Annotated Abstracts of Journal Articles
2015, 4rd Quarter
Annotations by Oliver Freudenreich, MD, FAPM and Mary Ann Cohen, MD, FAPM
January 2016
Also of interest:
Molina JM, Capitant C, Spire B, et al
N Engl J Med 2015; 373(23):2237-2246
ANNOTATION (Freudenreich & Cohen)
The Finding: This randomized trial that goes by the name of IPERGAY (conducted in France and Montreal, it stands for Intervention Preventive de l’Exposition aux Risque avec et pour les Gays) found that “on-demand” (i.e., right before sexual activity) pre-exposure prophylaxis in a high-risk group (men who have unprotected sex with men) was very effective in preventing new HIV infections. Patients were instructed to take two pills (loading dose) of TDF-FTC (tenofovir and emtricitabine combination) before unprotected sex and also two postexposure pills. Out of 400 patients, 16 acquired HIV; 2 in the pre-exposure prevention group versus 14 in the placebo group (relative risk reduction of 86%, 95% confidence interval, 40 to 98; P=0.002). Patients took a median of 15 pills per month.
Strength and Weaknesses: This was a large randomized trial in an important patient group (i.e., HIV-negative men who have unprotected sex with men) where risk reduction would make a real difference with regards to reducing overall new HIV infections, at least in countries (like France or the U.S.) where this mode of transmission is an important driver of the epidemic. The long-term efficacy of the on-demand approach as well as safety (the median follow-up was less than one year) remain to be established.
Relevance: IPERGAY is a landmark trial that establishes a possible way to reduce new HIV infections in a high-risk group. For some people, the on-demand approach to HIV prevention might be more appealing than taking a pill daily for prevention.
Background: Antiretroviral preexposure prophylaxis has been shown to reduce the risk of human immunodeficiency virus type 1 (HIV-1) infection in some studies, but conflicting results have been reported among studies, probably due to challenges of adherence to a daily regimen.
Methods: We conducted a double-blind, randomized trial of antiretroviral therapy for preexposure HIV-1 prophylaxis among men who have unprotected anal sex with men. Participants were randomly assigned to take a combination of tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC) or placebo before and after sexual activity. All participants received risk-reduction counseling and condoms and were regularly tested for HIV-1 and HIV-2 and other sexually transmitted infections.
Results: Of the 414 participants who underwent randomization, 400 who did not have HIV infection were enrolled (199 in the TDF-FTC group and 201 in the placebo group). All participants were followed for a median of 9.3 months (interquartile range, 4.9 to 20.6). A total of 16 HIV-1 infections occurred during follow-up, 2 in the TDF-FTC group (incidence, 0.91 per 100 person-years) and 14 in the placebo group (incidence, 6.60 per 100 person-years), a relative reduction in the TDF-FTC group of 86% (95% confidence interval, 40 to 98; P=0.002). Participants took a median of 15 pills of TDF-FTC or placebo per month (P=0.57). The rates of serious adverse events were similar in the two study groups. In the TDF-FTC group, as compared with the placebo group, there were higher rates of gastrointestinal adverse events (14% vs. 5%, P=0.002) and renal adverse events (18% vs. 10%, P=0.03).
Conclusions: The use of TDF-FTC before and after sexual activity provided protection against HIV-1 infection in men who have sex with men. The treatment was associated with increased rates of gastrointestinal and renal adverse events.
Perspective:
Fauci AS, Marston HD: Ending the HIV–AIDS pandemic—follow the science
N Engl J Med 2015; 373:2197-2199
The accompanying editorial puts this trial into the larger context of the use of combination antiretroviral therapy as an effective prevention tool. It ends with a call to action with regards to HIV testing and treatment since “science has spoken.”
