WHAT IS PREP FOR HIV PREVENTION?
PrEP refers to an experimental HIV prevention strategy that proposes using antiretrovirals (ARVs) to reduce the risk of HIV infection in healthy uninfected people at risk for acquiring the virus. With PrEP, individuals would take a single drug or a combination of drugs orally, or through intramuscular injection, with the hope that it would lower the risk of infection if exposed to HIV. There are for ARVs currently being tested in PrEP human safety and efficacy trials: maraviroc, tenofovir (TDF), rilpivirine (TMC278) and a combination of tenofovir and emtricitabine (FTC). Scientists have focused on these drugs because they can be conveniently taken orally once a day, may have relatively low rates of minor side effects compared to benefit when used as prevention, and because there is significant data on their long-term safety and resistance profiles in HIV positive people. And, in the case of rilpivirine, because it can be taken in long acting formulation by injection.
PrEP clinical trials are currently planned or underway in countries in Africa, Asia, Latin America and North America. Taken together, these trials are designed to answer questions about how PrEP works in different parts of the world, and in individuals who are exposed to HIV through anal, vaginal and intravenous routes. These trials have enrolled people with different types of behaviors that might put them at risk for HIV, including injection drug use and unprotected anal or vaginal sex. It’s important to learn how PrEP works in the context of different routes of exposure (for example via injection, anal or vaginal sex.)
Global public-sector, philanthropic and commercial investment in PrEP equaled US$62.3 million in 2011 and has totaled US$266 million over the past six years. There are currently nine ongoing or planned PrEP trials, most testing TDF and/or TDF/FTC, one testing TMC278LA and another testing maraviroc in addition to TDF and FTC.
In February 2012, the FDA granted priority review to Gilead’s application for once-daily TDF/ FTC as PrEP in adults. The FDA approved in July of 2012 Gilead’s application for use of TDF/ FTC as PrEP.
Following the noteworthy results of the iPrEx trial in 2010— which showed the safety and effectiveness of TDF/FTC as PrEP among gay men, MSM and transgender women—came results on the effectiveness of PrEP in heterosexual men and women. In July 2011, the Partners PrEP trial announced that the DSMB had recommended that the placebo arm be discontinued and the study results released due to clear evidence of HIV protection from daily oral TDF/FTC and daily oral TDF. The study showed that both regimens reduced the risk of acquiring HIV in HIV-negative women and men in serodiscordant partnerships. Additionally, the smaller TDF2 expanded safety study reported a reduction in risk for both men and women who took daily oral TDF/FTC.
In 2011, two studies released differing results on the use of PrEP in women. In April, the FEM- PrEP study was stopped early, having found no evidence of benefit in women using daily-oral TDF/FTC. Analysis of the results, released in March 2012, suggests that inadequate adherence may have undermined the effectiveness of TDF/ FTC. In September 2011, the VOICE oral TDF arm was dropped after a DSMB review found no reduction in risk of HIV. VOICE is continuing its evaluation of oral TDF/FTC, with final results expected in late 2012.
While proof-of-concept for PrEP has been demonstrated, ongoing trials are aiming to identify factors that may influence PrEP’s efficacy among different populations, including young MSM, injection drug users and heterosexual men and women. Studies are also ongoing that look at different dosing strategies, including intermittent, time-driven and exposure-based use of PrEP.