiovascular risk factors among patients with with their associated toxicities, especially NRTIs, and thus are the backbone human immunodeficiency virus disease. J Clin Endocrinol Metab 2007, of most currently investigated alternative regimens. Lipid elevations are 92:2506-2512. common side effects of protease inhibitor therapy (PIs). Their relevance, BMC Infectious Diseases 2014, Volume 14 Suppl 2 Page 43 of 45 http://www.biomedcentral.com/bmcinfectdis/supplements/14/S2/

however, lies in their association with clinical events. Not all PIs lead to the regimen had a modest 31% efficacy at 42 months after vaccination, but same extent of lipid increase, and not all are associated with myocardial protection was as high as 60% at 6 months after vaccination. A series of infarction and stroke. Lipid elevations are reversible after switching to new trials is expected to take place in the near future to try to improve other regimens, and the associated risk is time-dependent, so that there these numbers using a more potent vector than canarypox, gp140 rather remains time to manage cardiovascular risk. Moreover, in the complex than gp120, a water-in-oil adjuvant rather than aluminium salts, and array of cardiovascular risk factors, lipid elevations are just one factor, with increasing the number of booster immunizations. Protection in the RV144 their relative contribution to risk increasing with age, and the absolute trial correlated with the induction of antibodies (Ab) to the V2 region of number of events being low at younger ages. There are numerous gp120, not with neutralizing Abs. A major difficulty met in the development promising interventions for reducing cardiovascular risk substantially (e.g. of an efficacious HIV vaccine has indeed been to design proper smoking cessation, physical activity, statins), so that avoiding lipid immunogens able to elicit broadly neutralizing Abs (bnAbs) that can elevations due to PIs should not be the primary concern. Long-term viral neutralize a wide range of circulating virus strains. BnAbs are highly suppression still remains the most important consideration for selecting protective, as demonstrated by passive immunization experiments and by antiretroviral drugs, as uncontrolled HIV replication remains the major vectored immunoprophylaxis experiments using AAV as a vector in animal threat to long-term health of an infected person. Therefore, despite a lot of models such as macaques or humanized mice. Their efficacy in humans other options, the high genetic barrier to resistance of PIs reserves them a should be tested soon in upcoming clinical trials. On another hand, the place in first-line therapy for many patients. report that monkeys immunized with a simian CMV-SIV vaccine can clear SIV infection following viral challenge has emphasized the importance of self- renewing, long-lasting memory TEM cells that can differentiate into specific S13 effector T cells and control provirus activation, eventually resulting in the Is ART suspension never a good idea? - Cons clearance of infection. A HIV vaccine that could elicit both a bnAb response Guido Poli and the formation of specific TEM cells would obviously be an ideal vaccine. Vita-Salute San Raffaele University, Milano, 20132, Italy ItmightevenofferhopesforacureofHIVinfectionwhenused BMC Infectious Diseases 2014, 14(Suppl 2):S13 therapeutically in HIV-infected persons. The development of such a vaccine is still long and difficult but may not to be an unrealistic goal. In the mid ‘90s tremendous progress has marked the pharmacological approach to HIV-1 disease, resulting in the almost complete reversal of the “death sentence” that was associated with the diagnosis of HIV SESSION: THE HCV REVOLUTION infection and AIDS. However, the terrific advantages of combination antiretroviral therapy (cART) are not available homogeneously on a global S15 scale, with the number of individuals becoming infected still outscoring New anti-HCV agents in the pipeline that of infected people starting treatment. Even restricting the analysis to Fabien Zoulim those countries, including Europe, where cART is largely available, there INSERM U1052, Hospices Civils de Lyon, University of Lyon 1, Lyon, 69000, are several considerations supporting the concept that therapy France suspension could still be considered in specific settings, and not only for BMC Infectious Diseases 2014, 14(Suppl 2):S15 facing the management of accumulation of multidrug resistant viral species or therapy-related side effects. In fact, some of the most novel Opportunities to treat infection with hepatitis C virus (HCV) are evolving and exciting novelties in the field of HIV research have arisen from rapidly. From the introduction of interferona monotherapy in the early examples of either casual or programmed therapy suspension. In the case 90s’ to the approval of telaprevir and boceprevir based triple therapies of the so-called “Mississippi Baby”, a newborn (from a mother with with pegylated interferona and ribavirin in 2011, the chances of curing undiagnosed AIDS until the time of delivery) was treated with cART patients infected with HCV genotype 1 have improved dramatically to shortly after delivery; nonetheless, she became unequivocally infected, reach approximately 70%. Significant further improvements, which may but seroreverted after a few weeks. Later, cART was suspended for cure virtually all hepatitis C patientswithanalloral,interferon-free unknown reasons, surprisingly resulting in the lack of virus rebound and regimen will become available in the very near future. These new direct HIV detectability by multiple testing, leading to the hypothesis that she acting antivirals (DAA) target the viral polymerase with either nucleoside might represent the second case of “cure” after Tymothy Ray Brown, the analogues or non nucleosidic inhibitors, the viral protease, and the viral “Berlin patient”. In a second example, adult French patients who started NS5A protein. Several clinical trials have now shown that a combination their antiretroviral regimens very early after primary HIV infection, of sofosbuvir (nucleosidic polymerase inhibitor) with daclatasvir or underwent therapy suspension after a few years resulting in an ledipasvir (NS5A inhibitors), or sofosbuvir with simeprevir (protease unexpected high frequency of spontaneous control of HIV-1 viremia and inhibitor), or a combination of ABT-450 (proease inhibitor) with ritonavir disease progression (Post-therapy controllers, or VISCONTI cohort). The (ABT-450/r), the nonnucleoside polymerase inhibitor ABT-333 and the likelihood that they might represent conventional spontaneous NS5A inhibitor ABT-267, can achieve sustained virologic response in up to controllers of disease progression, such as LTNP or Elite controllers, is 95% of naive patients or previously treated patients, even in patients minimal in that their genetic profile is enriched in the BW35 MHC allele who failed prior treatment with first generation protease inhibitor. As that is counterselected in these categories. In summary, without these these DAAs are becoming available in early access treatment programs, and other example of cART suspension our current understanding of the treatment strategy studies are being performed to optimize treatment potential opportunities to tilt the balance in favor of the host rather than regimens with respect to the choice of DAAs and treatment duration, of the virus would be more limited and perhaps would prevent future based on viral genotypes, prior treatment exposure, and the presence of strategic approaches to achieve long-term control of HIV infection with liver cirrhosis. The next challenge will be to identify HCV infected patients minimal side effects related to cART. in the general population and to facilitate access to treatment.

S14 S16 Is an HIV vaccine achievable? - Pros Treatment of hepatitis C in HIV patients in the new DAA era Marc Girard Vicente Soriano French National Academy of Medicine and Denis Diderot University, Paris, Department of Infectious Diseases, Hospital Carlos III, Madrid, Spain 75006, France BMC Infectious Diseases 2014, 14(Suppl 2):S16 BMC Infectious Diseases 2014, 14(Suppl 2):S14 Of 35 million people currently living with HIV worldwide, around 4 million The development of an HIV/ AIDS vaccine has been a long and difficult (12%) have chronic hepatitis C. Although intravenous drug users are endeavor, which so far was met with a great many failures. New, recent overepresented within the HIV-HCV coinfected population, recent advances may however change the deal. The RV144 clinical trial in outbreaks of acute hepatitis C among homosexual men highlight that Thailand showed that a canarypox-gp120 prime-boost vaccination HCV can also be transmitted efficiently by sex. Progression to cirrhosis, BMC Infectious Diseases 2014, Volume 14 Suppl 2 Page 44 of 45 http://www.biomedcentral.com/bmcinfectdis/supplements/14/S2/

liver insufficiency and hepatocellular carcinoma occurs in coinfected understood how virus becomes latent. In this study, we found that in a patients more rapidly than in HCV-monoinfected individuals. Therefore, subset of memory precursor CD4+ T cells, HIV-1 completes steps in the antiviral therapy for hepatitis C has become a priority in this population. life cycle through integration but has limited gene transcriptional activity. Classical therapy based on interferon provided low rates of HCV cure in HIV-1 preferentially establishes latent infection in this subset of CD4+ T the HIV setting. Although the advent of first generation direct-acting cells. Other CD4+ T cells are not latency permissive because they either antivirals boceprevir and telaprevir increased sustained virological block viral entry/reverse transcription, or support high level viral gene response rates, it was at the cost of a high rate of side effects and transcription. We also investigated how CD8+ T cells could affect HIV-1 significant drug interactions with antiretrovirals. latent infection. We found that viral-specific CTLs could effectively block The recent approval of sofosbuvir and simeprevir has revolutionized the or clear HIV-1 latent infection. Since immunodominant CTL responses in field, as these agents in combination with peginterferon-ribavirin provide acute infection have been identified as the major selection force driving high rates of cure without adding noticeable toxicity and drug the development of CTL escape mutations, we hypothesized that patient interactions and with shorter treatment duration. Moreover, sofosbuvir latent viruses should carry mutated epitopes which could not be plus ribavirin alone provides cure to most patients with HCV genotypes 2 recognized by immunodominant CTLs. In fact, we confirmed that the vast and 3. On the other hand, the combination of sofosbuvir plus simeprevir majority (>98%) of latent viruses carried CTL escape mutations that may cure most patients infected with HCV genotypes 1 or 4 ineligible for render the infected cells insensitive to immunodominant CTLs. To solve interferon. this critical problem, we identified CTLs that could recognize antigens All these unprecedent successes, however, are currently challenged by from latent HIV-1 that were unmutated in chronically infected patient. We the very high cost of these medications. Unless their price goes down or further demonstrated that these CTLs were able to eliminate target cells new oral anti-HCV agents expected to be approved soon (i.e., daclatasvir infected with autologous virus derived from the latent reservoir. The and/or faldaprevir) are marketed at lower prices, it is unlikely a rapid predominance of CTL-resistant viruses in the latent reservoir poses a widespread use of antiviral therapy for chronic hepatitis C in coinfected major challenge to viral eradication. Our results demonstrate that HIV-1 patients. The risk is further marginalization of groups and persons. establishes latent infection in memory precursor CD4+ T cells. Chronically infected patients retain a broad spectrum viral specific CTL response and that appropriate boosting of this response may be required for the S17 elimination of the latent reservoir. HCV cure without interferon Marc Bourlière Hepato-Gastroenterology Department, Saint Joseph Hospital, Marseille, S19 13285, France Gene therapy and bone marrow transplantation BMC Infectious Diseases 2014, 14(Suppl 2):S17 Jan Van Lunzen University Medical Center Hamburg-Eppendorf, Hamburg, Germany The launch of first-generation protease inhibitors (PIs) was a major step BMC Infectious Diseases 2014, 14(Suppl 2):S19 forward in HCV treatment. However, this major advance was restricted to genotype 1 (GT-1) patients. This year the launch of Sofosbuvir a NS5B Despite the tremendous advances in antiretroviral combination therapy nucleotide inhibitor (Nis), Daclatasvir a NS5A inhibitor (NS5A.I) and over the last decade, eradication of HIV from the infected organism is still Simeprevir a second wave PIs open new perspective for IFN-free regimen. an elusive goal. Lifelong therapy is associated with potential long-term Both Sofosbuvir and Daclatasvir have a pan-genotypic activity. Sofosbuvir toxicity, adherence problems, and development of drug resistance. Thus, has highly potent antiviral activity across all genotypes in association with gene therapy approaches targeting viral eradication are still attractive. pegylated interferon and ribavirin (PR), thus allowing shortened treatment Here a number of studies have failed to show a clear clinical benefit yet. duration. Moreover, Sofosbuvir in combination with Daclatasvir without Current approaches were mainly limited by a low number of transduced ribavirin for 12 weeks was able to cure > 95% of naïve GT-1 and for 24 cells and genotoxicity. The use of new vector systems and the right choice weeks was able to cure 40 patients with treatment experienced, failure to of target cells and improved transduction protocols may overcome these triple therapy with first generation PIs, GT-1 patients. Sofosbuvir in obstacles. Recent reports on the use of newly developed transgenes either combination with Simeprevir for 12 weeks without ribavirin was able to allowing for an enrichment of transduced cells by an in vivo selection cure all GT-1 naïve patients and over 90% of treatment experienced GT-1 advantage or restoration of a functional immune system which is resistant patients. As the three drugs have potent antiviral activities against GT-4, to HIV infection nourished the hope for continuous progress in this field. such association must be potent in such patient but data are pending. Indeed the intriguing finding that HIV seems to be eradicated in an For GT-2, Sofosbuvir and ribavirin for 12 weeks are able to cure > 90% of individual case study after stem cell transplantation with a mutant naïve and treatment-experienced patients. For GT-3 patients, Sofosbuvir coreceptor (CCR5 delta 32 deletion) underlines the proof of the concept. and ribavirin for 24 weeks are able to cure around 90% of naïve and treatment experienced patients with the exception of treatment- experienced cirrhotic patients in whom SVR is around 60%. However the SESSION: EMERGING INFECTIOUS combination of Sofosbuvir and Daclatasvir for 24 week leads to more than 90% SVR in the naïve GT-3 population and trials are on-going for DISEASES treatment-experienced patients. All this data confirmed that HCV can be cure with interferon–free regimen and short duration of treatment. Other S20 combination with higher efficacy and very good safety profile are under Hepatitis E development and should be available within two years. Harry Dalton Royal Cornwall Hospital, Truro, TR1 3LJ, UK BMC Infectious Diseases 2014, 14(Suppl 2):S20 SESSION: A CURE FOR HIV? Until recently, HEV was thought not to occur in developed countries such S18 as the UK, except in travellers returning from endemic areas. However, it Update on HIV reservoirs has now become clear that autochthonous (locally acquired) HEV is Liang Shan common in developed countries, and is considered an “emerging disease”. John Hopkins University, Baltimore, Maryland, 21218-2683, USA Autochthonous HEV has been documented in Europe, the USA, Canada, BMC Infectious Diseases 2014, 14(Suppl 2):S18 Japan, and New Zealand. HEV infection acquired in these areas differs from that in developing countries in a number of important aspects: it is caused The stable latent reservoir for HIV-1 in resting memory CD4+ T cells is a by genotype 3 (and 4 in China and Japan); it most commonly affects major barrier to curing HIV-1/AIDS. Studies on HIV-1 latency focused on middle-aged/elderly males; it is zoonotic with a porcine primary host. regulation and reactivation of viral gene expression in the cells in which Although pig herds worldwide are infected with HEV genotype 3, and HEV viral latent infection is already established. However, it is not well has been detected in retail meats in the human food chain in a number of BMC Infectious Diseases 2014, Volume 14 Suppl 2 Page 45 of 45 http://www.biomedcentral.com/bmcinfectdis/supplements/14/S2/

developed countries, the route of transmission is not fully understood mammals. In vitro investigations have shown that the recent A(H7N9) since most cases of autochthonous infection are not obviously associated outbreak in Eastern China is due to a virus that replicates as efficiently as with pigs or pig products. HEV has also been transmitted by blood human-adapted influenza viruses. WHO experts consider this virus as an transfusion in a number of countries, and surprisingly high numbers of imminent threat. asymptomatic blood donors are viraemic at the time of donation: Germany 1:1200, Netherlands 1:2671, England 1:7000 and Sweden 1:7986. Our understanding of the clinical range of HEV infection in humans has S22 undergone a sea-change in recent years. Until 2008, HEV was thought to MERS-CoV cause only acute self-limiting infection. However, it is now evident that Marcel A Müller HEV may cause persistent disease in immune-compromised solid organ Institute of Virology, University of Bonn Medical Center, Bonn, 53113, transplant recipients, individuals with HIV and patients with Germany haematological malignancy. Patients with chronic HEV infection have no BMC Infectious Diseases 2014, 14(Suppl 2):S22 symptoms, but some develop rapidly progressive liver cirrhosis. The full clinical spectrum of HEV in developed countries is still emerging. In 2002/03, a novel coronavirus (CoV) termed severe acute respiratory In Cornwall (UK), we have been studying the disease prospectively for syndrome (SARS)-CoV emerged in China and caused an epidemic in which over a decade, one of the longest studies of its type in a developed approximately 800 of 8000 cases died. Ten years later, a newly emerged country. HEV has important extra-hepatic manifestations, which deserve Middle East respiratory syndrome (MERS)-CoV has been confirmed in 189 further investigation. For example, we have shown that HEV is patients of which 82 had a fatal outcome. All MERS cases were linked to neuropathogenic, and can cause a wide range of neurological illness. In the Arabian Peninsula and to date thirteen cases were imported into the particular, very recent data suggests that Guillain-Barré syndrome and European Union and Africa. The clinical presentation resembles that of neuralgic amyotrophy are associated with locally acquired HEV in SARS-CoV as both viruses affect mainly the lower respiratory tract. As for approximately 5% and 10% of cases respectively. other mammalian CoV, bats harbor a high diversity of related viruses and are suspected to be the animal reservoir. Recent studies have revealed that dromedary camels are the most likely intermediate host. MERS-CoV has S21 been circulating in dromedary camels for decades raising the question H7N9 flu whether earlier human cases may have remained undetected. Preliminary Bruno Lina serological surveys in Saudi Arabia could not determine increased National Research Center on Influenza Virus, Hospices Civils of Lyon, Claude seroprevalence for MERS-CoV antibodies in the population. The possibility Bernard University, Lyon, France of human to human transmission has been demonstrated but is clearly BMC Infectious Diseases 2014, 14(Suppl 2):S21 limited. The dipeptidyl peptidase-4 (DPP4) was identified as a cellular receptor for MERS-CoV entry. DPP4 was found predominantly on non- Aquatic wild birds are the reservoir of more than 100 influenza viruses ciliated bronchial epithelial and alveolar cells in the lower parts of the whose subtypes (HxNy) have never been responsible for sustained infection lungs. This might explain the lack of secondary infections because in humans. As a matter of fact, humans are usually not infected by avian exposure to high doses of viruses may be necessary. In-vitro studies influenza A viruses. However, sporadic cases of avian influenza virus showed that MERS-CoV inhibited important cellular pathways in particular infection are observed every year, mostly in Asia. By subsequent adaptation the interferon (IFN) response. Confirmatory in-vivo experiments are still these emerging viruses may result into human pandemic strains. limited due to the lack of a suitable animal model. Non-human primates Recently, a novel influenza A virus of the H7N9 subtype has been isolated were shown to be susceptible but did not develop a disease to an extent from severely diseased patients with pneumonia and acute respiratory as humans. A combination of pegylated IFN-alpha and ribavirin improved distress syndrome and, apparently, from healthy poultry in March 2013 in the clinical symptoms confirming previous in-vitro experiments. The Eastern China. This virus is a result of a triple reassortment event that development of vaccines is ongoing and vaccination programs in occurred in wild birds. Transmission to humans occurred in wet markets, dromedary camels might be the optimal choice to control the current mostly in large cities like Shanghai. Only a very limited number of cases outbreak and prevent future re-introductions into the human population. have been observed out of China (Malasia, Tawain and Canada). As opposed to H5N1 that infect mostly children, most of the H7N9 cases were reported in adults and elderly people. As of the 7th of April, the death toll of this emergence is 30% (122/413). No human to human transmission has been reported so far. This lack of transmission cannot be explained by the virological features of the H7N9 strains that harbours Cite abstracts in this supplement using the relevant abstract number, most of the known markers required to facilitate transmission in e.g.: Müller: MERS-CoV. BMC Infectious Diseases 2014, 14(Suppl 2):S22