AIDSFree Prevention Update: March 2013 Edition

Alsallaq, R.A., J.M. Baeten, C.L. Celum, et al. PLoS One (January 2013), Vol. 8 No. 1, pp. e54575.

The authors applied a mathematical model to assess the potential effect of an HIV combination intervention on HIV incidence in KwaZulu-Natal, South Africa. The combination intervention included high HIV testing coverage every four years, risk behavior reduction following diagnosis, antiretroviral therapy (ART) initiation at CD4 count of ≤350 cells/ml, and medical male circumcision. The authors analyzed individual components and then combined components to estimate population-level impact; explored the effect of expanding ART to all persons testing positive; assessed factors that determined impact; and measured the short- and long-term effect of the combined components. The combination intervention showed major reductions in HIV incidence-nearly 50 percent in four years and 60 percent after 25 years. The combined components had synergistic effects. ART had the greatest individual effect, reducing incidence by 33 percent. Expanding ART to all persons diagnosed HIV positive could reduce incidence by 63 percent at four years, and by 76 percent after 15 years. Uptake of testing and risk behavior reduction had the greatest short-term impact; periodic testing and ART retention had the greatest long-term impact. The full impact of combination prevention could be achieved in 10-15 years. The authors concluded that reducing HIV incidence is feasible in high-prevalence settings with combination interventions implemented at high coverage and with robust evaluation to assess population-level impact.

McNairy, M.L., M. Cohen, & W.M. El-Sadr. Current HIV/AIDS Reports (January 2013), e-publication ahead of print.

The authors discussed “treatment as prevention” (TasP) in the framework of a combination intervention: HIV testing, linkage to care, retention in care, and adherence. TasP can increase demand for testing, expand testing services, and improve linkage and retention in care and adherence to treatment, yet the challenge is to improve each component to attain effectiveness. Several modeling studies have suggested that TasP can potentially eliminate HIV in a high-burden setting. However, testing coverage, linkage and retention in care rates, and ART adherence are substantially lower in real settings, highlighting that each element needs strengthening. HIV testing is the entry point for TasP, while linkage to care is considered the weakest component in the continuum of care. TasP requires life-long retention in care, unlike other biomedical prevention interventions. TasP as a combination prevention intervention needs to be tailored to contexts and populations, and it may impact the greater health system. Integrated prevention and care services for high-risk groups may achieve positive results in reducing risk behaviors. In one study the authors discussed, Gardner et al. (2011) found only trivial improvements in viral load suppression when improving only one element in the continuum of care; however, with improvements across all elements, viral load suppression increased from 19 percent to 66 percent. The authors concluded that only by strengthening each component can TasP achieve impact at the population level.

Izulla, P., L.R. McKinnon, J. Munyao, et al. Journal of Acquired Immune Deficiency Syndromes (February 2013), Vol. 62 No. 2, pp. 220-225.

The authors examined efficacy of post-exposure prophylaxis (PEP) among HIV-uninfected female sex workers (FSWs) in Nairobi, Kenya, and explored determinants of PEP use, adherence, and subsequent HIV incidence. The findings showed that PEP was fairly acceptable, and no HIV infections were observed during the year after PEP initiation, although the precise efficacy was undetermined. Of 2,900 FSWs recruited from 2008-2010, 11 percent (n=326) requested PEP. In multivariate regression analysis, PEP users were less likely than non-users to have a regular partner (55 vs. 73 percent); were more likely to report consistent condom use (85 vs. 68 percent); had a history of HIV testing (89 vs. 76 percent); used alcohol (84 vs. 76 percent); had higher gonorrhea rates (6.9 vs. 2.6 percent); and reported a previous abortion (average 0.74 vs. 0.62).  Requests for PEP were mostly from FSWs with “first-time” clients; and 85 percent of women reported condom breakage as the reason for seeking PEP. Delayed timing was an issue; 25 percent initiated PEP 36 hours post-exposure, suggesting an opportunity to improve risk reduction counseling. Fifty-six percent of users adhered for at least 10 days. The authors concluded that PEP may be useful as HIV prevention for FSWs; but research should further assess reasons associated with PEP use. PEP guidelines for FSWs in sub-Saharan Africa are needed.

Celum, C. & J.M. Baeten. The Lancet (February 2013), e-publication ahead of print.

The authors provide commentary on advances in HIV prevention, specifically focusing on approaches for serodiscordant couples and other high-risk groups in sub-Saharan Africa. Prevention strategies, e.g., pre-exposure prophylaxis, should be prioritized to highest-risk populations (ensuring linkages to services), and combined with other prevention inventions. HIV prevention should not only target serodiscordant couples; this would be insufficient to reverse the epidemic. While HIV transmission within serodiscordant couples comprises an important portion of HIV incidence, HIV risk from outside partners is another mode of transmission. The authors referred to a modeling study by Bellan et al. (2013) estimating that extra-couple transmissions accounted for 32-65 percent and 10-47 percent of new HIV infections in men and women, respectively. HIV prevention strategies should both target couple-focused activities, e.g., couples HIV testing and counseling, and persons who have partners with HIV-positive or unknown serostatus, while also aiming to reduce extra-couple transmission. Additionally, young women are at high HIV risk before forming a partnership; therefore, continued prevention activities are needed for this group. The authors concluded that evidence-based combination prevention strategies should focus on high-risk groups, including serodiscordant couples, and on achieving high coverage for these groups, to achieve substantial impact on the epidemic.

Kahle, E.M., J.P. Hughes, J.R. Lingappa, et al. Journal of Acquired Immune Deficiency Syndromes (March 2013), Vol. 62 No. 3, pp. 339-347.

Using data from three prospective studies on heterosexual HIV serodiscordant couples in seven African countries, the authors developed and validated a quantitative risk scoring tool to determine couples at highest HIV risk. The analysis found that a separate set of factors, applied together and quantified, can identify serodiscordant couples at high risk of HIV transmission. Scores greater or equal to 5, of a maximum score of 12, were related to annual HIV incidence of more than 3 percent; e.g., a score ≥ 6 identified 67 percent of the observed HIV seroconversions among only 28 percent of the study population. The risk score model included the following factors: plasma HIV-1 RNA concentrations, unprotected sex, young age, marital status, no or few children in the partnership, and uncircumcised status of uninfected men; the combination of risk factors allows for more predictive capability. The risk scoring tool can be applied to clinical and research studies and to inform implementation of HIV prevention strategies to target those at highest risk and maximize cost-effectiveness. The authors concluded that a simple risk scoring tool could be an effective approach to identifying HIV serodiscordant couples at highest risk of HIV.

Kirby, D., R. Dayton, K. L’Engle, et al. FHI 360 (2012).

To address the lack of programs focusing on multiple sexual partners among youth, FHI 360, in collaboration with the United States Agency for International Development’s Integrated Youth Working Group, developed the resource,Promoting Partner Reduction: Helping Young People Understand and Avoid HIV Risks from Multiple Partnerships. The publication includes a set of 17 participatory activities to support youth in various capacities, including educating participants on HIV transmission rates in different types of sexual partnerships; discussing reasons for engaging in multiple sexual partnerships; conducting behavior change communication to reduce partners and practice skills to refuse engagement; and examining the role of gender norms. The activities provide a forum for youth to discuss complex issues, such as transactional sex, and promote behavior change to reduce high-risk behaviors. The youth activities were field-tested in Botswana, Kenya, and the United States, and the resource was piloted by programs in South Africa and Swaziland.

Institute of Medicine (IOM). February 2013. Washington, DC: The National Academies Press.

When the U.S. President’s Emergency Plan for AIDS Relief (PEPFAR) was reauthorized in 2008, the U.S. Congress requested that the Institute of Medicine (IOM) evaluate the effectiveness of PEPFAR in the global HIV/AIDS response.  Through a rigorous, mixed-methods evaluation, the IOM Committee assessed PEPFAR’s HIV programs and services for general and key populations; impact on children and adolescents; gender-specific initiatives; health systems strengthening; actions supporting a transition to a sustained response; and knowledge management. The evaluation highlighted that PEPFAR is the leading global HIV/AIDS donor, and since its inception in 2003, it has benefited millions of lives by supporting HIV prevention, care, and treatment programs. PEPFAR has also strengthened health systems and collaborated with country partners to develop HIV policies and guidance. While the program's initial objective was to rapidly scale-up HIV services, a continued shift towards country-driven efforts, lasting infrastructure development, and health systems strengthening is necessary. PEPFAR's achievements are noteworthy, yet unmet needs remain across HIV services. For instance, the evaluation notes the continuing of improving linkages between and retention in services. The evaluation also provides recommendations to support the continued U.S.response to HIV, categorized into four areas: scaling up HIV programs; strengthening country systems for the HIV response, especially capacity building, supply chain, and financial management; evolving to a sustainable “country-led” management response with partner countries; and developing comprehensive knowledge management to improve effectiveness.

Marrazzo, J., Ramjee, G., Nair, G., et al. Presentation at the 20th Conference on Retroviruses and Opportunistic Infections (CROI), March 3-6, 2013, Atlanta, Georgia. Abstract number: Paper #26LB.

The authors presented findings from the Vaginal and Oral Interventions to Control the Epidemic Study (MTN 003) in South Africa, Uganda, and Zimbabwe during the 20th Conference on Retroviruses and Opportunistic Infections. This randomized, double-blind, placebo-controlled study assessed pre-exposure prophylaxis for HIV among 5,000 women with daily use of 1 percent vaginal tenofovir gel, oral tenofovir, or oral tenofovir/emtricitabine. None of the three products was effective in HIV prevention, and most participants did not use the products daily as recommended. Younger, single women were less likely to use the products and more likely to become infected with HIV during the trial, compared with older, married women. For instance, in South Africa, women under age 25 had a higher HIV incidence than women aged 25 and older (8.7 and 4.7 per 100 person-years, respectively); similarly, unmarried women had higher HIV incidence than married women (7.5 and 0.9 per 100 person-years, respectively). Blood samples from 773 participants indicated that most did not have expected levels of the drugs, suggesting they were not used as recommended. The author stressed the need for an acceptable and effective HIV prevention method for women, particularly unmarried and young women. Identifying the determinants of adherence and perceptions of HIV risk among this population is critical.

Bellen, S.E., K.J. Fiorella, D.Y. Melesse, et al. The Lancet (February 2013), e-publication ahead of print.

Using Demographic and Health Survey data from 2003-11 on 27,201 cohabitating couples in 18 sub-Saharan African countries, the authors developed a mathematical model to estimate HIV transmission rates attributed to three routes: before a cohabitating relationship; during extra-couple intercourse; and between serodiscordant couples. Extra-couple transmission played a key role in facilitating HIV incidence for both men and women, particularly for men. Prior to a cohabiting partnership, women had a period of high HIV risk. Within couples, men more often transmitted HIV to women. The authors estimated that HIV incidence in 2011 was driven by extra-couple transmission in 30-65 and 10-47 percent of men and women, respectively. The model estimated that extra-couple intercourse accounted for HIV infection between 50-80 percent of men and 31-74 percent of women in serodiscordant couples, and between 18-51 percent of men and 13-29 percent of women in concordant (HIV-positive) couples. Ranges varied by country, and the authors suggested interpreting with caution the fitted transmission coefficients. They concluded that behavioral and biomedical interventions that focus only on serodiscordant couples will be inadequate to decrease HIV incidence at the population level. Policy decisions should acknowledge the role of extra-couple transmission, and HIV prevention efforts should address the general sexually active population, including serodiscordant couples.

Townsend, L., C. Mathews, and Y. Zembe. Prevention Science (2013), Volume 14, pp. 88-105.

The authors of this review assessed 19 studies and summarized the effectiveness of several interventions for HIV prevention activities in low- and middle-income countries (LAMIC). All studies either targeted or measured condom use; the majority found increased condom use (n=13); with 12 of these interventions providing condoms. Individual counseling based on information, motivation, and behavior skills (IMB) was a relatively effective strategy to increase condom use. Thirteen studies included interventions to reduce multiple sexual partnerships, but findings showed little effect on decreasing them. However, interventions that did succeed in reducing the number of partners incorporated group, large-scale, or community-based activities based on IMB values. Five studies that addressed the effects of alcohol use found mixed results, but again, group settings, particularly those including IMB components, were successful in reducing harmful alcohol consumption. Only two studies addressed gender-based violence, and one intervention was found effective. The authors recommended supplying condoms as an intervention component and addressing challenges such as access to or inconsistency of condom use for some populations. In settings where multiple sexual partnerships are customary, interventions should address social norms. The authors concluded that interventions targeting heterosexual men in LAMIC should address multiple sexual partners and alcohol use, and utilize combinations of effective behavioral interventions. Additional interventions targeting heterosexual males in LAMIC are needed.

Tetrault, J., M.J. Kozal, J. Chiarella, et al. Journal of Addiction Medicine (February 2013), e-publication ahead of print.

The authors conducted a cross-sectional analysis of 59 HIV-infected persons receiving opioid agonist treatment (OAT) – an effective treatment for reducing injection-related sharing and HIV risk in persons with opioid dependency – to assess the prevalence of risk behaviors, antiretroviral (ARV) resistance, and ARV resistance among persons with risk behaviors. Eighty percent of the participants had been receiving OAT for at least 12 weeks. The findings overall showed a presence of both continued risky behaviors and resistance: 14 percent of individuals receiving OAT engaged in unprotected sex; 7 percent shared injection drug equipment; 32 percent had a measureable viral load; and 15 percent had evidence of ARV resistance. In terms of ARV resistance by evidence of risk behavior, 22 percent of individuals engaging in risk behaviors had ARV resistance, and 14 percent with no risk behavior evidence also had resistance. These findings, which suggest that HIV-positive people on OAT continue to engage in risky behavior, placing partners at risk, show that addressing HIV resistance is essential. The authors concluded that improving HIV prevention and treatment programs for HIV-infected individuals with opioid dependence is necessary, especially in low-resource contexts.

Higa, D.H., N. Crepaz, K.J. Marshall, et al. AIDS and Behavior (February 2013), e-publication ahead of print.

To address gaps and facilitate implementation of effective behavioral interventions for men who have sex with men (MSM), the authors conducted a systematic review of HIV behavioral prevention interventions for MSM in the United States to identify how many targeted MSM; assess challenges to obtaining effective results in interventions that did not meet criteria to be deemed an evidence-based intervention (EBI); and compare non-EBI with EBIs. Of 33 MSM behavioral intervention studies identified, 27 percent (n=9) were EBIs. Seventy-three percent (n=24) were considered non-EBI, primarily because these did not show significant positive effects on a behavioral or biological outcome. Overall, compared with EBIs, non-EBIs significantly targeted HIV-negative MSM more frequently, and were less likely to be piloted or include peer and sexual communication components. The majority of non-EBIs were small group designs. Also, non-EBIs were significantly more likely to include substance use and use a non-HIV related comparison group. The authors provided several lessons learned from non-EBIs and considerations for MSM behavioral interventions, including involving MSM in the program design, pilot testing interventions, and utilizing peer and sexual communication components. Future behavioral interventions for MSM of color, particularly African Americans and Latinos, are necessary. Behavioral interventions targeting MSM need to be strengthened and should be included in comprehensive combination approaches.

Bärnighausen, T., D.E. Bloom, & S. Humair. Proceedings of the National Academies of Sciences of the United States of America (December 2012), Vol. 109 No. 52, pp. 21271-21276.

Following the successful results of HIV Prevention Trials Network 052, the authors of this study evaluated whether treatment as prevention (TasP) is a transformative HIV prevention approach, or if combinations of medical male circumcision (MMC) and antiretroviral treatment (ART) can yield similar results in South Africa, as it remains unclear how TasP can be financed or implemented. Applying a mathematical model to explore various combinations of coverage levels of the approaches, the authors showed that a combination of high ART and MMC coverage provides approximately the same significant decrease in HIV incidence as TasP, at a substantially lower cost – $5 billion less than cumulative discounted costs (2009-2020). In terms of cost per infection averted, MMC is most cost-effective ($1,100), with ART scale-up approximately six times more costly ($6,800); however, they are similar in cost per death averted. TasP is most expensive in cost per infection and per death averted ($8,400 and $7,700, respectively). The authors recommend scaling up ART while also increasing MMC; only after reaching high coverage levels should TasP be considered. In South Africa, MMC scale-up should be prioritized, with increasing ART, considering the synergies between the approaches. The authors concluded that TasP is effective; however, MMC and ART can realize similar benefits in reducing HIV incidence at a lower cost.

Abaasa, A., A. Crook, M. Gafos, et al. Trials (2013), Vol. 14 No. 33.

The authors used data from the Microbicides Development Programme 301 clinical trial to understand adherence and long-term use of vaginal microbicide gels among HIV serodiscordant couples in rural Uganda. Findings suggest that long-term, consistent microbicide gel use was high in this population. Of 554 HIV-negative women included in this analysis (approximately 65 percent of those enrolled in the trial), 5 percent seroconverted, 8 percent became pregnant before follow-up, and 87 percent reached follow-up (52 weeks). The average reported use of the microbicide gel at last sex was approximately 93 percent. Multivariate analysis showed that older women (aged 25-34 and 35 and older) were at least twice as likely to have reported consistently using the microbicide gel compared with younger women (aged 17-24). Consistent microbicide gel use was also independently associated with the number of rooms used for sleeping in a house; specifically, having three or more rooms was associated with a twofold increase in use. The authors suggest that younger women may need extra support in regularly using microbicide gel, and that further research is needed to understand the influence of household rooms on consistent use of the microbicide gel. The authors concluded that long-term use of the microbicide gel is feasible if an effective gel becomes available for HIV prevention programs.

Bor, J., A.J. Herbst, M-L. Newell, et al. Science (February 2013), Vol. 339, pp. 961-965.

The authors assessed the impact of antiretroviral therapy (ART) scale-up in the public sector on adult life expectancy in a high HIV prevalence setting, KwaZulu-Natal, South Africa, by using individual-level data on dates of death from a large community-based surveillance system. Life expectancy declined from 2000 to 2003 from 52.3 years to 49.2 years. However, adult life expectancy improved after 2004, reaching 60.5 years in 2011, an 11.3-year improvement. Both men and women had life expectancy gains (9.0 and 13.3 years, respectively). The adult cohort included over 101,000 individuals with data from 2000-2011; of note is that in 2004, South Africa initiated ART at government health facilities. The authors also evaluated the cost-effectiveness of ART delivery by comparing changes in adult survival at the population level with estimated costs of delivering ART in the community. Analysis indicated a cost-effectiveness ratio at $1593 per life-year saved, which was less than a quarter of the per-capita gross income of South Africa (2011). The authors, while acknowledging uncertainty regarding future trends, advocated for increased support for public-sector HIV treatment programs, given the increases in adult life expectancy associated with ART scale-up and the evident population-level impact.

Tanser, F., T. Bärnighausen, E. Grapsa, et al. Science (February 2013), Vol. 339, pp. 966-971.

Using data from a large population-based prospective cohort study - the HIV Prevention Trials Network 052 - the authors analyzed data on 16,667 individuals (HIV-uninfected at baseline), observing HIV seroconversions from 2004 to 2011. After controlling for confounding factors, they found that for an individual living in a community with high antiretroviral therapy (ART) coverage (30-40 percent), the risk of acquiring HIV was 38 percent lower than for a person living in a community with low ART coverage (<10 percent).To estimate the result of expanding HIV coverage on the risk of acquiring HIV, the authors analyzed the "time to seroconversion" on ART coverage in the community surrounding each uninfected person. A total of 1,413 HIV seroconversions occurred during this period. Crude HIV incidence was 2.63 new infections per 100 person-years, and the highest rate was 6.6 and 4.1 per 100 person-years for women aged 24 and men aged 29, respectively. Controlling for condom use did not alter the relationship between HIV coverage and HIV risk. The authors suggested that achieving a decline in HIV transmission at the population level is feasible with increasing ART coverage in sub-Saharan Africa.

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