HIV Prevention Update: Monthly Summaries of the Must-read Literature
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- Use of Hormonal Contraceptives and Risk of HIV-1 Transmission: A Prospective Cohort Study
Heffron, R., Donnell, D., Rees, H., et al. Lancet Infectious Diseases (October 2011), e-publication ahead of print.
According to this prospective study of 3,790 heterosexual HIV-1-serodiscordant couples in seven African countries, hormonal contraceptive use may double the risk of HIV transmission. The researchers found that endocervical secretions from the HIV-positive female study participants using injectable methods show higher concentrations of HIV-1 RNA. They also found a twofold increase of HIV-1 acquisition for HIV-negative females from their infected male partners, as well as a twofold increase in the number of HIV-positive female participants who infected their male partners. According to the authors, these results complement other longitudinal studies of sex workers in Kenya and family planning clients in Uganda and Zimbabwe. Based on these findings, the authors call for increased counseling for women on the potential risk of HIV-1 acquisition and transmission with the use of hormonal contraception, particularly injectable methods, and on the importance of the dual protection provided by condom use. They also advocate for non-hormonal or low-dose hormonal contraceptive methods for women with or at risk for HIV-1 infection. After Heffron presented these findings at the International AIDS Society conference in early July, the U.S. Agency for International Development (USAID) issued a guidance memo to its field offices recommending a cautious interpretation of the findings due to the limitations of observational data. The memo stated that, due to insufficient data and analysis, “USAID does not believe that a change in contraceptive policy or programming is appropriate or necessary at this time.” The Department of Reproductive Health and Research of the World Health Organization (WHO) also issued a statement on the study in October 2011. That statement echoed some of the concerns of USAID on the use of observational data, which, according to WHO, may be biased by self-selection or by the possibility that users of hormonal contraceptives differ from non-users in their sexual behavior and condom use. WHO has scheduled a technical consultation for late January 2012 to review the study data and current WHO recommendations on contraceptive use for women at risk of HIV and women living with HIV. Participants at the technical consultation will draft a statement on recommendations for contraceptive use in settings with high HIV incidence and prevalence.
Related HIV Prevention Knowledge Base Topic:
Contraception to Prevent Unintended Pregnancies among Women with HIV - HIV Vaccine Development—Improving on Natural Immunity
Johnston, M. I., & Fauci, A. New England Journal of Medicine (September 2011), Vol. 365 No. 10, pp. 873-875.
According to the authors of this opinion piece, the general theory (applied to most vaccine development) of mimicking infection to generate an immune system response does not apply to HIV infection because the body’s natural immune response to HIV infection is limited. Thus it is important to activate an “unnatural immunity”—one that is qualitatively and/or quantitatively different from the natural response to HIV infection. The authors suggest that one mechanism worth investigating could be broadly neutralizing antibodies, which neutralize a broad array of HIV strains. This type of antibody is naturally induced not at the point of HIV infection but only after long-term exposure, when the infected person has already entered an advanced disease stage. To improve the level of protection, the authors recommend that researchers develop a way to kick-start induction of neutralizing antibodies so they activate earlier. New research tools to develop faster-acting broadly neutralizing antibodies are in the works. Researchers continue to study how B cells may evolve to produce more efficient broadly neutralizing antibodies. As a result of this research, the authors are optimistic that an effective and efficient vaccine based on broadly neutralizing antibodies will one day be available.
- PEPFAR Announces Largest Study of Combination HIV Prevention
Office of the Global AIDS Coordinator (September 2011).
In mid-September, the U.S. President’s Emergency Plan for AIDS Relief (PEPFAR) announced awards for a new research initiative focusing on combination prevention approaches to HIV. The three awards, totaling $45 million over four years, went to the London School of Hygiene and Tropical Medicine, the Harvard School of Public Health, and Johns Hopkins University. All of the research projects will begin in 2011 and 2012 and will be linked to the PEPFAR Scientific Advisory Board to provide real-time answers to critical research questions. The London School of Hygiene and Tropical Medicine, in collaboration with the HIV Prevention Trials Network, which is funded by the National Institutes of Health, will assess a strategy linking household-based HIV testing to universal community-based HIV treatment in Zambia and South Africa. The Centers for Disease Control and Prevention will provide funding to the Harvard School of Public Health to assess how scaling up an integrated set of HIV-prevention interventions in Botswana may impact HIV incidence. Johns Hopkins University will evaluate the impact of an integrated set of biomedical, behavioral, and structural prevention interventions to reduce HIV incidence in Tanzania. According to Ambassador Eric Goosby, U.S. Global AIDS Coordinator, all of the studies will include a research component on antiretroviral-based interventions to contribute to the emerging research on treatment as prevention.
Related HIV Prevention Knowledge Topic: An Overview of Combination Prevention
- The Relationship between Intimate Partner Violence, Rape and HIV amongst South African Men: A Cross-Sectional Study
Jewkes, R., Sikweyiya, Y., Morrell, R., et al. PLoS One (September 2011), Vol. 6 No. 9, pp. 1-6.
This cross-sectional household study of 1,229 randomly selected South African men aged 18 to 49 found that HIV prevalence was significantly higher in younger men who had repeatedly perpetrated physical violence against their partners than in those who had not. According to the authors, these results may suggest a possible reason why women who experience violence demonstrate higher HIV seroprevalence. The authors did not detect a correlation between perpetration of rape and HIV seroprevalence, although they did find high rates of HIV among men who had raped. The authors argue that prophylaxis for HIV following rape remains an important part of post-rape care for HIV-negative survivors. According to the authors, these findings are similar to other studies, which have found a strong correlation between men’s violent acts and risky sexual practices. They write that the study shows how perpetration of violence by men may affect not only the health of their female partners but also their own health. Based on these results, the authors encourage HIV-prevention programming that seeks to address gender inequities and promotes less violence and more respect within relationships.
Related Technical Brief: Gender-based Violence and HIV
- Early Retention in HIV Care and Viral Load Suppression: Implications for a Test and Treat Approach to HIV Prevention
Mugavero, M. J., Amico, K. R., Westfall, A. O., et al. Journal of Acquired Immune Deficiency Syndromes (September 2011), e-publication ahead of print.
This study, assessing the effects that early retention in care may have on test-and-treat strategies, finds that higher rates of early retention in HIV care are associated with increased viral load (VL) suppression and lower cumulative VL burden. Using a measure to assess viremia copy-years—an estimate of cumulative HIV burden—the authors find that early retention in HIV care is associated with time to viral load suppression (greater than 50 copies/mL), and that each time a patient did not return for care it increased the risk of delayed viral load suppression by 17 percent. They also found that patients with higher viremia copy-years demonstrated poorer visit adherence over the first two years in care. According to the authors, these findings have implications for a test-and-treat strategy, because failure to achieve and sustain viral load suppression increases the risk of HIV transmission. They advocate for making early retention in care an increasingly important goal for prevention activities. Moreover, they suggest that longitudinal measures of cumulative viremia, such as viremia copy-years, may provide a better indication of individual risk of HIV transmission, and should be explored as a population-level indicator of transmission risk and used in evaluations of test-and-treat interventions.
Related Technical Brief: Adult Adherence to Treatment and Retention in Care
Related HIV Prevention Knowledge Topic: Antiretroviral Therapy as an HIV Prevention Strategy
- Specific Microbicides in the Prevention of HIV Infection
Kelly, C. G., & Shattock, R. J. Journal of Internal Medicine (September 2011), e-publication ahead of print.
This primer on microbicides discusses the rationale for microbicide strategies, outlines some of the classes of inhibitors being developed as microbicides, and examines the most effective way to ensure that microbicides reach the cells they are targeting. The authors define microbicides as products designed for application at vaginal or rectal mucosae to inhibit or block early events in HIV infection, thus providing protection against HIV. According to the authors, there are microbicides that target specific stages in HIV infection and replication, such as HIV-fusion inhibitors, reverse transcriptase inhibitors, integrase inhibitors, and protease inhibitors, and they can each be delivered in a variety of formulations, including a gel formulation. Although the first generation of microbicides did not demonstrate efficacy in clinical trials, the more recent CAPRISA 004 trial of tenofovir gel provided proof-of-concept of vaginally applied microbicides. The gel formulation, used in CAPRISA 004, can provide a well-defined dose of microbicide to be delivered at a defined time. The most advanced of microbicides are based on highly active antiretroviral drugs (ARVs), such as tenofovir. Several studies have found a high level of acceptability of both vaginal and rectal gel administration of microbicides among users. However, according to the authors, this high level of acceptability does not necessarily translate into compliance. For example, in the CAPRISA 004 trial, only 41 percent of study participants used gel for only 50 percent or less of self-reported sex acts. They note that addressing this challenge will be important to produce a highly effective microbicide. They also write that resistance, identified as another challenge in microbicide use, may be addressed by using combinations of microbicides, considered the next generation of products.
Related AIDSTAR-One Prevention Knowledge Base Topic: Microbicides
- Optimal Time on HAART for Prevention of Mother-to-Child Transmission of HIV
Chibwesha, C. J., Giganti, M. J., Putta, N., et al. Journal of Acquired Immune Deficiency Syndromes (October 2011), Vol. 58 No. 2, pp. 224-228.
This retrospective cohort analysis of 1,813 HIV-infected pregnant women in Lusaka, Zambia, found that women who receive highly active antiretroviral therapy (HAART) for at least 13 weeks prior to delivery experience a 5.5-fold decreased risk of transmitting HIV to their infants compared to women on HAART for four or fewer weeks prior to delivery. According to the authors, these results confirm that mother-to-child transmission can be reduced to below 5 percent in African settings with the use of HAART. To achieve this, they encourage that HAART be initiated in eligible pregnant women at least 13 weeks prior to delivery, and in settings where this is not possible, at least four weeks prior to delivery. The study also found that a positive syphilis screen during pregnancy can also lead to increased risk of vertical transmission. The authors stress the importance of encouraging women to seek antenatal care early in pregnancy, and urge medical staff to determine eligibility for HAART and provide linkages to appropriate treatment and care services. The authors also urge an increased focus on improving clinical and laboratory services and the integration of HAART services into antenatal clinic settings. Moreover, they urge antenatal clinics to increase the screening and treatment of syphilis, and to provide credentials for nurses and midwives to prescribe HAART.
Related HIV Prevention Knowledge Topic: Prevention of Mother-to-Child Transmission of HIV
- Epidemiological Impact of Tenofovir Gel on the HIV Epidemic in South Africa
Williams, B., Abdool Karim, S., Karim, Q. A., et al. Journal of Acquired Immune Deficiency Syndromes (October 2011), Vol. 58 No. 2, pp. 207-210.
According to this mathematical modeling, widespread use of tenofovir gel—a vaginal microbicide—will lead to significant reductions in the rate of new HIV infections and AIDS-related deaths over the next 20 years in South Africa. The authors found that more than 2 million new infections and 1 million deaths due to AIDS can be averted if women use tenofovir gel in 80 percent or more of sexual encounters (high coverage). Use in lower coverage (25 percent) of sexual encounters also yields up to 500,000 fewer infections and 290,000 fewer deaths. The authors estimate that at lower coverage, the cost of preventing one HIV infection is 28 percent of the life-time cost of providing antiretroviral therapy. They state that with U.S. $0.50 per application, providing women with access to tenofovir gel in South Africa is cost-saving and cost-effective. However, they acknowledge that in countries where HIV prevalence and incidence are lower and cost per infection rises as the incidence falls, the use of tenofovir gel will be less cost-effective if used in the general population, but will be more cost-effective if targeted to higher-risk groups, such as sex workers. The authors state that the cost-effectiveness of using tenofovir gel microbicides compares favorably to other prevention methods and expect that cost-effectiveness will increase as new drugs and delivery mechanisms are rolled out.
Related AIDSTAR-One Prevention Knowledge Base Topic: Microbicides
- Partners and Clients of Female Sex Workers in an Informal Urban Settlement in Nairobi, Kenya
Ngugi, E., Benoit, C., Hallgrimsdottir, H., et al. Culture, Health and Sexuality (September 2011), e-publication ahead of print.
Female sex workers with a romantic partner have fewer sexual partners overall and are less likely to have clients who do not use condoms, compared to female sex workers without a partner. These results are from a comparative analysis looking at the number of partners and condom use behavior among female sex workers and women working in other economic activities in Kibera, Nairobi. The authors found that female sex workers with a partner had 50 percent fewer sexual partners (clients) in a week, and that having a regular relationship acts as a protective factor against acquiring HIV. According to the authors, this reduction is due to the monetary contributions that romantic partners contribute, allowing sex workers to take in fewer clients and/or refuse clients who will not use a condom. Most of the literature to date on sex workers’ romantic partners has focused on the association of intimate partner violence with these relationships. These results indicate that romantic partners may serve as a form of harm reduction, and that future research and programming should focus on their ability to assist in risk reduction of HIV and to provide economic and social support to their partners.
Related HIV Prevention Knowledge Topic: An Overview of Structural Approaches to HIV Prevention
Related Spotlight on Prevention (PDF, 725 KB): A Holistic Approach to HIV Prevention Programming for Female Sex Workers
- Sustainability of Programs to Reach High Risk and Marginalized Populations Living with HIV in Resource Limited Settings: Implications for HIV Treatment and Prevention
Montague, B., Vuylsteke, B., & Buve, A. BioMed Central Public Health (September 2011), e-publication ahead of print.
Achieving the levels of antiretroviral coverage to successfully implement treatment as prevention among such hard-to-reach populations as sex workers presents an array of challenges. According to 2009 surveillance data from the World Health Organization, antiretroviral (ARV) coverage with a CD4 cell count threshold of 200 or less was 52 percent worldwide, while coverage on the higher threshold of CD4 count of 350 or less was only 36 percent. Although there is some skepticism about achieving high levels of ARV coverage among sex workers, data from another research study demonstrate that it is possible to achieve high levels of immunological reconstitution and virological suppression among female sex workers. Despite the challenges, the authors believe that not offering ARVs to female sex workers is not an option, and sustainability of these programs relies on the ability to transfer them to national HIV care programs. Unfortunately, these national programs now face declining resources from external donors, such as the President’s Emergency Plan for AIDS Relief (PEPFAR), and must balance high-cost case management interventions against expanded access to antiretroviral medications for the broader population. According to the authors, reaching sex workers with ARV programs will require intensive counseling and case management services focusing on retention and adherence issues. The authors stress that success will rely on increased political will and advocacy from both medical and public health providers.
Related HIV Prevention Knowledge Topic: An Overview of Structural Approaches to HIV Prevention
- Costing of HIV Programs: Will It Provide the Answers Needed?
The Cost of Providing Comprehensive HIV Treatment in PEPFAR-Supported Programs. Menzies, N. A., Berruti, A. A., Berzon, R., et al. AIDS (September 2011), Vol. 25 No. 14, pp. 1753-1760.
and
Can Cost Studies Improve the Performance of Donor-Financed HIV Treatment? Walker, D., Over, M., & Bertozzi, S. AIDS (September 2011), Vol. 25 No. 14, pp. 1795-1796.
The article by Menzies and colleagues finds that treatment costs (the on-site mean annual cost for patients on antiretroviral therapy [ART] was U.S. $896 at 34 sites studied) reduce over time as sites supported by the President’s Emergency Plan for AIDS Relief (PEPFAR) mature. According to the authors, this cost reduction may be due to a variety of factors, including investment reductions over time, established patient costs vs. newly initiated ART patient costs, and differences in factor input costs. They also found that recurrent costs, such as personnel, reduce over time due to decreasing investment costs and economies of scale that improve efficiency. The authors found a wide variation in per-patient costs among the 34 study sites and attribute some of this variation to differences in the package of services provided at each site. They encourage further investigation into identifying and promoting the most cost-effective elements of a care package. For example, they encourage programs to consider the trade-offs of focusing on preferred regimens (more expensive) for current patients and extending coverage for new clients. The editorial by Walker and colleagues also raises a number of factors that may have influenced the costs, such as the stage of illness of clients served, the quality of treatment, the use of on-site and off-site supervisors, integration with other health services, training, experience, and governance. They stress that an observational study such as the Menzies study may need a randomly selected sample size three to five times larger to more accurately determine what causes higher costs. They encourage building on the work by Menzies and colleagues to find the most effective and efficient way to achieve high-quality clinical outcomes with fewer resources. According to Walker and colleagues, identifying best practices, such as efficient drug procurement, use of task shifting, or reduction in unnecessary laboratory tests will provide examples for countries and programs of how to reduce costs while maintaining quality.
Related Content: AIDSTAR-One ART Treatment Costing Crosswalk Analysis
- Food Insecurity and Sexual Risk in an HIV Endemic Community in Uganda
Miller, C. L., Bangsberg, D. R., Tuller, D. M., et al. AIDS and Behavior (October 2011), Vol. 15 No. 7, pp. 1512-1519.
This qualitative study of 41 HIV-positive individuals found a close relationship between food insecurity and sexual risk-taking, including transactional sex, primary partner violence, and condom use among HIV-positive women and men living in Uganda. According to the authors, HIV-infected women who are food insecure in sub-Saharan Africa are extremely susceptible to risky sexual practices. The study found that recently widowed women raising children are routinely solicited for sex by men in their communities. Women who do not have access to land and/or food often engage in transactional sex to alleviate hunger and feed their children. Women who are dependent upon their partners for food display little negotiating power and often remain in abusive relationships. The authors stress that women’s access to food and land for food production must become a public health priority. They also recommend that food support and HIV prevention programs target households headed by single and widowed women, particularly those with children. They support the expansion of integrated microcredit programs that offer economic support and address gender and socioeconomic inequalities as well as expand educational opportunities for women and girls. They highlight the effectiveness of multi-level interventions that simultaneously target men, women, village leaders, and service providers; address structural barriers to food security; and incorporate the promotion of women’s rights through legal and policy reforms.
Related Technical Report: NuLife—Food and Nutrition Interventions for Uganda
Related Case Study: Coffee, Popcorn, Soup, and HIV
- Bangkok HIV Vaccine Conference
AIDS Vaccine 2011.
The AIDS Vaccine 2011 conference hosted by the Global HIV Vaccine Enterprise, the Faculty of Tropical Medicine at Mahidol University, and the Ministry of Public Health of Thailand took place in Bangkok from September 12 to 15, 2011. The conference, attended by more than 820 researchers, funders, and policymakers, examined scientific results and provided a forum to exchange ideas on HIV vaccine research and development issues. The presentations included an update on AIDS vaccine clinical trials, lessons from the development of other public heath vaccines that may be applied to an AIDS vaccine, global collaboration in finding a vaccine, lessons learned from HIV prevention, and new prevention strategies, including voluntary medical male circumcision, HIV pre- and post-infection strategies, and prevention of mother-to-child transmission. Finally, there were several discussions about future strategies for vaccine development, including information on development of an HIV-1 neutralizing antibody vaccine, vector-based HIV vaccines, and adjuvants for HIV vaccines. Among the findings presented at the conference were the results of a two-year follow-up of the AIDS vaccine clinical trial RV144, where researchers announced that they found two ways the immune system responds to HIV and will use this information to inform future research.
- Microbicide Trials Network Stops Tenofovir Arm of Study after Findings Show Drug Less Effective Than Anticipated
Microbicides Trials Network.
The Microbicides Trial Network (MTN) announced in late September that it will be stopping one arm of the study, Vaginal and Oral Interventions to Control the Epidemic (VOICE). The VOICE study, which began in September 2009 and involves more than 5,000 women at 15 sites in South Africa, Uganda, and Zimbabwe, compares two antiretroviral (ARV)-based approaches for preventing the sexual transmission of HIV in women. The three different pre-exposure prophylaxis (PrEP) strategies include tenofovir pills, tenofovir in a vaginal gel, and a combination of tenofovir and emtricitabine (Truvada pills). MTN decided to end one arm of the study after an interim review by the Prevention Trials Data and Safety Monitoring Board (DSMB) found that the trial will not be able to demonstrate that the tenofovir pills are effective in preventing HIV in the women enrolled in the trial. According to MTN, VOICE will continue to test the effectiveness and safety of the tenofovir gel and Truvada pills. Results from the other two arms are expected to be issued by the end of next year. In the last 18 months, data from four effectiveness trials of various PrEP strategies in women showed mixed results. According to advocates, the VOICE trial will add to this growing data set to help guide decisions on the best use of oral and topical PrEP among different populations.
Related AIDSTAR-One Prevention Knowledge Base Topic: Microbicides
- ReThinkHIV Initiative Launched
Rush Foundation and Copenhagen Consensus Centre.
The Copenhagen Consensus Centre, with funding from the Rush Foundation, recently launched the ReThinkHIV research initiative, which brings together leading health academics, including economists, epidemiologists, and demographers, to analyze HIV policy and economic decisions. The ReThinkHIV initiative is designed to identify effective HIV and AIDS interventions and apply a cost-benefit analysis to determine the most effective interventions. They recently commissioned six assessment papers and twelve perspective papers in six areas of competing priorities, including:
• Efforts to prevent sexual transmission
• Efforts to prevent non-sexual transmission
• Treatment and initiatives to reduce the impact of the HIV/AIDS epidemic
• Research and development efforts
• Social policy levers
• Initiatives to strengthen health systems.In late September, the Copenhagen Consensus Centre also convened an expert panel of five eminent economists, including three Nobel Laureates, to answer the hypothetical question, “If we successfully raised an additional US$10 billion over the next 5 years to combat HIV/AIDS in sub-Saharan Africa, how can it best be spent?” The expert panel concluded that policymakers should:
• Introduce infant male circumcision to substantially reduce HIV risk for new generations
• Ensure that mother-to-child transmission prevention interventions reach 90 percent of pregnant women
• Eliminate the possibility of HIV infection through blood transfusions
• Scale up treatment with life-saving antiretroviral drugs while focusing first on patients with low CD4 counts.The expert panel also expressed the need for more evidence on the effectiveness of AIDS interventions and provided a ranking of key investment areas.
- World Bank and USAID Emerging Issues in Today’s HIV Response Debate: Treatment as Prevention
AIDSTAR-One.
The sixth debate of the Emerging Issues in Today’s HIV Response Debate Series, entitled "Treatment as Prevention," will feature expert panelists arguing for and against the proposition:
"Countries should spend a majority of what is likely to be a flat or even declining HIV prevention budget on 'treatment as prevention'."
Recent studies have shown that persons living with HIV who are on antiretroviral therapy (ART) are much less infectious and therefore much less likely to transmit HIV to others. The HPTN-052 randomized study found a 96 percent reduction in HIV transmission from an HIV-infected person to his/her sexual partner, for the 76 percent of cases where intra-couple transmission took place. Results suggesting similar levels of risk reduction were reported in the 2010 Partners in Prevention study. What do these latest results mean for HIV prevention programming? Should "treatment as prevention" become HIV prevention policy in countries? For all persons, or only for adults in long-term sexual partnerships? Does the type of epidemic (i.e., concentrated, mixed, generalized) matter? How feasible are these interventions? Is it ethical not to implement them, given that their efficacy between long-term sexual partners is known? Should prevention resources be diverted away from other interventions, such as behavior change efforts, to fund increased ART? Who will pay for costs of the increased volumes of drugs? Do we know enough about the side effects or about drug resistance? These questions and others related to treatment as prevention will be discussed.
