In the past 12 months, research has shown that antiretroviral drugs in a vaginal gel can protect women from infection and that in pill form they can protect male homosexuals. A study also showed that when an HIV-positive person starts antiretroviral therapy, the chance of transmitting the virus to someone else falls steeply.
The two newer studies asked a simpler question: If uninfected heterosexuals take the pills daily and then go about their lives in places where HIV is prevalent, are their chances of getting infected reduced?
The answer is yes.
The success of this strategy — pre-exposure prophylaxis, or PrEP — suggests a future in which millions of people may take a daily antiretroviral to cut their risk of contracting HIV the way others take aspirin to reduce the chance of a heart attack or an acid suppressor to prevent heartburn.
AIDS experts called the studies’ results “game-changing” and “a major milestone” but also seemed worried that there isn’t a clear way to put them into practice.
“It is important that we take time to think how PrEP will be used in the real world,” said Jonathan Mermin, director of HIV/AIDS prevention at the Centers for Disease Control and Prevention, which sponsored one of the studies, conducted in Botswana. “PrEP is not for everyone, and it will not solve the epidemic.”
The co-director of the other study, which was run in Kenya and Uganda, suggested that people might practice PrEP episodically, as in times of youthful sexual exploration.
“Clearly there are periods in people’s lives when they are at greater risk and periods when they are at lower risk,” said Jared Baeten, a physician and researcher at the University of Washington. “PrEP might be ideally suited for those periods of higher risk.”
There are also practical problems to putting PrEP into action.
Worldwide, about 34 million people are living with HIV. In the developing world, chiefly Africa, 6.6 million people are taking antiretroviral therapy, which consists of three drugs taken each day. More than twice that number should be taking it but don’t because of a lack of medicine, clinics and practitioners. To make and deliver drugs for tens of millions of uninfected people is a task that no one has faced seriously.
In the University of Washington study, called “Partners PrEP,” 4,758 couples were recruited from nine locations starting in July 2008. In each couple, one person was infected with HIV, and the other wasn’t.
The uninfected partners were randomly assigned to take a drug called tenofovir; tenofovir and emtricitabine, which is a combination sold under the trade name Truvada; or a placebo. Everyone was provided condoms and counseling on how to avoid becoming infected.
Through the end of May, there had been 47 infections in people assigned the placebo, 18 in those taking tenofovir (a 62 percent reduction) and 13 in those taking Truvada (73 percent fewer).
Women and men were equally protected. The rate of serious side effects was similar in the three arms of the study, although the researchers did not provide details about complications in their announcement.
The protective effect of PrEP emerged much earlier in the study than expected, and an outside panel of monitors decided over the weekend that it would be unethical to keep giving some people the placebo. Those people will be offered the active drugs.
In the Botswana study, 1,219 men and women were enrolled and assigned to take either Truvada or the placebo. Nine taking Truvada became infected, compared with 24 taking a placebo — a 63 percent reduction in those on the active drug. People taking Truvada had a greater frequency of side effects such as nausea and dizziness.
Although the results of the two studies were similar, they differed greatly from one called FEM-PrEP reported earlier this year. In it, 2,000 women in Kenya, Zimbabwe and South Africa took Truvada or a placebo, and Truvada provided no protection. The researchers are trying to figure out why.
Baeten thinks a big reason his experiment showed promising results is that the subjects took their pills 97 percent of the time. (In the CDC study in Botswana, participants took them 84 percent of the time). He speculated that FEM-PrEP failed to show protection because its participants skipped too many doses.
“I think adherence is the biggest driver of the difference between our study and theirs,” he said.
The Botswana study cost $31 million, paid by the U.S. government. The study in Kenya and Uganda had a budget of $63 million provided by the Bill and Melinda Gates Foundation, but not all of the money was used because the experiment closed early.