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  XIX International AIDS Conference
July 22-27, 2012
Washington, DC
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HIV Prevention at AIDS 2012
  XIX International AIDS Conference. Washington, DC, USA, 22-27 July 2012

Jared Baeten, MD PhD
Connie Celum, MD MPH
University of Washington

"ART and PrEP ......most promising new approaches for decreasing HIV spread.....benefits of earlier ART.....cost-effectiveness .......important clinical benefits......Demonstration projects of PrEP will address: will at-risk persons want PrEP, will they use it, will it change sexual risk taking (and to what degree), and how to deliver PrEP in an efficient and effective fashion......Data suggest populations are ready for PrEP, at least in a subset(see below).....microbicides.....Some, but not all, studies have observed an increased risk for women to acquire HIV infection when they are using hormonal contraception, especially injectable depot medroxy-progesterone acetate (DMPA, otherwise known as branded Depo-Provera).....an uncountable number of discussions were devoted to trying to determine whether hormonal methods of contraception - perhaps particularly injectable methods - increase HIV risk as well as what the research and public health response should be......HIV testing is the cornerstone of prevention.....A major focus of AIDS 2012 was the challenges and potential strategies to address losses in the cascade of linkages to HIV care, ART, and prevention interventions......Home-based testing initiatives.....The FDA recently approved an oral fluid self-test for HIV, OraQuick.....Injection drug use .......injection exposure is responsible for 2/3 of HIV cases in Eastern Europe and Central Asia but HIV-infected drug users there have ART coverage of <10% - such stunning disproportionate access to care is an inequity that is unforgivable in its effects on morbidity and new infections.....cost-effectiveness assessment of needle-syringe exchange programs.....MSM....Trends in HIV prevalence and HIV testing in CDC studies from 5 US cities (San Francisco, Los Angeles, New York, Baltimore, and Miami).....Prevalence was high.....black MSM, detailed that 12% of men were newly-diagnosed with HIV at study entry, emphasizing the incredible need for HIV testing........voluntary medical male circumcision (VMMC) program.....adverse events of 2.3% .....effectiveness of VMMC has been observed to be 57% for reducing HIV acquisition among men"

The past two years have seen a number of important breakthroughs in HIV prevention. For perhaps the first time ever, the discussion among researchers, policymakers, and activists is the possibility that sufficiently powerful HIV prevention tools may now be available to radically change the course of the epidemic. Indeed, the theme of AIDS 2012 was "Turning the Tide Together." A number of sessions from the meeting have weblinks available and we have included some of these below.

Many speakers spoke to the possibility of substantially altering the course of the epidemic - eliminating mother-to-child transmission, significantly increasing the numbers of persons receiving antiretroviral therapy, combining multiple effective prevention strategies together to drive down the number of new infections in populations. Plenary talks that broadly addressed strategies for reducing new HIV infections in substantial ways and through multiple approaches included the following:

· Dr. Anthony Fauci, from the US National Institute of Allergy and Infectious Diseases (http://pag.aids2012.org/flash.aspx?pid=1559), speaking about moving from scientific advances to public health implementation

· Phil Wilson, from (http://pag.aids2012.org/flash.aspx?pid=1558), from the Black AIDS Institute, speaking about ending the US HIV epidemic

· Dr. Nelly Mugo (http://pag.aids2012.org/flash.aspx?pid=1555), from the Kenyatta National Hospital in Kenya, speaking about implementing effective prevention for highest impact - emphasizing that populations most at risk are the priority, interventions that will work in those populations should be chosen (and chosen carefully), and delivery at large-enough scale is essential in order to have impact.

· Dr. Yogan Pillay (http://pag.aids2012.org/flash.aspx?pid=1544), from the National Department of Health in South Africa, speaking about integrating HIV prevention and care with other health services.

In addition, Hillary Clinton, US Secretary of State, gave a rousing speech during the first morning's plenary session (http://pag.aids2012.org/flash.aspx?pid=6983) that is well worth watching.

ART and PrEP: Antiretrovirals for HIV prevention

Antiretroviral-based HIV prevention strategies - including antiretroviral treatment (ART) to reduce the infectiousness of HIV infected persons and oral and topical pre-exposure prophylaxis (PrEP) for uninfected persons to prevent HIV acquisition - are the most promising new approaches for decreasing HIV spread. Observational studies among HIV serodiscordant couples have associated ART initiation with a reduction in HIV transmission risk of 80-92%, and the HPTN 052 randomized trial demonstrated that earlier initiation of ART (i.e., at CD4 counts between 350 and 550 cells/mm3), in the context of virologic monitoring and adherence support, resulted in a 96% reduction in HIV transmission. A number of ongoing and recently-completed clinical trials have assessed the efficacy of PrEP for HIV prevention using daily oral combination emtricitabine/tenofovir, with trials demonstrating HIV protection efficacy as high as 75%, and secondary analyses suggesting ~90% HIV protection in those with high adherence. Adherence is likely key to efficacy of antiretrovirals for HIV prevention, both as ART and PrEP. Critical unanswered questions for successful delivery of antiretroviral-based HIV prevention include how to target ART and PrEP to realize maximum population benefits, whether HIV infected persons at earlier stages of infection would accept ART to reduce their risk for transmitting HIV and highest-risk HIV negative persons would use PrEP, and whether high adherence could be sustained to achieve high effectiveness.

In a Thursday plenary Dr. Gottfried Hirnschall from WHO spoke of expanded use of ART for HIV prevention (http://pag.aids2012.org/flash.aspx?pid=1547). By the end of 2011, 8 million persons were on ART, a global public health achievement; however, a new goal has emerged = 15 million by 2015. Even at that level, though, the majority of persons already infected with HIV will not yet be treated (see table below) and new infections will continue to occur.


The challenges to continued expansion of treatment are clear: HIV testing that is unavailable or complex, fall-off in accessing and sustaining HIV care (known as the HIV care cascade - with fall-off in individuals tested, linked to care, offered ART, initiated ART, and sustained adherence), and motivation to initiate and sustain treatment, all grounded on the need for funding to grow and sustain treatment programs. Nonetheless, the optimism was strong that continued expansion in treatment can be done and can impact numbers of new infections and thus the course of the epidemic.

The challenges of treatment for HIV prevention in real-world settings are just beginning to be worked out, as countries determine how fast and by how much they can expand treatment availability, and link treatment access to prevention messaging. Some data from the conference were not encouraging: among 500 HIV serodiscordant heterosexual couples from Uganda participating in an observational study of the effect of ART on HIV transmission, HIV incidence was essentially identical among those receiving versus not receiving ART (2.09 vs. 2.30 per 100 person-years, p=0.8). The authors emphasized that ART for prevention can be undermined by outside partnerships, cofactors for HIV transmission, and intermittent adherence (Birungi, abstract TUAC0103). Still, a systematic review of studies of ART and transmission found a summary rate ratio of 0.34 (i.e., 66% reduction in HIV transmission risk) overall and 0.16 (84%) in a subset of studies (Anglemyer, abstract MOPDC0105).

An important discourse at the conference was the balance of the clinical and prevention benefits of earlier ART against the potential individual and public health risks. Many argue that the balance is strongly towards benefits of earlier ART - with clear, dual clinical and prevention benefits from earlier ART initiation. Updated data from HPTN 052 presented as a late-breaker emphasized that ART started above a CD4 count of 350 cells/mm3 resulted in important clinical benefits (Grinsztejn, abstract THLBB05 http://pag.aids2012.org/flash.aspx?pid=3892). Another late-breaker analyzed cost-effectiveness data from HPTN 052 for two of the participating countries in that study - India and South Africa - and found that earlier ART initiation, because of its dual treatment and prevention benefits, is very cost effective, looking at both a short and long-term horizon (Walensky, abstract FRLBC01 http://pag.aids2012.org/flash.aspx?pid=3899).

Just prior to AIDS 2012, WHO released its first guidance on PrEP (http://www.who.int/hiv/pub/guidance_prep/en/index.html) - with recommendations focused on learning from demonstration projects as countries and researchers work on defining delivery of this novel intervention. Demonstration projects of PrEP will address: will at-risk persons want PrEP, will they use it, will it change sexual risk taking (and to what degree), and how to deliver PrEP in an efficient and effective fashion.

Understanding whether priority populations will take PrEP is a key next-step question for the field. Data suggest populations are ready for PrEP, at least in a subset. Among MSM in Australia (Holt, abstract TUAC0301 http://pag.aids2012.org/flash.aspx?pid=1179), those who were HIV negative appeared keen to see PrEP available and expressed skepticism about the effectiveness of treatment for preventing transmission. Among MSM and transgender women in northern Thailan (Yang, abstract TUAC0303 http://pag.aids2012.org/flash.aspx?pid=1436), about 75% were "somewhat or very likely" to use PrEP - higher among those aware of PrEP, with insurance, or who had a prior history of STIs. A multi-city focus group study among women in the US (Auerbach, abstract FRLBD04 http://pag.aids2012.org/flash.aspx?pid=3870) found that PrEP was described as an important option, would be "additional" not a substitute to condoms, and would be used if side effects and costs were low.

Antiretroviral resistance is a potential risk of PrEP use - for those who become infected with HIV and who also have sufficiently high PrEP use to select for resistance (those who stay HIV uninfected and those who become infected but have no/low PrEP use will not be at risk for resistance). A late-breaker abstract compared three mathematical models to consider antiretroviral resistance that might arise because of PrEP use in an African context (Nichols, abstract FRLBX04 http://pag.aids2012.org/flash.aspx?pid=3905). In all models, less than 4% of resistance circulating in communities over twenty years would be attributable to PrEP - resistance arising out of poor adherence to antiretroviral therapy and onward transmission of resistant variants far exceeded that that would result from PrEP.

A special session on PrEP and microbicides - including excellent talks on the status of the field, basic science in support of developing optimized products, learning from pharmacology, and thinking towards implementation - is well worth watching (http://pag.aids2012.org/session.aspx?s=654).

Hormonal contraception and HIV risk.

At the International AIDS Society meeting on HIV pathogenesis last year in Rome, and then later published in Lancet Infectious Diseases, a prospective study was reported which compared rates of HIV acquisition in women and HIV transmission from women to men among hormonal contraceptive users and nonusers who were members of 3790 heterosexual HIV serodiscordant couples (in which one partner was HIV seropositive and the other seronegative) from 7 African countries. In both analyses - HIV transmission to women and HIV transmission from infected women to their male partners - hormonal contraceptive users, and particularly injectable hormonal users, faced a doubling in HIV risk compared to non-users of hormonal contraception. Those data garnered considerable international attention, including a formal review by a WHO technical committee, which recommended no change regarding the medical eligibility for use of injectable contraception but noted that women at high risk for HIV should be especially counseled to use condoms for HIV protection if they chose injectable contraceptive methods.

Hormonal contraception is used widely and plays an important role in preventing unintended pregnancies and reducing maternal morbidity and mortality. Some, but not all, studies have observed an increased risk for women to acquire HIV infection when they are using hormonal contraception, especially injectable depot medroxy-progesterone acetate (DMPA, otherwise known as branded Depo-Provera). This injectable contraceptive is currently the most popular contraceptive method used in southern and East Africa as it is easy to use, fast to administer, and can be used discretely. For women in regions where HIV rates are high and injectable contraceptive use is common, such as southern and East Africa, understanding the possible link between injectable contraceptive use and HIV infection is a public health priority.

The challenge with studies on this issue is that observational data are potentially open to bias, and hormonal contraceptive users could be less likely to use condoms (and, even more importantly, less likely to use condoms but more likely to falsely report using them), which could result in confounding in the analysis. To some, this potential confounding is less problematic, as it reflects a "total effect" of contraception on HIV risk (i.e., contraception may have both biologic and behavioral effects that together increase risk) while others feel trying to isolate the biologic component only is important.

At AIDS 2012, one oral abstract session, several symposia (including http://globalhealth.kff.org/AIDS2012/July-26/Hormonal-Contraception.aspx), and an uncountable number of discussions were devoted to trying to determine whether hormonal methods of contraception - perhaps particularly injectable methods - increase HIV risk as well as what the research and public health response should be. A series of sensitivity results were presented (Heffron, abstract WEAC0202 http://pag.aids2012.org/flash.aspx?pid=1367) building off the serodiscordant couples analysis published earlier in the year in Lancet Infectious Diseases. In these sensitivity analyses, additional statistical adjustments were performed, in response to questions about alternative statistical approaches that were raised since publication of that manuscript. Analyses adjusted for additional measures of sexual behavior, restricted analysis to periods with consistent use of hormonal contraception, and limited the analysis to only women who were determined to have consistently used injectable DMPA. All analyses demonstrated a similar trend to what had been published earlier: women using injectable contraceptives had an approximate 2-fold increased risk of acquiring HIV compared to women not using a hormonal contraceptive method. In the analysis that attempted to analyze only DMPA users, the risk of HIV infection was nearly 4 times greater. Through these analyses, the attempt was to isolate a biologic effect of contraception on HIV risk - albeit recognizing that the self-reported sexual behavior data may still be misreported.

A systematic review of the data associating contraceptive use with HIV acquisition in women, requested by WHO, was presented (Polis, abstract WEAC0203 http://pag.aids2012.org/flash.aspx?pid=1303). The authors concluded that the evidence does not support an association between oral contraceptive use and HIV acquisition. For injectable contraception, particularly DMPA, the results across studies are inconsistent - with insufficient data either to establish a clear causal relationship or to rule out such a relationship. The results of this systematic review fed directly into the WHO technical review of the question earlier this year and reflect the uncertainty in the field.

Two abstracts (Fichorova, abstract WEAC0201 http://pag.aids2012.org/flash.aspx?pid=1184) and (Thurman, abstract MOAA0103 http://pag.aids2012.org/flash.aspx?pid=1459) explored biologic mechanisms by which DMPA could influence HIV risk. The first study found higher concentrations of beta-defensin 2 and lower concentrations of the anti-inflammatory regulator IL-1RA in cervical swabs from women using DMPA compared to women not using hormonal contraception. The second found increased vaginal mucosal leukocytes after DMPA initiation in women, also potentially indicating an immunologic basis - such as increased activated cellular targets and HIV cellular receptors - for DMPA to increase HIV risk.

At the end of the oral abstract session devoted to the topic of hormonal contraception and HIV risk, the session chairs polled the audience with a small series of questions, essentially asking "would you prescribe DMPA to a family member living in a high HIV prevalence setting?" The vote seemed split about 50:50 - clearly, there is uncertainty on this incredibly important question.

HIV testing strategies

HIV testing is the cornerstone of HIV prevention - essential for achieving high uptake of effective HIV prevention and care services. A major focus of AIDS 2012 was the challenges and potential strategies to address losses in the cascade of linkages to HIV care, ART, and prevention interventions.

New HIV testing and diagnostic testing strategies have received important attention. A study in Lilongwe, Malawi demonstrated a significant increase in HIV testing with opt-out testing on the surgical wards; the proportion of patients who were seen by an HIV testing counselor increased from 10% to 72%, of whom only 4% refused and the HIV prevalence was 10% among those tested (Haac, abstract TUPE183). Home testing was found to be highly acceptable and cost-effective in Mazabuka, Zambia (Hansen, abstract TUPE190). In addition, a systematic review and meta-analysis of home-based testing in Africa found that the pooled proportion of 83% of persons tested across 16 studies conducted in 5 countries (Uganda, Malawi, Kenya, South Africa and Zambia) (Sabapathy, abstract THPDE0301). Home-based testing initiatives that included community sensitization campaigns, linkage of testing to provision of results, provision of incentives, and without targeting of subpopulations achieved higher uptake of HIV testing. An evaluation of home-based testing and linkages of care in rural KwaZulu-Natal demonstrated 91% uptake of HIV testing, a remarkable 30% HIV prevalence, with high linkages to HIV care: 86% who were eligible for ART by South African guidelines had initiated ART by 6 months, during which time viral suppression among ART-eligible participants increased from 13% to 80% (Barnabas, abstract LBPE34).

The FDA recently approved an oral fluid self-test for HIV, OraQuick. One observed self-testing study assessed the rate of label comprehension at 99% and the OraQuick assay correctly identified HIV status in 96% (Lee, abstract TUPE187). With respect to home-based testing in low prevalence settings and reaching marginalized populations through use of oral fluid HIV tests, the Amsterdam Public Health Service is initiating a home-based HIV testing program that incorporates oral fluid self-testing and internet-based counseling, targeting MSM and immigrants from endemic countries (van der Helm, abstract THPDE0306).

A session focused on couples and families highlighted the high prevalence of HIV serodiscordant couples for HIV prevention. A nationally representative HIV seroprevalence survey in Mozambique in 2009 indicated that 1 in 10 couples in Mozambique are in an HIV serodiscordant partnership (Bradley, abstract TUPDC0201). An evaluation of the PMTCT program in the Zambian Defense Forces health facilities demonstrated how incorporation of couples counseling from 2009-11 increased uptake of antiretroviral prophylaxis by 20% compared to 2005-8 (Chilila, abstract TUPDC0206). A study of HIV disclosure in Vulindlela, KwaZulu-Natal, South Africa (Bearnot, abstract TUAC0104) found that among 687 HIV+ persons in the CAPRISA ART program, 73% of whom were female, that disclosure was common - 99% vs 83% among ART experienced vs ART naïve participants - and that disclosure occurred soon after diagnosis (median of 1 day). However, disclosure of HIV status to sexual partners was 32% and 26% among ART experienced vs ART naïve participants, and was less common among HIV+ women than men (24% vs 45%). Additional work is needed to promote and facilitate HIV disclosure.

Key populations

Important reminders about the significance of key populations - both because of risk but also because of activism - were present throughout the meeting. Multiple symposia were dedicated to important populations. Three Thursday plenaries were powerful reminders of the interface of stigma, power, and HIV prevention and care: from Dr. Paul Semugoma (speaking about global MSM issues http://pag.aids2012.org/flash.aspx?pid=1549), Cheryl Overs (speaking about prevention among sex workers http://pag.aids2012.org/flash.aspx?pid=1548), and Debbie McMillan (speaking poignantly from experience about injection drug use and transgender stigma http://pag.aids2012.org/flash.aspx?pid=926). Additional highlights included:

Youth. A late-breaker abstract (Handa, abstract FRLBD01 http://pag.aids2012.org/flash.aspx?pid=3872) detailed data from the Government of Kenya's Cash Transfer for Orphans and Vulnerable Children, a national flagship social protection program reaching 150,000 families. The program reduced the probability of sexual debut by 6.7%, more in males, and number of sexual partners and unprotected sex acts for adolescents. Another late-breaker detailed high HIV incidence - 4.2% -- among young women (aged 20-24) in Swaziland, measured as part of a national seroincidence survey (Reed, abstract FRLBX02 http://pag.aids2012.org/flash.aspx?pid=3906).

Sex workers. A systematic review was presented, taking data from 102 studies, covering nearly 100,000 female sex workers from 50 countries, that explored HIV prevalence and risk of infection in this population - the pooled odds ratio for HIV infection for those in higher-prevalence settings was 11.9 (Baral, abstract THAC0501). An abstract from Sri Lanka described a police training intervention to reduce arrest of female sex workers for condom possession and to improve attitudes about condom use (Vidanapathirana, abstract THAC0505, http://pag.aids2012.org/flash.aspx?pid=1412). Police demonstrated increased knowledge, improved attitudes about sex workers and PLWHA, and willingness to support the national HIV/AIDS program. Of note, right before AIDS 2012 began, the organization Human Rights Watch released a report documenting police using possession of condoms in support of prostitution charges in several US cities (http://www.hrw.org/reports/2012/07/19/sex-workers-risk-0) - a practice that was decried repeatedly during the AIDS 2012.

Injection drug users. Injection drug use accounts for new infections and is a barrier to effective HIV care. For example, injection exposure is responsible for 2/3 of HIV cases in Eastern Europe and Central Asia but HIV-infected drug users there have ART coverage of <10% - such stunning disproportionate access to care is an inequity that is unforgivable in its effects on morbidity and new infections.

One abstract detailed a systematic cost-effectiveness assessment of needle-syringe exchange programs in Eastern Europe and Central Asia (Wilson, abstract THAC0401), finding that programs were estimated to avert 10-40% of HIV infections and to be cost-saving or cost-effective in the majority of settings. A late-breaker mathematical modeling analysis (Marshall, abstract FRLBC05 http://pag.aids2012.org/flash.aspx?pid=3895) found that combining effective interventions - needle and syringe exchange, HIV testing, ART, substance abuse treatment - has the greatest potential to substantially reduce new infections. An empirical analysis of HIV transmissions among injection drug users from Amsterdam documented declining HIV incidence, accompanied by decreasing injection risk behaviors and low rates of sexually transmitted infections - an argument for harm reduction strategies (Grady, abstract MOAC0401 http://pag.aids2012.org/flash.aspx?pid=1322).

Men who have sex with men. In a session devoted to the US MSM epidemic (http://globalhealth.kff.org/AIDS2012/July-23/health-disparities.aspx), a number of interesting abstracts were presented. Trends in HIV prevalence and HIV testing in CDC studies from 5 US cities (San Francisco, Los Angeles, New York, Baltimore, and Miami) were described (Oster, abstract MOAC0104 http://pag.aids2012.org/flash.aspx?pid=1385). Prevalence was high, with stable prevalence in younger men (aged 18-22), likely (and sadly) reflecting stable incidence. HIV testing rates increased over time, suggesting some reason for optimism, if testing can be translated to linkage to care and prevention. Two oral abstracts from HPTN 061, a multi-city study of HIV risk among 1553 black MSM, detailed that 12% of men were newly-diagnosed with HIV at study entry, emphasizing the incredible need for HIV testing (Mayer, abstract MOAC0105 http://pag.aids2012.org/flash.aspx?pid=1216), and an incidence of nearly 3% per year (nearly 6% in those younger than 30), emphasizing ongoing, high HIV risk and the need for combination prevention strategies for this population (Koblin, abstract MOAC0106 http://pag.aids2012.org/flash.aspx?pid=4470). A late-breaker abstract described HIV prevalence, sexual risks, and HIV knowledge among men who have sex with men in Malawi (Wirtz, abstract FRLBX03, http://pag.aids2012.org/flash.aspx?pid=3907) - 10% were married, HIV prevalence was 14.8%, 91% were unaware of their HIV status, 60% felt that vaginal sex was the highest risk form of sex, indicating low knowledge of transmission risk. A separate session of oral abstracts addressed MSM issues in a variety of global settings (http://pag.aids2012.org/session.aspx?s=284) and the journal The Lancet released a special issue on MSM globally, including a (http://globalhealth.kff.org/AIDS2012/July-24/The-Lancet.aspx).

Male circumcision

The prevention benefit of male circumcision in reducing female-to-male HIV transmission risk was demonstrated in three landmark randomized trials completed in 2006. Implementation of circumcision services has become a clear public health priority.

A session on male circumcision roll-out included a presentation on Kenya's successful voluntary medical male circumcision (VMMC) program (Mwandi, abstract MOPDE0104), in which 312,000 circumcisions were performed from 2008-11 in 260 sites. The median age of men was 17 years. Clinical officers performed 56% and nurses 42% of MCs with an incidence of adverse events of 2.3% and decreasing adverse event rate in 2011. Twice as many (12%) circumcisions were performed in mobile clinics in 2011. Partner testing of men undergoing VMMC was introduced in 2010, and among clients ≥15 years old, 74% of their partners were tested.

A comparative analysis of two high volume fixed site and mobile VMMC programs in Gauteng and KwaZulu-Natal, South Africa reported comparable adverse event and service quality with half the cost per VMMC procedure for the roving mobile team strategy in rural KwaZulu-Natal (Soboil, abstract MOPDE0106). A review of 30 published and ongoing studies of VMMC in terms of timing of resumption of sex, risk compensation, women's views on VMMC, and found resumption of sex before wound healing in 24-42% (including 12-48% among HIV+ men) (Agot, abstract MOPDE01017). A subset of studies that included women's views indicated a high proportion with misconceptions about sexual abstinence; 77% were unaware of the need for sexual abstinence until wound healing. Thus, engagement of women as stakeholders and strong endorsement of partner testing as part of VMMC roll-out in Africa is likely to facilitate delay of sex until wound healing and reduce risk compensation.

A second oral session focused on VMMC strategies and impact. The effectiveness of VMMC has been observed to be 57% for reducing HIV acquisition among men at 66 months in a long-term follow-up study of Kisumu trial participants (Bailey, abstract TUAC0402), demonstrating long-term and sustained benefits of VMMC. In Orange Farm, South Africa where another of the three RCTs of VMMC was conducted, 2 cross-sectional surveys were conducted in 2007-8 and 2010-11, 3 years after the RCT results (Auvert, abstract TUAC0403). The prevalence of circumcision increased from 17-54% in that interval, and age-standardized HIV prevalence decreased from 12.5% to 9.3%. An estimated 536 HIV infections were averted. This study demonstrates that a successful roll-out of VMMC can reduce HIV prevalence and avert a significant number of new infections.

A major focus to facilitate roll-out of VMMC is evaluation of devices such as the Shang Ring and PrePex, which are less invasive, simpler, faster, and can be implemented by nurses and potentially other cadres of trained health workers. A RCT of 400 men in which the Shang Ring was compared to conventional surgical techniques in Kenya and Zambia found that the Shang Ring was faster (7 vs 20 min), had comparable advese event rates (3% among both study groups) and higher satisfaction among men 96% vs 70-85%). Providers also had a strong preference for the Shang Ring (Awori, abstract TUAC0404). An open label study of the safety and of the PrePex device in Rwanda enrolled 575 adult males who had the PrePex device placed by trained nurses (Vincent, abstract TUAC0405). The PrePex device removed the entire foreskin in 100% of men and related adverse events were observed in 0.35%. The average procedure time was 2 minutes and 51 seconds in the last 125 men. Additional safety studies of the Shang Ring and PrePex devices are underway, and if safety and acceptability continue to be high, they will be reviewed by WHO for and PEPFAR for implementation.