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Oral Abstracts of the 21St International AIDS Conference 18–22

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Oral Abstracts of the 21St International AIDS Conference 18–22 ONLINE ONLINE OPEN PEER-REVIEWD PEER-REVIEWD ONLINE A PEER-REVIEWD OPEN ACCESS OPEN HIV/AIDS JOURNAL HIV/AIDS JOURNAL CCESS ONLINEONLINE CCESS A OPEN OPEN PEER-REVIEWD ONLINE HIV/AIDS JOURNAL HIV/AIDS HIV/AIDS JOURNAL PEER-REVIEWD PEER-REVIEWD OPEN ACCESSONLINEPEER-REVIEWD A ONLINEPEER-REVIEWD CCESS HIV/AIDS JOURNALPEER-REVIEWD OPEN ACCESS CCESS A OPEN ONLINE ONLINE HIV/AIDS JOURNAL ONLINE PEER-REVIEWDHIV/AIDS JOURNALONLINEONLINE PEER-REVIEWDOPEN ACCESS PEER-REVIEWD ONLINE ONLINE OPEN ACCESSONLINE OPEN HIV/AIDS JOURNAL CCESS OPEN ACCESS HIV/AIDS JOURNAL PEER-REVIEWD PEER-REVIEWD PEER-REVIEWD HIV/AIDS JOURNAL PEER-REVIEWD A HIV/AIDS JOURNAL OPEN ACCESS PEER-REVIEWD PEER-REVIEWD PEER-REVIEWDONLINE HIV/AIDS JOURNAL HIV/AIDS JOURNAL OPEN ACCESS ONLINE ONLINEONLINE HIV/AIDS JOURNAL HIV/AIDS PEER-REVIEWD A PEER-REVIEWD ONLINE ONLINE HIV/AIDS JOURNAL CCESS HIV/AIDS JOURNALOPEN ONLINE PEER-REVIEWDONLINE PEER-REVIEWD HIV/AIDS JOURNAL OPEN PEER-REVIEWDJOURNAL HIV/AIDS HIV/AIDS JOURNAL HIV/AIDS JOURNAL CCESS ONLINE A A ONLINE OPEN ACCESS HIV/AIDS JOURNAL ONLINE HIV/AIDS JOURNAL CCESS PEER-REVIEWD OPEN ACCESS HIV/AIDS JOURNAL OPEN ACCESS ONLINE HIV/AIDS JOURNAL HIV/AIDS ONLINE OPEN OPEN ACCESS HIV/AIDS JOURNAL PEER-REVIEWD OPEN HIV/AIDS JOURNALPEER-REVIEWD PEER-REVIEWD OPEN ACCESS PEER-REVIEWD CCESS A OPEN PEER-REVIEWDONLINE PEER-REVIEWD PEER-REVIEWD HIV/AIDS JOURNALAbstractHIV/AIDS JOURNAL SupplementHIV/AIDS JOURNAL PEER-REVIEWD OPEN ACCESS CCESS PEER-REVIEWD A PEER-REVIEWD Oral abstracts of the 21st International AIDS Conference A CCESS OPEN ACCESS 18–22 July 2016, Durban, South Africa OPEN HIV/AIDS JOURNAL Volume 19, Supplement 5 Scan this QR code with your mobile device to view July 2016 the special issue online 21st International AIDS Conference Abstract Supplement Journal of the International AIDS Society 2016, 19 (Suppl 5) http://www.jiasociety.org/index.php/jias/article/view/21264 | http://dx.doi.org/10.7448/IAS.19.6.21264 ORAL ABSTRACTS TUAA0101 CXu1;THe1; G Haret-Richter1; D Franck2; B Policicchio1; E Brocca-Cofano1;DMa1; J Stock1; R Tracy3; A Landay4; C Wilson2; Microbial translocation during hyperacute SIV infection 1 1 1,2 3 3 4 5 C Apetrei and I Pandrea A Ericsen ; M Lauck ; M Mohns ; S Dinapoli ; J Mutschler ; 1 3 1 5 5 5 Center for Vaccine Research, University of Pittsburgh, Pittsburgh, PA, J Greene ; J Weinfurter ; G Lehrer-Brey ; K Crosno ; E Peterson ; 2 1 1 6,7 6,7 5,8 United States. University of Colorado, Denver, CO, United States. M Reynolds ; R Wiseman ; B Burwitz ; J Sacha ; T Friedrich ; 3 4 J Brenchley4 and D O’Connor1,5 University of Vermont, Burlington, VT, United States. Rush University, Chicago, IL, United States 1Department of Pathology and Laboratory Medicine, University of Presenting author email: [email protected] Wisconsin-Madison, Madison, WI, United States. 2Virology Training Program, University of Wisconsin-Madison, Madison, WI, United Introduction: High dietary fats were reported to induce intestinal States. 3University of Wisconsin-Madison, Madison, WI, United dysbiosis, drive gut inflammation and breakdown the intestinal States. 4Laboratory of Molecular Microbiology, National Institute of epithelial barrier, granting intestinal flora access to the bloodstream. Allergy and Infectious Disease, Bethesda, MD, United States. As microbial translocation is a major determinant of the chronic 5Wisconsin National Primate Research Center, Madison, WI, United immune activation and HIV/SIV disease progression, we investigated States. 6Vaccine & Gene Therapy Institute, Oregon Health & Sciences whether fat diet impacts HIV/SIV pathogenesis. University, Beaverton, OR, United States. 7National Primate Research Methods: The non-progressive African green monkey (AGM) model Center, Oregon Health & Sciences University, Beaverton, OR, of SIV is an ideal system to assess the role of fat diet on disease United States. 8Department of Pathobiological Sciences, University progression, because they do not develop SIV-related intestinal of Wisconsin-Madison, Madison, WI, United States dysfunction. We included four AGMs that received a fat diet prior Presenting author email: [email protected] and after SIVsab infection, and five controls in which the impact on key parameters of SIV infection such as: viral loads, CD4+ T cell Introduction: Within the first weeks of human immunodeficiency counts, microbial translocation, immune activation and inflammation virus (HIV) infection, virus replication reaches systemic circulation. were compared and contrasted. Despite the critical, causal role of virus replication in determining Results: LPS levels increased in the AGMs receiving fat diet prior and transmissibility and kinetics of disease progression, there is limited after SIV infection. Fat-rich diet also resulted in increases of immune understanding of the conditions required to transform a small activation (HLA-DR CD38, CD69 and Ki-67) and inflammation localized transmitted founder population into a large and hetero- (inflammatory cytokines-IL-6, IL-17 and C reactive protein), leading geneous systemic infection. to a prolonged depletion of CD4+ T cells compared to controls. Methods: Cynomolgus and rhesus macaques were infected with However, these significant alterations of key parameters that are simian immunodeficiency virus (SIV) and followed longitudinally. associated with the lack of disease progression in natural hosts of Plasma levels of SIV were monitored using qRT-PCR. Bacterial genomic SIVs did not reach the levels described during progressive HIV/SIV DNA in plasma was characterized and quantified longitudinally using infection. Furthermore, these changes did not result in significant 16S ribosomal deep sequencing and qPCR. ELISA-based assays were increases in the levels of viral replication in the AGMs receiving a used to monitor intestinal permeability (IFABP) and perturbation of fat diet. bacteria-specific host factors (sCD14 and EndoCab). Flow cytometry Conclusions: Administration of fat-rich diet resulted in alterations of was used to track peripheral blood lymphocyte populations. In vitro markers of pathogenicity in the non-progressive SIV infection of assays were performed by exposing freshly isolated peripheral blood AGMs. Although not major, these changes were significant, suggest- mononuclear cells to bacterial lysate prepared from major transloca- ing that a diet very rich in fats may negatively impact HIV tors. Effects of bacterial lysate on CD4 T cell activation and CD8 T pathogenesis, especially if combined with other behavioural risk cell cytotoxicity were measured using flow cytometry. Statistical signi- factors reported to impact gut integrity or systemic inflammation, ficance was calculated using ANOVA or Wilcoxon signed-rank testing. such as alcohol consumption, drug usage and smoking. Detailed Results: Prior to the peak of viremia, we observed a transient high- studies on the correlations between fat diet, alterations in the level influx of microbial genomic DNA into peripheral blood. intestinal microbiota, metabolic markers, liver function and SIV This microbial translocation was accompanied by perturbation of progression to AIDS are in progress. bacteria-specific host factors in plasma, as well as expansion of the CD4CCR5 T cell compartment. Exposure of freshly isolated peripheral blood mononuclear cells to lysate prepared from major translocating taxa revealed differential taxa-specific effects on the TUAA0103 CD4CCR5 T cell compartment and cytotoxic granule expression HIV infection is associated with preservation of MAIT cells within CD8 T cells. Conclusions: Altogether, our data identify the influx of microbial in the lungs but alteration of their phenotype and T cell products into blood during hyperacute SIV infection as a candidate receptor repertoire modifier of early interactions between the antiviral host response EB Wong1,2,3; B Xulu1; S Prakadan4,5; AK Shalek4,5,6,7; U Lalloo8; and nascent HIV infection. Over the next few months, we will P Baijnath9,10; M Suleman10; V Moodley10; M Mitha10; P Maharaj10; explore the effect of inducing microbial translocation during SIV C Costiniuk11; M Nielsen12; Z Mhlane1; F Karim1; D Lewinsohn13 and infection, with particular interest on microbial reactivity within the T Ndung’u1,5,14 CD4CCR5 target cell compartment. 1KwaZulu Natal Research Institute for Tuberculosis and HIV, Durban, South Africa. 2Division of Infectious Diseases, Massachusetts General Hospital, Boston, MA, United States. 3Department of Medicine, TUAA0102 Harvard Medical School, Boston, MA, United States. 4Institute for Impact of a fat-rich diet on the pathogenesis of SIV infection Medical Engineering & Science, Massachusetts Institute of in the African green monkey host Technology, Cambridge, MA, United States. 5Department of 1 21st International AIDS Conference Abstract Supplement Journal of the International AIDS Society 2016, 19 (Suppl 5) http://www.jiasociety.org/index.php/jias/article/view/21264 | http://dx.doi.org/10.7448/IAS.19.6.21264 Oral Abstracts Chemistry, Massachusetts Institute of Technology, Cambridge, MA, Introduction: For the improved design of strategies towards HIV-1 United States. 6Ragon Institute of Harvard, MGH and MIT, functional cure, it is important to identify biomarkers that could Cambridge, MA, United States. 7Broad Institute, Cambridge, MA, predict the duration of post-treatment virological control. United States. 8Durban University of Technology, Durban, South Methods: We studied 46 patients that received 24 or 60 weeks Africa. 9Department of Pulmonology
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