ATLANTA — A large study to determine if pre-exposure prophylaxis could prevent HIV transmission among high-risk women failed to show any significant differences between those who took oral medication or vaginal gel or placebo medications in protection against acquiring infections.

The VOICE (Vaginal and Oral Interventions to Control the Epidemic) trial failed, said Jeanne Marrazzo, MD, of the University of Washington, in Seattle, probably because the women at greatest risk of HIV infection did not take their medications: Overall, 50% to 58% of women assigned to treatment arms did not have detectable drug in their systems at any of the blood samples.

“Even when we stratified for those people who were taking the drug or not taking the drug, we still could not observe a significant difference in HIV acquisition,” Marrazzo told MedPage Today during a press briefing at the annual Conference on Retroviruses and Opportunistic Infections.

The five-arm placebo-controlled trial tested three active treatments in a population of young African women:

    Oral tenofovir (Viread). This arm of the trial, with 1,007 enrolled was ended prematurely when it was observed that 52 infections had occurred in the tenofovir arm compared with 35 infections in the placebo arm (P=0.07) – a rate of 6.3 per 100 person-years compared with a rate of 4.2 per 100 person-years in the placebo participants.
    Oral tenofovir/emtricitabine (Truvada). Among the 1,003 women in the study, there were 61 infections (4.7 per 100 person-years) in women on the active drug versus 60 (4.6 per 100 person-years) among the women on placebo pills.
    Tenofovir vaginal gel. Of the 1,007 women in this arm of the trial, there were 5.9 infections per 100 person-years on the active gel versus 6.8 infections per 100 person-years among those on the placebo gel.
    Placebo pills were given to 1,009 women.
    Gel placebo was given to 1,003 women.

None of the differences in the active treatment groups was significant.

“Adherence was greatest among the women who were older than 25, who were married, and who had partners older than 28 years of age,” Marrazzo said. “These are people in a stable relationship where HIV infection would be expected to be low.”

The women who didn’t take the medication regularly were younger, single, and had multiple relationships – that is, the women with highest risk for infection.

The researchers saw no significant differences in infection rates in either group when active agents were compared with placebo.

“The VOICE results reinforce what we already know from previous trials – these interventions work when they are used, and they don’t work when they are not used,” Mitchell Warren, executive director of AVAC, an AIDS advocacy group based in New York, said in a statement. “Pre-exposure prophylaxis is still a valuable option for many women, and men, who recognize their risk and can take it consistently.

“Now we have a dual responsibility to understand who might benefit from daily pre-exposure prophylaxis and ensure that they can access it, and to accelerate the development of additional options that can meet the urgent needs of others.”

Jonathan Mermin, MD, director of CDC’s Division of HIV/AIDS Prevention, concurred in a statement, that the failure of VOICE was “likely because very few were taking the study drugs as directed. Less than one-third of participants assigned to the two study arms evaluating daily oral tenofovir and daily oral tenofovir/emtricitabine had any study drug detected in their blood.

“Given the low levels of adherence in the study, this result is not surprising: Pre-exposure prophylaxis must be taken consistently to work effectively.

“Both oral regimens evaluated in VOICE have been previously shown to be highly effective in lowering the risk of HIV acquisition if taken consistently. Other studies have shown efficacy of daily oral pre-exposure prophylaxis among multiple high risk populations — including men who have sex with men and heterosexual women and men, including those in HIV discordant couples — and higher levels of protection with consistent use of pre-exposure prophylaxis. In these trials, pre-exposure prophylaxis reduced the risk of HIV infection by between 44% to 75% among participants overall, but among those with detectable levels of medication in their blood, the risk was reduced by roughly 90 percent.”

Source: MedPage Today.