HIV Prevention Update: Monthly Summaries of the Must-read Literature
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- Is the Sexual Behaviour of HIV Patients on Antiretroviral Therapy Safe or Risky in Sub-Saharan Africa? Meta-Analysis and Meta Regression
Berhan, A., & Berhan, Y. AIDS Research and Therapy (May 2012), Vol. 9 No. 14, e-publication ahead of print.
This meta-analysis is the first to examine the sexual behaviors of people on antiretroviral therapy (ART) in sub-Saharan Africa. It compares the sexual behavior of 3,218 people on ART with 1,911 HIV-infected people not on ART; it also includes longitudinal studies examining the behavior of HIV-positive individuals both pre- and post-ART initiation. Among HIV-positive individuals on ART, the authors find a statistically significant reduction in unprotected sex overall and a reduction in the number of sex partners and in the frequency of unprotected sex with partners who are either HIV-negative or of unknown serostatus. According to the authors, these results differ from results of meta-analyses conducted in higher-income countries, which found no statistically significant difference in the frequency of unprotected sex among those on ART and those not on ART. One theory the authors propose for this difference is that rates of high-risk sexual behavior were much higher among Africans at the start of the trial. They also theorize that individuals on ART who experience a dramatic improvement in their health may have renewed hope of living longer and thus may decide to protect their partners from HIV infection or themselves from new and possibly ART-resistant strains of HIV. The authors also believe that improved adherence to clinic visits may mean that individuals hear repeated counseling messages on practicing safer sex.
- Integrating Prevention of Mother-to-Child HIV Transmission Programs to Improve Uptake: A Systematic Review
Tudor Car, L., Van Velthoven, M.H., Brusamento, S., et al. PLoS One (April 2012), Vol. 7 No. 4, e-publication ahead of print.
Integration of prevention of mother-to-child transmission (PMTCT) programs and other health care services at the same facility has long been considered essential for successful scale-up of PMTCT programs. This meta-analysis of five studies in sub-Saharan Africa, built upon a Cochrane systematic review methodology, finds that integrated PMTCT programs show limited, non-generalizable evidence of improved PMTCT intervention uptake. According to the authors, these findings are consistent with a recent Cochrane review on strategies for integrating primary health services at the point of delivery in lower-income countries, which found a lack of evidence for the effectiveness of these strategies. The authors find that there is little consensus on a standard method for integrating services, and that individual programs often define the concept very differently. However, regardless of the model used, each of the programs reviewed failed to achieve target coverage. The authors encourage programs and future research studies to evaluate additional outcomes of integration, including cost-effectiveness, impact on quality of care, human resources, stigma, and context. The authors agree with current guidance that integration of PMTCT programs must be assessed in terms of the epidemiological context and the health system’s readiness for integration. They also encourage additional research on integration of PMTCT to understand how integration affects scale-up of effective PMTCT programs.
- Barriers to HIV Treatment Among People Who Use Injection Drugs: Implications for “Treatment as Prevention”
Milloy, M.J., Montaner, J., & Wood, E. Current Opinion in HIV and AIDS (May 2012), e-publication ahead of print.
According to the authors of this article, treatment as prevention strategies for people who inject drugs (PWID) will only be successful when structural issues, including punitive addiction treatment policies and criminalization of injection drug use, are consistently and effectively addressed. The authors find that PWID continue to experience low rates of HIV testing and of access and adherence to highly active antiretroviral treatment (HAART), as well as higher rates of HIV-related morbidity and mortality. They write that HIV treatment success among PWID depends on the ability to not only identify and address individual-level factors but also structural factors inhibiting access and adherence to treatment. The authors cite criminalization and incarceration of PWID as some of the major social and structural factors interrupting or leading to discontinuation of ART. According to the authors, lack of social support and lack of privacy for taking medications have also been identified as reasons for stopping ART use. The authors also point out that, in Asia and the former Soviet Union, state-run compulsory detention centers may inhibit treatment adherence because detainees lack appropriate evidence-based care and are often subjected to forced detoxification and indentured labor. The authors call for de-emphasizing the criminal justice-based approach to illicit drug use, particularly incarceration. Instead, they recommend a more comprehensive approach that offers substitution therapies, directly observed treatment, and other evidence-based addiction treatment services.
- Moderation and Mediation of an Effective HIV-Risk Reduction Intervention for South African Adolescents
O’Leary, A., Jemmott III, J.B., Jemmott, L.S., et al. Annals of Behavioral Medicine (May 2012), e-publication ahead of print.
This cluster-randomized controlled trial examined the efficacy of the “Let Us Protect Our Future” sexual risk-reduction intervention strategy for sixth-grade adolescents in South Africa. The study was designed to identify moderators—stable characteristics not changed by the intervention and associated with differential responses to an intervention—of the intervention’s efficacy. According to the authors, having a father present in the home, parental strictness, and religiosity all positively affected the efficacy of the intervention in reducing unprotected sexual relations. Living with their fathers also reduced the likelihood that the participants had any sex in the last three months. The authors state that these moderators reveal the importance of parents, particularly fathers, and their opinions in the decision making of young adolescents. Although the authors acknowledge the difficulty of changing moderators, such as parental strictness and religiosity, they encourage parents to discuss sexual issues and their level of approval and disapproval with their children. They also discuss the importance of including parents, especially fathers, in day-to-day activities such as homework. They encourage future skills building on avoiding risk situations as opposed to sex refusal. The authors stress that this type of mediation analysis is an efficient and cost-effective method for identifying and prioritizing components within an intervention and encourage its use in identifying moderators in all successful HIV prevention interventions.
- Antiretroviral Treatment Interruptions Predict Female Genital Shedding of Genotypically Resistant HIV-1 RNA
Graham, S.M., Jalalian-Lechak, Z., Shafi, J., et al. Journal of Acquired Immune Deficiency Syndromes (May 2012), e-publication ahead of print.
According to the authors, as treatment as prevention strategies are scaled up, one of the most important threats to this population-level prevention strategy may be antiretroviral-resistant HIV. Based on results from this study, they find that interruptions of antiretroviral therapy (ART) of 48 hours or more may cause the emergence of resistant strains in female genital tract secretions. They stress that adherence to ART was a key determinant of genital tract resistance among the 102 female participants. During a 12-month period following initiation of non-nucleoside reverse transcriptase inhibitor (NNRTI) medication, drug-resistant virus was detected in the genital tracts of five women. The authors believe that this number could rise if the women who left the study due to withdrawal and/or loss to follow-up were also measured for antiretroviral resistance in the genital tract. Both unavoidable interruptions due to drug toxicity or systemic illness and avoidable interruptions due to late refills led to increased interruptions on average of four days or more. They stress that structural barriers to adherence, including transportation difficulties and pharmacy stock-outs, may also contribute to treatment interruptions and an increased risk of transmission of drug-resistant HIV-1 virus. They call on governments and program managers to increase efforts to prevent treatment interruptions by improving program effectiveness, promoting consistent and timely adherence and refills, and using less toxic ART.
- Willingness of Kenyan HIV-1 Serodiscordant Couples to Use Antiretroviral Based HIV-1 Prevention Strategies
Heffron, R., Ngure, K., Mugo, N., et al. Journal of Acquired Immune Deficiency Syndromes (May 2012), e-publication ahead of print.
According to the authors of this cross-sectional study, nearly 40 percent of HIV-positive Kenyans in stable serodiscordant relationships (where the partner is HIV-negative) expressed reservations about initiating early antiretroviral therapy (ART) for the purpose of treatment as prevention, particularly about the potential side effects. The HIV-negative partners expressed a high willingness (nearly 90 percent) to use pre-exposure prophylaxis (PrEP) on a long-term basis. The authors also find that control of the method was a factor in decision making since, when given a hypothetical choice, the HIV-negative partner chose PrEP and the HIV-positive partner chose ART when medically necessary. The larger PrEP study found that HIV-positive partners indicated a higher level of willingness to initiate ART when they were experiencing lower CD4 counts or symptomatic diseases, or had had personal experience with ART use. Based on these results, the authors suggest that serodiscordant couples use a dual HIV prevention strategy, where the HIV-negative partner uses PrEP until the HIV-positive partner is willing and able to initiate ART. They stress that before developing treatment as prevention strategies, it is extremely important to understand any concerns and preferences couples have about using ART for HIV prevention.
- Antiretroviral Prophylaxis for HIV Prevention Reaches a Key Milestone
Abdool Karim, S., & Abdool Karim, Q. The Lancet (May 2012), Vol. 379 No. 9831, pp. 2047-48.
According to the authors of this editorial, the recent recommendation by the U.S. Food and Drug Administration (FDA) Advisory Committee to support the use of tenofovir-emtricitabine (TDF) for HIV prevention paves the road for implementation of pre-exposure prophylaxis (PrEP) at a global level. PrEP offers HIV-negative women, particularly young women, with an HIV prevention method they can control, since it does not rely on the HIV-positive male partner’s willingness to initiate and consistently adhere to early antiretroviral therapy (ART). The authors outline some concerns with PrEP, including inconsistent data on the effectiveness of PrEP (e.g., results from FEM-PrEP and VOICE trials); the high expense of implementing PrEP; the need to ensure that all eligible HIV-positive individuals have antiretroviral drugs before providing them to HIV-negative individuals for treatment as prevention; the possibility that HIV-negative individuals who use PrEP will reduce their reliance on higher-efficacy HIV prevention strategies, such as condoms; and the fear that PrEP use could increase drug resistance, particularly when taken inadvertently by those with unidentified HIV infection. The authors believe that the affordability question could be addressed through economies of scale and the evolution of health systems as they roll out PrEP. They highlight the need for further research to identify additional drugs and formulations (e.g., rings, gels, injectables) and alternative dosing strategies (e.g., before sex, intermittent, once a month). They also stress that once PrEP is introduced as an HIV prevention tool, improved formulations, efficacy, and safety will quickly follow.
- Effect of ART Coverage on Rate of New HIV Infections in a Hyper-endemic, Rural Population: South Africa
Tanser, F., Bärnighausen, T., Grapsa, E., et al. 19th Conference on Retroviruses and Opportunistic Infections, Seattle, Washington (April 2012), paper #136LB.
This longitudinal study from KwaZulu Natal, South Africa, presented at the 19th Conference on Retroviruses and Opportunistic Infections (CROI), demonstrates that HIV incidence can be reduced once 30 percent or more of all treatment-eligible HIV-positive individuals (CD4+ <200 cells/µL and CD4+ <350 cells/µL for pregnant women) are placed on antiretroviral therapy (ART). Using a population-based HIV surveillance survey that samples 10,000 individuals each year, the authors followed 16,588 men and women who had taken at least two HIV tests between 2004 and 2011. Between 2007 and 2009, the HIV incidence rate averaged 3.0 to 3.5 percent and yet fell starting in 2009, when more than 30 percent of HIV-positive individuals were on ART. In 2010, the rate averaged 2.5 percent, and in 2011 the rate fell to 2 percent. The authors estimate that incidence was lowered by 40 percent when more than 30 percent of those eligible were on ART compared to when less than 10 percent were on treatment. The authors suggest that HIV incidence will continue to fall because of the introduction in August 2011 of increased treatment eligibility to CD4+ <350 cells/µL for all adults in South Africa. They stress that these data demonstrate that treatment as prevention may be an efficacious HIV prevention tool in rural hyper-endemic African settings.
- Towards Elimination of Mother-to-Child Transmission of HIV: The Impact of a Rapid Results Initiative in Nyanza Province, Kenya
Dillabaugh, L.L., Lewis Kulzer, J., Owuor, K., et al. AIDS Research and Treatment (April 2012), e-publication ahead of print.
This article reports on a study that examined the use of a Rapid Results Initiative (RRI)—which is designed to effect organizational change and improve performance within a limited time period—to address challenges in delivery of prevention of mother-to-child (PMTCT) services implemented between April and June 2011 at 119 Kenyan health facilities. RRI includes two distinct phases: needs assessment, and implementation and monitoring. According to the authors, this RRI was developed to increase service provision and uptake of highly active antiretroviral therapy (HAART) for HIV-positive mothers and infants. Following RRI initiation, they found HAART uptake increased by more than 40 percent among all HIV-positive pregnant women, a rate that continued to improve post-RRI. The authors believe this increase will bring the health facilities closer to reaching the goal of providing HAART to 30 percent of all eligible HIV-positive women. They also found a 13 percent increase in assessment for HAART eligibility through improved CD4 testing, a 30 percent increase in polymerase chain reaction (PCR) testing leading to improved early infant diagnosis and increased male involvement. The authors attribute part of this success to community mobilization as well as the leadership and involvement of the Ministry of Health. They encourage further research to determine the longer-term impact of the RRI on improving high-quality, cost-effective PMTCT services.
- Syndromic Diagnosis of Sexually Transmitted Infections Does Not Tell the Full Story
Mlisana, K., Naicker, N., Werner, L., et al. Symptomatic Vaginal Discharge Is a Poor Predictor of Sexually Transmitted Infections and Genital Tract Inflammation in High-Risk Women in South Africa. Journal of Infectious Diseases (July 2012), e-publication ahead of print.
Cohen, M. Classical Sexually Transmitted Diseases Drive the Spread of HIV-1: Back to the Future. Journal of Infectious Diseases (July 2012), e-publication ahead of print.
Risk of HIV acquisition continues to be significantly affected by the prevalence of sexually transmitted infections (STIs). According to the authors, low- and middle-income countries continue to rely on syndromic diagnosis—recognition of the signs and symptoms of STIs, particularly vaginal discharge—due to limited laboratory infrastructure for STI testing. Mlisana et al. found that syndromic STI diagnosis is not the most effective method for diagnosis because it tends to be poorly predictive of laboratory-diagnosed STI. The study, which followed 242 HIV-negative high-risk women over two years, collected data on symptoms of STIs and conducted laboratory diagnostic tests every six months; it also tested for HIV monthly. According to the authors, only a small percentage of the women (12.3 percent) displayed visible discharge even when they tested positive for laboratory-diagnosed discharge-causing STIs. Based on these results, 87.7 percent of STIs in this cohort of high-risk women would have been left untreated, causing a more than threefold increased risk of acquiring HIV among these women. According to the authors, gonorrhea—which syndromic diagnosis frequently misses—was the STI most associated with HIV. Mlisana and colleagues recommend that health providers rely more on laboratory testing and point-of-care STI testing. They stress that the costs associated with laboratory diagnostic tools are outweighed by the impact on reducing the risk of HIV acquisition. Cohen agrees with this and recommends a redoubling of efforts to recognize and fully treat classical STIs.
- Sustainability of Donor Programs: Evaluating and Informing the Transition of a Large HIV Prevention Program in India to Local Ownership
Bennett, S., Singh, S., Ozawa, S., et al. Global Health Action (December 2011), e-publication ahead of print.
This evaluation examines the logic model for transition to local ownership of AVAHAN, a large-scale HIV prevention project in India funded by the Bill & Melinda Gates Foundation. According to the authors, the overarching goal of the transition strategy is to ensure a sustained impact throughout the transition to local ownership. The logic model includes several activities, such as supporting the organizational capacities of government and nongovernmental organizations (NGOs), ensuring immediate impacts (e.g., NGOs and community are prepared for transition), and institutionalizing AVAHAN activities within the government system (e.g., routinization, system feedback), which leads to the transition goal of a sustained HIV response. The major activities of the transition identified by the authors include developing capacity among communities, NGOs, and government entities; aligning AVAHAN’s technical and managerial functions with government norms and standards; and promoting and sustaining services for most-at-risk populations. The authors emphasize that this is the first prospective analysis of a transition and institutionalization process seeking to determine how these processes affect sustainability and allowing for programmatic adjustments throughout the transition process. They expect that this evaluation will promote a smooth transfer of AVAHAN to community ownership and will, where appropriate, be adopted for use within the government system. They encourage the adoption of this evaluation design for other donor programs entering the transition phase of local adaptation and ownership.
- A Controlled Study of Funding for Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome as Resource Capacity Building in the Health System in Rwanda
Shepard, D., Zeng, W., Amico, P., et al. American Journal of Tropical Medicine and Hygiene (May 2012), Vol. 86 No. 5, pp. 902-07.
Challenging assertions that financing for HIV and AIDS has diverted attention and funds from other diseases and health issues, including malaria, measles, and malnutrition, the authors of this six-year study found that this has not been the case in Rwanda, and that in some countries such funding has improved overall health services by updating facilities and making other structural upgrades. Comparing such variables as vaccines administered, visits for child growth monitoring, and non-HIV-related hospitalizations at 25 rural health centers that had begun offering antiretroviral therapy (ART) and 25 centers that had not introduced ART, the authors find no statistically significant adverse effects of HIV and AIDS services on non-HIV services. According to the authors, these results are consistent with results from other studies in Africa and are in part due to Rwanda’s decision to integrate HIV and AIDS services within general health services and to increased donor support. There have been some criticisms of the study, most notably by Victoria Fan and Amanda Glassman of the Center for Global Development, who point out that treatment was not randomly assigned and thus affected the internal and external validity testing of the hypothesis. They also note that the generalizability of the study’s findings is very limited because the study looks only at existing clinics that offer ART rather than new facilities exclusively for HIV and AIDS.
- PEPFAR and Maximizing the Effects of Global Health Assistance
Ezekiel, E. Journal of the American Medical Association (May 2012), Vol. 307 No. 19, 2097-99.
This editorial builds upon last month’s Journal of the American Medical Association article by Bendavid and colleagues, which found that adult mortality from all causes declined more in African countries that receive a larger share of the funding from the U.S. President’s Emergency Plan for AIDS Relief (PEPFAR)—PEPFAR “focus countries”—than in African “non-focus countries” that receive less. Ezekiel stresses that PEPFAR’s success must be measured not only by overall adult mortality and the number of infected individuals receiving antiretroviral therapy (ART), but also by whether PEPFAR is prolonging life, giving people a higher quality of life, and allowing people to lead economically, socially, culturally, and personally productive lives. He challenges policymakers to look beyond the reduction of overall adult mortality and ask whether the investment in PEPFAR—which receives 75 percent of all U.S. global health funding—is worth it. Ezekiel writes that the real question is not whether PEPFAR is doing good, but whether the investment in PEPFAR comes at the cost of investing in other highly effective and lower-cost interventions that save lives and improve health. He reminds readers that in most low-income countries, HIV and AIDS are not the most pressing health problem, according to overall mortality rates or disability-adjusted life years (DALYs) lost. Respiratory and diarrheal diseases, infection and asphyxia at birth, and malaria together cause significantly more deaths and DALYs lost than HIV and AIDS. He writes that there are a number of cost-effective vaccines (e.g., for rotavirus) and interventions (e.g., insecticide-treated bed nets, nutrition programs for underweight children) that are not being scaled up due to limited funding.
- Fourth Edition of the Monitoring and Evaluation Toolkit: HIV, Tuberculosis, Malaria and Health and Community Systems Strengthening
The Global Fund for AIDS, Tuberculosis and Malaria (April 2012)
This toolkit, developed in collaboration with international technical agencies and monitoring and evaluation experts, consists of five parts. Part 1 provides information on Global Fund M&E requirements in the context of performance-based funding. Parts 2 through 5 describe indicators and considerations for HIV programs, tuberculosis (TB) programs, malaria programs, and health and community systems strengthening grants. It also provides updates on Global Fund processes (e.g., alignment with the joint Health Systems Funding Platform), technical and programmatic issues (e.g., updated indicators), and monitoring and evaluation systems (e.g., data quality assessments). According to the authors, the primary audiences for the toolkit include national program managers, public health leaders, monitoring and evaluation officers, donor agencies, technical and implementing partners, and nongovernmental organizations that work with HIV, TB, and malaria programs.
- Lost in Transition: Transgender People, Rights and HIV Vulnerability in the Asia-Pacific Region
United Nations Development Programme and Asia Pacific Transgender Network (May 2012)
According to the authors of this report, transgender persons in Asia and the Pacific region still lack access to health services, HIV interventions, and social protection, even when they are experiencing extremely high HIV prevalence—up to 49 percent in one study in Delhi in 2009. This comprehensive report, which gathered materials from across the region, highlights the lack of targeted and rigorous research on the health needs of transgender persons; it also recommends that governments, civil society, development partners, and the transgender community conduct further research and adapt health care, HIV, and sexual health services to meet those needs. The authors particularly call on health professionals to recognize and respect the diversity in gender identity and self-expression of transgender people. The authors implore governments to adopt more socially equitable policies and practices to protect the rights of transgender people. Several transgender community activists quoted in the report point out that national HIV programming often treats transgender people the same as men who have sex with men, thus ignoring the physical and social differences between the populations. They do note that recent advocacy efforts among the transgender community focusing on human rights and the right to health care and on repealing laws that criminalize transgender people are an encouraging development.
- AIDS 2012
AIDS 2012: XIX International AIDS Conference.
The International AIDS Conference, held this year in Washington, DC, from July 22-27, is the premier gathering for those working in the field of HIV, as well as policymakers, persons living with HIV, and other individuals committed to ending the pandemic. It is a chance to assess where we are, evaluate recent scientific developments and lessons learned, and collectively chart a course forward.
The AIDS 2012 program will present new scientific knowledge and offer many opportunities for structured dialogue on the major issues facing the global response to HIV. A variety of session types – from abstract-driven presentations to symposia, bridging, and plenary sessions – will meet the needs of various participants. Other related activities, including the Global Village, satellite meetings, exhibitions, and affiliated independent events, will provide an exceptional opportunity for professional development and networking.