Why Women May Not Be Protected From HIV by Intermittent PrEP Dosing

On the heels of news that gay men had very high levels of protection from HIV infection through intermittent pre-exposure prophylaxis (PrEP) timed around sexual activity, a mathematical model predicts that most women would need to stick with a daily dose of Truvada (tenofovir/emtricitabine) to prevent HIV infection from vaginal sex.

Thus, while the evidence for intermittent or "on demand" PrEP for gay men and other men who have sex with men (MSM) is encouraging, a breakthrough in using highly-effective intermittent PrEP for women would appear to be more elusive. However, investigation of new drugs and new delivery mechanisms could prove useful in expanding women's HIV prevention options.

Researchers presented the mathematical model at the HIV Research for Prevention (HIV R4P) conference in Cape Town, South Africa, on Oct. 30, one day after the ANRS IPERGAY study team released interim data suggesting Truvada protected men from anal HIV infection when taken on demand.

Developed by researchers from the University of North Carolina, the model estimates two standard doses per week of Truvada (or a daily standard dose of tenofovir) would be sufficient to prevent HIV replication in rectal tissue. But in vaginal tissue, that daily standard dose of Truvada would only be sufficient to prevent HIV replication in more than 75 percent of a study population; the same dose would be sufficient to prevent HIV replication in cervical tissue in only half of a study population. Tenofovir alone would be insufficient to prevent HIV replication in cervical and vaginal tissues in over half of a study population.

This model could help explain why two large clinical trials looking at PrEP for women failed to show efficacy. Participants in the VOICE and FEM-PrEP trials of Truvada and tenofovir were counseled to take one of the medications daily. However, VOICE participants only took the drugs about 29% of the time, while FEM-PrEP participants took the drugs about 36% of the time.

Jeanne Marrazzo, M.D., one of the principal investigators for the VOICE study, was at the HIV R4P conference and spoke with TheBodyPRO.com about the mathematical model.

"It is a beautiful piece of work," she said. "Unfortunately, it confirms what we know -- that women got the short end of the stick when it comes to their risk of HIV and STIs, and the way these drugs are distributed … In men, the dosing is much more forgiving because you get considerably more drug delivery to the vulnerable sites of infection -- namely, for men who practice receptive anal sex, the rectum."

"So if you look at concentrations of these drugs at the rectum versus the cervix and the vagina, you can probably get away [with taking Truvada] four days a week for rectal protection but, for women, you can't do that," she explained. "You have to really go for daily dosing."

The U.S. Centers for Disease Control and Prevention's guidelines on PrEP, released in May 2014, recommend daily oral PrEP "as one prevention option for adult heterosexually active men and women who are at substantial risk of HIV acquisition."

The prescription of oral PrEP for "coitally-timed or other noncontinuous daily use" is not recommended.

The international scientific community is currently investigating a number of alternative drugs and delivery systems.

The FACTS 001 study is testing whether tenofovir formulated as a vaginal gel, when used before and after sex, is safe and effective at preventing HIV and genital herpes acquisition.

"Those results are probably going to be out early next year, and I think they're going to be very important in helping us decide whether the field should move ahead with that product," explained Marrazzo.

Two sister studies -- the Ring Study and ASPIRE -- are looking at whether a monthly vaginal ring that releases an antiretroviral drug called dapivirine prevents HIV infection in women and is safe for long-term use.

"That's not only a different delivery system, aimed at getting around the issues of daily adherence, but also a new drug," Marrazzo said.

Finally, scientists are investigating a long-acting injectable formulation of the third-generation integrase inhibitor drug cabotegravir. Initial results have been encouraging.

Katherine Moriarty is a consultant and freelance writer, based in Vancouver. She has 10 years of experience in the intersecting fields of public health and community development, with a focus on bloodborne virus policy and programming.