Daily drug shown effective in preventing HIV infections

After a decade of controversy and halting progress, preexposure prophylaxis may finally be about to take its place in the vanguard of AIDS prevention. 

In September, for the first time, the World Health Organization expanded the population recommended for this option, which involves taking daily doses of antiviral medication. If a person is exposed to HIV, the drugs should defeat the virus before it establishes a permanent foothold.

Previously, preexposure prophylaxis, or PrEP, was reserved only for those deemed at high risk, such as couples in which one partner is infected, or men who have sex with men. But in the updated guidelines, WHO officials now say that anyone “at significant risk” should take the drugs. The HIV prevention advocacy group AVAC called the change a “potentially profound development” that stands to greatly expand PrEP among adolescents and young women. About 380,000 women ages 15 to 24 become infected every year, most of them living sub-Saharan Africa, which remains the most severely affected region of the world.

The new recommendation followed the release of two studies that reported some of the highest success rates so far using the drug Truvada, which contains the antiviral drugs tenofovir and emtricitabine (SN: 12/18/10, p. 16), as a daily preventative. Early next year, highly anticipated research on antimicrobial vaginal rings will be completed, and studies of long-acting antiretroviral injections are under way. Public health officials hope that PrEP will one day be viewed in the same light as birth control — a prevention strategy with enough approaches for men and women to choose the method best suited for their lives.

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“It is a really exciting time,” says Meredith Clark, who heads preclinical activities at CONRAD, a nonprofit based in Arlington, Va., that focuses on contraception and HIV prevention. “A lot is happening. A lot is changing.”

The outlook was not always so rosy. Early in the epidemic, doctors hypothesized that it would be possible to prevent infections with PrEP, which interferes with viral replication. But many early studies were abandoned before they even got off the ground, as they grew beset with allegations of unethical behavior, fears of drug resistance and other problems. Other early studies yielded results that were lukewarm, in large part because study participants did not use the drugs consistently, which is recommended to prevent infection. Researchers have also fielded social opposition — the president of one well-known AIDS nonprofit referred to Truvada as a “party drug” that would encourage risky behavior and discourage the use of condoms. (The drug does not protect against other sexually transmitted infections and is not considered a substitute for condoms.)

At the same time, some studies with PrEP began to show remarkable effectiveness. The U.S. Food and Drug Administration approved Truvada in 2012, but its effectiveness outside the carefully controlled and monitored world of clinical trials was unclear. In September, researchers from Kaiser Permanente reported in the journal Clinical Infectious Diseases that after more than two years, no new infections occurred among 657 people in San Francisco who were instructed to take the drug daily.

“It adds really compelling data that prophylaxis can work,” says Jonathan Volk, an infectious disease physician and epidemiologist at Kaiser, and one of the study’s authors. A similar study from the United Kingdom, with support from drug manufacturer Gilead Sciences, compared 275 men who received PrEP for a year with 269 who were told to wait a year before receiving it. During that time, 20 men who were deferred became infected, compared with three offered PrEP — an 86 percent reduction in risk. Those results appeared last month in The Lancet.

The challenge is that the drug doesn’t work if it stays in the bottle. Pills carry the potential for stigma, since they are among the same medicines used to treat HIV infection. Addressing those concerns, a vaginal ring under investigation might increase adherence and offer a more discreet HIV prevention. Two large studies, The Ring Study and the ASPIRE study, are being conducted by the nonprofit International Partnership for Microbicides and the Microbicide Trials Network, which is funded by the National Institutes of Health. Those studies have enrolled more than 4,000 women in sub-Saharan Africa. The ring contains the antiviral drug dapivirine, and lasts for one month. Also under development is a rectal microbicide containing tenofovir, which would be used only as necessary, not daily.

It’s not clear how well a topical microbicide would work. Studies have been weak or inconsistent. One study of a vaginal gel microbicide, published in 2010, found that women who used the product before and after sex had a reduced risk of infection of about 40 percent overall (SN: 8/14/10, p. 9). However, effectiveness would have been higher in that study if women had used it consistently, says Clark, from CONRAD, which was one of the study sponsors.

She points out that one reason some people in general have not been keen on PrEP was that they weren’t convinced it would work, which affected their motivation to use it. “Now that we have success stories, it will change how people view it and adopt it,” she says.

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In addition to microbicides, two long-acting injectable antiviral agents (rilpivirine and cabotegravir) are under development. Those products also have the potential to eliminate the need for daily use and offer protection that is easy to keep private. But this approach has two main concerns, says Ian McGowan of the University of Pittsburgh, who is principal investigator of the Microbicide Trials Network. “These products have very long half-lives, which would complicate the management of any side effects that might occur,” he says. “Also during periods when there were low drug levels, there’s a real risk that anyone acquiring HIV infection would develop antiviral resistance.”

Like others in the field, he is encouraged by the variety of methods now under development, which should help expand the number of people who will be more protected — though he cautions that PrEP should not replace condoms. Until more methods of PrEP are on the market, public health officials will work to make antiviral tablets available to those at greatest risk. Right now, the number of people outside North America who are taking PrEP “is horribly small,” says Peter Godfrey-Faussett, science adviser to UNAIDS, a global health agency that is part of the United Nations.

“I think we’ve established beyond any reasonable doubt that a daily pill form is absolutely proven now to work, providing you take it,” he says. “The challenge now is to make this new exciting tool available in the settings where it is needed.”