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 only currently licensed PrEP method involves taking a daily dose of two antiretrovirals, tenofovir and emtricitabine, in a single pill marketed as Truvada or Descovy. 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 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 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 among people who inject drugs, heterosexual men and women, and heterosexual couples in which one partner was living with HIV and one was not. The Food and Drug Administration consequently approved the use of Truvada for PrEP in 2012. The Centers for Disease Control and Prevention (CDC) issued comprehensive clinical guidelines in 2014 recommending that daily PrEP be considered for HIV prevention in people who are at substantial risk for HIV. 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 among MSM and transgender women in real-world settings, outside the supportive structure of a clinical trial. In 2019, the U.S. Preventive Services Task Force recommended that clinicians offer daily oral PrEP to all people at high risk of acquiring HIV.
PrEP Poses Particular Challenge for 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 acquisition via vaginal sex. Both men and women who are prescribed oral PrEP should take the pill daily as directed, according to CDC 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 for HIV acquisition. 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. 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. 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.
Two other PrEP demonstration studies have illustrated that counseling and support may be essential for maintaining adherence in certain populations. The HPTN 073 demonstration study of daily PrEP for black MSM in the United States, which offered counseling and referrals in addition to Truvada, found in 2016 that nearly 70 percent of participants continued taking PrEP six months after enrolling in the study. The NIAID-supported CHAMPS PlusPills demonstration study of daily PrEP in South Africans 15 to 19 years old found in 2017 that adherence was moderate and diminished substantially when study visits became less frequent.
NIAID Invests in Development of Long-Acting PrEP
It is clear from PrEP studies to date that the challenge of taking a daily pill 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, implants, and antibodies. Scientists are designing these products to be inserted, injected, infused or implanted from once a month to once a year. In 2020, two large NIAID-sponsored clinical trials found that a PrEP regimen containing an investigational long-acting form of the HIV drug cabotegravir injected once every eight weeks was safe and more effective than daily oral PrEP at preventing HIV acquisition. One trial enrolled more than 4,500 cisgender men and transgender women who have sex with men, and the companion study enrolled more than 3,200 cisgender women in southern and east Africa. View an infographic on NIAID-supported research on long-acting HIV prevention.