FHI issued a statement Monday morning announcing that the FEM-PrEP trial – looking at once-daily administration of the antiretroviral drug Truvada (emtricitabine and tenofovir) versus a placebo among high-risk heterosexual, HIV-negative women for preventing HIV infection – has been halted due to inability to determine effectiveness. Investigators found that new HIV infections among participants in the Truvada arm equaled the number of infections in those assigned to the placebo arm.
“The FEM-PrEP outcome is surprising and disappointing, given a number of earlier studies suggesting the promise of pre-exposure prophylaxis (PrEP) using antiretrovirals,” the FHI release stated, alluding to the iPrEx study results announced in late November which found that daily dosing of Truvada among high-risk men who have sex with men (MSM) indicated a 44 percent reduction in the incidence of HIV, with detectable levels of the study drug in participants’ blood strongly correlating with the prophylactic effect.
A scheduled interim review of the trial data by the Independent Data Monitoring Committee (IDMC) found that FEM-PrEP would be “highly unlikely to be able to demonstrate the effectiveness of Truvada in preventing HIV infection in the study population, even if it continued to its originally planned conclusion,” according to the FHI statement. The IDMC found that the trial was conducted to a high standard.
Over the next few months the trial will be closed down and since final analyses have not been conducted, FHI cannot say for certain whether or not Truvada works to prevent HIV infection in women. The U.S. Centers for Disease Control (CDC) is recommending that women refrain from using PrEP for HIV prevention at this time. There are a number of possible reasons for the study findings, including low adherence to study regimen, a true lack of effect of the product among women (versus MSM), or other factors still to be determined.
The FEM-PrEP clinical trial was implemented by FHI with research centers in Africa, and was funded by the U.S. Agency for International Development and the Bill & Melinda Gates Foundation.
“The premature closing from FEM-PrEP does not predict the findings from either VOICE or Partners PrEP,” said Mitchell Warren of AVAC, a global advocate for an AIDS vaccine and other HIV prevention methods in a press release. VOICE and Partners PrEP are two other ongoing trials looking at the effectiveness of oral PrEP. “It is too soon to tell whether the differences observed between iPrEx and FEM-PrEP are due to the route of exposure, pill-taking behavior, biological differences in drug activity, or some other factor.”
FHI released some preliminary findings from the trial:
- As of Feb. 18, 2011, the study had screened 3,752 women and enrolled 1,951: 739 in Bondo, Kenya; 764 in Pretoria, South Africa; 432 in Bloemfontein, South Africa; and 16 in Arusha, Tanzania. The most common reason for women not being enrolled was existing HIV infection. The overall HIV prevalence was 21 percent among women screened for enrollment across the sites.
- Preliminary data indicate about 90 percent of the participants were retained in the study.
- Adherence to study product was approximately 95 percent when the study product was available for use.
- Women reported an average of 3.7 vaginal sex acts in the seven days prior to enrollment, consistent with the average of 3.6 acts reported during follow-up.
- As of February 18, the approximate rate of new HIV infections among trial participants was five percent per year. A total of 56 new HIV infections had occurred, with an equal number of infections in those participants assigned to Truvada and those assigned to a placebo pill.
- Women participating in FEM-PrEP used an effective method of contraception at the time of enrollment—66 percent were using injectables and 30 percent were using oral contraceptives. The overall pregnancy rate was nine percent; the highest pregnancy rates were among women using oral contraceptives.
- The use of Truvada in FEM-PrEP was associated with some known side effects that were not serious.
The FHI release noted that further analysis of the FEM-PrEP data will better explain the observed higher pregnancy rate among women in the active drug arm of the trial, compared to those in placebo arm.
**Update: On a conference call convened by AVAC Tuesday, FHI representatives explained that self-reported adherence to the study drug was approximately 95 percent, excluding external factors such as stopping medication due to pregnancy. Trial investigators have blood specimens from partipants at certain intervals during the trial that they are testing for drug levels. Results from those tests will be reported in the coming months.