The daily use of a vaginal gel or oral medication does not appear to prevent HIV infection in young, unmarried African women, according to the results of a large HIV prevention trial released at the Conference on Retroviruses and Opportunistic Infections in Atlanta in the US on Monday.
The Vaginal and Oral Interventions to Control the Epidemic (Voice) study tested whether a gel containing 1% of the antiretroviral (ARV) drug tenofovir or tablets containing tenofovir or Truvada were effective in protecting South African, Ugandan and Zimbabwean women against HIV infection if applied or taken once a day. It was conducted by the US government-funded Microbicide Trials Network.
Of the 5 029 women enrolled in the study, 4 077 were South African – mostly from Durban, Johannesburg and Klerksdorp. About 80% of the participants were single and nearly half of them were younger than 25. Women were divided into groups that either received tenofovir or dummy gels, tenofovir or dummy tablets, or Truvada or dummy tablets.
Researchers reported that the women in the study, especially those from South Africa, became infected with HIV much faster than they had anticipated. “We expected to see an HIV incidence – how many women became newly infected for every 100 participants in a year – of about 3%, but it was nearly double that at 5.7%. And, at some South African sites it was nearly 10%,” said study author Jeanne Marazzo from the University of Washington in Seattle.
“South African women lived in areas with higher baseline HIV-infection rates than those in Zimbabwe and Uganda, which partly explains them acquiring HIV at faster rates,” she said.
The study results however showed that most participants did not use their gel or pills daily as recommended.
Researchers tested women’s blood to determine if the drugs they were given were present, but a drug was detected in less than a third of the blood samples of participants assigned to use tablets and in less than a quarter of those designated to use gel.
This was in sharp contrast with the results of interviews conducted with the women in which 90% claimed they were using the products. “Moreover, those least likely to use their assigned products – single women under the age of 25 – were also the most likely to acquire HIV,” study researchers said.
Parts of the Voice study – the testing of tenofovir pills and gel – were stopped in late 2011 after it was found that, while the tenofovir products were safe to use, they were ineffective.
HIV scientists and advocates were however awaiting the results of the Truvada arm of the study, as well as drug adherence levels in general, as several other trials have shown that both Truvada and tenofovir are highly effective in reducing the risk of HIV infection.
The Caprisa 004 study, conducted in KwaZulu-Natal, found that if the tenofovir gel was used before and after sex, it reduced the risk of acquiring HIV by almost 40%. The iPrEx study, conducted among men who have sex with men, found that there were 45% fewer HIV infections among men who took Truvada tablets than those who used a dummy pill. The Partners PrEP study was conducted among heterosexual couples in which one of the partners had HIV and tested both tenofovir and Truvada pills. It showed that the daily use of Truvada reduced HIV risk by 75% and 67% with tenofovir.
In July 2012 the US Food and Drug Administration approved the use of Truvada for HIV prevention, that is, the use of Truvada pills by people who are HIV-negative and are at high risk of getting infected with the virus. This decision was largely based on results of the iPrEx and Partners PrEP studies.
The Voice study results are however consistent with those of the FEM-PrEP study, which tested the daily use of Truvada and involved a similar population of women. As in Voice, most FEM-PrEP participants didn’t follow their daily regimen. “No intervention is going to be effective if it’s not used, and the point is that the majority of women in Voice didn’t use any of the study products as recommended,” said study author Zvavahera Chirenje of the University of Zimbabwe.
Product adherence levels
In the other studies, product adherence levels were significantly higher than in the Voice study and they were conducted among populations who may have perceived their risk of HIV infection as higher than the women in the Voice study – resulting in them using the products more diligently.
Researchers hope to further analyse results which will tell them why the women in the Voice study didn’t use the products, including how the perception of HIV risks may have played a role. “Young people often perceive themselves to be of a lower infection risk, thinking: 'It won’t happen to me',” Marazzo said.
According to Marazzo the study results point to the fact that preventative devices containing ARVs, but with long lasting effects, could be more appropriate among single, African women. Such devices include vaginal rings, injections or implants that last for a month or longer at a time and don’t require women to intervene on a daily basis.
Mitchell Warren from the global HIV advocacy organisation Avac said the Voice study provided an urgent reminder that products must meet the needs of the people using them. “Biomedical tools do not work in a vacuum, but rather in the complex realities of women’s and girls’ lives,” he said.
“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,” Warren said.