The disappointing results of the Vaginal and Oral Interventions to Control the Epidemic (Voice) trial this week - that most participants had willingly not taken a potentially life-saving anti-HIV pill or used a protective vaginal gel - left researchers with the million-dollar question: Why would young, single African women not take free drugs that could potentially save them from contracting a life-threatening infection?
The Voice study tested whether a daily antiretroviral pill that contained either tenofovir or Truvada (a combination of tenofovir and emtricitabine), or a once-a-day vaginal gel consisting of 1% tenofovir, were effective in protecting South African, Ugandan and Zimbabwean women against HIV infection. Previous studies have shown that the medication shields HIV-negative people from contracting HIV, depending on how regularly they use it.
The American government's iPrEx study, conducted among men who have sex with men, found that men who took a daily Truvada pill 90% of the time had a 72.8% lower chance of HIV infection than those who did not take it.
Further, the Partners PrEP study of Washington University revealed that the HIV-negative partners in heterosexual, discordant couples - where one person has the virus and the other one does not - were up to 75% less likely to get infected with HIV if they took a Truvada tablet once a day.
In the Partners PrEP trial, eight out of 10 participants took their drugs correctly, and more than half did so in the iPrEx study. But, in the Voice trial, less than a third of women used their pills consistently and fewer than a quarter used their gel. Single African women younger than 25 were the least likely to use their products and the most likely to contract HIV, the study showed.
The iPrEx and Partners PrEP studies were, however, conducted on different populations - gay men and discordant couples - where the incentive to take the medicine might have been higher, said Kevin Rebe of the Anova Health Institute's Health4Men clinic in Cape Town.
"When an HIV-negative person is sexually involved with an HIV-infected person, the negative person is likely to perceive his or her risk of getting infected as pretty high which may motivate them to take treatment regularly," he said.
The "predictability" of someone's life
According to Rebe, who has five HIV-negative patients on preventative antiretrovirals, the "predictability" of someone's life closely relates to how well they adhere to their HIV medication regimen.
"Patients with structured lives who watch a soapie every night at the same time they take their antiretrovirals tend to take their medication much more consistently than those with chaotic lives. Unfortunately, people in need of preventative antiretrovirals, such as sex workers and young people who have regular unprotected sex, generally lead more chaotic lives - making them less able to adhere to their medication [requirements]."
A study, known as the FEM-PrEP trial, which tested whether Truvada prevented HIV-infection in African women, was halted halfway through because fewer than half of the participants were taking their pills. As in the Voice study, most participants were young and unmarried.
"This is a clear indication that there isn't a magic bullet that fits all," said Linda-Gail Bekker of the Desmond Tutu HIV Centre at the University of Cape Town. "Just like with contraception, not all people prefer to take a daily pill. Some opt for an implant, or a monthly injection; others for condoms," she said.
As part of a larger international study, Bekker's centre is investigating how often HIV-negative women in Cape Town are prepared to take a Truvada pill - daily, three times a week, or before and after sex. The study results have not been released, but initial analysis indicates that men are able to plan their sex lives better than women and that sexual activity peaks at the weekend.
"Although these results are preliminary findings, they're significant in the sense that they may indicate that intermittent pre-exposure prophylaxis (taking preventative antiretrovirals only a few times a week) will work better among men and that weekends are the periods when the most protection will be needed."
It still provides protection
A modelling study has found that if Truvada is taken four times a week, it still provides protection.
However, Rebe said that "we don't yet know what will work for African women, but we do know that when patients have to take drugs less frequently, their likelihood of adhering to the treatment increases".
According to Quaraisha Abdool Karim from the Centre for the Aids Programme of Research in South Africa, the Voice trial could have benefitted from conducting a pretrial, during which researchers would first establish whether participants were amenable to taking a daily pill.
Abdool Karim was one of the lead researchers in the Centre for the Aids Programme of Research in South Africa 004 study, which found that the application of a tenofovir vaginal gel before and after sex reduced the chances of HIV infection by almost 40%. The trial, which like the Voice study was mostly conducted among young, single African women, was criticised for only requiring participants to use the gel at the time of sex, rather than daily.
"But during our pretrial, we discovered that most of the KwaZulu-Natal women who took part in our research had migratory partners working elsewhere. They therefore only saw the need to use the gel while their husbands or boyfriends were at home. For that population, a daily gel would most likely not have worked," said Abdool Karim.
The study achieved adherence levels of 70%.
Other self-controlled HIV preventative options, such as implants, injections and vaginal rings that contain antiretrovirals, are being tested.
"These alternatives may work better for single women," Bekker said.
She said the preventative use of antiretrovirals, also known as pre-exposure prophylaxis, is not a lifelong treatment; it's rather a "seasonal" intervention.
"It's much like using oral contraception; there are periods in your life when you need it and times that you don't. HIV risk comes and goes and prevention methods need to be adjusted accordingly."