HIV Prevention Update: Monthly Summaries of the Must-read Literature
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- Tenofovir Gel Discontinued in VOICE Trial
Microbicides Trial Network (November 2011).
In late November 2011, the Microbicides Trial Network (MTN) announced it was discontinuing 1 percent tenofovir gel in the Vaginal and Oral Interventions to Control the Epidemic (VOICE) trial in South Africa, Uganda, and Zimbabwe. The large-scale VOICE HIV prevention trial was designed to measure the effectiveness of daily use of two different antiretroviral (ARV) oral pre-exposure prophylaxis (PrEP) tablets (oral tenofovir and oral Truvada) and of tenofovir vaginal microbicide gel. (The oral tenofovir was discontinued in September 2011 due to futility.) A routine review of the study data by the Data and Safety Monitoring Board found that the incidence of HIV was nearly identical for the tenofovir gel group and for a control group using a placebo gel (6 percent in the former and 6.1 in the latter) and concluded that the tenofovir gel was not effective in preventing HIV in the women enrolled in the trial. The VOICE trial is one of three major trials to measure the effectiveness of tenofovir gel. The CAPRISA 004 trial, which ended in 2010, found tenofovir gel to be 39 percent more effective than a placebo. FACTS 001, another major safety and effectiveness trial of tenofovir gel that uses a dosing strategy different from VOICE’s, launched in 2011 with 2,200 women in South Africa; results are expected in 2014. The VOICE trial will continue to test the safety and effectiveness of the oral Truvada tablet against a placebo pill used by a control group.
- Combination Prevention: A Deeper Understanding of Effective HIV Prevention
Hankins, C. A., & de Zalduondo, B. O. AIDS (November 2011), Vol. 24 Suppl. 4, pp. S70-S80.
Anchored in the “know your epidemic” imperative, combination prevention is a mix of behavioral, biomedical, and structural interventions, ideally informed by evidence and based on human rights, that address both the immediate risks and the underlying causes of vulnerability to HIV. This paper presents the programmatic opportunities and evaluation challenges of combination prevention strategies in sub-Saharan Africa. According to the authors, tailoring programs with the Modes of Transmission methodology—a single-year “snapshot” of incident infections using HIV and STI prevalence and behavioral data—shifts the focus from where the epidemic has been to where the epidemic may be going and to the social, economic, geographic, and cultural conditions that shape the epidemic country by country. Adding a comprehensive review of HIV prevention policy and programs as well as a costing analysis (“know your response”) can reveal program gaps and strengths in the national response and, when appropriate, lead to a reorientation of programming. The authors believe that tailoring programs to local epidemiology and contexts while focusing on evidence-informed and human-rights-based interventions addresses barriers to prevention and allows for context-specific and cost-effective programming that can achieve intended outcomes. They stress that effective combination prevention requires enhanced coordination in program design, resourcing, management, and evaluation, as well as flexible design to incorporate emerging biomedical prevention tools.
- Voluntary Medical Male Circumcision for HIV Prevention: The Cost, Impact, and Challenges of Accelerated Scale-Up in Southern and Eastern Africa
PLoS Medicine and PLoS One (November 2011), e-publication ahead of print.
The Joint United Nations Programme on HIV/AIDS (UNAIDS) and the U.S. President’s Emergency Plan for AIDS Relief (PEPFAR) have co-published a collection of nine new articles on voluntary medical male circumcision (VMMC) in PLoS Medicine and PLoS One. The articles—four reviews and five research papers—discuss the use of VMMC for HIV prevention at the individual, community, and population levels in East and Southern Africa. According to Catherine Hankins, Steven Forsythe, and Emmanuel Njeuhmeli, who authored the first article and introduce the entire series, male circumcision is the oldest and most common surgical procedure; 67 percent of men in sub-Saharan Africa are circumcised. They point out that VMMC is highly cost-effective, with one new HIV infection averted for every five to fifteen procedures performed, and that scaling up safe and efficient VMMC services will produce individual- and population-level benefits. They stress the need for national and local leadership, tailored communication efforts—including campaigns targeting women—and gains in efficiency at the clinical level to decrease procedure times and increase access. The other eight papers explore more in-depth policy and programmatic issues, including frameworks, logistics, demand creation, and human resources issues. UNAIDS and PEPFAR have launched a joint five-year action framework to accelerate immediate roll-out and expansion of VMMC services in 14 high-priority countries through a coordinated, country-driven effort.
- HIV Partner Notification Is Effective and Feasible in Sub-Saharan Africa: Opportunities for HIV Treatment and Prevention
Brown, L. B., Miller, W. C., Kamanga, G., et al. Journal of Acquired Immune Deficiency Syndromes (December 2011), Vol. 56 No. 5, pp. 437-442.
Active partner notification, also known as provider-assisted partner notification, is effective, feasible, and acceptable, and will increase early referral to care and mitigate risk among high-risk uninfected partners. These results were found among 245 newly diagnosed HIV-positive clients randomly assigned to three different methods of partner notification at sexually transmitted infection clinics, including active partner notification. Although passive referral—when clients are encouraged to disclose HIV exposure to their partners—has been the norm in sub-Saharan Africa, the results demonstrate that active partner notification is more effective for partners seeking testing and counseling services (40 to 62 percent vs. 15 to 34 percent). Of the eligible participants in all three groups, a high proportion provided an accurate partner location. The authors found that provider-assisted partner notification was particularly important for increasing male partner participation in counseling (50 percent of male partners sought testing services in the provider-assisted groups compared to 15 percent in the passive referral group). The authors hypothesize that provider-assisted notification may increase male involvement in prevention of mother-to-child transmission (PMTCT) programs. Although negative consequences—including violence—have been a concern related to active partner notification, only two such incidents were reported among study participants. Given that prior history of abuse in a relationship can be a predictor of abuse following disclosure, the authors advocate screening for intimate partner violence and emotional abuse during all post-test counseling.
- Safety and Efficacy of the PrePex Device for Rapid Scale-Up of Male Circumcision for HIV Prevention in Resource-Limited Settings
Bitega, J. P., Ngeruka, M. L., Hategekimana, T., et al. Journal of Acquired Immune Deficiency Syndromes (December 2011), Vol. 58 No. 5, pp.127-134.
This six-week study, which assessed the safety and efficacy of the PrePex device for nonsurgical circumcision among 55 adult males in Rwanda, found that the device is safe and effective and may be appropriate for use in mass circumcision campaigns. Because the procedure can be conducted by trained personnel who are not physicians and does not require local anesthesia or sterile environments, it may be especially appropriate for resource-limited settings. The PrePex device is a ring designed to compress the foreskin to cut blood flow; placement by experienced personnel takes less than five minutes. Following placement 100 percent of the men returned immediately to work. This compares favorably to men who received the Shang Ring, an adult male circumcision device that requires anesthesia during placement; 80 percent of these men did not return to work until two days after placement. About a week after placement of the PrePex device, the dead tissue can be removed bloodlessly, with 25 days needed for complete healing. Participants may experience some pain during placement, for which the authors suggest administering ibuprofen.
- Antiretrovirals for Safer Conception for HIV-Negative Women and Their HIV-1-Infected Male Partners: How Safe and How Available?
Mastro, T., Cohen, M., & Rees, H. Journal of Acquired Immune Deficiency Syndromes (December 2011), Vol. 25 No. 16, pp. 2049-2051.
This is a review of Preexposure Prophylaxis and Timed Intercourse for HIV-discordant Couples Willing to Conceive a Child (Vernazza, P., Graf, I., Sonnenberg-Schwan, U. et al. AIDS [December 2011], Vol. 25 No. 16, pp. 2005-2008).
In this review in the Journal of Acquired Immune Deficiency Syndromes, the authors discuss a recent small-scale study based in Switzerland by Vernazza and colleagues that measured the rate of infection between HIV-1-infected men and their HIV-negative female partners seeking to conceive during the time of maximum fertility. The men in the study had been on antiretroviral therapy (ART) for at least six months prior to conception, and the women had received two doses of pre-exposure prophylaxis (PrEP) for HIV prior to every act of intercourse. The Vernazza study found that of 244 episodes of vaginal intercourse without barrier methods, no woman became infected, and 75 percent conceived. Because these results are not based on clinical trials but are a conception algorithm, the authors of this editorial feel compelled to raise two critical questions. First, how safe is this method of timed intercourse, using ART and PrEP to prevent infection, since the precise risk of HIV-1 acquisition associated with conception is still difficult to quantify? Second, how can these results be translated from a developed-country setting to developing-country settings, where the majority of HIV-1-discordant couples reside, and where resources are lacking to minimize HIV-1 transmission risk during conception? Although the authors acknowledge the promising results of the Vernazza study, they point out that there are risks involved—pregnancy increases women’s susceptibility to HIV-1, HIV-1 in the male genital tract is generally not completely eliminated during ART, and other sexually transmitted infections increase the risk of HIV-1 transmission—that the study did not assess.
- Optimal Uses of Antiretrovirals for Prevention in HIV-1 Serodiscordant Heterosexual Couples in South Africa: A Modelling Study
Hallet, T. B., Baeten, J. M., & Heffron, R. PLoS Medicine (November 2011), Vol. 8 No. 11, pp. 1-12.
This individual-based mathematical model measured the impact and cost-effectiveness of pre-exposure prophylaxis (PrEP) and/or earlier initiation of antiretroviral therapy (ART) among HIV-1 serodiscordant couples in South Africa on transmission and life-years saved and found strategic use of both to be cost-effective. According to the authors, although the initial costs of using PrEP prior to ART initiation are high, the long-term benefits of reducing future ART costs among HIV-1-uninfected partners offset initial costs. They also found that use of a highly effective PrEP regimen (one that reduces the risk of HIV transmission by at least 70 percent) with a relatively low cost of delivery (less than 40 percent of the annual cost of ART) can be as cost-effective as earlier initiation of ART. Used among high-risk couples, the effectiveness of PrEP can drop as low as 40 percent, yet still compare favorably to the cost-effectiveness of earlier initiation of ART. For high-risk couples, combining PrEP and ART (administering PrEP to the HIV-negative partner prior to ART initiation for the HIV-positive partner) may provide the most impact in lowering risk and the highest cost-effectiveness. Finally, the authors found that among lower-risk couples, earlier initiation of ART (at CD4 counts less than 500 cells/mm³) may be the most cost-effective method. The authors recognize that this study may provide important cost-effectiveness data but also implore policymakers to include other considerations such as equitable access and couples’ preferences in determining options.
- Pre-exposure Prophylaxis for HIV Prevention: How to Predict Success
Kashuba, A., Patterson, K. B., Dumond, J. B., et al. The Lancet (December 2011), e-publication ahead of print.
The authors of this commentary provide impact results for seven prevention trials testing the use of antiretroviral drugs (both for pre-exposure prophylaxis [PrEP] and for treatment as prevention) to prevent sexual transmission of HIV-1: CAPRISA 004, IPrEX, TDF2, PIP, FEM-PrEP, VOICE (MTN-003), and HPTN 052. According to the authors, the trials produced differing results demonstrating both successful prevention of HIV (CAPRISA 004, iPrEx, TDF2, and PIP) and ineffectiveness in preventing HIV (VOICE and Fem-PrEP). Each of the trials focused on different populations with distinct routes of HIV transmission and produced different results for antiretroviral drug concentrations in mucosal tissues. For example, oral administration of co-formulated tenofovir-emtricitabine (TDF-FTC) produced 100-fold higher concentrations of tenofovir in rectal tissues as opposed to cervicovaginal tissue. According to the authors, the low cervical and vaginal tissue concentrations could have affected the results of the use of oral TDF in the VOICE trial. The protective effect provided by TDF in the PIP trial may be a result of the reliance on discordant couples and higher adherence levels among these couples. The authors acknowledge that to date the only measure for adherence is through self-reports or pill counts. They advocate the use of evidence of strong and durable tissue conditions of active agents as well as the use of rigorous measures of adherence in future PrEP studies.
- Breakthrough of the Year: HIV Treatment as Prevention and ARVs as HIV Prevention: A Tough Road to Wide Impact
Cohen, J. Science (December 2011), Vol. 334 No. 6063, p. 1628.
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Shelton, J. Science (December 2011), Vol. 334 No. 6063, pp. 1645-1646.
Science magazine has chosen the finding that antiretroviral drugs reduce the risk of heterosexual transmission of HIV as its Breakthrough of the Year. As outlined by the Science staff writer, Jon Cohen, the $73 million HPTN 052 clinical trial, which demonstrated that antiretroviral therapy (ART) reduces the risk of heterosexual transmission by 96 percent, provided the unambiguous data that treatment as prevention reduces HIV transmission. These results have prompted national leaders, including President Barack Obama, to take action in rolling out the “AIDS-free generation” plan, which includes treatment as prevention as a main cornerstone. Although many consider this to be a pivotal development, others caution that, due to resource constraints and implementation challenges, it is not likely that treatment as prevention can end the epidemic any time soon. In an editorial in the same issue of Science, James Shelton suggested that ART programming faces formidable obstacles for wide-scale prevention of HIV infection. He argues that achieving impact at the population level will be difficult due to a number of challenges: infected and uninfected populations at high risk, early infectiousness, adherence issues, drug resistance, risk compensation, drug toxicity, high costs, and the difficulty of reaching most-at-risk populations. He warns that infectiousness in the early stages will continue to generate clusters of rapid transmission, which account for one-third of transmission events in generalized epidemics. He cautions that core prevention programs—behavior change, male circumcision, and condoms—complement treatment as prevention and must not be jeopardized in the process of scaling up treatment as prevention interventions.
- Moving Forward on Women’s Gender-Related HIV Vulnerability: The Good News, the Bad News and What To Do About It
Gupta, G. R., Ogden, J., & Warner, A. Global Public Health (December 2011), Vol. 6 No. S3, pp. S370-S382.
The authors of this article argue that, although gender inequality continues to affect HIV vulnerability, national programs still do not adequately address this issue. The authors challenge governments to translate rhetoric on gender inequality into action to reduce gender-related vulnerability and risk at the national level. They argue for increasing research investments to assess how gender inequalities affect women’s and men’s HIV vulnerability in particular contexts. The authors review successful strategies that have been adopted at the individual level, such as improving the economic status of women, addressing violence against women, and changing harmful gender norms. However, according to the authors, there are still significant gaps in knowledge on certain topics, including sexuality in different social and cultural contexts and during different phases in life, the complexities of designing programs that empower women within a particular context, and sexual risk-taking of women in stable relationships. The authors advocate that governments and their collaborating partners must develop national strategies that address a number of core elements, including integrating gender-related programming into the larger national response, conducting a social analysis, creating an enabling legal environment, increasing community participation and ownership, and including women living with HIV in national and local program planning.
- Creating a Different International HIV Response for Young People
Chandler, C. Global Public Health (December 2011), Vol. 6 No. S3, pp. S344-S356.
Young people have often been stereotyped in the response to HIV and AIDS, resulting in programming not based on their actual needs and realities. According to the author of this paper, these generalizations have contributed to less than effective programming and a continuance of high rates of HIV among young people (40 percent of all new infections globally occur in individuals under the age of 25). To lessen the HIV incidence rate among young people, the author recommends three discrete but interrelated actions. First, she advocates using qualitative and quantitative youth-focused, age-disaggregated data derived from the local context to design programming. Second, she urges program developers to develop targeted interventions based on epidemiological data about the needs of youth in specific contexts (e.g., young sex workers, young people who use drugs). Finally, she emphasizes the need to include structural approaches in all HIV programs focused on youth. She encourages program developers and policymakers to address the age-related stigma, discrimination, and human rights abuses that increase young people’s vulnerability to HIV, including parental consent laws and age barriers to services. According to the author, incidence among youth will fall only when youth are no longer targeted with “one-size-fits-all” programming.
- Linkages Between HIV and Family Planning Services Under PEPFAR: Room for Improvement
Boonstra, H. Guttmacher Policy Review (Fall 2011), Vol. 14 No. 4, pp. 1-7.
The Obama administration released two guidance documents in 2011 that make clear the linkages between HIV services and family planning services. According to Boonstra, although these documents endorse HIV testing and counseling, referrals for prevention of mother-to-child transmission (PMTCT), and treatment services in family planning programs, they prohibit the use of funds from the President’s Emergency Plan for AIDS Relief (PEPFAR) for acquiring contraceptives (aside from male and female condoms) for women in HIV care, treatment, and PMTCT programs. The author writes that PEPFAR’s strategy of relying on the U.S. Agency for International Development (USAID) family planning assistance program to provide contraceptives is shortsighted due to the program’s limited funds and political vulnerability. Moreover, there are countries and areas within countries that have a PEPFAR treatment program but no USAID family planning program. The author applauds the administration’s shift toward actively pursuing two-way linkages between HIV and family planning services, and the Global Health Initiative’s approach to develop and disseminate policies and guidelines that support linkages, build the capacity of HIV and family planning care providers, and strengthen referral systems. However, she also calls on U.S. Government agencies to further support the field by providing examples of successful linkages, conducting an analysis of existing family planning programs where PEPFAR programs exist, and actively supporting contraceptive use among HIV-positive women.
- What Works to Meet the Sexual and Reproductive Health Needs of Women Living with HIV/AIDS
Gay, J., Hardee, K., Croce-Galis, M., et al. Journal of Acquired Immune Deficiency Syndromes (November 2011), e-publication ahead of print.
This meta-analysis of 35 studies and eight programmatic evaluations from 15 developing countries analyzes programs that focus on reducing unintended pregnancies, HIV transmission, and reproductive morbidity and mortality among women living with HIV. The authors identify a variety of promising practices to address the sexual and reproductive health and rights of women living with HIV, including providing contraceptives and family planning counseling as part of HIV services, ensuring early postpartum visits that provide family planning and HIV information and services, providing youth-friendly services, supporting education and skills-building, supporting disclosure, providing cervical cancer screening, promoting condom use for dual protection against pregnancy and HIV, and providing counseling within treatment programs that increases other protective behaviors, including condom use. The authors advocate for additional programming resources to implement and scale up these promising practices, and call for policies on integrated services. They also acknowledge the gaps that remain in programming and research, particularly the question of the use of hormonal contraception and its associated risk of greater vulnerability to HIV.
- Global HIV/AIDS Response: Epidemic Update and Health Sector Progress Towards Universal Access, Progress Report 2011
Joint United Nations Programme on AIDS, World Health Organization and UNICEF (December 2011)
According to the 2011 progress report issued in December 2011 by the Joint United Nations Programme on AIDS (UNAIDS), World Health Organization, and UNICEF, nearly 50 percent of people who are eligible for antiretroviral therapy now have access to lifesaving treatment. The report finds that new HIV infections have been reduced by 21 percent since 1997, while deaths from AIDS-related illnesses have decreased by 21 percent since 2005. According to Michel Sidibé, Executive Director of UNAIDS, many of these gains are due to a massive scale-up in access to HIV treatment (47 percent of the estimated 14.2 million people eligible for treatment in low- and middle-income countries were accessing antiretroviral therapy in 2010). According to the report, HIV treatment, as well as behavior change and voluntary medical male circumcision (VMMC), is contributing to early signs of reducing the number of new HIV infections. For example, in Botswana, a country with high HIV incidence, the number of new HIV infections is 30 percent to 50 percent lower today than it would have been without the introduction of antiretroviral therapy. The report discusses a new UNAIDS framework for AIDS investments focusing on high-impact, evidence-based, high-value strategies based on six interventions: focused activities on key populations at higher risk of acquiring the virus; prevention of new HIV infections in children; behavior change programs; condom promotion and distribution; treatment, care, and support for people living with HIV; and VMMC in countries with high HIV prevalence.
- New Online Resources on MSM and Legal Issues
Global Commission on HIV and the Law and the Global Forum on MSM & HIV (MSMGF) (December 2011)
On December 1, 2011, the Global Commission on HIV and the Law released a set of regional dialogue resources on the impact of the legal environment on the health and human rights of people living with and affected by HIV. These documents are a result of seven regional dialogues held from February to September 2011 around the globe. A final report from the Global Commission is expected to be released in early 2012. In addition to these resources, the Global Forum on MSM and HIV (MSMGF) recently launched a new collection of resources featuring case studies, toolkits, and testimonial videos from grassroots MSM advocates in Cameroon, Uganda, and Zimbabwe highlighting the connection between HIV and the law. According to the MSMGF, the resources provide smaller community-based organizations with information and legal advocacy tools on the health and human rights of men who have sex with men (MSM). The website also highlights five recommendations that the MSMGF made to the Global Commission on HIV and the Law:
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• Review and repeal laws that undermine the HIV response among MSM.
• Address inappropriate enforcement of laws inhibiting MSM access to services.
• Establish stronger laws protecting the health and rights of MSM.
• Create enabling environments for MSM to claim their rights.
• Adopt a rights-based approach to HIV programming and integrating laws within national AIDS responses.
- PEPFAR Scientific Advisory Board Recommendations on Implementation of Treatment as Prevention
PEPFAR Scientific Advisory Board (December 2011)
Following the release of the results of the HPTN 052 clinical trial in late spring 2011, the President’s Emergency Plan for AIDS Relief (PEPFAR) Scientific Advisory Board released a set of six recommendations on the implementation of HPTN 052 for PEPFAR’s treatment programs and other treatment issues. The recommendations below include detailed explanations of scientific rationale, public health impact, resource implications, implications for PEPFAR, gaps in knowledge, and cross-cutting issues:
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• Accelerate the scale-up of antiretroviral therapy (ART) to all HIV-infected individuals with a CD4 cell count of less than 350 cells/mm³, irrespective of World Health Organization (WHO) disease stage for treatment and prevention (goal: 90 percent coverage).
• Offer ART to all patients with HIV-related tuberculosis (TB), irrespective of CD4 cell count, and integrate ART into TB treatment.
• Endorse WHO guidelines for prevention of mother-to-child transmission (PMTCT) in pregnant and breastfeeding women with a CD4 cell count greater than 350 cells/mm³, with a preference for Option B (ART throughout pregnancy and breastfeeding) where locally appropriate.
• Support the use of ART in specific populations with a CD4 cell count of more than 350 cells/mm³ to prevent transmission to others.
• Intensify efforts to establish effective programs for engaging key affected populations in HIV prevention, care, and treatment programs. Particular efforts should be undertaken to ensure that key affected populations eligible for treatment receive ART in an enabling environment that supports their human rights.
• Seek and secure sufficient resources to implement the recommendations, given the scientific basis for and potential impact of their implementation. - Criminalize Hate Not HIV Campaign
International Planned Parenthood Federation (December 2011)
In July 2011, the International Planned Parenthood Federation (IPPF) launched the Criminalize Hate Not HIV Campaign to serve as a counterbalance to the growing international trend of criminalization of HIV transmission. The foundation of the campaign is to address HIV prevention with an evidence-based human rights approach toward people with HIV that encourages health-seeking behavior. According to IPPF, 20 percent of the countries in the world have either general criminal or public health laws or HIV-specific legislation under which HIV transmission or exposure has been prosecuted. According to IPPF, there is no evidence that these laws contribute to HIV prevention, but rather they hamper an effective response to HIV prevention and are ineffective in protecting the most vulnerable from infection. In November, the Campaign published a series of interviews entitled “Behind Bars” that outlines how criminal laws affect people’s work and private lives. The Campaign interviewed an array of doctors, lawyers, researchers, advocates, and parliamentarians who face personal and professional dilemmas daily because of these criminal laws. IPPF argues that “Behind Bars” demonstrates how criminal law can contribute to a climate of denial, secrecy, and fear, ultimately fueling the spread of HIV. The Campaign advocates for legal changes, such as anti-discrimination and confidentiality laws, to replace laws that criminalize HIV transmission.
