JOHANNESBURG, 5 March 2013 (PlusNews) - A three-year clinical trial involving over 5,000 women in East and Southern Africa has found that pre-exposure prophylaxis (PrEP) - whether a vaginal gel or an oral tablet - is not effective at preventing HIV infection in young, unmarried women.
The Vaginal and Oral Interventions to Control the Epidemic (VOICE) study - involving HIV-negative women in South Africa, Uganda and Zimbabwe - aimed to test the safety, effectiveness and acceptability of three HIV-prevention methods: daily use of a vaginal gel containing the antiretroviral (ARV) drug tenofovir; daily use of oral tablets containing tenofovir, and daily use of oral Truvada, a combination of tenofovir and another ARV, emtricitabine. In 2011, VOICE stopped testing oral tenofovir and tenofovir gel after reviews found that it was not effective, leaving only the Truvada arm of the trial to continue.
But ultimately none of the products worked among the women enrolled in the trial, as most participants did not use them daily as recommended, researchers found.
Of the 5,029 women enrolled in VOICE, 312 acquired HIV during the trial - an overall HIV incidence of 5.7 percent - nearly twice the rate that researchers had expected when designing the study.
"Although there may be other explanations for why these products don't always work to prevent HIV, it's hard to ignore the fact that so few women in our study used them. Clearly an approach of daily product use is not going to work for the population of women who participated in VOICE," said Jeanne Marrazzo, one of the trial's investigators.
"We can't determine whether the products were effective with very, very low rates of product use," Marrazzo noted.
Adherence makes all the difference in PrEP, which involves giving anti-HIV drugs to HIV-negative people to prevent infection in case of exposure. According to Mike Chirenje, another trial investigator, in other trials where the products had been used consistently, Truvada had been found to be effective in preventing HIV transmission.
In July 2011, scientists announced that the Partners PrEP trial had ended a year early after finding overwhelming evidence of the effectiveness of oral tenofovir and Truvada in preventing HIV infection among sero-discordant couples; earlier in the year, a major randomized clinical trial, HPTN 052, found that treating an HIV-infected individual reduced the risk of sexual transmission of HIV to an uninfected partner by as much as 96 percent.
In 2010, the Centre for the AIDS Programme of Research in South Africa (CAPRISA) found that a vaginal gel containing tenofovir used before and after sex prevented four out of ten HIV infections.
But in April 2011, the FEM-PrEP study found that giving HIV-negative women Truvada to prevent them from getting HIV was ineffective: there was no difference in HIV incidence between women taking Truvada and women taking placebo. Adherence levels in this study were also low, Chirenje told journalists during a telephone briefing.
Researchers analysed blood samples from 773 VOICE study participants and found adherence to the medication was low across all groups: the drug was detected in 29 percent of blood samples from women in the Truvada group, 28 percent in the oral tenofovir group and 23 percent among those in the tenofovir gel arm. To make matters worse, young, single women were the least likely to use PrEP, despite their higher risk of becoming HIV-positive. In the Truvada arm of the trial, the ARV was detected in the blood of only 21 percent of younger, single women, compared to 54 percent of those married and over age 25.
An adherence rate of 80 percent would "give you a really good signal of what's working," Chirenje told IRIN/PlusNews.
Adherence was calculated to be 90 percent, however, based on what the trial participants told researchers and on monthly counts of unused gel applicators and leftover pills. Trial investigators are currently analysing the results to determine why the women did not use the products.
“Biomedical tools do not work in a vacuum but rather in the complex realities of women’s and girls’ lives. The women of VOICE and other prevention trials have much to tell us. Now we need to listen to what they are saying and design prevention options based on a better understanding of their reproductive and sexual health needs and desires, their perceptions of personal risk for HIV infection, and their interest in and ability to use the products offered in those trials,” Mitchell Warren, executive director of the AIDS Vaccine Advocacy Coalition (AVAC), said in a statement.