IV drugs taken on a daily basis to prevent infection can be taken intermittently and still substantially reduce the risk of infection, at least in some populations, a new study suggests.
The study, published online by the New England Journal of Medicine on Tuesday to correspond with World AIDS Day, raises the possibility that people at high risk of infection could take the drugs around the time of intercourse and reduce the risk of transmission of the HIV virus.
That would be an alternative to an approach known as PrEP — pre-exposure prophylaxis — which involves taking a daily dose of HIV drugs. While highly effective, the daily regimen costs more and may trigger more side effects than an “as needed” approach — factors that might discourage some people from using PrEP.
The new study, conducted in France and Canada, focused only on men and transgendered women (who were born as men) who have unprotected anal sex.
Dr. Kenneth Mayer, a Boston physician who treats people with HIV and studies ways to prevent transmission of the virus, called the trial an important one. On-demand PrEP isn’t likely to replace daily PrEP, but will give some people at high risk of infection another option, said Mayer, who was not involved in the research.
One of the principle investigators agreed.
“We’re not saying that one approach is better than the other. But we are saying that people are different and they have different lifestyles,” said Dr. Cecile Tremblay, a professor of microbiology and infectious diseases at the University of Montreal. “For some of them, it’s better to take it continuously. But for some other people, it’s not good for them continuously because they won’t be able to adhere to that kind of regimen.”
Because the study only involved men and transgendered women who have anal sex without using condoms, its findings cannot be applied to women who are at risk of infection through vaginal sex, said Mayer, who is the medical research director at the Fenway Institute. That’s because HIV drugs reach a higher concentration in anal tissues than in vaginal tissues, he said. “Right now we have one study in one population that shows a benefit.”
That said, the benefit was substantial. In fact, the protective effect of the on-demand PrEP was so clear that researchers stopped enrolling participants when they were roughly a fifth of the way to their original target of 1,900. Once a clinical trial proves that a treatment works, it is no longer ethical to randomly assign people to get a placebo instead.
The clinical trial was supported by the National Agency of Research on AIDS and Viral Hepatitis, the Canadian HIV Trials Network, the Pierre Berge Endowment for Prevention, and the Bill and Melinda Gates Foundation. Gilead Sciences donated the drugs and the placebo used and provided funding for some of the testing.
Participants who were given the drugs — half were given a placebo — were told to take two pills at some point in the 24 hours before they thought they were going to have sex and one pill in the 24 hours after sex. The pre-sex pills had to be taken at least two hours prior.
After enrolling 400 people and following them for a period of time — the median period was 9.3 months — they found 14 people taking the placebo became infected compared with only two assigned to take the antiretroviral drug, a combination of tenofovir and emtricitabine. That translates into an 86 percent reduction in the risk of being infected, the authors reported.
The protection may even have been greater. Testing showed the two people who were infected with HIV and in the group assigned to take the drugs hadn’t been following the regimen as directed. There was no evidence of the drugs in their blood.
“Everybody who had drug in their system was protected,’’ said Tremblay, the Canadian principle investigator for the trial. The principle investigator from France — where 90 percent of the subjects were enrolled — was Dr. Jean-Michel Molina, of the University of Paris and France’s National Institute of Health and Medical Research.
The authors warned they couldn’t tell if this approach would be safe for people who have sex infrequently. On average, participants in the study took 15 pills a month — which meant they often had the drugs in their systems.
While the findings are very promising, the authors also warned that in the real world results may differ. For one thing, people in a clinical trial — who are interacting with researchers and being asked about their behavior — may follow a drug regime more religiously than people who aren’t being monitored.
And it’s one thing to do something for the duration of a study, another to do it routinely for life. “The short follow-up for our study may have increased the likelihood of an exaggerated estimate of efficacy due in part to high initial adherence,” the authors wrote.
In reality, PrEP is an underutilized tool, said Dr. Thomas Frieden, director of the Centers for Disease Prevention and Control in Atlanta. A report released by the CDC last week said that some health care providers do not know about PrEP, and, as a result, some people who could benefit from it aren’t being counseled to take it.
Frieden said PrEP could be especially useful in populations where infection rates are high. He noted that in some US cities young black men who have sex with men have an estimated lifetime risk of infection of more than 50 percent.
The proportion of gay and bisexual men who had unprotected anal sex rose between 2005 and 2011, Frieden and some CDC colleagues wrote in an article on the state of HIV infections in the US. The journal published the CDC article as a companion to the PrEP study.
The CDC team noted that, as of 2012, only 39 percent of HIV-positive people in the United States were receiving medical care and that the failure to treat more is driving new infections. Frieden said 69 percent of transmissions of the virus are from people who have been diagnosed as HIV-positive but who are not receiving medical care.
“To me the single biggest gap is a treatment gap,” the CDC director told STAT in an interview.
It is now recommended that people diagnosed as HIV-positive should be started on antiretroviral drugs immediately to drive down the amount of virus in their bodies. That both helps control their infection and lowers the risk that they will infect others.
An earlier version of this story misstated the incidence of HIV among urban young black men who have sex with men.