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US Preventive Services Task Force
Evidence Report
June 11, 2019

Preexposure Prophylaxis for the Prevention of HIV Infection: Evidence Report and Systematic Review for the US Preventive Services Task Force

Author Affiliations
  • 1Pacific Northwest Evidence-based Practice Center, Department of Medical Informatics and Clinical Epidemiology, Oregon Health & Science University, Portland
  • 2Division of General Internal Medicine and Geriatrics, Oregon Health & Science University, Portland
  • 3Oregon Health & Science University–Portland State University School of Public Health, Portland
JAMA. 2019;321(22):2214-2230. doi:10.1001/jama.2019.2591

Importance  Effective prevention strategies for HIV infection are an important public health priority. Preexposure prophylaxis (PrEP) involves use of antiretroviral therapy (ART) daily or before and after sex to decrease risk of acquiring HIV infection.

Objective  To synthesize the evidence on the benefits and harms of PrEP, instruments for predicting incident HIV infection, and PrEP adherence to inform the US Preventive Services Task Force.

Data Sources  Ovid MEDLINE, the Cochrane Central Register of Controlled Trials, the Cochrane Database of Systematic Reviews, and EMBASE through June 2018, with surveillance through January 2019.

Study Selection  English-language placebo-controlled randomized clinical trials of oral PrEP with tenofovir disoproxil fumarate/emtricitabine or tenofovir disoproxil fumarate monotherapy; studies on the diagnostic accuracy of instruments for predicting incident HIV infection; and studies on PrEP adherence.

Data Extraction and Synthesis  Dual review of titles and abstracts, full-text articles, study quality, and data abstraction. Data were pooled using the Dersimonian and Laird random-effects model for effects of PrEP on HIV infection, mortality, and harms.

Main Outcomes and Measures  HIV acquisition, mortality, and harms; adherence to PrEP; and diagnostic test accuracy and discrimination.

Results  Fourteen RCTs (N = 18 837), 8 observational studies (N = 3884), and 7 studies of diagnostic accuracy (N = 32 279) were included. PrEP was associated with decreased risk of HIV infection vs placebo or no PrEP after 4 months to 4 years (11 trials; relative risk [RR], 0.46 [95% CI, 0.33-0.66]; I2 = 67%; absolute risk reduction [ARD], −2.0% [95% CI, −2.8% to −1.2%]). Greater adherence was associated with greater efficacy (RR with adherence ≥70%, 0.27 [95% CI, 0.19-0.39]; I2 = 0%) in 6 trials. PrEP was associated with an increased risk of renal adverse events (12 trials; RR, 1.43 [95% CI, 1.18-1.75]; I2 = 0%; ARD, 0.56% [95% CI, 0.09%-1.04%]) and gastrointestinal adverse events (12 trials; RR, 1.63 [95% CI, 1.26-2.11]; I2 = 43%; ARD, 1.95% [95% CI, 0.48%-3.43%]); most adverse events were mild and reversible. Instruments for predicting incident HIV infection had moderate discrimination (area under the receiver operating characteristic curve, 0.49-0.72) and require further validation. Adherence to PrEP in the United States in men who have sex with men varied widely (22%-90%).

Conclusions and Relevance  In adults at increased risk of HIV infection, PrEP with oral tenofovir disoproxil fumarate monotherapy or tenofovir disoproxil fumarate/emtricitabine was associated with decreased risk of acquiring HIV infection compared with placebo or no PrEP, although effectiveness decreased with suboptimal adherence.