Welcome To The Thirty-Ninth Issue Of HIV This Week

HIV This Week: what scientific journals said

Welcome to the thirty-ninth issue of HIV This Week! In this issue, we cover sex work (two feminist Brazilian programmes empower sex workers to meet their sexual and reproductive health needs; self-treatment for sexually transmitted disease among sex workers in Tashkent, Uzbekistan is not without risk), living with HIV (placing people living with HIV in charge of their sexual health through sexual rights approaches), HIV testing (oral fluid HIV testing: what do sensitivity, specificity and the positive predictive value mean anyway?; late HIV diagnosis due to late testing among unsuspecting French citizens), politics of disease (governance and emerging infections; dietary intake among people living with HIV in Accra, Ghana is not just a matter for dieticians), basic science (how HIV hides out in the reservoirs and escapes control; anti-cholesterol statins for HIV suppression: what next?), post- exposure prophylaxis (Abidjan health care workers have trouble completing a full month of antiretroviral prophylaxis), pre-exposure prophylaxis (encouraging results of the first phase II trial among women in Cameroon, Ghana and Nigeria), treatment (barriers to adherence in five African countries; predicting adherence by evaluating patients’ perceptions of necessity and concerns about side effects; advantages of protease inhibitor-based regimens; training traditional healers to recognise oral manifestations of HIV), and mother-to-child transmission (achieving low transmission rates in Burkina Faso; measuring time to an undetectable viral load by regimen in European HIV-infected pregnant women: nevirapine based regimens are fastest).

To find out how you can access a majority of scientific journals free of charge, please see the last page of this issue or check the HIV This Week blog on the UNAIDS website at http://hivthisweek.unaids.org.

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Don’t forget that you can find a wealth of information on the HIV epidemic and responses to it at http://www.unaids.org.

Cate Hankins Tanya Lemay Chief Scientific Adviser Interim Research Officer

1. Sex work Chacham AS, Diniz SG, Maia MB, Galati AF, Mirim LA. Sexual and reproductive health needs of sex workers: two feminist projects in Brazil. Reprod Health Matters 2007;15:108-18. The sexual and reproductive health needs of sex workers have been neglected both in research and public health interventions, which have almost exclusively focused on STI/HIV prevention. Among the reasons for this are the condemnation, stigma, and ambiguous legal status of sex work. This paper describes work carried out by two feminist NGOs in Brazil,

UNAIDS_CSA-RO_HIVthisweek_39_071026 Mulher e Saude (MUSA) in Belo Horizonte and Coletivo Feminista Sexualidade e Saude in Sao Paulo, to promote sexual and reproductive health for sex workers. MUSA’s project “In the Battle for Health”, was begun in 1992; sex workers were trained as peer educators and workshops were offered on self-care for sex workers and their clients. In Sao Paulo, the Coletivo project “Get Friendly with Her”, begun in 2002, offers clinic consultations and self- care workshops on sexuality, contraception, STI/HIV prevention and self-examination. Health care needs during menstruation and unhealthy vaginal practices led to promotion of the diaphragm as a contraceptive, for prevention of reproductive tract infection and to catch menstrual blood. Meeting the sexual and reproductive health needs of sex workers depends on the promotion of their human rights, access to health care without discrimination, and attention to psychosocial health issues, alcohol and drug abuse, and violence from clients, partners, pimps, and police. Editors’ note: Promoting the sexual and reproductive health of sex workers falls on fertile ground when it takes a holistic approach that first and foremost respects the sex worker as a person with rights, needs, and strengths. Building the skills of peer counsellors, offering self-care training workshops, and addressing the broader concerns that preoccupy sex workers are among the building blocks for successful programmes. Alibayeva G, Todd CS, Khakimov MM, Giyasova GM, Botros BA, Carr JK, Bautista CT, Sanchez JL, Earhart KC. Sexually transmitted disease symptom management behaviours among female sex workers in Tashkent, Uzbekistan. Int J STD AIDS 2007 May;18:324-8.

The objective of this cross-sectional study was to assess prevalence and correlates of self- treatment of sexually transmitted diseases (STD) among female sex workers (FSW) in Tashkent, Uzbekistan. Enrolled FSW completed a self-administered questionnaire, HIV serologic testing and optional pelvic examination. STD diagnosis was based on physical examination and/or microscopic findings. Of 448 women, 337 (75.0%) accepted examination; of these, 316 (93.8%) received at least one STD-related diagnosis. Nearly half (45.4%) reported prior STD self-treatment, which was associated with HIV infection (age-adjusted odds ratio [AOR] = 3.20, 95% confidence interval [CI] = 1.45-7.53) and condom knowledge (AOR = 2.10, 95% CI = 1.16-3.80). For those with history of STD, immediate resumption of sex work before completing treatment was common (87.0%). STD self-treatment is common among FSW in Tashkent, particularly women with HIV infection. Confidential venues for STD care and condom utilization programmes targeted to FSW and their clients are needed to prevent STD in this setting. Editors’ note: Self treatment is common among sex workers worldwide when medications are available without a prescription, access to health care services is limited, or services themselves are unwelcoming. The association between self-care and HIV infection in this Uzbekistan study is intriguing – it may suggest missed opportunities for preventive care and counselling support – but self-care is also associated with condom knowledge. This speaks in favour of qualitative research to better understand these associations and action research engaging sex workers in programme design to better meet their sexual and reproductive health needs. 2. Living with HIV Shapiro K, Ray S. Sexual Health for People Living with HIV. Reprod Health Matters 2007;15:67-92 (supplement). Sexual health is defined in terms of well-being, but is challenged by the social, cultural and economic realities faced by women and men with HIV. A sexual rights approach puts women

UNAIDS_CSA-RO_HIVthisweek_39_071026 2 and men with HIV in charge of their sexual health. Accurate, accessible information to make informed choices and safe, pleasurable sexual relationships possible is best delivered through peer education and health professionals trained in empathetic approaches to sensitive issues. Young people with HIV especially need appropriate sex education and support for dealing with sexuality and self-identity with HIV. Women and men with HIV need condoms, appropriate services for sexually transmitted infections, sexual dysfunction and management of cervical and anogenital cancers. Interventions based on positive prevention, that combine protection of personal health with avoiding HIV/STI transmission to partners, are recommended. HIV counselling following a positive test has increased condom use and decreased coercive sex and outside sexual contacts among discordant couples. HIV treatment and care have reduced stigma and increased uptake of HIV testing and disclosure of positive status to partners. High adherence to antiretroviral therapy and safer sexual behaviour must go hand-in-hand. Sexual health services have worked with peer educators and volunteer groups to reach those at higher risk, such as sex workers. Technological advances in diagnosis of STIs, microbicide development and screening and vaccination for human papillomavirus must be available in developing countries and for those with the highest need globally. Editors’ note: The sexual health of people living with HIV may be poorly addressed by care providers who are uncomfortable with sexuality in general, let alone the sexuality of people living with HIV, despite the individual and community benefits of sexual health and positive prevention. Training is needed to ensure that education on condom use and appropriate medical care are provided in a context that acknowledges and promotes safe and enjoyable sexual relationships for people living with HIV. 3. HIV Testing Debattista J, Bryson G, Roudenko N, Dwyer J, Kelly M, Hogan P, Patten J. Pilot of non-invasive (oral fluid) testing for HIV within a clinical setting. Sex Health 2007;4:105-9. The objectives of the present study were: to determine the sensitivity and specificity of oral fluid testing compared with the performance of standard blood-based HIV enzyme immunoassay; to assess the feasibility of oral fluid specimen collection from clients for the purposes of HIV testing within a clinical setting; and to assess the clinical and laboratory impact regarding staffing, material resources, expertise and funding of oral fluid testing. A parallel comparative trial of oral fluid and blood testing was conducted among a group of HIV positive clients and a group of unknown HIV serostatus clients where each client was offered both tests. An ambulatory HIV clinic recruited 175 known HIV positive clients and 179 persons were recruited through an inner city sexual health clinic while attending for routine sexual health checks. Client responses to oral fluid collection were assessed. The sensitivity and specificity of oral fluid testing were calculated. Results revealed that, of the 176 confirmed HIV reactive blood test results, the OraSure (OraSure Technologies, Beaverton, OR, USA) assay failed to detect only one of these, demonstrating a sensitivity of 99.4%. Of the 178 blood specimens that were tested as non-reactive by the AxSYM (Abbott Laboratories, Abbott Park, IL, USA) Combo system, OraSure recorded four of the corresponding oral fluid specimens as reactive (assumed to be false-positive), giving a specificity of 97.6%. Although evaluation of patients undergoing the test showed a large proportion (88.6%) preferred the OraSure test to conventional blood testing, a large minority of these (22.6%) made such a preference conditional on the OraSure test being as reliable as current blood testing. In conclusion, this limited clinic based trial of oral fluid

UNAIDS_CSA-RO_HIVthisweek_39_071026 3 testing for HIV antibodies among an outpatient population has demonstrated the potential of oral fluid as a specimen for HIV testing. However, the lower performance of the test compared with current serum-based tests may limit the usefulness of OraSure to epidemiological studies or as an alternative screening tool in outreach settings among higher risk populations. Editors’ note: Sensitivity (ability of a test to recognise true positives) and specificity (ability of a test to correctly identify true negatives) are important test characteristics. They can be improved by use of a second test based on a slightly different principle. However, it is the positive predictive value that makes all the difference. A positive result on a test with the performance characteristics of the Orasure gingival exudate test will have a high positive predictive value (meaning that if it is positive it has a high likelihood of being a true positive) in a high HIV prevalence population but a low positive predictive value when HIV prevalence in a population is low. Delpierre C, Dray-Spira R, Cuzin L, Marchou B, Massip P, Lang T, Lert F; The VESPA Study Group. Correlates of late HIV diagnosis: implications for testing policy. Int J STD AIDS 2007;18:312-7. To develop new strategies aimed to reduce the delay in seeking HIV diagnosis, Delpierre and colleagues proposed to identify correlates of late diagnosis of HIV infection in France. Late testing was studied among the 1077 patients diagnosed from 1996 and enrolled in the ANRS- EN12-VESPA, a representative sample of the French HIV-infected population. Patients were defined as ‘late testers’ if they had presented either clinical AIDS events or CD4 cell count <200/mm(3) at diagnosis. In all, 33.1% were classified as late testers, among whom 42.6% had discovered their HIV infection at the time of AIDS events. This proportion increased with age and was higher for heterosexual men and migrants. Among the non-migrants heterosexual population, late diagnosis was more frequent among people in longstanding couples, with children and conversely was less likely among individuals with large number of sexual partners. Being on welfare benefit before diagnosis was associated with a lower risk of late diagnosis. Among migrants, lack of recent steady partnership was associated with an increased risk, as being diagnosed during the first year of stay in France. The authors results showed low risk factors of infection were risk factors of late testing. Public communication should aim at improving the awareness of HIV risk in longstanding couples with stable employment, both among homosexual and heterosexual populations. Among migrants, HIV testing with informed consent short after entry should be improved, especially towards individuals not in couples. Editors’ note: When HIV infection is not suspected by either the patient or the health care provider, late diagnosis and subsequent poorer prognosis may result. France is a low HIV prevalence country in which provider-initiated testing would normally be focused on patients with signs and symptoms of HIV, including tuberculosis; on patients seeking sexual and reproductive health care (e.g. for pregnancy, contraception, sexually transmitted disease); and on people recently arrived from high HIV prevalence settings (migrants or those who have been sexually active in those settings). This study supports the concept of ‘know your status’ campaigns where people have an opportunity to consider being tested for HIV as part of a general population programme. 4. Politics of disease Elizabeth M. Prescott. The Politics of Disease: Governance and Emerging Infections. Journal of Global Health Governance 2007 Jan;[online].

UNAIDS_CSA-RO_HIVthisweek_39_071026 4 http://diplomacy.shu.edu/academics/global_health/journal/PDF/Prescott-article.pdf Infectious disease outbreaks demand a timely and proportional response. The responsibility for this action falls to those with the power to harness the processes and systems by which a society operates in order to effect the changes necessary to limit transmission of an illness. Controlling emerging and re-emerging infectious diseases can require extreme actions and coordination between many national and international actors making the ability to respond a reflection of the capacity of a governing system. In the absence of good governance, opportunities are created for disease to emerge, while at the same time, an aggressive response is often hindered. Failures in governance in the face of infectious disease outbreaks can result in challenges to social cohesion, economic performance and political legitimacy. Overall, the need for coordination of actions despite a high degree of uncertainty and high costs makes curtailing infectious disease a challenge in the absence of good governance. Editors’ note: Whether speaking of an acute infectious disease outbreak or a chronic, endemic, eroding disease, it is clear that good governance, coordination, and harmonisation are the keys to an effective response. The Three Ones have relevance for far more than HIV! Wiig K, Smith C. An exploratory investigation of dietary intake and weight in human immunodeficiency virus-seropositive individuals in Accra, Ghana. J Am Diet Assoc 2007;107:1008-13. In Africa, the human immunodeficiency virus and acquired immunodeficiency syndrome complex is commonly referred to as “slim disease” because, as the disease progresses, food intake and metabolism are altered, leading to visible body weight loss. In this descriptive, cross-sectional pilot study, 50 HIV-seropositive adults attending the Korle Bu Teaching Hospital in Accra, Ghana, were interviewed during the late spring of 2003. Demographics, medical HIV history and current status of their HIV disease, food safety, and food security information were collected. One 24-hour dietary recall was completed, height and weight were measured, and body mass index (BMI) was calculated for each participant. Results show that women participants had a higher mean BMI and maintained it through disease progression compared with men (P<0.02). The majority of the participants cited cost as a barrier in purchasing adequate amounts of food (92%). Fruit and vegetable intake was low overall (

UNAIDS_CSA-RO_HIVthisweek_39_071026 5 Connick E, Mattila T, Folkvord JM, Schlichtemeier R, Meditz AL, Ray MG, McCarter MD, Mawhinney S, Hage A, White C, Skinner PJ. CTL Fail to Accumulate at Sites of HIV-1 Replication in Lymphoid Tissue. J Immunol 2007;178:6975-83. The inability of HIV-1-specific CTL to fully suppress virus replication as well as the failure of administration of exogenous CTL to lower viral loads are not understood. To evaluate the hypothesis that these phenomena are due to a failure of CTL to localize at sites of HIV-1 replication, Connick and colleagues assessed the distribution of HIV-1 RNA and HIV-1- specific CTL identified by HIV-1 peptide/HLA class I tetrameric complexes (tetramers) within lymph nodes of 14 HIV-1-infected individuals who were not receiving antiretroviral therapy. A median of 0.04% of follicular compared with 0.001% of extrafollicular CD4(+) cells were estimated to be producing HIV-1 RNA, a 40-fold difference (p = 0.0001). Tetramer-stained cells were detected by flow cytometry in disaggregated lymph node cells from 11 subjects and constituted a significantly higher fraction of CD8(+) cells in lymph node (mean, 2.15%) than in PBMC (mean, 1.52%; p = 0.02). In situ tetramer staining in three subjects’ lymph nodes, in which high frequencies of tetramer-stained cells were detected, revealed that tetramer-stained cells were primarily concentrated in extrafollicular regions of lymph node and were largely absent within lymphoid follicles. These data confirm that HIV-1-specific CTL are abundant within lymphoid tissues, but fail to accumulate within lymphoid follicles where HIV-1 replication is concentrated, suggesting that lymphoid follicles may be immune-privileged sites. Mechanisms underlying the exclusion of CTL from lymphoid follicles as well as the role of lymphoid follicles in perpetuating other chronic pathogens merit further investigation. Editors’ note: This work takes us one step further to understanding how HIV finds a safe harbour in reservoirs within lymph nodes. For reasons that remain unknown, the human foot soldiers - cytotoxic lymphocytes - don’t penetrate the lymphoid follicles where HIV is amassing its armies. Nabatov AA, Pollakis G, Linnemann T, Paxton WA, de Baar MP. Statins Disrupt CCR5 and RANTES Expression Levels in CD4 T Lymphocytes In Vitro and Preferentially Decrease Infection of R5 Versus X4 HIV-1. PLoS ONE 2007;2:e470. Statins have previously been shown to reduce the in vitro infection of human immunodeficiency virus type 1 (HIV-1) through modulation of Rho GTPase activity and lipid raft formation at the cell surface, as well as by disrupting LFA-1 incorporation into viral particles. Here Nabatov and colleagues demonstrate that treatment of an enriched CD4(+) lymphocyte population with lovastatin (Lov), mevastatin (Mev) and simvastatin (activated and non-activated, Sim(A) and Sim(N), respectively) can reduce the cell surface expression of the CC-chemokine receptor CCR5 (P<0.01 for Sim(A) and Lov). The lowered CCR5 expression was associated with down-regulation of CCR5 mRNA expression. The CC-chemokine RANTES protein and mRNA expression levels were slightly increased in CD4(+) enriched lymphocytes treated with statins. Both R5 and X4 HIV-1 were reduced for their infection of statin- treated cells; however, in cultures where statins were removed and where a decrease in CCR5 expression was observed, there was a preferential inhibition of infection with an R5 versus X4 virus. In conclusion, the results indicate that the modulation of CC-chemokine receptor (CCR5) and CC-chemokine (RANTES) expression levels should be considered as contributing to the anti-viral effects of statins, preferentially inhibiting R5 viruses. This observation, in combination with the immuno-modulatory activity exerted by statins, suggests they may possess more potent anti-HIV-1 activity when applied during the early stages of infection or in lowering viral transmission. Alternatively, statin treatment could be

UNAIDS_CSA-RO_HIVthisweek_39_071026 6 considered as a way to modulate immune induction such as during vaccination protocols. Editors’ note: These are ‘early days’ for statins, the well known anti-cholesterol drug class, as potential HIV treatment candidates. They may have both anti-viral and immuno-modulatory effects but so far these are all in vitro findings, meaning in the laboratory, as opposed to in vivo findings in human subjects. 6. Post-exposure prophylaxis Ehui E, Kra O, Ouattara I, Eholie S, Kakou A, Bissagnene E, Kadio A. [Management of accidental exposure to blood in the Treichville teaching hospital, Abidjan (Cote-d’Ivoire).] [Article in French] Med Mal Infect 2007 May 16; [Epub ahead of print] – still The aim of this study was to assess care and preventive measures for accidental exposure to blood (AEB) in Abidjan. A retrospective study of all AEB reported in the Infectious and Tropical Diseases Center of the Treichville University Hospital was made between January 2000 and December 2005. Epidemiology, management, clinical and biological post-exposure follow-up were analyzed. Results revealed that one hundred eighty-two accidental exposures to blood were managed over 6 years (151 needlesticks, 14 ocular projections of blood, 12 cuts, and 5 mucocutaneous exposures to blood). 94 men (51.6%) and 68 women (48.4%) were included [sex ratio 1.4] mean age 33.8 years+/-7.4 years. Physicians (29.1%), nurses (19.8%), assistant nurse (12.1%), and medical students (11.4%) were the professional categories which declared most accidents. Among them, only 51.1% was correctly vaccinated against hepatitis B. The average delay of consultation was 26.5 hours (1-240 hours), and 82.9% of victims consulted before the 48 th hour. Antiretroviral prophylaxis was prescribed to 151 patients among whom 45% with bi-therapy (Zidovudine and Lamivudine), and 55% with HAART including an anti-protease. Only 60 patients had one actual month of treatment. Despite the weak follow-up, no case of HIV seroconversion was reported 6 months after exposure. In conclusion, this work underlines once again the high frequency of AEB in Abidjan despite under reporting, and calls for the implementation of a policy to train health care workers on AEB preventive measures. Editors’ note: Completing a full month of post-exposure prophylaxis can be a challenge even when medication is provided free of charge to health care workers who understand well the rationale. Side effects can deter many from the full course. As found elsewhere in the world, only half of these health care workers were adequately immunized against hepatitis B - a disease for which a good vaccine exists and which they are much more likely to encounter in their daily work through blood and body fluid exposures. 7. Pre-exposure prophylaxis Peterson L, Taylor D, Roddy R, Belai G, Phillips P, Nanda K, Grant R, Clarke EE, Doh AS, Ridzon R, Jaffe HS, Cates W. Tenofovir Disoproxil Fumarate for Prevention of HIV Infection in Women: A Phase 2, Double-Blind, Randomized, Placebo-Controlled Trial. PLoS Clin Trials 2007;2:e27. The objective of this trial was to investigate the safety and preliminary effectiveness of a daily dose of 300 mg of tenofovir disoproxil fumarate (TDF) versus placebo in preventing HIV infection in women. This was a phase 2, randomized, double-blind, placebo-controlled trial. The study was conducted between June 2004 and March 2006 in Tema, Ghana; Douala, Cameroon; and Ibadan, Nigeria. Peterson and colleagues enrolled 936 HIV-negative women at high risk of HIV infection into this study. Participants were randomized 1:1 to once daily use of 300 mg of TDF or placebo. The primary safety endpoints were grade 2 or higher serum

UNAIDS_CSA-RO_HIVthisweek_39_071026 7 creatinine elevations (>2.0 mg/dl) for renal function, grade 3 or 4 aspartate aminotransferase or alanine aminotransferase elevations (>170 U/l) for hepatic function, and grade 3 or 4 phosphorus abnormalities (<1.5 mg/dl). The effectiveness endpoint was infection with HIV-1 or HIV-2. Results revealed that study participants contributed 428 person-years of laboratory testing to the primary safety analysis. No significant differences emerged between treatment groups in clinical or laboratory safety outcomes. Study participants contributed 476 person-years of HIV testing to the primary effectiveness analysis, during which time eight seroconversions occurred. Two were diagnosed in participants randomized to TDF (0.86 per 100 person-years) and six in participants receiving placebo (2.48 per 100 person-years), yielding a rate ratio of 0.35 (95% confidence interval = 0.03-1.93), which did not achieve statistical significance. Owing to premature closures of the Cameroon and Nigeria study sites, the planned person-years of follow-up and study power could not be achieved. In conclusion, daily oral use of TDF in HIV-uninfected women was not associated with increased clinical or laboratory adverse events. Effectiveness could not be conclusively evaluated because of the small number of HIV infections observed during the study. Editors’ note: You may remember the controversy over the Cameroon site of this trial – the President halted the study. Despite this, encouraging safety results have been obtained in this first Phase II trial of pre-exposure prophylaxis to be completed. Tenofovir (TDF) 300 mg once daily did not induce excessive kidney, liver or bone metabolism abnormalities. With the restricted number of participants lowering the power of the study, preliminary indications of a protective effect were not possible. 8. Treatment Mouala C, Roux P, Okome M, Sentenac S, Okome F, Nziengui U, Olivier F, Benjaber K, Rey JL. [Assessment of compliance with ARV treatment in Africa] [Article in French] Med Trop (Mars) 2006;66:610-4. This study was conducted in health facilities in the capitals of five sub-Saharan African countries (Cotonou, Benin; Bangui, Central African Republic; Libreville, Gabon; Yaounde, Cameroon; and Casablanca, Morocco). The purpose was to investigate factors promoting and impeding compliance with antiretroviral therapy (ART) and cotrimoxazole (CTX) prophylaxis in adult patients. Patients were interviewed immediately after follow-up examination to identify the problems that they encountered and the solutions that they proposed to improve compliance. Compliance was assessed based on three measurement modalities, i.e. skipping medication during the four days prior to attendance, counting the number of remaining tablets, and attendance assiduity. Compliance scores varied according to measurement modality from 65% to 90%. All patients underlined the impact of treatment on their daily life and the difficulty of following the prescribed regimen properly. Impeding factors for compliance were treatment-related hunger, lack of information, out-of-pocket expenses (including laboratory tests, transportation, and loss of income), side effects, long waiting time at the treatment centres, and fear of stigma and discrimination. Efforts to increase access to treatment can only be successful if accompanied by measures to promote compliance. Editors’ note: In English, the term ‘adherence’, implying a patient-provider partnership to make treatment work, is used in preference to ‘compliance’ which has a connotation of rules to be obeyed. This 5 country study reveals that adherence can be affected by multiple barriers, including financial, logistical, and social ones. The shared challenge is to find ways to overcome these, in the interest of optimal treatment

UNAIDS_CSA-RO_HIVthisweek_39_071026 8 outcomes for individuals, less drug resistance in the community, and improved treatment access for all those in need. Horne R, Cooper V, Gellaitry G, Date HL, Fisher M. Patients’ Perceptions of Highly Active Antiretroviral Therapy in Relation to Treatment Uptake and Adherence: The Utility of the Necessity-Concerns Framework. J Acquir Immune Defic Syndr 2007 Jul 1;45(3):334-41. Horne and colleagues’ objective was to test the utility of the necessity-concerns framework in predicting highly active antiretroviral therapy (HAART) uptake and adherence. This was a prospective follow-up study. Consecutive patients who were not currently receiving HAART were referred by their HIV physician. Immediately after a recommendation of HAART, patients completed the Beliefs about Medicines Questionnaire assessing their perceptions of personal necessity for HAART and concerns about potential adverse effects. The influence of these beliefs on the decision to accept or decline HAART and adherence 12 months later were assessed. Results revealed that one hundred fifty-three participants were given a recommendation of HAART, and 136 (88.9%) returned completed questionnaires. Thirty- eight participants (28%) initially rejected the treatment offer. Uptake of HAART was associated with perceptions of personal necessity for treatment (odds ratio [OR] = 7.41, 95% confidence interval [CI]: 2.84 to 19.37) and concerns about potential adverse effects (OR = 0.19, 95% CI: 0.07 to 0.48). There was a significant decline in adherence over time. Perceived necessity (OR = 2.19, 95% CI: 1.02 to 4.71) and concerns about adverse effects (OR = 0.45, 95% CI: 0.22 to 0.96), elicited before initiating HAART, predicted subsequent adherence. These associations were independent of clinical variables and depression. In conclusion, the necessity-concerns framework is a useful theoretic model for understanding patient perspectives of HAART and predicting uptake and adherence, with implications for the design of evidence-based interventions. Editors’ note: If finances, logistics, and social concerns are not major barriers to treatment adherence, then factors such as whether a wo/man thinks s/he needs treatment or is worried about side effects can predict who may need additional support to achieve optimal adherence. Walmsley S. Protease Inhibitor-Based Regimens for HIV Therapy: Safety and Efficacy. J Acquir Immune Defic Syndr 2007;45 Suppl 1:S5-S13. Antiretroviral (ARV) treatment strategies for HIV-infected patients continue to evolve. Over the past few years, there was a shift towards the use of non-nucleoside reverse transcriptase inhibitor-based regimens, mostly because of better tolerability, a lower pill burden, and improved adherence relative to using protease inhibitor (PI)-based regimens. Although the 2 strategies do afford similar potency and durability, the PI-based regimens provide a higher genetic barrier to the development of ARV resistance. This has become progressively more important for reasons that include increasing rates of baseline ARV resistance in newly infected patients and the risk of developing ARV resistance in treated populations with suboptimal adherence. With the introduction of novel ARVs and reformulated agents with more convenient dosing requirements, improved tolerability, and unique resistance characteristics, boosted PI-based strategies are increasingly being considered when initiating therapy in ARV-naive patients. In this article, the evidence for the use of boosted PIs as early therapy is reviewed, with emphasis on data available from comparative randomized controlled trials. Editors’ note: The boosted protease inhibitor- based strategies described in this overview of trends in treatment are not recommended by the World Health Organisation for initiating therapy as first line choices in low- and

UNAIDS_CSA-RO_HIVthisweek_39_071026 9 middle-income countries – they are reserved for second line. However, it is encouraging to learn that tolerability is improving and dosing requirements are becoming more convenient – characteristics that are important in either case. Rudolph MJ, Ogunbodede EO, Mistry M. Management of the oral manifestations of HIV/AIDS by traditional healers and care givers. Curationis. 2007;30:56-61. In many communities of South Africa, traditional healers are often the only means of health care delivery available. The level of knowledge and ability to recognize oral lesions of 32 traditional healers and 17 care-givers were assessed after a two-day workshop. The data collection instrument was a structured questionnaire, complimented by enlarged clinical photographs of the common oral manifestations of HIV related disease. Prior to the workshop, 46 (93.9%) of the 49 respondents had never had any formal information on oral health and 43 (87.8%) were unfamiliar with the symptoms of oral diseases. Thirty-five (71.4%) recognized bleeding gums from A4-size photographs and 11 (22.4%) recognized oral thrush. The recognition of other oral manifestations of HIV/AIDS were; oral hairy leukoplakia (41.0%), angular cheilitis (43.6%), herpes virus infection (56.4%), oral ulcerations (56.8%), and in children, parotid enlargement (27.3%), and moluscum contagiosum (56.8%). Traditional healers and caregivers constitute an untapped resource with enormous potential. A positive bridge should be built to link traditional healing with modern medicine in the struggle against AIDS. Editors’ note: Training traditional healers alongside other care givers in the recognition and diagnosis of diseases of the mouth associated with HIV infection, combined with active referral pathways for HIV testing, treatment of oral diseases, and HIV care and support would help fill a gap in human resources for health in South Africa and other high HIV prevalence countries. 9. Mother-to-child transmission Simpore J, Pietra V, Pignatelli S, Karou D, Nadembega WM, Ilboudo D, Ceccherini-Silberstein F, Ghilat-Avoid-Belem WN, Bellocchi MC, Saleri N, Sanou MJ, Ouedraogo CM, Nikiema JB, Colizzi V, Perno CP, Castelli F, Musumeci S. Effective program against mother-to-child transmission of HIV at Saint Camille Medical Centre in Burkina Faso. J Med Virol 2007;79:873- 9. The present research was aimed to prevent mother-to-child transmission of HIV; to use RT- PCR in order to detect, 6 months after birth, infected children; and to test the antiretroviral resistance of both children and mothers in order to offer them a suitable therapy. At the Saint Camille Medical Centre, 3,127 pregnant women (aged 15-44 years) accepted to be enrolled in the mother-to-child transmission prevention protocol that envisages: (i) Voluntary Counselling and Testing for all the pregnant women; (ii) Antiretroviral therapy for HIV positive pregnant women and for their newborns; (iii) either powdered milk feeding or short breast-feeding and RT-PCR test for their children; (iv) finally, pol gene sequencing and antiretroviral resistance identification among HIV positive mothers and children. Among the patients, 227/3,127 HIV seropositive women were found: 221/227 HIV- 1, 4/227 HIV-2, and 2/227 mixed HIV infections. The RT-PCR test allowed the detection of 3/213 (1.4%) HIV infected children: 0/109 (0%) from mothers under ARV therapy and 3/104 (2.8%) from mothers treated with Nevirapine. All children had recombinant HIV-1 strain (CRF06_CPX) with: minor PR mutations (M36I, K20I) and RT mutations (R211K). Among them, two twins had Non-Nucleoside Reverse Transcriptase Inhibitor mutation (Y18CY). Both mothers acquired a major PR mutation (V8IV), investigated 6 months after a single-dose of

UNAIDS_CSA-RO_HIVthisweek_39_071026 10 Nevirapine. Prevention by single-dose of Nevirapine reduced significantly mother-to-child transmission of HIV, but caused many mutations and resistance to antiretroviral drugs. Based on present study the antiretroviral therapy protocol, together with the artificial- feeding, might represent the ideal strategy to avoid transmission of HIV from mother-to- child. Editors’ note: Not having to wait into the second year of life to know whether your baby is infected or not is a great advantage for parents. Using two or more antiretroviral drugs for prophylaxis clearly reduces both HIV transmission and the risk of drug resistance in the mother and baby but success in rolling out single drug programmes remains elusive. It is also clear that breast milk replacement with milk powder can save lives only if sustainable access to milk powder can be ensured, the water supply is safe, and equipment is not contaminated. A better alternative if equipment is available is heat treating breast milk. European Collaborative Study; Patel D, Cortina-Borja M, Thorne C, Newell ML. Time to undetectable viral load after highly active antiretroviral therapy initiation among HIV-infected pregnant women. Clin Infect Dis 2007;44:1647-56. There have been no clinical trials in resource-rich regions that have addressed the question of which highly active antiretroviral therapy (HAART) regimens are more effective for optimal viral response in antiretroviral-naive, human immunodeficiency virus (HIV)-infected pregnant women. Data on 240 HIV-1-infected women starting HAART during pregnancy who were enrolled in the prospective European Collaborative Study from 1997 through 2004 were analyzed. An interval-censored survival model was used to assess whether factors, including type of HAART regimen, race, region of birth, and baseline immunological and virological status, were associated with the duration of time necessary to suppress viral load below undetectable levels before delivery of a newborn. Result revealed that protease inhibitor- based HAART was initiated in 156 women (65%), 125 (80%) of whom received nelfinavir, and a nevirapine-based regimen was initiated in the remaining 84 women (35%). Undetectable viral loads were achieved by 73% of the women by the time of delivery. Relative hazards of time to achieving viral suppression were 1.54 (95% confidence interval, 1.05-2.26) for nevirapine-based HAART versus PI-based regimens and 1.90 (95% confidence interval, 1.16- 3.12) for western African versus non-African women. The median duration of time from HAART initiation to achievement of an undetectable viral load was estimated to be 1.4 times greater in women receiving PI-based HAART, compared with women receiving nevirapine- based HAART. Baseline HIV RNA load was also a significant predictor of the rapidity of achieving viral suppression by delivery, but baseline immune status was not. The authors of this study concluded that nevirapine-based HAART (compared with PI [mainly nelfinavir]- based HAART), western African origin, and lower baseline viral load were associated with shorter time to achieving viral suppression. Editors’ note: Knowing which regimen is most effective in achieving an undetectable viral load by delivery seems like such a basic, essential question to answer. Almost three quarters of the women in this study had undetectable viral loads by the time of delivery, with nevirapine based treatment acting more quickly than the protease inhibitor-based regimens.

That was HIV This Week, signing off.

Editors’ notes on journal access

UNAIDS_CSA-RO_HIVthisweek_39_071026 11 For readers in all countries: All abstracts in HIV This Week are freely available on the Web.

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For employees of UNAIDS or WHO: If you work for WHO or UNAIDS, you can access a number of journals by going to the WHO library. You can also see the full list of journals you can access freely on the web (including usernames and passwords) by going to the WHO Library website, accessible through the home page of WHO intranet https://intranet.who.int/ under Information Resources. If you work for UNAIDS, HIV This Week is also available on the intranet at the link https://intranet.unaids.org/HIVThisWeek/2007/index.htm.

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