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

To identify the key insights or developments described in this article
1 Credit CME
Abstract

Importance  A 2019 review for the US Preventive Services Task Force (USPSTF) found oral preexposure prophylaxis (PrEP) associated with decreased HIV infection risk vs placebo or no PrEP in adults at increased HIV acquisition risk. Newer PrEP regimens are available.

Objective  To update the 2019 review on PrEP, to inform the USPSTF.

Data Sources  Ovid MEDLINE, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, and Embase (January 2018 to May 16, 2022); surveillance through March 24, 2023.

Study Selection  Randomized clinical trials of PrEP vs placebo or no PrEP or newer vs older PrEP regimens and diagnostic accuracy studies of instruments for predicting incident HIV infection.

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.

Main Outcomes and Measures  HIV acquisition, mortality, and harms; and diagnostic test accuracy.

Results  Thirty-two studies were included in the review (20 randomized clinical trials [N = 36 543] and 12 studies of diagnostic accuracy [N = 5 544 500]). Eleven trials in the 2019 review found oral PrEP associated with decreased HIV infection risk vs placebo or no PrEP (n = 18 172; relative risk [RR], 0.46 [95% CI, 0.33-0.66]). Higher adherence was associated with greater efficacy. One new trial (n = 5335) found oral tenofovir alafenamide/emtricitabine (TAF/FTC) to be noninferior to tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) in men who have sex with men (RR, 0.47 [95% CI, 0.19-1.14]). Two new trials found long-acting injectable cabotegravir associated with decreased risk of HIV infection vs oral TDF/FTC (RR, 0.33 [95% CI, 0.18-0.62] in cisgender men who have sex with men and transgender women [n = 4490] and RR, 0.11 [95% CI, 0.04-0.31] in cisgender women [n = 3178]). Discrimination of instruments for predicting incident HIV infection was moderate in men who have sex with men (5 studies; n = 25 488) and moderate to high in general populations of persons without HIV (2 studies; n = 5 477 291).

Conclusions and Relevance  In adults at increased HIV acquisition risk, oral PrEP was associated with decreased risk of acquiring HIV infection compared with placebo or no PrEP. Oral TAF/FTC was noninferior to oral TDF/FTC, and injectable cabotegravir reduced the risk of HIV infection compared with oral TDF/FTC in the populations studied.

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Article Information

Accepted for Publication: June 6, 2023.

Corresponding Author: Roger Chou, MD, Oregon Health & Science University, Pacific Northwest Evidence-based Practice Center, 3181 SW Sam Jackson Park Rd, Mail Code: BICC, Portland, OR 97239 (chour@ohsu.edu).

Author Contributions: Dr Chou had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Chou.

Acquisition, analysis, or interpretation of data: All authors.

Drafting of the manuscript: Chou, Bougatsos, Ahmed.

Critical revision of the manuscript for important intellectual content: Chou, Spencer, Blazina, Selph.

Statistical analysis: Chou, Selph.

Obtained funding: Chou, Bougatsos.

Administrative, technical, or material support: Spencer, Bougatsos, Blazina.

Supervision: Chou, Bougatsos.

Conflict of Interest Disclosures: None reported.

Funding/Support: This research was funded under AHRQ contract 75Q80 120D00006, Task Order 75Q80121F32009, from the Agency for Healthcare Research and Quality (AHRQ), US Department of Health and Human Services, under a contract to support the USPSTF.

Role of the Funder/Sponsor: Investigators worked with USPSTF members and AHRQ staff to develop the scope, analytic framework, and key questions for this review. AHRQ had no role in study selection, quality assessment, or synthesis. AHRQ staff provided project oversight, reviewed the report to ensure that the analysis met methodological standards, and distributed the draft for peer review. Otherwise, AHRQ had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. The opinions expressed in this document are those of the authors and do not reflect the official position of AHRQ or the US Department of Health and Human Services.

Additional Contributions: We gratefully acknowledge the AHRQ medical officer (Howard Tracer, MD). The USPSTF members, expert consultants, peer reviewers, and federal partner reviewers did not receive financial compensation for their contributions.

Additional Information: A draft version of this evidence report underwent external peer review from 5 content experts (Susan Buchbinder, MD [HIV Prevention Research, San Francisco Department of Public Health; Departments of Medicine and Epidemiology and Biostatistics, University of California San Francisco]; Jessica Haberer, MD, MS [Global Health Research, Massachusetts General Hospital; Harvard Medical School]; Sybil Hosek, PhD [Stroger Hospital of Cook County; Division of Infectious Diseases, Rush University]; Douglas Krakower, MD [Division of Infectious Diseases at Beth Israel Deaconess Medical Center; The Fenway Institute; Departments of Medicine and Population Medicine, Harvard Medical School]; and 1 anonymous reviewer) and 5 federal partner reviewers from the Centers for Disease Control and Prevention, National Institutes of Health Sexual & Gender Minority Research Office, National Institute of Allergy and Infectious Diseases, and National Institute of Child Health and Human Development. Comments from reviewers were presented to the USPSTF during its deliberation of the evidence and were considered in preparing the final evidence review.

Editorial Disclaimer: This evidence report is presented as a document in support of the accompanying USPSTF recommendation statement. It did not undergo additional review after submission to JAMA.

AMA CME Accreditation Information

Credit Designation Statement: The American Medical Association designates this Journal-based CME activity activity for a maximum of 1.00  AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Successful completion of this CME activity, which includes participation in the evaluation component, enables the participant to earn up to:

  • 1.00 Medical Knowledge MOC points in the American Board of Internal Medicine's (ABIM) Maintenance of Certification (MOC) program;;
  • 1.00 Self-Assessment points in the American Board of Otolaryngology – Head and Neck Surgery’s (ABOHNS) Continuing Certification program;
  • 1.00 MOC points in the American Board of Pediatrics’ (ABP) Maintenance of Certification (MOC) program;
  • 1.00 Lifelong Learning points in the American Board of Pathology’s (ABPath) Continuing Certification program; and
  • 1.00 credit toward the CME [and Self-Assessment requirements] of the American Board of Surgery’s Continuous Certification program

It is the CME activity provider's responsibility to submit participant completion information to ACCME for the purpose of granting MOC credit.

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