HIV This Week

Welcome to the sixty-first issue of HIV This Week !  In this issue, we cover cost-effectiveness (contraception is still the best kept HIV prevention secret; strikingly optimistic scale-up of male circumcision in 5 years to 85% prevalence sidesteps provider-initiated HIV testing ) , biomedical prevention trials (what happened in the STEP vaccine trial?, what happened in the cellulose sulfate (Ushercell) microbicide trial?), non-biomedical HIV prevention trials (promising behavioural results in a combined microfinance and training trial in South Africa; how can you get pregnant with no sex: baseline data in a multi-component community-based HIV prevention trial recruiting rural youth in Zimbabwe), paediatric morbidity (half of 9 month old babies with HIV infection do not reach their 3 rd birthday in an observational study in Zambia), complementary alternative medicine (what are the dangers in London?; traditional herbal and other remedies in KwaZulu-Natal), epidemiology (Ukraine takes the prize at the epidemic top in Europe), sexual transmission (men who have sex with men: herpes simplex virus-2 and HIV-1 viral load are key factors; genital tract HIV-1 shedding and genital tract infections: haven’t we known this for a long time?), accountability (living up to our commitments and meeting the needs of those we serve), herpes simplex virus-2 (more good news on acyclovir: reducing HIV shedding in co-infected women in Chiang Rai, Thailand), integrating service delivery (time to make it happen for synergistic effects on the epidemic; why syringe exchange and substance use programmes need to come out of their silos), and HIV testing (what will it take to improve testing uptake among men in rural western Uganda).

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HIV This Week Issue #61

H W Reynolds, B Janowitz, R Wilcher, W Cates. Contraception to prevent HIV-positive births: current contribution and potential cost savings in PEPFAR countries. Sex. Transm. Inf. 2008;84;ii49-ii53

Reynolds et al aimed to estimate the number of HIV-positive births currently prevented by contraceptive use in the President’s Emergency Plan for AIDS Relief (PEPFAR) focus countries and to estimate the first year cost savings to each country if unintended and unwanted HIV-positive births were prevented via contraceptive use rather than providing antiretroviral prophylaxis for HIV-positive pregnant women (prevention of mother-to-child transmission services). Data from publicly available sources yielded estimates of (1) contraceptive and HIV prevalence; (2) the number of women of reproductive age; (3) the number of annual births to HIV-infected women; (4) the rates of pregnancy and vertical HIV transmission; (5) the proportions of unintended and unwanted births; and (6) the cost per HIV-positive birth averted by family planning and prevention of mother-to-child transmission services. The number of HIV-positive births currently averted by contraceptive use and the number of unwanted and unintended HIV-positive births are the product of these estimates. Cost savings are the difference in the costs of family planning and prevention of mother-to-child transmission services. The study found that the annual number of unintended HIV-positive births currently averted by contraceptive use ranges from 178 in Guyana to over 120,000 in South Africa. The minimum annual cost savings to prevent just the unwanted HIV-positive births ranges from $26,000 in Vietnam to over $2.2 million in South Africa. The authors concluded that contraception is already having an important effect on reducing the number of infant HIV infections. This contribution could be strengthened by additional efforts to provide contraception to HIV-infected women who do not wish to become pregnant. Moreover, the effect of contraception can be achieved at a cost savings compared with prevention of mother-to-child transmission services.

Editors’ note: Despite low contraceptive prevalence rates, contraception is already preventing many unintended HIV-positive births. Contraception helps women with HIV delay pregnancy until they are emotionally and physically ready and can access appropriate antenatal and safe delivery care, as well as antiretroviral regimens. Important cost savings could be incurred if more women living with HIV were able to prevent mistimed or unwanted pregnancy in the first place rather than interrupting mother-to-child transmission through antiretroviral prophylaxis. Cost-effective compared with other approaches to prevent mother-to-child transmission, family planning really is the best-kept secret of HIV prevention.

Auvert B, Marseille E, Korenro§mp EL, Lloyd-Smith J, Sitta R, Taljaard D, Pretorius C, Williams B, Kahn JG. Estimating the resources needed and savings anticipated from roll-out of adult male circumcision in Sub-Saharan Africa. PLoS ONE. 2008;3(8):e2679.

Trials in Africa indicate that medical adult male circumcision reduces the risk of HIV by 60%. Medical adult male circumcision may avert 2 to 8 million HIV infections over 20 years in sub-Saharan Africa and cost less than treating those who would have been infected. This paper estimates the financial and human resources required to roll out medical adult male circumcision and the net savings due to reduced infections. Auvert and colleagues developed a model which included costing, demography, and HIV epidemiology and used it to investigate 14 countries in sub-Saharan Africa where the prevalence of male circumcision was lower than 80% and HIV prevalence among adults was higher than 5%, in addition to Uganda and the Nyanza province in Kenya. The authors assumed that the roll-out would take 5 years and lead to a male circumcision prevalence among adult males of 85%. They also assumed that surgery would be done as it was in the trials. They calculated public program cost, number of full-time circumcisers and net costs or savings when adjusting for averted HIV treatments. Costs were in USD, discounted to 2007. 95% percentile intervals (95% PI) were estimated by Monte Carlo simulations. In the first 5 years the number of circumcisers needed was 2 282 (95% PI: 2 018 to 2 959), or 0.24 (95% PI: 0.21 to 0.31) per 10,000 adults. In years 6-10, the number of circumcisers needed fell to 513 (95% PI: 452 to 664). The estimated 5-year cost of rolling out medical adult male circumcision in the public sector was $919 million (95% PI: 726 to 1 245). The cumulative net cost over the first 10 years was $672 million (95% PI: 437 to 1,021) and over 20 years there were net savings of $2.3 billion (95% PI: 1.4 to 3.4). The authors conclude that a rapid roll-out of medical adult male circumcision in sub-Saharan Africa requires substantial funding and a high number of circumcisers for the first five years. These investments are justified by medical adult male circumcision’s substantial health benefits and the savings accrued by averting future HIV infections. Lower ongoing costs and continued care savings suggest long-term sustainability.

Editors’ note: This modelling optimistically assumes that the proportion of men circumcised in these 15 countries plus Nyanza Province, Kenya will rise from a range of 0 to 70% (in 2007 the number of uncircumcised males aged 15 to 49 was 30.5 million) to 85% in five years. This would require very high demand for services as well as unprecedented capacity for well-trained, adequately equipped, health care personnel to meet that demand safely. Although relevant costs were contained in the modelling, the cost of HIV testing and counselling was not, with the authors stating that it ‘may not be required by many male circumcision programmes’. WHO/UNAIDS advise health professionals to recommend voluntary HIV testing to all individuals seeking male circumcision services. Asymptomatic HIV-positive men and healthy men of unknown serostatus who do not wish to be tested should not be refused circumcision unless there are medical contraindications. However, consistent with provider-initiated testing policies, men requesting circumcision should be given the opportunity to learn their HIV status.

Buchbinder, SP, Mehrotra, DV, Duerr, A, Fitzgerald, DW, Mogg, R, Li, D, Gilbert, PB, Lama, JR, Marmor, M, del Rio, C, McElrath, MJ, Casimiro, DR, Gottesdiener, KM, Chodakewitz, JA, Corey,L, Robertson, MN, and the Step Study Protocol Team*. Efficacy assessment of a cell-mediated immunity HIV-1 vaccine (the Step Study): a double-blind, randomised, placebo-controlled, test-of-concept trial Lancet 2008 Epub

Observational data and non-human primate challenge studies suggest that cell-mediated immune responses might provide control of HIV replication. The Step Study directly assessed the efficacy of a cell-mediated immunity vaccine to protect against HIV-1 infection or change in early plasma HIV-1 levels. Buchbinder and colleagues undertook a double-blind, phase II, test-of-concept study at 34 sites in North America, the Caribbean, South America, and Australia. They randomly assigned 3000 HIV-1-seronegative participants by computer-generated assignments to receive three injections of MRKAd5 HIV-1 gag/pol/nef vaccine (n=1494) or placebo (n=1506). Randomisation was pre-stratified by sex, adenovirus type 5 (Ad5) antibody titre at baseline, and study site. Primary objective was a reduction in HIV-1 acquisition rates (tested every 6 months) or a decrease in HIV-1 viral-load setpoint ( early plasma HIV-1 RNA measured 3 months after HIV-1 diagnosis). Analyses were per protocol and modified intention to treat. The study was stopped early because it unexpectedly met the pre-specified futility boundaries at the first interim analysis. This study is registered with ClinicalTrials.gov, number NCT00095576. In a pre-specified interim analysis in participants with baseline Ad5 antibody titre 200 or less, 24 (3%) of 741 vaccine recipients became HIV-1 infected versus 21 (3%) of 762 placebo recipients (hazard ratio [HR] 1·2 [95% CI 0·6–2·2]). All but one infection occurred in men. The corresponding geometric mean plasma HIV-1 RNA was comparable in infected male vaccine and placebo recipients (4·61 vs 4·41 log10 copies per mL, one tailed p value for potential benefit 0·66). The vaccine elicited interferon-γ ELISPOT responses in 75% (267) of the 25% random sample of all vaccine recipients (including both low and high Ad5 antibody titres) on whose specimens this testing was done (n=354). In exploratory analyses of all study volunteers, irrespective of baseline Ad5 antibody titre, the hazard ratio of HIV-1 infection between vaccine and placebo recipients was higher in Ad5 seropositive men (hazard ratio 2·3 [95% CI 1·2–4·3]) and uncircumcised men (3·8 [1·5–9·3]), but was not increased in Ad5 seronegative (1·0 [0·5–1·9]) or circumcised (1·0 [0·6–1·7]) men.

Editors’ note: This study was stopped for futility, not safety, when the first interim analysis showed that, even if it had gone its full course, the trial would have not been able to prove or disprove the hypothesis that the vaccine could prevent infection and/or lower viral set point in those that did become infected. Further analyses showed that uncircumcised men in the vaccine arm, particularly if they reported unprotected insertive anal sex, were more likely to seroconvert, as were men who had high levels of antibodies to adenovirus 5, a common virus used as a vaccine vector. The vaccine did not infect them but rather seemed to increase their risk of becoming infected when exposed to HIV. Many questions are being asked about mucosal immune responses and pre-existing vector immunity but confounding due to herpes simplex virus 2, host genetic factors, or sexual network clustering has not been ruled out and is under study.

Van Damme L, Govinden R, Mirembe FM, Guédou F, Solomon S, Becker ML, Pradeep BS, Krishnan AK, Alary M, Pande B, Ramjee G, Deese J, Crucitti T, Taylor D; CS Study Group. Lack of effectiveness of cellulose sulfate gel for the prevention of vaginal HIV transmission. N Engl J Med. 2008;359(5):463-72.

Women make up more than 50% of adults living with human immunodeficiency virus (HIV) infection or the acquired immunodeficiency syndrome (AIDS) in sub-Saharan Africa. Thus, female-initiated HIV prevention methods are urgently needed. Van Damme and colleagues performed a randomized, double-blind, placebo-controlled trial of cellulose sulfate, an HIV-entry inhibitor formulated as a vaginal gel, involving women at high risk for HIV infection at three African and two Indian sites. The primary end point was newly acquired infection with HIV type 1 or 2. The secondary end point was newly acquired gonococcal or chlamydial infection. The primary analysis was based on a log-rank test of no difference in the distribution of time to HIV infection, stratified according to site. A total of 1398 women were enrolled and randomly assigned to receive cellulose sulfate gel (706 participants) or placebo (692 participants) and had follow-up HIV test data. There were 41 newly acquired HIV infections, 25 in the cellulose sulfate group and 16 in the placebo group, with an estimated hazard ratio of infection for the cellulose sulfate group of 1.61 (P=0.13). This result, which is not significant, is in contrast to the interim finding that led to the trial being stopped prematurely (hazard ratio, 2.02 [corrected]; P=0.05 [corrected]) and the suggestive result of a preplanned secondary (adherence-based) analysis (hazard ratio, 2.02; P=0.05). No significant effect of cellulose sulfate as compared with placebo was found on the risk of gonorrheal infection (hazard ratio, 1.10; 95% confidence interval [CI], 0.74 to 1.62) or chlamydial infection (hazard ratio, 0.71; 95% CI, 0.47 to 1.08). The authors concluded that cellulose sulfate did not prevent HIV infection and may have increased the risk of HIV acquisition.

Editors’ note: This trial was stopped prematurely after its independent data safety monitoring board ruled that the cellulose sulfate gel may have increased the risk of HIV infection compared to placebo. A second study of the same product underway in Nigeria was also stopped because of the safety concerns in the first trial. The results were not statistically significant but subsequent study showed that at high concentrations cellulose sulfate does inhibit HIV but at low concentrations it increases HIV infection (Tao et al. AIDS Res Hum Retro 2008; 24:925-9). A polyanionic compound derived from cotton, cellulose sulphate is not safe for mucosal application in humans.

Pronyk PM, Kim JC, Abramsky T, Phetla G, Hargreaves JR, Morison LA, Watts C, Busza J, Porter JD. A combined microfinance and training intervention can reduce HIV risk behaviour in young female participants. AIDS. 2008 Aug 20;22(13):1659-65.

Pronyk and colleagues aimed to assess effects of a combined microfinance and training intervention on HIV risk behaviour among young female participants in rural South Africa. The study was secondary analyses were conducted using quantitative and qualitative data from a cluster randomized trial, the Intervention with Microfinance for AIDS and Gender Equity study. Eight villages were pair-matched and randomly allocated to receive the intervention. At baseline and after 2 years, HIV risk behaviour was assessed among female participants aged 14-35 years. Their responses were compared with women of the same age and poverty group from control villages. Intervention effects were calculated using adjusted risk ratios employing village level summaries. Qualitative data collected during the study explored participants’ responses to the intervention including HIV risk behaviour. The authors found that after 2 years of follow-up, when compared with controls, young participants had higher levels of HIV-related communication (adjusted risk ratio 1.46, 95% confidence interval 1.01-2.12), were more likely to have accessed voluntary counselling and testing (adjusted risk ratio 1.64, 95% confidence interval 1.06-2.56), and less likely to have had unprotected sex at last intercourse with a nonspousal partner (adjusted risk ratio 0.76, 95% confidence interval 0.60-0.96). Qualitative data suggest a greater acceptance of intrahousehold communication about HIV and sexuality. Although women noted challenges associated with acceptance of condoms by men, increased confidence and skills associated with participation in the intervention supported their introduction in sexual relationships. In addition to affecting impacts on economic well being, women’s empowerment and intimate partner violence, interventions addressing the economic and social vulnerability of women may contribute to reductions in HIV risk behaviour .

Editors´note: The original trial which collected these data, known as the IMAGE trial, suggested that microfinance combined with gender and HIV training lead to improvements in household economic well being, women’s empowerment, and reductions in levels of intimate partner violence. This secondary analysis reveals improvements in risk behaviours, increased communication about sex, and greater uptake of HIV testing, with potential synergies between these. The IMAGE trial has made its mark by highlighting the potential for structural interventions that address the economic and social vulnerability of women to contribute to measurable health gains. These findings underscore the need for further innovation and operational research.

Cowan FM, Pascoe SJ, Langhaug LF, Dirawo J, Chidiya S, Jaffar S, Mbizvo M, Stephenson JM, Johnson AM, Power RM, Woelk G, Hayes RJ. The Regai Dzive Shiri Project: a cluster randomised controlled trial to determine the effectiveness of a multi-component community-based HIV prevention intervention for rural youth in Zimbabwe - study design and baseline results. Trop Med Int Health. Volume 13, Issue 10, Date: October 2008, Pages: 1235-1244

Cowan et all set out to assess the effectiveness of a community-based HIV prevention intervention for adolescents in terms of its impact on (1) HIV and Herpes simplex virus type 2 (HSV-2) incidence and on rates of unintended pregnancy and (2) reported sexual behaviour, knowledge and attitudes. These were assessed through a cluster randomised trial of a multi-component HIV prevention intervention for adolescents based in rural Zimbabwe. Thirty communities were selected and randomised in 2003 to early or deferred intervention implementation. A baseline bio-behavioural survey was conducted among 6791 secondary school pupils (86% of eligibles) prior to intervention implementation. At baseline, prevalences were 0.8% (95% CI: 0.6-1.0) for HIV and 0.2% (95% CI: 0.1-0.3%) for HSV-2. Four girls (0.12%) were pregnant. There was excellent balance between study arms. Orphans who made up 35% of the cohort were at increased risk of HIV [ age-sex adjusted odds ratio 3.4 (95% CI: 1.7-6.5)]. 11.9% of young men and 2.9% of young women reported that they were sexually active (P < 0.001); however, there were inconsistencies in the sexual behaviour data. Girls were less likely to know about reproductive health issues than boys (P < 0.001) and were ). This is one of the first rigorous evaluations of a community-based HIV prevention intervention for young people in southern Africa. The low rates of HIV suggest that the intervention was started before this population became sexually active. Inconsistency and under-reporting of sexual behaviour re-emphasise the importance of using externally validated measures of sexual risk reduction in behavioural intervention studies.

Editors´note: This community-based HIV prevention trial targeting young people, their parents, and adults in the community to change individual behaviour, as well as societal and cultural norms about adolescent sexuality to reduce risk more broadly, will report results in Dakar at the ICASA conference next month. These baseline findings from 2003 reveal good balance between the study arms and low levels of HIV and herpes simplex virus 2 infection. A striking finding that emphasises the need to validate self-report of sexual behaviours is the fact that none of the four young women that were pregnant reported having had sexual intercourse.

Sutcliffe CG, Scott S, Mugala N, Ndhlovu Z, Monze M, Quinn TC, Cousens S, Griffin DE, Moss WJ. Survival from 9 months of age among HIV-infected and uninfected Zambian children prior to the availability of antiretroviral therapy. Clin Infect Dis. 2008 Sep 15;47(6):837-44.

Few prospective studies have measured survival rates among human immunodeficiency virus (HIV)-infected children in sub-Saharan Africa prior to the availability of antiretroviral therapy. In the context of an observational study of the immunogenicity of measles vaccine in Zambia, Sutcliffe and colleagues prospectively followed up children from approximately 9 months of age and assessed survival rates, risk factors for mortality, and circumstances at the time of death according to HIV-infection or HIV-exposure status. There were 56 deaths among 492 study children during follow-up to 3 years of age. Thirty-nine percent of the 105 children with HIV infection died during the study period, compared with 5.0% of the 260 HIV-seropositive but uninfected children and 1.6% of the 127 HIV-seronegative children. Estimated survival probabilities from 9 through 36 months of age were 52% among HIV-infected children, 95% among initially HIV-seropositive but uninfected children, and 98% among HIV-seronegative children. In multivariable analyses, history of a clinic visit within the 4 weeks prior to study entry (adjusted hazard ratio, 4.6; 95% confidence interval, 1.5-13.5), hemoglobin level <8 g/dL at study entry (adjusted hazard ratio, 4.4; 95% confidence interval, 1.5-12.6), and CD4(+) T lymphocyte percentage <15% at study entry (adjusted hazard ratio, 3.2; 95% confidence interval, 1.1-9.5) were associated with mortality among HIV-infected children. Only approximately one-half of HIV-infected Zambian children who were alive at 9 months of age survived to 3 years of age, supporting the urgent need for the prevention of mother-to-child transmission of HIV and the early diagnosis and treatment of HIV infection in children in sub-Saharan Africa .

Editors’ note: Limited access to care, poor nutritional status, and frequent exposure to endemic co-infections contribute to extremely high mortality rates among HIV-infected children in sub-Saharan Africa, as seen here in Zambia. Diarrhoea, pneumonia, failure to thrive, and neurological abnormalities are all markers of rapid disease progression, highlighting the importance of pre-emptive diagnosis of HIV infection, ideally at 6 weeks of age using nucleic acid-based tests, and initiation of antiretroviral treatment regardless of CD4 count. HIV transmission from mothers to their babies can be prevented and paediatric HIV infection can be treated – political will and resources are urgently needed.

Ladenheim D, Horn O, Werneke U, Phillpot M, Murungi A, Theobald N, Orkin C. Potential health risks of complementary alternative medicines in HIV patients. HIV Med. Volume 9, Issue 8, Pages: 653-659

The objective of this study was to determine the prevalence and purpose of complementary alternative medicines use in people receiving treatment for HIV infection. To identify and quantify potential health risks of complementary alternative medicines use in this population and to explore options for improved pharmacovigilance. A cross-sectional questionnaire survey of 293 patients receiving antiretroviral (ARV) therapy at three specialist HIV out-patient clinics in central London, UK was conducted. The use of herbal medicines and supplements was explored, and potentially adverse side effects or significant drug interactions with conventional therapies were identified. Of the 293 patients included, 61% (n=179) were taking herbal remedies or supplements and 35% (n=103) were using physical treatments. Twenty-seven per cent (n=80) used a combination of both. Twenty per cent (n=59) potentially compromised their HIV management through using complementary alternative medicines therapy. Ten per cent (n=29) were advised to stop their complementary alternative medicines and 15% (n=43) were made aware of potential drug interactions and adverse effects and were advised to monitor their care. There are potentially significant health risks posed by the concomitant use of complementary alternative medicines in patients taking ARV therapy. Medical practitioners need to be able to identify complementary alternative medicine use in HIV-positive patients and recognize potential health risks. Patients should be encouraged to disclose CAM use to their clinicians and other healthcare professionals.

Editors’ note: Many patients living with chronic illnesses and their associated physical and psychological problems use alternative medicines. This study found potentially serious health risks in patients living with HIV, of whom 20% received warnings and 10% were advised to stop their alternative medicines. Some people were at risk of adverse reactions to them while others risked antiretroviral drug side effects or sub-therapeutic drug levels due to possible interference with the cytochrome P metabolism system used by protease inhibitors and non-nucleoside reverse transcriptase inhibitors.

Peltzer K, Preez NF, Ramlagan S, Fomundam H. Use of traditional complementary and alternative medicine for HIV patients in KwaZulu-Natal, South Africa. BMC Public Health. 2008;8:255.

Traditional medicine use has been reported is common among individuals with moderate and advanced HIV disease. The aim of this cross-sectional study was to assess the use of traditional complementary and alternative medicine for HIV patients prior to initiating antiretroviral therapy in three public hospitals in KwaZulu-Natal, South Africa. Using systematic sampling, 618 HIV-positive patients were selected from outpatient departments from three hospitals and interviewed with a questionnaire. Traditional complementary and alternative medicine was commonly used for HIV in the past six months by study participants (317, 51.3%) and herbal therapies alone (183, 29.6%). The use of micronutrients (42.9%) was excluded from traditional complementary and alternative medicine since mostly vitamins were provided by the health facility. Herbal therapies were the most expensive, costing on average 128 Rand (US$16) per patient per month. Most participants (90%) indicated that their health care provider was not aware that they were taking herbal therapies for HIV (90%). Herbal therapies were mainly used for pain relief (87.1%) and spiritual practices or prayer for stress relief (77.6%). Multivariate logistic regression with use of herbs for HIV as the dependent variable identified being on a disability grant and fewer clinic visits to be associated with use of herbs, and traditional complementary and alternative medicine use for HIV identified being on a disability grant, number of HIV symptoms and family members not contributing to main source of household income to be associated with traditional complementary and alternative medicine use. Traditional herbal therapies and traditional complementary and alternative medicine are commonly used by HIV treatment naïve outpatients of public health facilities in South Africa. Health care providers should routinely screen patients on traditional complementary and alternative medicine use when initiating ART and also during follow-up and monitoring keeping in mind that these patients may not fully disclose other therapies.

Editors’ note: This study revealed that treatment naive HIV patients in South Africa use a variety of traditional herbal therapies and other complementary/alternative medicines that they may be reticent to discuss fully with their care providers and that may negatively affect household income. Creating trust and involving patients more in treatment decision-making processes may help determine which aspects of their alternative treatment can be safely incorporated into their medical regimen.

Kruglov YV, Kobyshcha YV, Salyuk T, Varetska O, Shakarishvili A, Saldanha VP. The most severe HIV epidemic in Europe: Ukraine’s national HIV prevalence estimates for 2007. Sex Transm Infect. 2008 Aug;84 Suppl 1:i37-i41.

The objective of this study was to revise the national HIV estimates and quantify the magnitude of the HIV epidemic in Ukraine at the end of 2007. Internationally recommended methods – the Workbook and Spectrum – were employed to generate the estimates. This enables comparison of results with other countries using the same methodology. Estimation of the size of most at-risk populations nationally was performed using capture-recapture, multiplier and triangulation methods. HIV prevalence among most at-risk populations was estimated by linked HIV sentinel and behavioural surveillance among injecting drug users, and men who have sex with men, and unlinked sentinel surveillance among sex workers. The range of HIV prevalence and extrapolation for populations at lower risk were determined by consensus among national stakeholders. Results were reviewed by national stakeholders and endorsed by the government of Ukraine. At the end of 2007, an estimated 395 000 adults (range 230 000-573 000) aged 15-49 were living with HIV in Ukraine. Adult HIV prevalence was estimated at 1.63%, which represents the highest adult HIV prevalence of any country in Europe. The authors conclude that the HIV epidemic in Ukraine continues to grow at a record pace, concentrated among most at-risk populations, the majority of whom are unaware of their HIV status. The results emphasise the need to accelerate the coverage and quality of prevention programmes among most at-risk populations and their sexual partners.

Editors’ note: The process of developing these HIV estimates for Ukraine, the country with the highest HIV prevalence of any country in Europe, helped generate a national consensus that is key to the engagement of all stakeholders in designing, financing, staffing, and implementing a new national 5 year programme. A robust epidemiological baseline is marking a ‘know your epidemic’ line in the sand. Now, the response has to match it.

Butler DM, Smith DM, Cachay ER, Hightower GK, Nugent CT, Richman DD, Little SJ. Herpes simplex virus 2 serostatus and viral loads of HIV- 1 in blood and semen as risk factors for HIV transmission among men who have sex with men. AIDS. 2008;22(13):1667-71.

Human immunodeficiency virus type 1 blood plasma viral load is correlated with the sexual transmission of HIV, although transmission from men involves virus from semen instead of blood. Butler and colleagues quantified HIV-1 RNA in the blood and semen of men who did or did not transmit HIV to their sex partners. They compared the relationships of HIV-1 transmission risk with blood plasma viral load, seminal plasma viral load, herpes simplex virus 2 serostatus and other factors. In this case-control study, participants were men evaluated for primary HIV infection and their recent male sex partners. They were interviewed, and clinical specimens were collected. Epidemiologic and phylogenetic linkages were determined by history and molecular techniques. Couples were grouped on the basis of transmission after exposure. Fisher’s exact test and Wilcoxon tests were used for comparisons between groups. Multivariable logistic regressions were fit to identify independent predictors of transmission. HIV-transmitting partners (n = 15) had a higher median seminal plasma viral load (P < 0.015) and median blood plasma viral load (P < 0.001) than nontransmitting partners (n = 32). Herpes simplex virus 2 serostatus was associated with transmission only when the HIV-infected source partner was herpes simplex virus 2 seropositive and the HIV-exposed partner was not (odds ratio 16, P < 0.03). Adjusting for other factors, HIV transmission was significantly associated with blood plasma viral load (odds ratio 13.4, P < 0.02) but not seminal plasma viral load (odds ratio 0.69, P = not significant). The authors conclude that blood and seminal plasma viral load were both associated with human immunodeficiency virus type 1 transmission, but blood plasma viral load was the stronger predictor in this cohort. Herpes simplex virus 2 coinfection was associated with the risk of transmission but not acquisition of human immunodeficiency virus type 1 .

Editors’ note: Fifteen ‘transmitting’ pairs and 32 ‘non-transmitting’ pairs were compared in this study of men who have sex with men. Herpes simplex virus-2 infection was associated with transmission when the source person was co-infected but made no difference if the non-HIV-infected man was HSV-2 sero-positive. This is consistent with the negative findings from trials of herpes suppression to reduce HIV acquisition and support continuation of the trials assessing herpes suppression in co-infected people to reduce HIV transmission. The jury is still out on whether it is cell-free virus in semen (measured in seminal plasma viral load) or cell-associated virus (not measured) that increases risk of HIV transmission – in this study cell-free virus levels were associated with transmission.

Johnson LF, Lewis DA. The Effect of Genital Tract Infections on HIV-1 Shedding in the Genital Tract: A Systematic Review and Meta-Analysis. Sex Transm Dis. 2008; 35(11): 946-959 This article reviews the effect of genital tract infections and associated clinical conditions on the detection and concentration of HIV-1 shedding in the genital tract. A search of the PubMed, Embase, and AIDSearch databases was conducted. Meta-analysis was performed on those studies that reported the effect of genital tract infections on the detection of HIV-1 shedding. Thirty-nine studies met the inclusion criteria. The odds of HIV-1 detection in the genital tract were increased most substantially by urethritis (OR 3.1, 95% CI: 1.1-8.6) and cervicitis (OR 2.7, 95% CI: 1.4-5.2). The odds of HIV-1 detection were also increased significantly in the presence of cervical discharge or mucopus (OR 1.8, 95% CI: 1.2-2.7), gonorrhoea (OR 1.8, 95% CI: 1.2-2.7), chlamydial infection (OR 1.8, 95% CI: 1.1-3.1), and vulvovaginal candidiasis (OR 1.8, 95% CI: 1.3-2.4). Other infections and clinical conditions were found to have no significant effect on the detection of HIV-1, although HSV-2 shedding was found to increase the concentration of HIV-1 shedding, and genital ulcer disease was found to increase the odds of HIV-1 detection significantly after excluding one biased study ( OR 2.4, 95% CI: 1.2-4.9). This analysis shows that infections that are associated with significant increases in leukocyte concentrations in the genital tract are also associated with significant increases in HIV-1 shedding. These infections are likely to be particularly important in promoting the sexual transmission and mother-to-child intrapartum transmission of HIV-1, and should therefore be the focus of HIV prevention strategies.

Editors’ note: This systematic review and meta-analysis confirms that genital tract infections increase both the detection and the concentration of HIV-1 in the genital tract, particularly when the infection is symptomatic and recruits lots of white blood cells to the scene. Encouraging people living with HIV to recognise and seek prompt and effective treatment for genital symptoms is important in limiting HIV transmission. Various genital tract infections differ substantially in their impact on HIV shedding in the genital tract and further study is needed to determine which type of HIV shedding (proviral DNA, cell-associated RNA or cell-free RNA) is the principal determinant of HIV-1 infectiousness.

Collins C, Coates TJ, Szekeres G. Accountability in the global response to HIV: measuring progress, driving change. AIDS. 2008 Suppl 2:S105-111.

Accountability implies that institutions and individuals are answerable for their commitments and responsibilities. The concept of accountability is highly relevant in the global response to HIV because governments, donors and other actors have often failed to keep their commitments to expand funding and service delivery levels. Many governments have not been held accountable for failing to address the HIV-related needs of their populations adequately. Accountability is about more than passing judgement. Effective accountability mechanisms can be powerful tools to improve service delivery by providing constructive assessments and motivating decision makers to avoid negative external critiques. An impressive variety of HIV-related accountability projects have emerged over the past few years, the most prominent being the ongoing monitoring of government compliance with the United Nations General Assembly Special Session (UNGASS) Declaration of Commitment. Other accountability efforts are essential in order to capture perspectives and priorities outside of governments and aid agencies. Many civil society-based accountability projects are now tracking HIV policy, service delivery and funding levels. Collins and colleagues make several suggestions to increase the impact of accountability efforts, including connecting accountability to sustained advocacy, holding multiple actors accountable, continually assessing what measures of success will be most powerful in driving improved outcomes, and supporting and building the capacity of civil society monitoring efforts. They also suggest exploring how the International AIDS Conferences could serve as an expanded platform for accountability.

Editors’ note: Accountability means measuring progress toward goals, commitments, and responsibilities for action at all levels: Accountability is a powerful tool to improve the quality, accessibility, and equitable delivery of services. Thus, accountability is an important social justice issue in the response to HIV. More robust accountability efforts, which build capacity for and stimulate constructive dialogue between health consumers and policy makers while measuring the appropriateness of programme choices, require increased financial and technical support. They are well worth the investment.

Dunne EF, Whitehead S, Sternberg M, Thepamnuay S, Leelawiwat W, McNicholl JM, Sumanapun S, Tappero JW, Siriprapasiri T, Markowitz L.Suppressive Acyclovir Therapy Reduces HIV Cervicovaginal Shedding in HIV- and HSV-2-Infected Women, Chiang Rai, Thailand. J Acquir Immune Defic Syndr. 2008 Sep 1;49(1):77-83.

Herpes simplex virus type 2 infection is important in the HIV epidemic and may contribute to increased HIV transmission. Dunne and colleagues evaluated the effect of suppressive acyclovir therapy on cervicovaginal HIV-1 shedding. HIV-1- and herpes simplex virus type 2- coinfected women aged 18-49 years with CD4 counts >200 cells/muL were enrolled in a randomized crossover trial of suppressive acyclovir therapy (NCT00362596, http://www.clinicaltrials.gov). For each woman, monthly plasma and weekly cervicovaginal lavage specimens were collected; the mean of the monthly median cervicovaginal lavage HIV-1 viral load and plasma HIV-1 viral load was compared. Sixty-seven women were enrolled; at baseline, median CD4 count was 366 cells/muL, and median HIV-1 plasma viral load was 4.6 log10 copies/mL. The mean cervicovaginal lavage HIV-1 viral load was 1.9 (SD 0.8) log10 copies/mL during the acyclovir month and 2.2 (SD 0.7) log10 copies/mL during the placebo month (P < 0.0001); the mean decrease in HIV was 0.3 log10 copies/mL. The mean plasma HIV viral load during the acyclovir month (3.78 log10 copies/mL) was reduced compared with the placebo month (4.26 log10 copies/mL, P < 0.001). Acyclovir reduced HIV genital shedding and plasma viral load among HIV-1- and herpes simplex virus type 2-coinfected women. Further data from clinical trials will examine the effct of suppressive therapy on HIV transmission.

Editors’ note: This first randomized, controlled crossover trial, meaning that women co-infected with HIV and herpes simplex virus-2 served as their own controls, found that acyclovir significantly reduced genital HIV-1 shedding. These immunocompetent women were not taking any antiretroviral drugs. Furthermore, acyclovir, which is commonly available and inexpensive, also reduced blood plasma HIV. These findings hold out promise for the trials of herpes suppression to reduce HIV transmission.