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For full PDF access to this issue HIV This Week Issue # 69

In the generalized epidemics of HIV in southern sub-Saharan Africa, men who have sex with men have been largely excluded from HIV surveillance and research. Epidemiologic data for men who have sex with men in southern Africa are among the sparsest globally, and HIV risk among these men has yet to be characterized in the majority of countries. A cross-sectional anonymous probe of 537 men recruited with non-probability sampling among men who reported ever having had sex with another man was conducted in Malawi, Namibia, and Botswana using a structured survey instrument and HIV screening with the OraQuick© rapid test kit. The HIV prevalence among those between the ages of 18 and 23 was 8.3% (20/241); 20.0% (42/210) among those 24-29; and 35.7% (30/84) among those older than 30 for an overall prevalence of 17.4% (95% CI 14.4-20.8). In multivariate logistic regressions, being older than 25 (aOR 4.0, 95% CI 2.0-8.0), and not always wearing condoms during sex (aOR 2.6, 95% CI 1.3-4.9) were significantly associated with being HIV-positive. Sexual concurrency was common with 16.6% having ongoing concurrent stable relationships with a man and a woman and 53.7% had both male and female sexual partners in proceeding 6 months. Unprotected anal intercourse was common and the use of petroleum-based lubricants was also common when using condoms. Human rights abuses, including blackmail and denial of housing and health care was prevalent with 42.1% (222/527) reporting at least one human rights abuse. Men who have sex with men are at higher risk of HIV exposure for HIV infection and human rights abuses in Malawi, Namibia, and Botswana. Concurrency of sexual partnerships with partners of both genders may play important roles in HIV spread in these populations. Further epidemiologic and evaluative research is needed to assess the contribution of men who have sex with men to southern Africa’s HIV epidemics and how best to mitigate this. These countries should initiate and adequately fund evidence-based and targeted HIV prevention programs for men who have sex with men.

Editors’ note: This simple epidemiology and human rights study, the first to link individual level rights abrogation to HIV biological outcomes in the African context, was implemented through collaboration with local community groups and can be replicated in similar settings. The overall findings of a high risk of exposure to both HIV and human rights abuses, in these three high HIV prevalence countries that criminalize same sex behaviour among consenting adults, are striking. Effective HIV prevention programming for men who have sex with men, particularly younger men, in Botswana, Malawi, and Namibia requires urgent governmental attention with dedicated funding and creative innovations, including use of the internet to reach this hidden population, training of health care providers, and strategies to address and minimise human rights abuses.

Human papillomavirus is a common sexually transmitted agent that causes anogenital cancer and pre-cancer lesions that have an inflammatory infiltrate, may be friable, and bleed. Chin-Hong and colleagues aimed to determine the association between anal HPV infection and HIV acquisition using a prospective cohort study design. They recruited 1409 HIV-negative men who have sex with men from a community-based setting in Boston, Denver, New York, and San Francisco. The authors used Cox proportional hazards regression modeling and assessed the independent association of HPV infection with the rate of acquisition of HIV infection. Of 1409 participants contributing 4375 person-years of follow-up, 51 HIV-seroconverted. The median number of HPV types in HPV-infected HIV-seroconverters was 2 (interquartile range 1-3) at the time of HIV seroconversion. After adjustment for sexual activity, substance use, occurrence of other sexually transmitted infections, and demographic variables, there was evidence (P = 0.002) for the effect of infection with at least two HPV types (hazard ratio 3.5, 95% confidence interval 1.2-10.6) in HIV seroconversion. The authors conclude that anal HPV infection is independently associated with HIV acquisition. Studies that incorporate high-resolution anoscopy to more accurately identify HPV-associated disease are needed to determine the relationship between HPV-associated disease and HIV seroconversion.

Editors’ note: HPV disease has long been considered to be opportunistic, taking advantage of HIV-induced immunosuppression but not increasing the risk of HIV acquisition. If, as this first study to do so suggests, anal HPV infection is independently associated with HIV acquisition, immunizing HPV-unexposed people to prevent invasive cancer and anogenital warts may have the potential to reduce the risk of HIV acquisition through anal sex.

New HIV infections are being observed among men who have sex with men (MSM). Understanding the fusion of risky sexual behaviours, stimulant drug use, and erectile dysfunction drug use with HIV seroconversion may provide direction for focused intervention. During the follow-up period (1998-2008), Ostrow and colleagues identified 57 HIV seroconverters among 1667 initially HIV-seronegative men. Time to seroconversion was modelled using Cox proportional hazards regression analysis for 7 combinations of sex drugs (inhaled nitrites or “poppers”, stimulants, and erectile dysfunction drugs) used at the current or previous semi-annual visit, adjusting for other risk factors including sexual behaviour, alcohol and other drugs used, and depression. Model-based adjusted attributable risks were then calculated. The risk of seroconversion increased linearly with the number of unprotected receptive anal sex partners, with hazard ratios ranging from 1.73 [95% confidence interval (CI): 0.75 to 4.01] for 1 partner, to 4.23 (95% CI: 1.76 to 10.17) for 2-4 partners, and to 14.21 (95% CI: 6.27 to 32.20) for 5+ partners, independent of other risk factors. After adjustment, risks for seroconversion increased from 2.99 (95% CI: 1.02 to 8.76) for men who reported using stimulants only (1 drug) to 8.45 (95% CI: 2.67 to 26.71) for men who reported using all 3 sex drugs. The use of any of the 7 possible sex drug combinations accounted for 63% of the 9-year HIV seroincidence in the Multicenter AIDS Cohort Study. When contributions of increased unprotected receptive anal sex partners and combination drug use were analyzed together, the total attributable risk for HIV seroconversion was 74%, with 41% attributable to unprotected receptive anal sex partners alone and a residual of 33% due to other direct or indirect effects of sex drug use. Use of poppers, stimulants, and erectile dysfunction drugs increased risk for HIV seroconversion significantly in this cohort. These data reinforce the importance of implementing interventions that target drug reduction as part of comprehensive and efficacious HIV prevention strategies.

Editors’ note: Whether or not and how vasoactive sex drug use could increase the likelihood of HIV infection through unprotected sex, over and above the disinhibiting effects of drug use, is unclear. Nonetheless, the magnitude of the risk posed by the use of stimulant, poppers, and erectile dysfunction drugs is clear – among men who used all three drugs the relative hazard for HIV seroconversion was 8 times that of men who reported no use of these sex drugs. With noninjection substance use seemingly on the increase among men who have sex with men, particularly the use of erectile dysfunction drugs as men age, attention addressed to the linked epidemics of substance use and high-risk sex should inform tailored harm reduction and safer sex strategies.

An effective vaginal microbicide against sexual HIV transmission remains elusive, with requirements for adherence to appropriate application of effective, nontoxic products being a major deterrent. Saxena and colleagues explored methods to enable sustained release of combinations of antiretroviral microbicides, utilizing intravaginal rings composed of biosoluble Acacia gum or non-biodegradable hydrogel of 2-hydroxyethyl methacrylate and sodium methacrylate, materials approved for use by the United States Food and Drug Administration. The reverse transcriptase inhibitors TMC120, PMPA, 3’-azido-3’-deoxythymidine, and a newly characterized anti-HIV agent, Boc-lysinated betulonic acid, were incorporated into vaginal rings with different combinations. Daily and cumulative release rates of these inhibitors in ring eluates were determined by high-performance liquid chromatography, gas chromatography, or immunoassay. Anti-HIV effects were measured by assessment of p24 Gag antigen in T-cell cultures exposed to HIV-1 isolates. Drug release rates were sustained at concentrations higher than the minimum effective dose for HIV inhibition. The release was maintained for no less than 15 and 28 days from the Acacia gum and 2-hydroxyethyl methacrylate and sodium methacrylate rings, respectively. Boc-lysinated betulonic acid showed more than 90% inhibition of HIV-1 infection in H9 cells, with little toxicity to normal cells. The intravaginal rings described here are capable of efficacious drug delivery. Incorporation of several antiretroviral agents, including betulinol derivatives, which act at multiple levels of the HIV life cycle, may provide a synergistic effect to achieve higher efficacy on the inhibition of HIV infection.

Editors’ note: Although many participants in microbicide gel trials report the unexpected benefit of improved sexual satisfaction with gel use, work is proceeding with alternate microbicide delivery systems that have other potential advantages. Those include sustained delivery through a ring that could be put into position monthly, for example. Not having to insert a microbicide before each sex act would likely appeal to many women, particularly if the vaginal ring releases locally active, effective, and safe antiretroviral drugs for prevention.

Legal barriers to conducting public health research on methods of protection for anal intercourse were lifted in the United States in 2003 when the US Supreme Court invalidated all state antisodomy laws. Although research funding has been available for the development of rectal microbicides, the female condom, which has already been approved for vaginal use, has not been evaluated for anal use. Although there is no evidence that the female condom is safe for anal intercourse, it has already been taken up for off-label use by some men who have sex with men. This demonstrates the urgent need for more protection options for anal intercourse and, more immediately, the need to evaluate the safety and efficacy of the female condom for anal intercourse.

Editors’ note: Among men aged 25 to 44 years in the USA, 3.9% report having had anal sex with another man and 40% report having had anal sex with a woman. It is estimated that four times as many women in the USA practice anal sex than do men who have sex with men. Although the ‘female condom’ is recommended by some health providers and health promoters for anal sex, it has not been assessed for safety, ease of insertion (for example, should the inner ring be removed?), or efficacy. With the development and testing of rectal microbicides lagging behind vaginal products, quick studies to determine the optimal method for using the female condom during anal intercourse are needed now.

This quasi-experimental, proof-of-concept study evaluated the effects of an intervention designed to help Nigerian men decrease risk for HIV, sexually transmitted infections, and unintended pregnancy. The intervention was delivered in groups during two 5-hour workshops, with a monthly 2-hour check-in session. A comparison condition consisted of a group-based half-day didactic workshop. Based on recruitment area, 149 men were assigned to the intervention and 132 to the comparison. Men were evaluated at baseline and 3-month post-intervention. At follow-up, men assigned to the intervention were almost four times more likely than comparison men to report condom use at last intercourse (P < 0.001) and to report fewer unprotected vaginal sex occasions, greater self-efficacy for negotiation, a more egalitarian power dynamic in their primary relationship, more positive expectations for condom use, and greater intention for future consistent condom use (all P values < 0.05). Findings suggest that this intervention is both feasible and effective.

Editors’ note: In addition to reducing HIV-related stigmatizing beliefs, this group-based cognitive-behavioural ‘mobilising men as partners’ intervention, tailored to the needs and culture of Nigerian men, resulted in significantly higher safer-sex self-efficacy and yet significantly less male-dominated power dynamics in primary relationships. Whether the results seen at 3 months would be sustained over time, whether there was community level influence supporting the positive changes (the intervention men were from different communities than the control men), and whether their female partners would corroborate the findings are all questions deserving further investigation.

Kalichman SC, Simbayi LC, Cloete A, Clayford M, Arnolds W, Mxoli M, Smith G, Cherry C, Shefer T, Crawford M, Kalichman MO. Integrated Gender-Based Violence and HIV Risk Reduction Intervention for South African Men: Results of a Quasi-Experimental Field Trial. Prev Sci. 2009 Apr 8. [Epub ahead of print]

South Africa is in the midst of one of the world’s most devastating HIV epidemics and there is a well-documented association between violence against women and HIV transmission. Interventions that target men and integrate HIV prevention with gender-based violence prevention may demonstrate synergistic effects. A quasi-experimental field intervention trial was conducted with two communities randomly assigned to receive either: (a) a five session integrated intervention designed to simultaneously reduce gender-based violence and HIV risk behaviours (N = 242) or (b) a single 3-hour alcohol and HIV risk reduction session (N = 233). Men were followed for 1-, 3-, and 6-months post intervention with 90% retention. Results indicated that the gender-based violence/HIV intervention reduced negative attitudes toward women in the short term and reduced violence against women in the longer term. Men in the gender-based violence/HIV intervention also increased their talking with sex partners about condoms and were more likely to have been tested for HIV at the follow-ups. There were few differences between conditions on any HIV transmission risk reduction behavioural outcomes. Further research is needed to examine the potential synergistic effects of alcohol use, gender violence, and HIV prevention interventions.

Editors’ note: Negative attitudes toward women in South Africa and societal acceptance of violence against women impede men from acting responsibly to reduce HIV risks for themselves and their partners. More than half of the men in this study reported a history of physically assaulting a sex partner and one in five had been detained for domestic violence. Although the study had an inherently weak study design (randomising two communities but examining individual level behaviour change), was conducted in one cultural group only (Xhosa), and 89% of the participants were unemployed and able to attend lengthy workshops, the findings are intriguing. The gender-based violence prevention group reported a number of positive changes in attitudes and behaviours toward women, but the alcohol prevention group appears to have offered greater potential for sexual risk reduction. A three-component programme of HIV sexual risk reduction, alcohol reduction, and gender violence prevention may achieve greater impact. However, until South Africa and other countries worldwide intervene effectively to penalise gender-based violence and create new social norms of respect and gender equality, counting on individual behaviour change alone is like swimming upstream against powerful currents.

To understand the dynamics of the HIV epidemic and to plan HIV treatment and prevention programs, it is critical to know how HIV incidence in a population evolves over time. Bärnighausen and colleagues used data from a large population-based longitudinal HIV surveillance in a rural community in South Africa to test whether HIV incidence in this population has changed in the period from 2003 through 2007. They observed 563 seroconversions in 8095 individuals over 16,256 person-years at risk, yielding an overall HIV incidence of 3.4 per 100 person-years (95% confidence interval 3.1-3.7). The authors included time-dependent period dummy variables (in half-yearly increments) in age-stratified Cox regressions in order to test for trends in HIV incidence. They first did regression analyses separately for women and men. In both regressions, the coefficients of all period dummy variables were individually insignificant (all p >/= 0.338) and jointly insignificant (p = 0.764 and p = 0.111, respectively). They then did regression analysis using the pooled data on women and men, controlling for sex and interactions between sex and age. Again, the coefficients of the eight period dummy variables were individually insignificant (all p >/= 0.387) and jointly insignificant (p = 0.701). They show for the first time that high levels of HIV incidence have been maintained without any sign of decline over the past 5 years in both women and men in a rural South African community with high HIV prevalence. It is unlikely that the HIV epidemic in rural South Africa can be reversed without new or intensified efforts to prevent HIV infection.

Editors’ note: Changes in HIV prevalence figures are difficult to interpret as they reflect both the incidence of new infections and mortality in people living with HIV. What we really need to know is the trend in HIV incidence as this reflects the effectiveness of prevention programming and predicts eventual treatment demand. The findings from this prospective, longitudinal study are highly disturbing: with a constant, unrelenting incidence of 3.4 per 100 person-years, 15 out of every 100 people who were HIV-negative at the start of the study in 2003 had seroconverted by its end 5 years later. The prevention programmes that have been operating clearly do not reach enough people with effective prevention messages, skills building, and support for changed sexual behaviour norms. Safe male circumcision services, positive prevention programmes, and community mobilisation to address the structural factors underlying risk in this rural KwaZulu-Natal community are additional approaches that deserve immediate attention.

HIV programs in generalized epidemics have traditionally relied on antenatal clinic sentinel surveillance data to guide prevention and to model epidemic trends. Antenatal clinic data, however, come from a subset of the population, and their representativeness of the population has been debated. Musinguzi and colleagues compared data from a national population-based Uganda HIV Sero-Behavioral Survey with those from antenatal clinic sentinel surveillance. Using geographic information system, Uganda HIV Sero-Behavioral Survey clusters within a 30 km radius of the antenatal clinic sites were mapped. Estimates of HIV prevalence from antenatal clinic surveillance were compared with those from Uganda HIV Sero-Behavioral Survey. They found that the antenatal clinic-based HIV prevalence, 6.0% [confidence interval (CI) 5.5% to 6.5%], was similar to that from Uganda HIV Sero-Behavioral Survey, 5.9% (CI 5.4% to 6.4%). The antenatal clinic-based estimate correlated with that of Uganda HIV Sero-Behavioral Survey catchment area women who were pregnant and those who had given birth in the 2 years preceding the survey. Antenatal clinic data overestimated prevalence in the 15-year to 19-year age group, were similar to Uganda HIV Sero-Behavioral Survey for ages 20-29 years, and underestimated prevalence in older respondents. Antenatal clinic data underestimated HIV prevalence among women (6.0% vs. 7.4%; CI 6.6% to 8.2%) and urban women (7.6% vs. 12.7%) but was similar for rural women (5.3% vs. 4.9%). Antenatal clinic -based surveillance remains an important tool for monitoring HIV programs. Antenatal clinic and Uganda HIV Sero-Behavioral Survey data were similar overall and for 15-year to 29-year olds, women who were pregnant, and women who had a birth in the 2 years before the survey. Antenatal clinic estimates were lower in those >/=30 years and in urban areas. Periodic serosurveys to adjust antenatal clinic -based estimates are needed.

Editors’ note: In a mature epidemic such as Uganda’s, antenatal surveillance is likely to underestimate HIV prevalence in older women because older women can be at significant risk of acquiring HIV after the reproductive age and women with HIV who are of reproductive age tend to have lower fertility. Antenatal surveillance does generally reflect the general population prevalence among 15 to 29 year olds and in the age group 15 to 19 years it can be used as a general proxy measure of HIV incidence. Thus, antenatal clinic surveillance, supplemented by periodic population-based sero-behavioural surveys to provide an adjusted picture of national HIV epidemics, remains a valid surveillance tool.

To reconstruct the past HIV incidence and prevalence in Thailand from 1980 to 2008 and predict the country’s AIDS incidence from 2009 to 2011, nonparametric backcalculation was adopted utilizing 100 quarterly observed new AIDS counts excluding paediatric cases. The accuracy of data was enhanced through a series of data adjustments using the weight method to account for several surveillance reporting issues. The mixture of time-dependent distributions allowed the effects of age at seroconversion and antiretroviral therapy to be incorporated simultaneously. Sensitivity analyses were conducted to assess model variations that were subject to major uncertainties. Future AIDS incidence was projected for various predetermined HIV incidence patterns. HIV incidence in Thailand reached its peak in 1992 with approximately 115 000 cases. A steep decline thereafter discontinued in 1997 and was followed by another strike of 42 000 cases in 1999. The second surge, which happened concurrently with the major economic crisis, brought on 60 000 new infections. As of December 2008, more than 1 million individuals had been infected and around 430 000 adults were living with HIV corresponding to a prevalence rate of 1.2%. The incidence rate had become less than 0.1% since 2002. The backcalculated estimates were dominated by postulated median AIDS progression time and adjustments to surveillance data. The authors’ analysis indicated that, thus far, the 1990s was the most severe era of HIV epidemic in Thailand with two HIV incidence peaks. A drop in new infections led to a decrease in recent AIDS incidence, and this tendency is likely to remain unchanged until 2011, if not further.

Editors’ note: Backcalculation reconstructs a past pattern of HIV incidence based on AIDS surveillance data and a plausible incubation period from HIV infection to AIDS diagnosis. The relatively short incubation period of 7 years used in this work may have lowered the estimates of backcalculated total infections. Although it makes logical sense that the large cuts of one-third to one-half in government HIV prevention budgets during the financial crisis of 1998 to 2000 could have led to an intriguing second peak in HIV incidence in Thailand, further study is needed to confirm this.

In Southeast Asia, HIV-infected patients frequently die during tuberculosis treatment. Many physicians are reluctant to treat HIV-infected tuberculosis patients with antiretroviral therapy and have questions about the added value of opportunistic infection prophylaxis to antiretroviral therapy, the optimum antiretroviral therapy regimen, and the benefit of initiating antiretroviral therapy early during tuberculosis treatment. Varma and colleagues conducted a multi-center observational study of HIV-infected patients newly diagnosed with tuberculosis in Thailand. Clinical data was collected from the beginning to the end of tuberculosis treatment. They conducted multivariable proportional hazards analysis to identify factors associated with death. Of 667 HIV-infected tuberculosis patients enrolled, 450 (68%) were smear and/or culture positive. Death during tuberculosis treatment occurred in 112 (17%). In proportional hazards analysis, factors strongly associated with reduced risk of death were antiretroviral therapy use (Hazard Ratio [HR] 0.16; 95% confidence interval [CI] 0.07-0.36), fluconazole use (HR 0.34; CI 0.18-0.64), and co-trimoxazole use (HR 0.41; CI 0.20-0.83). Among 126 patients that initiated antiretroviral therapy after tuberculosis diagnosis, the risk of death increased the longer that antiretroviral therapy was delayed during tuberculosis treatment. Efavirenz- and nevirapine-containing antiretroviral therapy regimens were associated with similar rates of adverse events and death. Among HIV-infected patients living in Thailand, the single most important determinant of survival during TB treatment was the use of antiretroviral therapy. Controlled clinical trials are needed to confirm our findings that early antiretroviral therapy initiation improves survival and that the choice of non-nucleoside reverse transcriptase inhibitor does not.

Editors’ note: The sequential arm (antiretroviral treatment given after 6 to 8 months of TB treatment) has already been shut down in one randomised controlled trial (SAPIT at CAPRISA, South Africa) due to a 55% lower mortality in the two integrated arms (immediate antiretroviral treatment and after 2 months of TB treatment). It is not surprising then that this prospective study in Thailand found that TB patients who took antiretroviral treatment had one-fifth the risk of dying as those who did not and those who started antiretroviral treatment earlier did better. Physicians need to overcome their concerns about overlapping toxicity, pill burden, and immune reconstitution inflammatory syndrome to place all their TB/HIV infected patients on cotrimoxasole and those with CD4+ counts under 350 cells on antiretroviral treatment.

Kiggundu and colleagues set out to assess the number of procedures required to achieve optimal competency (time required for surgery with minimal adverse events) in Rakai, Uganda, and thus facilitate the development of guidelines for training providers, as male circumcision reduces the acquisition of human immunodeficiency virus (HIV) in men and is recommended for HIV prevention. In a randomized trial, 3011 men were circumcised, using the sleeve method, by six physicians who had completed training, which included 15-20 supervised procedures. The duration of surgery from local anaesthesia to wound closure, moderate or severe surgery-related adverse events, and wound healing were assessed in relation to the number of procedures done by each physician. The median age of the patients was 24 years. The number of procedures per surgeon was 20-981. The mean time required to complete surgery was approximately 40 min for the first 100 procedures and declined to 25 min for the subsequent 100 circumcisions. After controlling for the number of procedures there was no significant difference in duration of the surgery by patient HIV status or age. The rate of moderate and severe adverse events was 8.8% (10/114) for the first 19 unsupervised procedures after training, 4.0% for the next 20-99 (13/328) and 2.0% for the last 100 (P for trend, 0.003). All adverse events resolved with management. The completion of more than 100 circumcisions was required before newly trained physicians achieved the optimum duration of surgery. Adverse events were higher immediately after training and additional supervision is needed for at least the first 20 procedures after completing training.

Editors’ note: This is the kind of operational research that will improve service outcomes if its results are now taken on board. They strongly suggest that time pressure should not be placed on newly trained surgeons, who will become more efficient with time in any case, and that they should be supervised for the first 20 circumcisions they perform after training, in addition to periodic supervision for the next 80. This surgical procedure, described in male circumcision circles as ‘minor surgery on a major organ’, warrants the strong emphasis being placed on safety and quality assurance.

Kline MW, Ferris MG, Jones DC, Calles NR, Mizwa MB, Schwarzwald HL, Wanless RS, Schutze GE. The Paeditric AIDS Corps: responding to the African HIV/AIDS health professional resource crisis. Paediatrics. 2009 Jan;123(1):134-6.

Health professional capacity for delivery of HIV care and treatment is severely constrained across sub-Saharan Africa. African health professional expertise in paediatrics is in particularly short supply. Here Kline et al describe a Paediatric AIDS Corps program that was designed to place paediatricians and other physicians in Africa on a long-term basis to expand existing health professional capacity for paediatric and family HIV care and treatment. In the first 2 years of this program, 76 physicians were placed in 5 African countries that have been hit hard by AIDS. Enrolment of HIV-infected children in care more than quadrupled over a 24-month period, to 26 590. The authors believe that this pilot program can serve as a model for larger-scale efforts to immediately expand access for African children and families to life-saving HIV care and treatment.

Editors’ notes: With health professional capacity for delivering HIV treatment and care severely constrained across sub-Saharan Africa, attention has turned to task-shifting to other health cadres, task-sharing which involves parts of procedures or tasks being taken on by different health care providers, recruiting and retaining new health caregivers, and hosting short-term volunteer projects. This programme, responding to the fact that children are underrepresented among patients on antiretroviral treatment in virtually every setting in sub-Saharan Africa, mobilised US graduates of residency training programmes in paediatrics, family medicine, and internal medicine for assignments of a year or longer in Botswana, Lesotho, Swaziland, Malawi, and Burkina Faso. They receive a living stipend, full benefits, a housing allowance, and student loan debt relief. The programme plans its own obsolescence by training local health professionals. Its success in improving paediatric treatment coverage while being locally acceptable will be of interest to many worldwide who would like to contribute in some way to improve the dire situation of the vast majority of the 2 million children living with HIV in Africa.

Kim JC, Askew I, Muvhango L, Dwane N, Abramsky T, Jan S, Ntlemo E, Chege J, Watts C. RADAR, School of Public Health, University of the Witwatersrand, Acornhoek, South Africa. Comprehensive care and HIV prophylaxis after sexual assault in rural South Africa: the Refentse intervention study. BMJ. 2009 Mar 13;338:b515.

Although international guidelines specify the central role of the health sector in providing comprehensive care, including HIV post-exposure prophylaxis (PEP), after sexual assault, in both industrialised and developing countries there are many challenges to providing timely and comprehensive services. A nurse-driven model of post-rape care was integrated into existing hospital services; the before and after study design evaluated impacts on quality of care, reviewing 334 hospital charts and conducting interviews with 16 service providers and 109 patients in a 450-bed district hospital in rural South Africa. The key measures for improvement examined were quality of care after rape (forensic history and examination, provision of emergency contraception, prophylaxis for sexually transmitted infections, referrals); provision of HIV counselling and testing and provision and completion of full 28 day course of PEP; and service utilisation (number of service providers seen on first visit and number of rape cases presenting to hospital per month). After completing baseline research, Kim and colleagues introduced a five-part intervention model, consisting of a sexual violence advisory committee, hospital rape management policy, training workshop for service providers, designated examining room, and community awareness campaigns. Existing services had been fragmented and of poor quality. After the intervention, there were considerable improvements in clinical history and examination, pregnancy testing, emergency contraception, prophylaxis for sexually transmitted infections; HIV counselling and testing, PEP, trauma counselling, and referrals. Completion of the 28-day course of PEP drugs increased from 20% to 58%. The authors conclude that it is possible to improve the quality of care after sexual assault, including HIV prophylaxis, within a rural South African hospital at modest cost, using existing staff. With additional training, nurses can become the primary providers of this care.

Editors’ note: Refentse means ‘we shall overcome’ in Venda, the language of this rural South African area and that is exactly what these investigators aimed to do. Aside from immediate genital and bodily injuries, sexual violence brings risks of HIV and sexually transmitted disease, unwanted pregnancy, urinary tract infections, chronic pelvic pain, miscarriage, depression, substance abuse, post-traumatic stress disorder, and suicide. They used formative research to conduct a baseline assessment with providers and patients to define problems and design a strategy for change. The process and its positive findings are an example for managers and providers of sexual assault care, but also of other services, who are keen to embark on a transparent, participatory process to improve their programme outcomes.

Gene transfer has potential as a once-only treatment that reduces viral load, preserves the immune system, and avoids lifetime highly active antiretroviral therapy. This study, which is to the knowledge of Mitsuyasu and colleagues the first randomized, double-blind, placebo-controlled, phase 2 cell-delivered gene transfer clinical trial, was conducted in 74 HIV-1-infected adults who received a tat-vpr-specific anti-HIV ribozyme (OZ1) or placebo delivered in autologous CD34(+) hematopoietic progenitor cells. There were no OZ1-related adverse events. There was no statistically significant difference in viral load between the OZ1 and placebo group at the primary end point (average at weeks 47 and 48), but time-weighted areas under the curve from weeks 40-48 and 40-100 were significantly lower in the OZ1 group. Throughout the 100 weeks, CD4(+) lymphocyte counts were higher in the OZ1 group. This study indicates that cell-delivered gene transfer is safe and biologically active in individuals with HIV and can be developed as a conventional therapeutic product.

Editors’ note: Gene therapy, which could prove a long-lived alternate to small molecule antiretroviral therapy, includes a variety of approaches. Ribozymes, used in this Phase II trial, are catalytic RNA molecules that can be engineered to target specific RNA sequences without ‘off target’ effects. These investigators hypothesized that a tat-vpr-specific anti-HIV ribozyme would make immune cell forbears change to produce a pool of mature bone marrow and lymph cells that would be protected from HIV replication. Although the trial did not show efficacy, viral loads were consistently lower in the treated group and there were no safety concerns. These are early days for gene therapy for HIV infection but initial results hold some promise.

Van der Borght and colleagues aimed to evaluate the effectiveness of an HIV workplace programme in sub-Saharan Africa. The international brewing company, Heineken, introduced an HIV workplace programme in its African subsidiaries in 2001. Beneficiaries from 16 sites in 5 countries were eligible. HIV type-1 (HIV-1)-infected individuals were assessed clinically and immunologically, and started highly active antiretroviral therapy if they had AIDS or had a CD4+ T-cell count <300 cells/microl. In this cohort, study patients were followed-up for vital status, new AIDS events, CD4+ T-cell count, and haemoglobin. Over the first 5 years of the programme, 431 adults were found to be HIV-1-infected. The mortality rate among those not yet taking highly active antiretroviral therapy was 2.6 per 100 person-years of observation. By October 2006, 249 patients had started highly active antiretroviral therapy at a median CD4+ T-cell count of 170 cells/microl; 59 (23.7%) patients were in CDC stage C. Among patients on highly active antiretroviral therapy, 25 died and 7 were lost to follow-up. The mortality rate was 3.7 per 100 person-years of observation overall, 14 per 100 person-years of observation in the first 16 weeks and 2.5 per 100 person-years of observation thereafter (P < 0.0001). At 4 years after start of treatment, 89% of patients were known to be alive. The CD4+ T-cell count increased by a median of 153 and 238 cells/microl after 1 and 4 years of highly active antiretroviral therapy, respectively. In this HIV workplace programme in sub-Saharan Africa, long-term high survival was achieved.

Editors’ note: Leading the way forward for private sector engagement in HIV in Africa, this private sector company began implementing an HIV workplace programme in May 2001 in Nigeria, Rwanda, Burundi, Republic of Congo, and Democratic Republic of Congo. Not only its own direct staff but also the African staffs of its subsidiaries, their spouses, and their children are entitled to free healthcare by the company. With voluntary and confidential HIV testing, assessment for treatment initiation, no drug stock-outs, and good treatment durability with low loss to follow-up, this small but well-managed and adequately funded programme achieved excellent treatment outcomes over 5 years. This is a good example of corporate social responsibility in action – cheers!

Attia and colleagues aimed to synthesize the evidence on the risk of HIV transmission through unprotected sexual intercourse according to viral load and treatment with combination antiretroviral therapy. They conducted a systematic review and meta-analysis, searching Medline, Embase, and conference abstracts from 1996-2009. The authors included longitudinal studies of serodiscordant couples reporting on HIV transmission according to plasma viral load or use of antiretroviral therapy and used random-effects Poisson regression models to obtain summary transmission rates [with 95% confidence intervals, (CI)]. If there were no transmission events they estimated an upper 97.5% confidence limit. They identified 11 cohorts reporting on 5021 heterosexual couples and 461 HIV-transmission events. The rate of transmission overall from antiretroviral therapy-treated patients was 0.46 (95% CI 0.19-1.09) per 100 person-years, based on five events. The transmission rate from a seropositive partner with viral load below 400 copies/ml on antiretroviral therapy, based on two studies, was zero with an upper 97.5% confidence limit of 1.27 per 100 person-years, and 0.16 (95% CI 0.02-1.13) per 100 person-years if not on antiretroviral therapy , based on five studies and one event. There were insufficient data to calculate rates according to the presence or absence of sexually transmitted infections, condom use, or vaginal or anal intercourse. Studies of heterosexual discordant couples observed no transmission in patients treated with antiretroviral therapy and with viral load below 400 copies/ml, but data were compatible with one transmission per 79 person-years. Further studies are needed to better define the risk of HIV transmission from patients on antiretroviral therapy.

Editors’ note: This study underscores the considerable uncertainty about the risk of HIV transmission under ‘Swiss Commission’ conditions, that is, viral load below 40 copies/ml, no other sexually transmitted infection, and consistent adherence to antiretroviral treatment. The Commission stated ‘much lower than one per 100,000 acts of sexual intercourse’ whereas this systematic review and meta-analysis of existing data found them compatible with one new infection for every 79 person-years of follow-up (or 7900 acts of sexual intercourse, if the yearly average is 100 contacts). Further studies are needed to quantify HIV transmission risk in different populations, including men who have sex with men for whom there are no comparable published data. In the meantime, since the Swiss Commission statement January 2008 UNAIDS has continued to reassert the importance of correct and consistent condom use – a key part of positive prevention and a cornerstone of HIV prevention for people without HIV.

Wood E, Kerr T, Marshall BD, Li K, Zhang R, Hogg RS, Harrigan PR, Montaner JS. Longitudinal community plasma HIV-1 RNA concentrations and incidence of HIV-1 among injecting drug users: prospective cohort study. BMJ. 2009 Apr 30;338:b1649.

To examine the relation between plasma HIV-1 RNA concentrations in the community and HIV incidence among injecting drug users, Wood and colleagues conducted a prospective cohort study in an inner city community in Vancouver, Canada. Injecting drug users, with and without HIV, were followed up every six months between 1 May 1996 and 30 June 2007. The main outcome measures were estimated community plasma HIV-1 RNA in the six months before each HIV-negative participant’s follow-up visit and associated HIV incidence. Among 622 injecting drug users with HIV, 12 435 measurements of plasma HIV-1 RNA were obtained. Among 1429 injecting drug users without HIV, there were 155 HIV seroconversions, resulting in an incidence density of 2.49 (95% confidence interval 2.09 to 2.88) per 100 person years. In a Cox model that adjusted for unsafe sexual behaviours and using nonsterile syringes, the estimated community plasma HIV-1 RNA concentration remained independently associated with the time to HIV seroconversion (hazard ratio 3.32 (1.82 to 6.08, P<0.001), per log(10) increase). When the follow-up period was limited to observations after 1 January 1998 (when the median plasma HIV RNA concentration was <20 000 copies/ml), the median viral load was no longer statistically associated with HIV incidence (1.70 (0.79 to 3.67, P=0.175), per log(10) increase). The authors concluded that a longitudinal measure of community plasma HIV-1 RNA concentration was correlated with the community HIV incidence rate and predicted HIV incidence independent of unsafe sexual behaviours and sharing used syringes. If these findings are confirmed, they could help to inform both HIV prevention and treatment interventions.

Editors’ note: This ecological study estimated community plasma viral load from the viral loads of injecting drug users on treatment in this urban community which has a centralised antiretroviral dispensation programme and HIV laboratory. The proportion of patients on 3 or more antiretroviral drugs increased from 8.4% in 1996 to 98.8% in 2007 while both median estimated community plasma HIV-1 RNA concentrations and HIV incidence fell. The likelihood that an HIV-negative injecting drug user had seroconverted since the last clinic visit was correlated with the median estimated community viral load during the prior 6 months. It is not possible to conclude from these data that the association was causal but the fact that the highest rates of HIV seroconversion occurred in the year after the highest community plasma HIV-2 concentration support this hypothesis. These findings no doubt influenced the provincial government to fund an innovative programme to expand access to treatment for street-involved people living in Vancouver’s downtown eastside and downtown Prince George, British Columbia.

This paper presents the findings, shares the methodology, and outlines the benefits of a multi-country participatory research process on a unique data source: stories about HIV and AIDS written by young Africans. Between 1997 and 2005, more than 105,000 young people from 37 countries participated in competitions inviting them to think up storylines for short fiction films to educate their communities about HIV as part of the ‘ Scenarios from Africa’ communication process. The winning stories were selected by juries made up of people living with HIV and other local specialists in prevention, treatment and care; former contest winners and other young people; and communication specialists, including the top African directors, who went on to transform the ideas into short films. In 2005, over 200 jurors selected 30 winners from the 22,894 stories submitted that year by 63,327 contest participants. After reading around 200 stories each and participating in the selection process, jurors compiled their observations and recommendations. The jurors’ findings reveal notable persistent shortcomings in existing communication efforts and identify key emerging needs. In some areas, they show remarkable consistency across the continent. Jurors view this as a powerful needs assessment, networking, and capacity building process that motivates action.

Editors’ note: Between 1997 and 2005 the Scenarios in Africa participatory communication initiative ran four contest cycles for storylines for short fiction films, producing an average of three films a year by Africa’s most celebrated filmmakers (viewable at www.globaldialogues.org) to trigger discussion about the epidemic in communities across West Africa. Analysis of 2005 submissions revealed a high level of understanding of basic facts, most marked among younger contestants. The most common recommendation made by the jurors was for destigmatisation to counter moralisation of the epidemic and to humanise people living with HIV. Jurors placed primary emphasis on fostering the life skills of young people so they can enact HIV prevention. Mobilised to submit stories by more than 1000 local organisations, the participating young people communicated rich insight into their contextualised understanding of the epidemic, information from the front lines of youth prevention in Africa with direct relevance for creating more enabling environments for HIV prevention.

The lifetime deferral for men who have sex with men has not been harmonized with the 12-month deferral for similar-risk activities through heterosexual contacts. This occurs primarily because of fears of increased transfusion transmission of known sexually and transfusion-transmitted viruses for which donor blood is (eg, HIV) or is not (eg, human herpesvirus 8 [HHV-8]) tested and also of fears of novel agents that may share the epidemiology and long asymptomatic phase of HIV. A 12-month men who have sex with men deferral could result in release of 1 HIV-infectious donation every 11 years in the United States. This risk is smaller than the risk from allowing the continued use of pooled whole blood-derived platelets (release of 1 infectious platelet dose every 1.67 years), a risk that is considered “tolerable.” Provided that measures to reduce the number of allogeneic-donor exposures to novel pathogens (which may be vector- or food-borne rather than sexually transmitted) are implemented, and the deferral for similar-risk activities through heterosexual contacts is extended to 5 years, a 5-year men who have sex with men deferral could be justified because of the interval between emergence of a novel pathogen and introduction of measures to protect the blood supply. Also, provided that measures to protect the blood supply from HHV-8 are implemented, a lifetime men who have sex with men deferral could be justified because of the uncertainty about the clinical consequences of transfusion transmission of HHV-8. Because such alternate measures, which would have had a greater impact on safety than the men who have sex with men deferral, have not been implemented to demonstrate a consistent approach to safety, maintenance of the current men who have sex with men deferral appears to be selectively precautionary and cannot be justified.

Editors’ note: Arguments have been advanced to harmonise the deferral periods for men who have sex with men with those for heterosexuals with similar-risk activities. Argentina, Brazil, Japan, Hungary, New Zealand, Russia, and South Africa have substituted a 1-, 5-, or 10-year deferral for the lifetime deferral of men who have sex with men. The USA, Canada, and the 19-nation European Blood Alliance maintain their current positions. This article argues cogently for a scientifically based, consistent approach to blood safety. It highlights the ramifications for blood safety of inconsistencies in national policies, arguing that the men who have sex with men lifetime deferral is selectively precautionary. More can be achieved by interventions to protect the blood supply against HHV-8 and by prohibiting the use of pooled whole blood-derived platelets. On balance, arguments can be made that extending the heterosexual deferral from 1 year to 5 years and harmonising the men who have sex with men deferral to 5 years would reasonably protect against an ‘HIV-like’ agent that could emerge in the future.

There has long been recognition that individual risk factors can only partially explain vulnerability to HIV infection, and that a broader range of socioeconomic, cultural and political factors must be taken into account. More recently this understanding has been applied to addressing obstacles to accessing HIV treatment. Yet, while structural interventions aimed at contextual factors related to HIV prevention and treatment have been shown to be effective, they have not been widely implemented. Using the situation of Zimbabwe as an example, Amon and Kasambala present an illustration of how contextual barriers can be understood in human rights terms, and how using a human rights analysis can specifically help define ‘structural-rights’ interventions and compel their implementation.

Editors’ note: This article, a must-read for all those interested in effective combination prevention, demonstrates how explicitly recognising human rights provides a mechanism to address structural level barriers to HIV prevention and care, reinforcing government and donor agency accountability to redress societal power differentials. In other words, situating concerns about the socioeconomic, cultural, and political barriers to HIV prevention within a context of human rights provides a framework for action founded on the obligations and responsibilities of states. Drawing on the current HIV and human rights crisis in Zimbabwe, specific examples are provided of concrete structural-rights interventions to address the right to earn a livelihood and own property; the right to freedom of expression, assembly, and information; the right to freedom from gender-based and sexual violence; and the right to the progressive realisation of health.

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Male circumcision significantly reduced the incidence of human immunodeficiency virus (HIV) infection among men in three clinical trials. Tobian and colleagues assessed the efficacy of male circumcision for the prevention of herpes simplex virus type 2 (HSV-2) and human papillomavirus (HPV) infections and syphilis in HIV-negative adolescent boys and men. They enrolled 5534 HIV-negative, uncircumcised male subjects between the ages of 15 and 49 years in two trials of male circumcision for the prevention of HIV and other sexually transmitted infections. Of these subjects, 3393 (61.3%) were HSV-2– seronegative at enrolment. Of the seronegative subjects, 1684 had been randomly assigned to undergo immediate circumcision (intervention group) and 1709 to undergo circumcision after 24 months (control group). At baseline and at 6, 12, and 24 months, the authors tested subjects for HSV-2 and HIV infection and syphilis, along with performing physical examinations and conducting interviews. In addition, they evaluated a subgroup of subjects for HPV infection at baseline and at 24 months. At 24 months, the cumulative probability of HSV-2 seroconversion was 7.8% in the intervention group and 10.3% in the control group (adjusted hazard ratio in the intervention group, 0.72; 95% confidence interval [CI], 0.56 to 0.92; P = 0.008). The prevalence of high-risk HPV genotypes was 18.0% in the intervention group and 27.9% in the control group (adjusted risk ratio, 0.65; 95% CI, 0.46 to 0.90; P = 0.009). However, no significant difference between the two study groups was observed in the incidence of syphilis (adjusted hazard ratio, 1.10; 95% CI, 0.75 to 1.65; P = 0.44). In addition to decreasing the incidence of HIV infection, male circumcision significantly reduced the incidence of HSV-2 infection and the prevalence of HPV infection, findings that underscore the potential public health benefits of the procedure.

Editors’ note: To date, limited statistical power, confounding by sexual practices correlated with a high risk of transmission, and determination of circumcision status only by self-report have plagued observational studies on male circumcision and sexually transmitted infections. This randomised, controlled trial in rural Uganda demonstrates that male circumcision in adolescent boys and men significantly reduces the incidence of herpes simplex virus-2 (HSV-2) infection and the prevalence of human papilloma virus (HPV) infection. Whether the latter is due to decreased HPV acquisition or increased HPV clearance is unclear but it does explain the lower risk of cervical cancer experienced by women whose partners are circumcised. The adjusted efficacy of male circumcision was 28% for the prevention of HSV-2, an infection thought to be a cofactor in HIV acquisition. This may explain in part the incontrovertible partial protection from HIV afforded by male circumcision.

Delany-Moretlwe S, Lingappa JR and Celum C. New Insights on Interactions Between HIV-1 and HSV-2. Curr Infect Dis Rep. 2009;11(2):135-42.

Herpes simplex type 2 (HSV-2) infection is common and frequently asymptomatic. Concerns exist about the high prevalence of HSV-2, particularly in areas of high HIV prevalence, because of observations that HSV-2 is associated with an increased risk of HIV acquisition, transmission, and disease progression. Several randomized trials have tested or are testing whether HSV-2 treatment can limit the spread of HIV, with mixed results. Although treatment with acyclovir, 400 mg twice daily, does not reduce HIV incidence, suppressive acyclovir and valacyclovir reduce HIV levels in plasma and in the genital tract. Ongoing trials are evaluating whether HSV suppression will reduce HIV transmission and disease progression. Until a protective HSV-2 or HIV vaccine is available, effective interventions that reduce the effect of HSV-2 on HIV transmission are critically needed.

Editors’ note: This excellent summary of what is known about the complex and bidirectional interactions between HIV-1 and herpes simplex virus–2 (HSV-2) was published before the May 8 th release of results from the multi-centre Partners in Prevention Study of 3408 discordant couples conducted in Botswana, Kenya, Rwanda, South Africa, Tanzania, Uganda and Zambia. To test whether HSV-2 daily suppressive therapy would reduce HIV transmission, HIV/HSV-2 co-infected partners were randomised to receive acyclovir 400 mg twice daily or matching placebo for 2 years while the uninfected partner was followed-up for HIV-1 seroconversion. Although acyclovir reduced the frequency of genital ulcers by 73% and HIV viral load by 40%, no significant difference was found in the rate of HIV transmission. A 17% reduction in HIV disease progression produced by low cost acyclovir was an intriguing result worthy of further study. With more than half a billion people infected with HSV-2, including up to 90% of people living with HIV, developing an HSV-2 vaccine continues to be a very high priority.

Advances in HIV treatment availability mean that the promise of highly active anti-retroviral treatment to turn HIV into a manageable chronic illness is becoming a reality for millions. However the mutability of the virus means that treatment adherence demands are high, and the supply of these life-saving treatments needs to be constant. The onus is generally placed on the individual to adhere, and there is little focus in research or policy on the state’s adherence to delivering treatment consistently. Bernays and colleagues undertook in-depth qualitative interviews to explore the narratives of HIV treatment experience among 41 people living with HIV and 18 HIV treatment service providers in Serbia and Montenegro, a transitional setting in which state delivered and funded HIV treatment is inconsistently available. Data were analysed inductively and thematically. Treatment shortages were common so the delivery of appropriate HIV treatment was not continuous. Access to reliable treatment and supply forecast information was weak and uneven. The insecure treatment situation fostered significant anxiety amongst people living with HIV. In the absence of reliable and sustained treatment access, information, and support, people living with HIV absorb the anxieties of system failures. This uncertainty led to an individuation of “treatment”. People living with HIV adopted rationing strategies to mediate their anxiety, energy and hope. This predominately resulted in varying forms of disengagement and neglect for social change. It is likely that this has significant negative implications for the promotion of HIV treatment advocacy and anti-stigma efforts.

Editors’ note: Adherence literature to date has focused primarily on patient adherence to treatment regimens rather than on the social and psychological effects of involuntary treatment interruptions. Fragile treatment delivery undermines the quality of life and capacity of people living with HIV to manage it as a manageable, chronic illness. Although some people in this study reduced their anxiety by fostering networks and resources to gain access to information and treatment, a form of social capital to generate security, others withdrew, trusting no one but their treatment provider and becoming less likely to disclose to others. This research highlights the clear need for a social science of scale-up .

Sopheab H, Morineau G, Neal JJ, Saphonn V, Fylkesnes K. Sustained high prevalence of sexually transmitted infections among female sex workers in Cambodia: high turnover seriously challenges the 100% Condom Use Programme. BMC Infect Dis. 2008;8:167.

Cambodia ’s 100% Condom-Use Programme, implemented nationally in 2001, requires brothel-based female sex workers to use condoms with all clients. In 2005, Sopheab et al conducted a sexually transmitted infection survey among female sex workers. This paper presents sexually transmitted infection prevalence and related risk factors, and discusses prevalence trends in the context of the 100% Condom-Use Programme in Cambodia. From March-May, 1079 female sex workers from eight provinces consented to participate, provided specimens for syphilis, chlamydia, and gonorrhoea testing, and were interviewed. Univariate and multivariate logistic regression analysis was used to determine factors associated with sexually transmitted infections. The prevalence of sexually transmitted infection was compared with data from the 1996 and 2001 sexually transmitted infection surveys. Most female sex workers were young (55% aged 15-24) and new to sex work ( 60% had worked 12 <or= months). Consistent condom use with clients was reported by 80% of female sex workers, but only 38% of female sex workers always used condoms with sweethearts or casual partners. Being new to sex work was the only factor significantly associated with “any sexually transmitted infection” (OR = 2.1). Prevalence of syphilis was 2.3%; chlamydia, 14.4%; gonorrhoea, 13.0%; and any sexually transmitted infection, 24.4%. Prevalence of each sexually transmitted infection in 2005 was significantly lower than in 1996, but essentially the same as prevalence observed in 2001. New female sex workers were found to have substantially higher prevalence than those with longer experience. The percent of female sex workers who used condoms consistently was high with clients but remained low with non-paying sex partners. Because of the high turnover of female sex workers, the prevention needs of new female sex workers should be ascertained and addressed. Despite 100% Condom-Use Programme implementation, the prevalence of sexually transmitted infections among female sex workers was the same in 2005 as it was in 2001. Limited coverage and weak implementation capacity of the programme along with questionable quality of the sexually transmitted infection services are likely to have contributed to the sustained high prevalence. The programme should be carefully reviewed in terms of intensity, quality, and coverage.

Editors’ note: Successful 100% condom use programmes in Thailand in late 1989 and Cambodia in late 1998 were rigorously conducted with high coverage and intensity. Sustaining such results given the high turnover among sex workers requires regular evaluations of programme quality and impact. Using curable bacterial sexually transmitted infection prevalence makes sense as they are good biological markers reflecting recent risk behaviour but different data collection methods, specimen-sampling techniques, and laboratory methods can make comparison of survey results hazardous. One thing is clear – Cambodia’s 100% condom-use programme, implemented nationally in 2001, should focus attention on ascertaining and addressing the prevention needs of new sex workers.

Monteiro S. STD/AIDS prevention in Portuguese-speaking Africa: a review of the recent literature in the social sciences and health. Cad Saude Publica. 2009;25(3):680-6.

The article reviews academic literature in the social sciences and health on the problems and challenges of sexually transmitted diseases and HIV prevention in Portuguese-speaking African countries. Based on a bibliographic survey of the SciELO, PubMed, and Sociological Abstracts databases between 1997 and 2007, the research under review was organized into two groups, according to content. The first group of studies sought to understand sexually transmitted diseases and HIV vulnerability among social groups by examining local cultural and socioeconomic factors as related to gender dynamics, sexuality, colour/race, religion and health care. The second group encompassed critical assessments of shortcomings in the sexually transmitted diseases and HIV educational messages delivered by governments and international agencies. Attention is called to the way in which the presence of traditional medicine systems and the occurrence of civil wars in the post-colonial period affect the sexually transmitted diseases and HIV epidemic in the African countries under study.

Editors’ note: The Portuguese-speaking African countries, known by the acronym PALOP (Países Africanos de Língua Oficial Portuguesa) are Mozambique, Angola, Cape Verde, Guinea-Bissau, Equatorial Guinea, and São Tomé and Principe. Although there are cultural and socio-economic similarities between these countries, appreciation of local contexts is critical to understanding how healthcare practices, gender roles, and the interpretation of prevention messages are mediated locally by cultural dynamics and socio-economic and political contexts. This review suggests that demystifying condom use in a pragmatic CNN approach (condoms, needles, and negotiation) as opposed to the moralizing ABC approach (abstinence, be faithful, and condoms for marginalized populations), along with frank and open discussions of sexuality in public fora and the media, would achieve positive results, particularly if accompanied by advances in citizenship rights and equal opportunities.

Institutional tuberculosis (TB) transmission is an important public health problem highlighted by the HIV pandemic and the emergence of multidrug- and extensively drug-resistant TB. Effective TB infection control measures are urgently needed. Escombe et al evaluated the efficacy of upper-room ultraviolet (UV) lights and negative air ionization for preventing airborne TB transmission using a guinea pig air-sampling model to measure the TB infectiousness of ward air. For 535 consecutive days, exhaust air from an HIV-TB ward in Lima, Peru, was passed through three guinea pig air-sampling enclosures each housing approximately 150 guinea pigs, using a 2-d cycle. On UV-off days, ward air passed in parallel through a control animal enclosure and a similar enclosure containing negative ionizers. On UV-on days, UV lights and mixing fans were turned on in the ward, and a third animal enclosure alone received ward air. TB infection in guinea pigs was defined by monthly tuberculin skin tests. All guinea pigs underwent autopsy to test for TB disease, defined by characteristic autopsy changes or by the culture of Mycobacterium tuberculosis from organs. 35% (106/304) of guinea pigs in the control group developed TB infection, and this was reduced to 14% (43/303) by ionizers, and to 9.5% (29/307) by UV lights (both p <0.0001 compared with the control group). TB disease was confirmed in 8.6% (26/304) of control group animals, and this was reduced to 4.3% (13/303) by ionizers, and to 3.6% (11/307) by UV lights (both p <0.03 compared with the control group). Time-to-event analysis demonstrated that TB infection was prevented by ionizers (log-rank 27; p <0.0001) and by UV lights (log-rank 46; p <0.0001). Time-to-event analysis also demonstrated that TB disease was prevented by ionizers (log-rank 3.7; p =0.055) and by UV lights (log-rank 5.4; p=0.02). An alternative analysis using an airborne infection model demonstrated that ionizers prevented 60% of TB infection and 51% of TB disease, and that UV lights prevented 70% of TB infection and 54% of TB disease. In all analysis strategies, UV lights tended to be more protective than ionizers. In conclusion, upper-room UV lights and negative air ionization each prevented most airborne TB transmission detectable by guinea pig air sampling. Provided there is adequate mixing of room air, upper-room UV light is an effective, low-cost intervention for use in TB infection control in high-risk clinical settings.

Editors’ note: Using the guinea pig air sampling model of the 1950s to advance further their DNA fingerprinting study which showed that 8.5% of 118 TB patients were responsible for 98.9% of the guinea pig infections (see issue 59 of HIV This Week), these authors turned their attention to preventing TB transmission. This is the first controlled evaluation assessing the effects on airborne TB transmission in a clinical setting of upper-room ultraviolet (UV) light that kills M. tuberculosis and negative ionization which gives airborne particles a charge that makes them stick to surfaces. Despite the high humidity of Lima (70 to 90%) which would affect UV germicidal efficacy, upper-room UV light had a marked effect reducing both TB infection (70%) and disease (54%). Although these are guinea pig studies, the evidence for this environmental control measure is strong. Upper-room UV lighting is relatively low cost compared to mechanical ventilation and should be expertly installed now in all waiting rooms, out-patient and emergency departments, and antiretroviral treatment facilities where undiagnosed and untreated TB patients are likely to be found. Designing simple UV fixtures for low-resource settings will facilitate scale-up further.

LoBue P. Extensively drug-resistant tuberculosis. Curr Opin Infect Dis. 2009;22(2):167-73.

The purpose of this review was to describe the origin, epidemiology, diagnosis, treatment, prevention, and control of extensively drug-resistant tuberculosis (XDR TB). XDR TB is defined as the occurrence of TB in persons whose Mycobacterium tuberculosis isolates are resistant to isoniazid and rifampin and to any fluoroquinolone and at least one of three injectable second-line drugs (i.e., amikacin, kanamycin, or capreomycin). As of June 2008, XDR TB has been found in 49 countries including the United States. It generally takes several weeks to detect XDR TB using conventional culture-based methods, although some progress is being made in developing rapid molecular tests. Treatment for XDR TB is difficult, usually requiring at least 18-24 months of four to six second-line anti-TB drugs. Treatment success rates are generally 30-50%, with very poor outcomes in HIV-infected patients. Management of contacts to infectious XDR TB patients is complicated by the lack of a proven effective treatment for XDR latent tuberculosis infection. XDR TB is an emerging global health threat. The disease is difficult and expensive to diagnose and treat, and outcomes are frequently poor. New rapid diagnostic tests and new classes of anti-TB drugs are needed to successfully combat this global problem.

Editors’ note: Following the death in 2006 in KwaZulu Natal of 52 of 53 patients diagnosed with XDR-TB (median survival of 16 days and 85% having acquired resistant TB rather than having developed it while under treatment), consultations were held, the definition of XDR-TB was changed, and WHO established a Global Task Force on XDR-TB. In 2007, WHO produced an eight-objective global response plan for MDR- and XDR-TB and published in 2008 its first resistance report to include XDR-TB. XDR-TB is most common in terms of absolute numbers in Eastern Europe and the former Soviet Republics of Central Asia. Given that MDR-TB is estimated to have increased from 270,000 cases in 2000 to 490,000 cases in 2006 and XDR-TB is estimated to represent approximately 7% of these, XDR-TB is deemed to be on the rise. The growing problem of anti-TB drug resistance and the high prevalence of HIV among TB patients in certain regions, particularly in sub-Saharan Africa, underscore the urgency of developing new TB resistance testing tools and new anti-TB treatments.

Androgen deficiency is common in HIV-infected women. Dolan Looby and colleagues investigated the long-term effects of transdermal testosterone on body composition, bone mineral density, quality of life, and safety. Twenty-five HIV-infected women with free testosterone below the median (</=3 pg/ml) of the female normal range were randomized to receive transdermal testosterone (300 mug twice weekly) or identical placebo over 18 months. Women demonstrated low androgen levels (1.3 +/- 0.1 pg/ml) with relatively low weight (22.8 +/- 0.6 kg/m) and low bone mineral density (-0.61 +/- 0.17 SD hip T score) at baseline. No statistically significant differences were seen between the groups at baseline. The discontinuation rate was 16% and did not differ between treatment groups (P = 0.24). Free testosterone by equilibrium dialysis increased over 18 months (7.9 +/- 1.8 vs. 0.3 +/- 0.4 pg/ml; P = 0.002, testosterone vs. placebo). Testosterone was well tolerated and did not affect lipids, liver, or safety indices. Lean mass (1.8 +/- 0.5 vs. 0.8 +/- 0.9 kg; P = 0.04) and BMI (1.6 +/- 0.4 vs. 0.8 +/- 0.6 kg/m; P = 0.03, testosterone vs. placebo) increased in response to testosterone, whereas fat mass remained unchanged. Testosterone increased bone mineral density at the hip (0.01 +/- 0.01 vs. -0.01 +/- 0.01 g/cm; P = 0.02) and trochanter (0.01 +/- 0.01 vs. -0.02 +/- 0.01 g/cm; P = 0.01, testosterone vs. placebo). Testosterone significantly improved depression indices (-6.8 +/- 2.2 vs. -1.9 +/-3.1; P = 0.02) and problems affecting sexual function (-1.8 +/- 0.8 vs. 0.5 +/-0.5; P = 0.01, testosterone vs. placebo). Long-term testosterone administration was well tolerated in HIV-infected women and resulted in significant improvements in body composition, bone mineral density, and quality of life indices. Further evaluation of the safety and efficacy of testosterone use among HIV-infected women is warranted.

Editors’ note: Androgen deficiency is highly prevalent among women living with HIV and is associated with reduced lean body mass, bone mineral density, and quality of life. Whereas treatment is routine in HIV-positive men with low testosterone levels, no treatment strategies exist for women with similar problems. This is the first long-term (18 months) randomised controlled trial in HIV-positive women of the effects of testosterone administered via a transdermal patch versus a control patch. Because it reveals very encouraging effects on bone mineral density, body composition, and quality of life without signs of virilisation, further studies of long-term treatment with testosterone for women living with HIV should proceed to see if these encouraging findings are confirmed.

Franco-Paredes C, Hidron A, Tellez I, Lesesne J, Del Rio C. HIV Infection and Travel: Pretravel Recommendations and Health-Related Risks. Top HIV Med. 2009;17(1):2-11.

In the current era of globalization and ease of air travel combined with the increased survival attained since the advent of potent antiretroviral therapy, HIV-infected individuals are travelling to remote and resource-limited areas of the world. Travel-related health risks in a patient with HIV depend on the patient’s immune status, destination, travel itinerary, and type of travel. HIV-infected patients with a CD4+ count of 200 cells/mm3 or lower, particularly those who are treatment-naive and newly diagnosed, are at increased risk of complications when travelling to resource-poor settings. These increased risks include those of acquiring gastrointestinal, respiratory, and endemic tropical infectious diseases. Individuals with a CD4+ count higher than 200 cells/mm3 (whether receiving antiretroviral treatment or not) are considered to have limited immune deficiency for the purpose of travel-related recommendations; in general, they may safely receive most recommended and required vaccines. Pretravel consultation before departure is crucial to address strategies to protect against vaccine-preventable diseases (routine, recommended, and required vaccinations); vector-borne diseases, particularly malaria; gastrointestinal infections; and sexually transmitted diseases. HIV-infected travellers who are ill, particularly those with fever, should undergo an immediate medical evaluation to rule out the possibility of a life-threatening infectious disease such as malaria.

Editors’ note: This excellent review should be required reading for all UN staff living with HIV who travel internationally or who live in resource-constrained settings. It compiles current knowledge on the use of live attenuated and inactivated vaccines by CD4+ count and provides practical advice. This includes delaying travel until 3 months after starting antiretroviral treatment to avoid immune reconstitution syndromes during travel, keeping medication with its official documentation in hand luggage with a back-up supply in checked luggage, hand hygiene with water and soap or alcohol-based solutions, knowing about potential protease inhibitor drug interactions with malaria treatment, careful attention to water and food safety to avoid enteric infections, adherence to safer sex strategies, and the importance of prompt evaluation of fever while travelling or on return .

Nachega and colleagues aimed to determine adherence to and effectiveness of antiretroviral therapy in adolescents vs. adults in southern Africa in an observational cohort study originating from Aid for AIDS, a private sector disease management program in southern Africa. Adolescents (age 11-19 years; n = 154) and adults (n = 7622) initiating antiretroviral treatment between 1999 and 2006 and having a viral load measurement within 1 year after antiretroviral treatment initiation were included. The primary outcomes were virologic suppression (HIV viral load </=400 copies/mL), viral rebound, and CD4 T-cell count at 6, 12, 18, and 24 months after antiretroviral treatment initiation. Secondary outcome was adherence assessed by pharmacy refills at 6, 12, and 24 months. The authors used a multivariate loglinear regression and Cox proportional hazards. A significantly smaller proportion of adolescents achieved 100% adherence at each time point (adolescents: 20.7% at 6 months, 14.3% at 12 months, and 6.6% at 24 months; adults: 40.5%, 27.9%, and 20.6% at each time point, respectively; P <0.01). Patients achieving 100% 12-month adherence were significantly more likely to exhibit virologic suppression at 12 months, regardless of age. However, adolescents achieving virologic suppression had significantly shorter time to viral rebound (adjusted hazard ratio 2.03; 95% confidence interval: 1.31 to 3.13;P <0.003). Adolescents were less likely to experience long-term immunologic recovery despite initial CD4 T-cell counts comparable to adults. Compared with adults, adolescents in southern Africa are less adherent to antiretroviral treatment and have lower rates of virologic suppression and immunologic recovery and a higher rate of virologic rebound after initial suppression. Studies must determine specific barriers to adherence in this population and develop appropriate interventions.

Editors’ note: Both because the number of adolescents on antiretroviral treatment continues to expand and because this population is most likely to benefit from optimal adherence with longest life expectancy on optimal treatment, determining the underlying reasons for the poor adherence that increases risk of morbidity and drug resistance is urgent. This study assessed adherence and outcomes among adolescents started on antiretroviral treatment when their CD4+ counts fell to 350 cells whose parents were employed by companies participating in a private sector employer-subsidized medical insurance programme in 9 countries in southern Africa. The adolescents were less likely than were adults to be on the non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimens which can achieve viral suppression with moderate levels (70-90%) of adherence. However, this cannot fully explain why adolescents were 50% less likely to maintain perfect adherence at all time points and were 70-75% less likely to be virologically suppressed at 1 and 2 years after treatment initiation. Equivalent studies in the public sector are needed to confirm these findings and qualitative studies are needed to determine the causes and provide avenues for solutions to what must be underscored as a priority treatment programme challenge.

Tuller DM, Bangsberg DR, Senkungu J, Ware NC, Emenyonu N, Weiser SD. Transportation Costs Impede Sustained Adherence and Access to HAART in a Clinic Population in Southwestern Uganda: A Qualitative Study. AIDS Behav. 2009 Mar 13. [Epub ahead of print]

The cost of transportation for monthly clinic visits has been identified as a potential barrier to antiretroviral adherence in sub-Saharan Africa and elsewhere, although there is limited data on this issue. Tuller and colleagues conducted open-ended interviews with 41 individuals living with HIV and attending a clinic in Mbarara, Uganda, to understand structural barriers to antiretroviral adherence and clinical care. Almost all respondents cited the need to locate funds for the monthly clinic visit as a constant source of stress and anxiety, and lack of money for transportation was a key factor in cases of missed doses and missed medical appointments. Participants struggled with competing demands between transport costs and other necessities such as food, housing and school fees. These findings suggest that transportation costs can compromise both antiretroviral adherence and access to care. Interventions that address this barrier will be important to ensure the success of antiretroviral programs in sub-Saharan Africa.

Editors’ note: With mean per capita income in Uganda the equivalent of 25 USD per month and monthly refill visit roundtrip transport costs ranging from 0.60 to 11.75 USD, it is not surprising that serious sacrifices by patients are required in other essential arenas such as food and school fees. These findings suggest that the concept of ‘access to medicine or lack thereof’ rather than the concept of ‘failure to adhere’, reframes the problem of missed doses as one anchored in structural and financial barriers that need to be addressed by treatment programmes and communities. Many ideas come to mind for piloting such as decentralisation to deliver drugs directly to the community through drug dispensaries, primary care clinics, and home-based care, along with transport cost subsidization for those being stabilised on their regimens and for subsequent 6 monthly control visits.

Uzochukwu BS, Onwujekwe OE, Onoka AC, Okoli C, Uguru NP, Chukwuogo OI. Determinants of non-adherence to subsidized anti-retroviral treatment in southeast Nigeria. Health Policy Plan. 2009 Mar 10. [Epub ahead of print]

The antiretroviral treatment programme in Nigeria is delivered through selected teaching and mission hospitals at a free/subsidized rate. The government aims to scale up antiretroviral treatment in the country. However, non-adherence to antiretroviral medication can lead to viral resistance, treatment failure, toxicities and waste of financial resources. This study examined the factors responsible for non-adherence to free/subsidized antiretroviral treatment in south-east Nigeria. The study was cross-sectional and descriptive. Information was collected from 174 patients selected by simple random sampling from the register of all patients who had been on antiretroviral therapy for at least 12 months at the beginning of the study period. Patients were identified during their clinic visits. Information on their socio-demographic profile, antiretroviral treatment and determinants of non-adherence to antiretroviral treatment was obtained from those who gave consent, using pre-tested interviewer-administered questionnaires. All patients clearly understood the need to take antiretroviral drugs throughout their lives, and what the costs entailed. They understood the need for periodic testing, the probability that complications would develop, cost of transportation to treatment site and the daily treatment regimen. Seventy-five per cent of respondents were not adhering fully to their drug regimen; the mean number of days that respondents had been off drugs was 3.57 days the preceding month. Reasons for non-adherence included: physical discomfort (side effects); non-availability of drugs at treatment site; forgetting to carry drugs during the day; fear of social rejection; treatment being a reminder of HIV status; and selling of own drugs to those unable to enrol in the projects. Being female, under 35 years, single, and having higher educational status were significantly associated with non-adherence. It is important that policy makers and programme managers address the factors responsible for non-adherence when scaling up subsidized ARV treatment in Nigeria and other parts of sub-Saharan Africa.

Editors’ note: With 74 treatment sites around the country in 2006 and ambitious treatment targets, Nigeria achieved only 15% access to treatment by the end of 2006 for those in need to treatment. Non-availability of drugs at the treatment centre (classic stock-outs) and side effects are the top two reasons for non-adherence in this study in Enugu Sate in southeastern Nigeria obtained using semi-structured questionnaires. Improved supply chain management, bimonthly rather than monthly dispensing to reduce transportation costs, and community/family/patient education about managing side effects and actively supporting adherence are some more obvious solutions.

Worldwide, approximately 2.5 million children (95% CI: 2.2-2.6) are living with HIV infection. In 2007 alone, approximately 420,000 children (95%CI:350,000-540,000) were newly infected with HIV – a vast majority of these infections were acquired through maternal-foetal transmission. Many of these infections could have been reduced by timely diagnosis and the delivery of interventions aimed at preventing mother-to-child HIV transmission. This perspective examines the attitudes preventing women from accessing HIV testing early on during pregnancy and the issues and challenges that remain in the institutionalization of interventions to prevent mother-to-child HIV transmission at labour and delivery. Socio-cultural and economic factors prevent women from accessing testing at an opportune time during pregnancy. In addition, a lack of adequate infrastructure often prevents timely delivery of interventions to those who access testing at the last minute (i.e., during labour and delivery). In the wake of a paediatric HIV epidemic and the need for lifelong provision of antiretroviral therapy to infected children, a simple strategy for provision of round-the-clock rapid testing and counselling services in the labour rooms may be cost saving to the healthcare systems worldwide.

Editors’ note: Although studies of programmes of point-of-care rapid HIV testing in labour and delivery have been conducted around the world, the need for additional infrastructure resources, such as round-the-clock counsellors and user friendly and accurate rapid tests, has been an impediment to wider implementation. With only 33% of women needing antiretroviral prophylaxis in pregnancy worldwide actually able to access it, innovations are needed to improve coverage. Labour and delivery are not times conducive to reflection on the personal advantages and disadvantages of knowledge of serostatus but two-stage counselling (short prepartum and extended postpartum), attention to privacy and confidentiality, timely confirmation of results to reduce false-positives and false-negatives, and community-based education engaging partners and highlighting the importance of preventing HIV transmission to infants could identify more babies in need of intrapartum and post-exposure prophylaxis and more mothers needing tailored infant feeding counselling in addition to evaluation for antiretroviral treatment, and care and support.

Lazarus R, Struthers H, Violari A. Hopes, fears, knowledge and misunderstandings: responses of HIV-positive mothers to early knowledge of the status of their baby. AIDS Care. 2009;21(3):329-34.

Little is known about how HIV-positive mothers experience and react to knowing the HIV status of their baby as diagnosed by the polymerase chain reaction (PCR) test at 4-6 weeks. This qualitative study drew on interviews with 20 mothers of HIV-negative and 18 mothers of HIV-positive babies after receiving their baby’s PCR results. Thematic analysis combined exploration of themes that appeared significant to the participants and those relevant to health care. Amongst the themes identified were the following: The period before getting the results involved active mental preparation and was emotionally stressful. Most women accepted the results, but some had doubts about their reliability. Mothers of HIV-negative babies were relieved, but mothers of HIV-positive babies were generally very distressed and expressed a sense of responsibility and guilt. Both groups of mothers had similar hopes for the future of their babies, but the timelines of mothers of HIV-positive babies tended to be shorter. Most women experienced significant levels of stress, but were able to call on support networks and use various individual coping mechanisms to manage their stress. Most women were formula feeding their babies, but regretted not being able to breastfeed. Many women had not planned their current baby and most did not intend to have more children, but many of the latter had not taken active steps to prevent further pregnancy. The findings provide pointers to shortcomings in health worker communication and suggest that more effective communication should take account of normative community views and be more closely attuned to the changing needs and experiences of HIV-positive mothers.

Editors’ note: This study in the urban township of Soweto in Johannesburg, South Africa supports the notion that HIV-positive mothers prefer learning their babies’ status early at 4 to 6 weeks rather than waiting for 12 or more months until maternal antibodies disappear. The need for improvement in health care worker communication is evident from the fact that most of the mothers of infected children planned to replacement feed although breastfeeding offers more benefits to HIV-positive infants than risks of re-infection. As well, although most women said this baby had been unplanned and they would not want to have another, health care workers concentrated on condoms as means of reducing risk of transmission to partners, rather than as contraceptives, and some discouraged sterilisation as a more permanent fertility control option. This is a good example of how data collected using qualitative, in-depth interviews guided by a set of open-ended questions posed to end-users can underscore the need for training and enhanced service delivery.