Two landmark studies confirm that a daily pill containing powerful drugs used to treat HIV infection can also help prevent new infection in healthy HIV-free people.
Both studies — one conducted by the U.S. Centers for Disease Control and Prevention (CDC) together with the Botswana Ministry of Health, and the other by the University of Washington and the Bill and Melinda Gates Foundation — found that healthy people taking daily doses of the anti-HIV drugs known as antiretroviral medications (ARVs) lowered their risk of acquiring HIV.
In the University of Washington study involving heterosexual couples in which one partner had HIV and the other did not, transmission was reduced by 73%, compared with placebo, when the uninfected partner took ARVs. In the CDC study, which involved healthy, sexually active men and women, taking ARVs reduced the risk of HIV infection by 63%.
The results confirm earlier research, released last November, that found that taking anti-HIV drugs preventively, a strategy known as pre-exposure prophylaxis, or PReP, helped prevent new infection among healthy gay men. But this is the first time that scientists have shown that heterosexual men and women, who make up the bulk of the 33 million HIV infections worldwide, can also use the drugs to prevent infection.
“This news is a major milestone,” Kevin Fenton, director of the National Center for HIV/AIDS, Viral Hepatitis, STD and TB Prevention at the CDC, told reporters. “Heterosexual men and women are the hardest hit [by HIV] worldwide, and these studies offer the first compelling evidence that PReP can work to reduce HIV infection among them.”
The CDC study involved more than 1,200 uninfected, sexually active heterosexual men and women in Botswana who were randomly assigned to a placebo or a daily dose of Truvada, a combination pill that contains the anti-HIV drugs tenofovir and emtricitabine. All of the participants were given male and female condoms and counseling in HIV risk reduction and received testing for sexually transmitted infections.
After an average follow up of 12 months, those taking the drug showed a significantly lower risk of becoming infected with HIV than those on placebo; among the 601 participants assigned to the drug, nine became HIV positive, compared with 24 who became infected among the 599 in the placebo group.
In the University of Washington study, the scientists focused on 4,758 heterosexual couples, in which one partner was HIV positive. The couples, who were in Kenya and Uganda, were divided into three groups: one group received tenofivir alone (Viread); a second received the tenofovir and emtricitabine pill (Truvada); and the third took a placebo.
After three years, the tenofovir group had 62% fewer HIV infections than the placebo group, while those taking Truvada had 73% fewer infections. Based on the results, the placebo arm of the study was discontinued, and those taking the dummy pills were allowed to take either of the anti-HIV medications.
“The review board noted a definitively established efficacy of treatment versus placebo,” Dr. Jared Baeten, the principal investigator on the study said during a teleconference with reporters.
Together with the previous trial showing the same protective benefits among healthy gay men taking ARVs, the results offer new hope in controlling the HIV epidemic — particularly in the absence of an HIV vaccine. PReP could potentially help AIDS workers begin to reverse the upward trajectory of cases that continues to plague developing nations around the globe. “This is an exciting moment for all of us in HIV prevention,” said Michael Thigpen, principal investigator of the CDC study.
The findings represent a turning point in the AIDS epidemic, a shift in focus from treating HIV to preventing it. The current trials, say experts, would not have been possible without advances in drug development, which have enabled scientists to create anti-HIV drugs that have fewer side effects and that can be taken once daily (as opposed to several times a day like the original anti-HIV medications). That’s critical when using the drugs in a healthy population, because such groups are less likely than HIV-postive patients to tolerate toxic side effects of medications.
Based on the November study of the benefits of PReP in healthy gay men, the CDC issued its first guidelines for Truvada use in that population for the purposes of HIV prevention. Dr. Jonathan Mermin, director of the Division of HIV/AIDS Prevention at the CDC, says the agency is currently reviewing the newly available data on PReP among heterosexual individuals and is planning on issuing recommendations for this population in coming months.
He notes that the effect may not translate so cleanly from a clinical trial to the real world, however. “We need more information on what happens outside the trial framework,” he told reporters. “Additional issues can come up, such as whether people can regularly attain the drugs, whether they will take them daily, and whether their risk behavior will change because they know they are taking a drug that is proven effective. Such behavior change can potentially reduce the efficacy of the prevention because they are increasing their risky behavior. So all of these factors, in addition to safety issues, have to come into play when we are thinking about widespread recommendations for the U.S. or other countries.”
Indeed, there are signs that PReP may not be as easy to implement in communities as it is in a clinic. In a study earlier this year that involved providing PReP to commercial sex workers at high risk of acquiring HIV in Kenya, Tanzania and South Africa, those taking Truvada did not lower their risk of becoming HIV positive compared to those taking placebo. The reason? Some of the women may not have been taking their medications regularly.
Still, figuring out how best to translate the positive results of the current trials to the real world is a problem that HIV experts are happy to have. “The excitement for me is adding more to the prevention tool kit against HIV,” said Fenton. “As we think about the complexities of the domestic epidemic as well as the global epidemic, it’s clear that we don’t find one magic pill to solve the issue of HIV. But combining this prevention strategy with effective condom and other risk reduction strategies, we can now begin to get a better handle on the effective combination of packages that can be used against the virus.”
To move these efforts along, Gilead Sciences, the maker of Truvada and Viread, announced on Tuesday that it would license its anti-HIV drugs to the international Medicines Patent Pool Foundation, which aims to supply medications at low cost to poor countries. Gilead is the first pharmaceutical company to cooperate with the patent pool.
It wasn’t long ago that preventing HIV was considered an elusive goal. But, increasingly, the scientific evidence suggests that blocking new HIV infections and reversing the tide of the AIDS epidemic is possible.