Oral PrEP Trial in Women Stopped Early

Today, researchers at Family Health International (FHI) announced that they would be closing a trial known as FEM-PrEP that was designed to determine whether oral administration of the antiretroviral (ARV) drug Truvada was able to prevent HIV infection—a strategy known as pre-exposure prophylaxis (PrEP)—ahead of schedule. The trial will be closed early because the trial’s independent data monitoring committee determined during an interim review of the data that it would be highly unlikely that the trial would be able to demonstrate the effectiveness of Truvada even if it continued until its originally planned conclusion.

As its name suggests, FEM-PrEP was designed to determine if Truvada—a combination of the ARVs tenofovir (TDF) and emtricitabine (FTC)—was effective in blocking HIV infection in women. As of February 18, nearly 2,000 women at increased risk of HIV infection were enrolled in the FEM-PrEP trial, primarily in Kenya and South Africa, with 16 volunteers enrolled in Tanzania. At that time, 56 new HIV infections had occurred and these infections were split evenly between the Truvada and placebo arms.

The early closure of this trial is a disappointment to the PrEP field, which was buoyed recently by positive results from two large trials. Last July, researchers reported results of the CAPRISA 004 trial of 889 high-risk South African women that showed a vaginal microbicide candidate consisting of a gel containing 1% of the antiretroviral TDF was able to reduce HIV incidence by 39%. Then, in November, results of the iPrEx trial of nearly 2,500 men and transgendered women who have sex with men showed that daily administration of Truvada was 44% effective in preventing HIV infection.

Researchers have not analyzed the full data set collected in the FEM-PrEP trial, but will do so in a few months once follow up of the volunteers is completed. Until then, there is no explanation for why Truvada, which was effective in men who have sex with men (MSM), was not effective in the heterosexual women enrolled in this trial. Adherence will likely be one of the factors researchers will investigate. Another question may be whether the concentration of drug necessary to block vaginal transmission is different.

The only intriguing piece of information released by FHI today was that the pregnancy rate during the trial was higher among study participants in the Truvada arm. All women in the trial were required to use contraception at enrollment, yet the overall pregnancy rate during the trial was 9%. During pregnancy, women were required to stop taking Truvada because of safety concerns. Researchers will investigate several factors to try to determine what could have led to the higher rate of pregnancy in the Truvada arm.

The US Centers for Disease Control and Prevention released interim guidance on the use of Truvada for PrEP in MSM earlier this year based on the iPrEx findings. Today, due to the closure of the FEM-PrEP trial, the agency cautioned against women using PrEP at this time, while saying that it is not yet clear from this trial alone whether or not Truvada works in protecting women against HIV infection.

There are still two other ongoing trials of PrEP in women. The VOICE trial is testing oral TDF and Truvada, in addition to a 1% TDF gel in 5,000 women at clinical research centers in sub-Saharan African, and the Partners PrEP trial is evaluating oral TDF and Truvada in the uninfected partners of serodiscordant couples in Kenya and Uganda. Another trial is also evaluating the efficacy of PrEP in injection drug users.