Pre-exposure prophylaxis, or PrEP, is a strategy in which healthy people routinely take one or more antiretroviral drugs to reduce their risk of getting HIV. The one currently validated PrEP method involves taking a daily dose of two antiretrovirals, tenofovir and emtricitabine, in a single pill marketed as Truvada. NIAID supports research to develop longer-acting forms of this HIV prevention strategy.
NIAID Study First to Establish PrEP Efficacy
The NIAID-supported clinical trial called iPrEx was the first to establish the effectiveness of PrEP. In 2010, this randomized controlled trial found that daily Truvada reduced the risk of acquiring HIV infection among nearly 2,500 men who have sex with men (MSM). Since many study participants did not take the medication daily as prescribed, the reduction in risk for the whole study population was just 44 percent. However, those men who had detectable drug in their blood—indicating that they were taking Truvada regularly—had a 92 percent lower risk of acquiring HIV infection than participants who received a placebo.
Subsequently, three more large-scale randomized controlled trials of daily PrEP found that it substantially reduced the risk of acquiring HIV infection among injection drug users, heterosexual men and women, and heterosexual couples where one partner was living with HIV and one was not. The U.S. Food and Drug Administration consequently approved the use of Truvada for PrEP in 2012.
The U.S. Centers for Disease Control and Prevention issued comprehensive clinical guidelines in 2014 recommending that daily PrEP be considered for HIV prevention in people who are at substantial risk for HIV infection. The World Health Organization issued a similar recommendation in 2015 after two European studies showed that PrEP was highly effective at reducing the risk of HIV infection among MSM and transgender women in real-world settings, outside the supportive structure of a clinical trial.
PrEP Poses Particular Challenge for Women
No large randomized controlled trial has found daily PrEP to be effective in a study population of exclusively women. In the two major studies of PrEP in women—the FEM-PrEP trial, completed in 2012, and the NIAID-supported VOICE study, completed in 2013—the overwhelming majority of participants did not take the study medication daily as prescribed. Daily pills for HIV prevention were not desirable to these women, who lived in sub-Saharan Africa, and did not fit into their lifestyles. In a promising development, a NIAID-funded clinical trial called HPTN 067 reported in 2015 that three-quarters of participating young women in Cape Town, South Africa who were informed of the evidence that daily PrEP was safe and effective could follow a daily PrEP regimen.
Findings from a NIAID-funded study in 2014 helped explain why strong adherence to PrEP is particularly important for the HIV prevention strategy to work in women. A mathematical model developed by scientists at the University of North Carolina predicted that women must take Truvada daily to prevent HIV infection via vaginal sex. Both men and women who are prescribed Truvada for PrEP should take the pill daily as directed, according to Centers for Disease Control and Prevention guidelines.
Real-World Studies of PrEP
All of the PrEP clinical trials to date have found that the more days per week a study participant takes PrEP, the greater his or her reduction in risk of HIV infection. Since PrEP clinical trial participants receive frequent counseling and support for HIV prevention, scientists have been interested in learning how well people stick to PrEP regimens in settings that lack this supportive framework. Consequently, many studies of PrEP adherence have been conducted in contexts that are closer to real-world settings. In these open-label studies and demonstration projects, all participants have been offered Truvada for PrEP and have been informed of its proven effectiveness when taken as prescribed.
NIAID has supported four such studies to date, two of which have reported results. The large, iPrEx-OLE open-label study of daily PrEP among MSM in the Americas found in 2014 that adherence was greatest among those who had a higher risk of HIV infection. Investigators in the PrEP Demonstration Project made the same observation of MSM and transgender women in Miami, San Francisco, and Washington, D.C., in 2015. The project’s investigators found a moderate level of adherence to PrEP overall. These study findings show that when people are made aware of their level of risk for HIV infection and made aware that PrEP works, they are more likely to opt to take PrEP and adhere to the daily regimen.
Investigators will report the results of NIAID’s HPTN 073 demonstration study of daily PrEP in black men who have sex with men in the first quarter of 2016. The NIAID-supported CHAMPS demonstration study of daily PrEP in 15- to 19-year-old South Africans is ongoing and expected to end in summer 2017.
NIAID Invests in Development of Long-Acting PrEP
It is clear from all the PrEP studies to date that the challenge of taking Truvada daily will limit the global impact of this valuable HIV prevention method. Therefore, to foster the development of a variety of HIV prevention products that may be more desirable to some people than a daily pill, NIAID is investing in research on long-acting forms of HIV prevention, including drug-infused vaginal rings, injectable drugs and implants. Scientists are designing these products to be inserted, injected or implanted from once a month to once a year. For more information about them, see an infographic on long-acting HIV prevention.