What PrEP clinical trials have happened or are happening?

PrEP clinical trials have happened or are happening in Africa, Asia, South America, and North America. They include different people who may be exposed to HIV through unprotected anal and vaginal sex and sharing needles to inject drugs. The different populations include gay and bi men; transwomen; heterosexual women; heterosexual serodiscordant couples (where one partner is HIV positive and the other is HIV negative); and injection drug users. To note, in the clinical research world, researchers use the term “men who have sex with men” (MSM) to describe gay and bi men, transwomen, and others who were born male and who have sex with men but who may or may not identify as gay or bisexual.

We have seen a range of results from completed PrEP clinical trials. Here’s how they stack up.

For gay and bi men and transwomen who participated in PrEP clinical trials:

  • The iPrEx study compared Truvada with a placebo pill in nearly 2,500 gay and bi men and transwomen in six countries. All of the participants also got safer sex counseling and condoms, regular sexually transmitted infection (STI) check-ups and treatment, and HIV testing.
  • The analysis showed that the group assigned to receive Truvada had a 42% reduction in HIV risk compared with those who received placebo. However, the Truvada group included people who were offered Truvada but did not take the pills. When the researchers looked at data only from people with detectable levels of the drugs in their blood (a sign than the medication was being taken regularly), they found that transmissions dropped by as much as 92%. Further analyses indicate that drug levels corresponding to daily use are associated with 99% protection against HIV.

For heterosexual women and men who participated in PrEP clinical trials:

  • The Partners PrEP study looked at Truvada or Viread alone compared with a placebo in more than 4,500 heterosexual men and women in Kenya and Uganda who were in couples where one partner was HIV positive and the other was HIV negative (what scientists call “serodiscordant” couples). Focusing just on the men and women assigned to take Truvada, the researchers found a reduction in new infections of up to 75%. In those with detectable drug in their blood, it looked like PrEP cut infections by at least 90%. Again, good adherence mattered.
  • A similar smaller study in Botswana, called TDF2, looked at Truvada compared with a placebo in more over 1,200 heterosexual men and women and found similar rates of efficacy as Partners PrEP. For participants who were assigned to take Truvada, the risk of HIV infection dropped by around 62%.
  • Another study, called Fem-PrEP, was conducted with over 2,100 women in Kenya, South Africa, and Tanzania. The study had to be stopped early because there was no difference in effect between Truvada PrEP and a placebo. A later look at drug blood levels found that most of the women assigned to take Truvada did not use them as recommended. Adherence was too low to detect any protective effect.
  • The VOICE (Vaginal and Oral Interventions to Control the Epidemic) trial looked at of daily Truvada and drug-containing vaginal microbicide gel in more than 5,000 women in South Africa, Uganda, and Zimbabwe. There were five study groups where participants were randomized to use one of the following products daily: tenofovir gel, placebo gel, oral tenofovir tablet, oral Truvada, or an oral placebo pill. All study arms were stopped because none of the products were effective in preventing HIV infection. Even though participants self-reported high adherence, analysis of blood samples showed that most of the participants did not actually use the study drugs. Again, similar to Fem-PrEP, no protective effect was seen because adherence was low.

Given the Fem-PrEP and VOICE trials’ results, researchers are trying to figure out the social and behavioral factors that play out in HIV prevention trials, beyond whether the medications themselves work. Age, marital status, competing needs, HIV stigma, perceptions about HIV risk, and beliefs and attitudes about taking pills and prophylactic drugs are all factors to consider in understanding why this type of prevention strategy was not a good fit for women in the communities where these studies took place.

For people who inject drugs who participated in PrEP clinical trials:

  • The Bangkok Tenofovir Study compared Truvada with a placebo pill in more than 2,400 participants who reported injecting drugs during the previous year in Bangkok, Thailand. Truvada was associated with a nearly 49% overall reduction in risk of HIV infection in IDU participants. Protection increased to 74% among those who took the study drug via directly observed therapy during clinic visits. Because participants in the study may have been both injecting drugs and having sex without condoms, it still unclear whether Truvada specifically prevents “parenteral” HIV acquisition—that is, acquisition through injection rather than sex.

THE MESSAGE IS CLEAR: If you don’t take PrEP consistently it can’t protect you from HIV, but if you do take it regularly it can offer strong protection.

To stay on top of ongoing and upcoming PrEP research, please refer to the BETA for research updates and highlights.

The hope is we will get a better picture of how well PrEP works across different settings and groups of people.