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HIV Prevention Tops the News at AIDS 2014

, by Liz Highleyman

AIDS2014_logo_600x191Biomedical prevention has garnered more headlines than HIV treatment in recent years, and the news coming out of the 20th International AIDS Conference last week in Melbourne was no exception.

WHO PrEP Guidelines

Before the start of the conference, the World Health Organization (WHO) released new guidelines for HIV prevention, diagnosis, treatment, and care for key populations. The biggest story was its recommendation that gay and bisexual men who are at risk for HIV infection consider using antiretroviral drugs for pre-exposure prophylaxis, or PrEP, with some news outlets reporting that WHO had advised all men who have sex with men to start Truvada (tenofovir/emtricitabine).

The Food and Drug Administration’s 2012 approval of Truvada for PrEP was based in part on data from the international iPrEx trial, which showed that once-daily Truvada reduced the risk of HIV infection for gay and bisexual men and transgender women by 44% overall, rising to more than 90% among participants with blood drug levels indicating regular use.

“These recommendations highlight how HIV uninfected people can play an important role in getting to zero transmissions,” iPrEx protocol chair and San Francisco AIDS Foundation medical director Robert Grant from the Gladstone Institutes told BETA. “These medications have a proven record of safety and effectiveness for treatment and prevention.”

Presenting the guidelines at AIDS 2014, Fabio Mesquita, Brazil’s HIV and STI health director, stressed that “evidence is the strongest that PrEP clearly can work” for gay men. There has only been one study of PrEP using tenofovir alone for people who inject drugs (the Bangkok Tenofovir Study), and demonstration projects are still warranted for sex workers and other populations.

Chris Beyrer (photo: Liz Highleyman)

Chris Beyrer (photo: Liz Highleyman)

Addressing the exaggerated media reports at a press briefing, International AIDS Society incoming president Chris Beyrer emphasized that the WHO guidelines state that PrEP is “an additional prevention option for men who want it” as part of a comprehensive set of services that would also include condoms, counseling, screening and treatment for other sexually transmitted infections, and addressing legal and policy barriers that impede access to services. Like birth control options for women, he explained, PrEP is just one option, and choices can change over a lifetime.

More Data from iPrEx

Grant presented late-breaking findings at the conference from iPrEx OLE, an optional open-label extension phase of the trial after the randomized Truvada vs. placebo phase was completed (abstract TUAC0105LB). Results were published simultaneously in The Lancet Infectious Diseases.

As BETA previously reported, OLE enrolled more than 1,600 HIV-negative iPrEx participants; three-quarters elected to take PrEP, while the rest served as an untreated control group. At this stage all participants knew whether they were using Truvada, and about midway through they were informed about the primary study findings showing that PrEP worked if taken regularly. Among people who opted not to take PrEP, concern about side effects was the main reason.

Among people who elected to take PrEP—whether or not they actually did so regularly —the annual HIV incidence rate was 1.8%, compared to 2.6% for those who opted out. Overall PrEP effectiveness during the OLE was about 50%. However, among participants who took at least four doses of Truvada per week according to drug levels in blood samples, there were no new HIV infections—an efficacy of 100%. Effectiveness fell to 84% for those who took two or three doses, and PrEP showed no significant efficacy for those who took fewer than two weekly doses.

Robert Grant (photo: Gregory Fowler)

Robert Grant (photo: Gregory Fowler)

“[T]hese results demonstrate that PrEP remains highly effective, even in real-world circumstances in which adherence may not be perfect,” Grant stated in a study press release.

As seen previously, poor adherence was the Achilles heel of PrEP. Only about one-third of OLE participants took Truvada regularly, with younger people being less likely to have measurable blood drug levels. However, adherence was better among people who reported more high-risk sex or more sexual partners, indicating that they adjusted their adherence based on their perceived risk.

IPERGAY: Intermittent PrEP

Another ongoing study, IPERGAY, is looking at intermittent or “on demand” PrEP used before and after sex rather than every day. This trial began enrolling gay and bisexual men in France and Quebec in early 2012. They were randomly assigned to take two Truvada or placebo pills 2 to 24 hours before they expected to have sex, and two more pills at 24 and 48 hours afterwards.

While data on effectiveness are not yet available, Jean-Michel Molina from University of Paris Diderot reported early findings on adherence (abstract TUAC0103). The 129 men included in this interim analysis, out of the total 350 now enrolled in the pilot phase, had an average age of 35 and reported having anal sex a median of 10 times per week with an average of two partners.

About 80% of participants reported that they had used PrEP the last time they had sex. Based on pill counts, they took an average of 15 pills per month, meaning they were on PrEP about half the time. Blood drug level measurements showed detectable tenofovir and/or emtricitabine in approximately 75% to 90% of participants. The study also measured drug levels in hair—a method that lets researches assess drug levels over time—and found that about 50% of samples had detectable tenofovir levels.

While people who have a lot of sex may benefit more from consistent daily PrEP, intermittent use may be a good option for people who have sex less frequently but on a predictable schedule. Taking PrEP only when needed could significantly reduce cost and allay concern about side effects (though these are generally mild and transient—if they occur at all—even with daily PrEP).

Treatment as Prevention

In 2011 researchers reported results from the HPTN 052 study showing that the rate of HIV transmission within heterosexual couples decreased by 96% when HIV-positive partners in heterosexual serodiscordant (mixed status) couples started antiretroviral therapy (ART) immediately, rather than waiting for their CD4 count to fall below 350 cells/mm3.

These findings put “treatment as prevention” on the map and was part of the impetus—in addition to improving the long-term health of people with HIV—for national and WHO guidelines recommending earlier ART.

While the evidence supporting “TasP” remains irrefutable, providing universal access to well-tolerated ART and getting people to start and stay on treatment remains a challenge worldwide. Participants in treatment as prevention trials benefit from regular HIV testing, extensive prevention counseling, and other services, and we are only now learning how well it will work in “real world” use.

Kristin Wall from Emory University reported findings from a study in Zambia which found that counseling and HIV testing for couples may play a key role in the risk reduction observed in studies like HPTN 052 (abstract WEAC0101). In this study, serodiscordant heterosexual couples who received joint counseling and testing prior to the positive partner starting ART saw an 82% lower rate of HIV incidence among the negative partners. Among couples who received counseling but the positive partner did not start treatment, transmission risk still fell by 70%. But when positive partners started ART without prior couples counseling, the decline in incidence was only 30%.

Circumcision

Two studies presented at the conference looked at adult male circumcision as an HIV prevention method. A pair of randomized trials conducted in Uganda and South Africa found that men who underwent elective circumcision reduced their risk of HIV acquisition by approximately 60%. WHO has since recommended the roll-out of adult circumcision in high-prevalence countries as one component of a comprehensive prevention effort.

Kévin Jean (photo: Gregory Fowler)

Kévin Jean (photo: Gregory Fowler)

At AIDS 2014 the French National AIDS Research Agency team behind one of these studies, in Orange Farm near Johannesburg, reported that male circumcision not only protected men but was also beneficial for their female partners. Researcher Kévin Jean and colleaguesfound that HIV incidence among women who only had sex with circumcised men was 18%, compared with 30% among women who had sex with uncircumcised men (abstract FRAE0105LB).

In a related presentation, Jillian Pintye from the University of Washington in Seattle reported on changes in syphilis incidence in Partners PrEP, a trial of Truvada and tenofovir PrEP for heterosexual couples in Africa (abstract MOPDC0103). Overall, there were 221 new cases of syphilis among the 4,716 mostly married serodiscordant couples included in this analysis, in which about half the men were circumcised at enrollment.

Syphilis incidence fell by 42% among men who were circumcised compared with uncircumcised men, and the effect was even stronger—a 59% reduction—for female partners of circumcised men. Syphilis rates fell for both HIV-positive and HIV-negative men (by 62% and 36%, respectively), though the latter difference was not statistically significant. Among women, those who were HIV positive saw a smaller decrease than HIV-negative women (48% vs. 75%, respectively), with both reductions being significant.

Risk Compensation

One widely expressed but so far unsubstantiated concern about biomedical prevention concerns “risk compensation,” or an increase in sexual risk behavior such as condomless sex when people think they are otherwise protected.

Kimberly Koester from the iPrex team reported findings from a qualitative analysis of reasons for and feelings about PrEP use in OLE (abstract TUAC0102). This analysis

confirmed earlier findings that taking antiretrovirals for prevention did not increase sexual risk behavior. In fact, reported risk behavior actually declined during follow-up in both the PrEP and no-PrEP groups. Overall, participants reported that using PrEP contributed to feeling less stress, fear, and guilt about their sex lives.

In another study, researchers with the Population Council of Zambia looked at risk compensation among men who underwent adult circumcision for HIV prevention (abstract MOPDC0105). They surveyed a random sample of community members every two years, asking about their circumcision status and risk behavior. In the first survey, only 5% of the men were circumcised, but this rose to 12% in the second round of questioning and 21% by the third.

Conducting various statistical analyses in an attempt to control for other factors such as demographics and personal risk aversion, they saw only minor changes, if any, in sexual risk behavior, including frequency of sex without condoms, number of partners, and paying for sex. While the different methods produced inconsistent results, the researchers concluded say that there was no clear evidence of a significant change in risk behavior in either direction.

Finally, a meta-analysis by Caitlin Kennedy and colleagues with the Evidence Project looked at sexual behavior after people started ART, which has implications for TasP (abstract WEAC0104). The researchers found that none of the 15 included studies—most of which enrolled heterosexuals in Africa—detected evidence of risk compensation. On the contrary, starting treatment was consistently associated with an increase in condom use.

Social and Cultural Aspects

While the science behind biomedical prevention is sound, much remains to be learned about what the new prevention technologies mean for affected communities. The entire AIDS 2014 conference week featured a full slate of prevention-related sessions looking at how PrEP is starting to be used “on the ground,” especially by gay and bi men.

PrEP was one of the topics at a pre-conference hosted by the Global Forum on MSM and HIV (MSMGF). The San Francisco AIDS Foundation also sponsored an evening satellite titled “Gay Men’s health and PrEP: The New Voices of Community Activism.”

“There’s an extraordinary cultural shift ongoing in the gay community, especially in the U.S.,” said community PrEP expert and Aidsmap reporter Gus Cairns, describing the MSMGF meeting. “A very rich and respectful discussion arose, and what we ended up agreeing on is that the PrEP debate has enabled people to start talking about things that have been a bit taboo or frozen in the HIV conversation. The PrEP debate has thrown a hand grenade into discourse about prevention in the gay community, and that can only be a good thing.”

Liz Highleyman (liz (at) hivandhepatitis.com) is a freelance medical writer and editor-in-chief of HIVandHepatitis.com.

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