Major Finding: Taking a daily pill containing the antiretroviral drugs emtricitabine and tenofovir along with using conventional HIV prevention strategies reduced the risk of acquiring HIV by 44% on average in men or transgender women who have sex with men.
Data Source: Randomized, blinded, placebo-controlled trial in 2,499 subjects in six countries.
Disclosures: The National Institutes of Health and the Bill and Melinda Gates Foundation funded the study. Gilead Sciences donated the FTC-TDF and placebo tablets, and provided some travel funding for investigators. Two of the investigators worked for Gilead. Disclosures for individual investigators are posted with the article at
Taking a daily pill containing two antiretroviral drugs plus exposure to conventional HIV prevention strategies reduced the risk of acquiring HIV by an average of 44% in the people at highest risk of getting infected – men and transgender women who have sex with men, a study has shown.
The Preexposure Prophylaxis Initiative (iPrEx) study randomized 2,499 subjects in six countries to take a daily pill containing placebo or a combination of emtricitabine and tenofovir disoproxil fumarate (FTC-TDF).
All of the study subjects also received regular HIV testing, condoms, counseling on reducing risks for HIV, and management of sexually transmitted infections.
During a median follow-up of 1.2 years (and a maximum of 2.8 years), 36 of 1,251 subjects in the FTC-TDF group (3%) acquired HIV, compared with 64 of 1,248 subjects in the placebo group (5%).
The preventive efficacy of FTC-TDF was significant but not as high as investigators had hoped, according to Dr. Robert M. Grant of the University of California, San Francisco, and his associates (N. Engl. J. Med. 2010 Nov. 23 [doi:10.1056/NEJMoa1011205]).
Although most subjects reported taking the pills, objective measures of exposure to the drugs suggested substantially lower adherence rates. When intracellular assays showed that subjects had been exposed to FTC-TDF, they were much less likely to acquire HIV. Evidence of FTC-TDF was seen in only 3 of 34 HIV-infected subjects (9%), compared with 22 of 43 HIV-negative subjects (51%) in the FTC-TDF group.
“It's very exciting news,” Dr. Moupali Das said in an interview. “These are extremely promising results,” said Dr. Das of the University of California, San Francisco, and director of research in the HIV prevention section of the San Francisco Deapartment of Public Health.
Dr. Das was not involved in the iPrEx study.
The findings are consistent with results from a separate preexposure prophylaxis trial reported earlier in 2010, which showed an overall 39% reduction in HIV infections in women who agreed to apply a 1% tenofovir gel vaginally before and after sex, Dr. Das noted.
The randomized, double-blind placebo-controlled Centre for the AIDS Programme of Research in South Africa (CAPRISA) 004 trial studied 889 sexually active African women (Science 2010;329:1168-74).
The iPrEx study enrolled subjects at multiple centers in the United States, South Africa, Brazil, Ecuador, Peru, and Thailand.
Patients in the FTC-TDF group were significantly more likely to develop nausea (2%) in the first 4 weeks of treatment, compared with the placebo group (less than 1%).
“It's a groundbreaking study,” but several factors will temper excitement among clinicians, said Dr. Grant Colfax, director of HIV prevention for the San Francisco Department of Public Health.
Dr. Colfax was not involved in the iPrEx study.
The FTC-TDF pill is expensive, costing $750 per month or more in the United States, he noted in an interview. Subjects in the study got comprehensive care with monthly HIV testing, state-of-the-art prevention counseling, free condoms, and more, which might not be representative of the real world.
“This was not just giving someone a pill and walking out of the office,” Dr. Colfax said.
Two subjects in the FTC-TDF group who later were found to have had HIV at enrollment both developed resistance to FTC, compared with one of eight subjects on placebo with HIV at enrollment.
People at risk for HIV should not start taking FTC-TDF without reviewing the risks and benefits with their physician, Dr. Colfax said.
The study does not answer questions about the advisability of implementing this prevention strategy in all or even most HIV-negative people at risk for acquiring the infection, Dr. Das agreed.
“It will be important to see the results of the upcoming trials on different ways to provide preexposure prophylaxis,” results of which should be available in the near future, Dr. Das said.
The Web site of the nonprofit group AVAC: Global Advocacy for HIV Prevention (www.avac.org
In the meantime, there might be some specific populations in whom preexposure prophylaxis with FTC-TDF makes sense while research continues, she added.