Pre-Exposure Prophylaxis for the Prevention of HIV Infection [Entered Retrospectively]

Project Summary Title and Description

Title
Pre-Exposure Prophylaxis for the Prevention of HIV Infection [Entered Retrospectively]
Description
Background: Effective prevention strategies for HIV infection are an important public health priority. Pre-exposure prophylaxis (PrEP) involves use of antiretroviral therapy (ART) regularly (e.g., daily) or before and after HIV exposure events to decrease the risk of acquiring HIV infection. Purpose: To synthesize evidence for the U.S. Preventive Services Task Force (USPSTF) on effects of PrEP on risk of HIV acquisition, mortality, harms, and other clinical outcomes; effects of adherence on PrEP-associated outcomes; and accuracy of methods for identifying potential candidates for PrEP. Data Sources: We searched the Cochrane Central Register of Controlled Trials and Cochrane Database of Systematic Reviews, MEDLINE, and Embase from inception to June 2018 and manually reviewed reference lists; additional surveillance for new literature was conducted through January 25, 2019. Study Selection: Randomized, controlled trials on the benefits and harms of PrEP versus placebo or no PrEP in adults without HIV infection at high risk of becoming infected; studies on the diagnostic accuracy of instruments for predicting incident HIV infection; studies on effects of adherence to PrEP on risk of HIV infection; and studies on rates of adherence to PrEP in U.S. populations. Data Extraction: One investigator abstracted data and a second investigator checked data abstraction for accuracy. Two investigators independently assessed study quality using methods developed by the USPSTF. Data Synthesis (Results): In populations at higher risk of acquiring HIV infection, PrEP was associated with decreased risk of HIV infection versus placebo or no PrEP (11 trials; relative risk [RR], 0.46 [95% confidence interval (CI), 0.33 to 0.66; I2=67%; absolute risk reduction, -2.0% [95% CI, -2.8% to -1.2%] after 4 months to 4 years). Effects were consistent across HIV risk categories and for PrEP with tenofovir disoproxil fumarate plus emtricitabine or tenofovir alone. There was a strong association between higher adherence and greater efficacy (adherence ≥70%: 6 trials; RR, 0.27 [95% CI, 0.19 to 0.39]; I2=0%; adherence >40% to <70%: 3 trials; RR, 0.51 [95% CI, 0.38 to 0.70]; I2=0%; and adherence ≤40%: 2 trials; RR, 0.93 [95% CI, 0.72 to 1.20]; I2=0%; p<0.00001 for interaction). No trial reported effects of nondaily dosing except for one trial of event-driven PrEP (RR, 0.14 [95% CI, 0.03 to 0.63]). There was no difference between PrEP and placebo or no PrEP in risk of serious adverse events (12 trials; RR, 0.93 [95% CI, 0.77 to 1.12]; I2=56%). PrEP was associated with increased risk of renal adverse events (12 trials; RR, 1.43 [95% CI, 1.18 to 1.75]; I2=0%; absolute risk difference, 0.56% [95% CI, 0.09% to 1.04%]) and gastrointestinal adverse events (12 trials; RR, 1.63 [95% CI, 1.26 to 2.11]; I2=43%; absolute risk difference, 1.95% [95% CI, 0.48% to 3.43%]); most adverse events were mild and resolved with discontinuation of PrEP or with longer therapy. The association between PrEP and fracture was not statistically significant (7 trials; RR, 1.23 [95% CI, 0.97 to 1.56]; I2=0%). There were no differences between PrEP and placebo in risk of sexually transmitted infections, but most trials were blinded. Among women who became pregnant in trials of PrEP, PrEP was not associated with increased risk of spontaneous abortion (3 trials; RR, 1.09 [95% CI, 0.79 to 1.50]; I2=0%) or other adverse pregnancy outcomes. Instruments for predicting risk of incident HIV infection had moderate discrimination and require further validation. Adherence to PrEP in U.S. populations of men who have sex with men varied from high to low. Limitations: Restricted to English language, statistical heterogeneity in some pooled analyses, most randomized trials were conducted in low-income settings, limited evidence on adherence in U.S. populations, and evidence lacking in adolescents and pregnant women. Conclusions: In adults at increased risk of HIV infection, oral PrEP with tenofovir or tenofovir disoproxil fumarate plus emtricitabine is associated with decreased risk of HIV infection compared with placebo or no PrEP, although effectiveness decreases with inadequate adherence. PrEP is associated with increased risk of renal and gastrointestinal adverse events. Evidence on the accuracy of instruments for identifying persons at high risk of HIV infection is limited, with further validation needed.
Attribution
N/A
Authors of Report
N/A
Methodology description
Study Selection: Randomized, controlled trials on the benefits and harms of PrEP versus placebo or no PrEP in adults without HIV infection at high risk of becoming infected; studies on the diagnostic accuracy of instruments for predicting incident HIV infection; studies on effects of adherence to PrEP on risk of HIV infection; and studies on rates of adherence to PrEP in U.S. populations. Data Extraction: One investigator abstracted data and a second investigator checked data abstraction for accuracy. Two investigators independently assessed study quality using methods developed by the USPSTF.
PROSPERO
N/A
DOI
10.26300/wj46-ck14
Notes
Data was entered retrospectively via the upload of the evidence and quality tables in Word. The files uploaded for this project include: Appendix Table 1. Characteristics of Randomized Controlled Trials of HIV PrEP Appendix Table 2. Results of Randomized Controlled Trials of HIV PrEP Appendix Table 3. Adherence and Subgroups Information of Randomized Controlled Trials of HIV PrEP Appendix Table 4. Quality Assessment of Randomized Controlled Trials of HIV PrEP Appendix Table 5. Characteristics of Diagnostic Accuracy Studies of HIV Risk Assessment Tools Appendix Table 6. Results of Diagnostic Accuracy Studies of HIV Risk Assessment Tools Appendix Table 7. Quality Assessment of Diagnostic Accuracy Studies of HIV Risk Assessment Tools Appendix Table 8. Characteristics of Cohort Studies of HIV PrEP Appendix Table 9. Results of Cohort Studies of HIV PrEP Appendix Table 10. Adherence Information of Cohort Studies of HIV PrEP Appendix Table 11. Quality Assessment of Cohort Studies of HIV PrEP
Funding Source
This report is based on research conducted by the Pacific Northwest Evidence-based Practice Center (EPC) under contract to the Agency for Healthcare Research and Quality (AHRQ), Rockville, MD (Contract No. HHSA-290-2015-00009-I, Task Order No. 10)

Key Questions

1. Key Question 1. What Are the Benefits of Pre-Exposure Prophylaxis (PrEP) in Persons Without Pre-Existing HIV Infection Versus Placebo or No PrEP (Including Deferred PrEP) on the Prevention of HIV Infection and Quality of Life? Key Question 1a. How Do the Benefits of PrEP Differ by Population Subgroups? Key Question 1b. How Do the Benefits of PrEP Differ by Dosing Strategy or Regimen?
2. Key Question 2. What Is the Diagnostic Accuracy of Provider or Patient Risk Assessment Tools in Identifying Individuals at Increased Risk of HIV Acquisition Who Are Candidates for PrEP?
3. Key Question 3. What Are Rates of Adherence to PrEP in U.S. Primary Care–Applicable Settings?
4. Key Question 4. What Is the Association Between Adherence to PrEP and Effectiveness for Preventing HIV Acquisition?
5. Key Question 5. What Are the Harms of PrEP Versus Placebo or Deferred PrEP When Used for the Prevention of HIV Infection?

Associated Extraction Forms

Associated Studies (each link opens a new tab)

TitleAuthorsYear
Preexposure prophylaxis is efficacious for HIV-1 prevention among women using depot medroxyprogesterone acetate for contraception.2014
Bone mineral density in HIV-negative men participating in a tenofovir pre-exposure prophylaxis randomized clinical trial in San Francisco.2011
Liver and renal safety of tenofovir disoproxil fumarate in combination with emtricitabine among African women in a pre-exposure prophylaxis trial.2014
Daily oral emtricitabine/tenofovir preexposure prophylaxis and herpes simplex virus type 2 among men who have sex with men.
Renal function of participants in the Bangkok tenofovir study--Thailand, 2005-2012.2014
Bone Mineral Density Changes Among Young, Healthy African Women Receiving Oral Tenofovir for HIV Preexposure Prophylaxis.2016
Pregnancy incidence and outcomes among women receiving preexposure prophylaxis for HIV prevention: a randomized clinical trial.-- Not Found --
Changes in glomerular kidney function among HIV-1-uninfected men and women receiving emtricitabine-tenofovir disoproxil fumarate preexposure prophylaxis: a randomized clinical trial.
Effects of Emtricitabine/Tenofovir on Bone Mineral Density in HIV-Negative Persons in a Randomized, Double-Blind, Placebo-Controlled Trial.2015
Changes in renal function associated with oral emtricitabine/tenofovir disoproxil fumarate use for HIV pre-exposure prophylaxis.2014
Pre-exposure prophylaxis does not affect the fertility of HIV-1-uninfected men.2014
Risk of drug resistance among persons acquiring HIV within a randomized clinical trial of single- or dual-agent preexposure prophylaxis.2015
CD4(+) cell count, viral load, and drug resistance patterns among heterosexual breakthrough HIV infections in a study of oral preexposure prophylaxis.2014
HIV pre-exposure prophylaxis in transgender women: a subgroup analysis of the iPrEx trial.2015
Efficacy of preexposure prophylaxis for HIV-1 prevention among high-risk heterosexuals: subgroup analyses from a randomized trial.2013
High medication adherence during periconception periods among HIV-1-uninfected women participating in a clinical trial of antiretroviral pre-exposure prophylaxis.2014
Are Centers for Disease Control and Prevention Guidelines for Preexposure Prophylaxis Specific Enough? Formulation of a Personalized HIV Risk Score for Pre-Exposure Prophylaxis Initiation.2017
Development and validation of the San Diego Early Test Score to predict acute and early HIV infection risk in men who have sex with men.
Assessing the Performance of 3 Human Immunodeficiency Virus Incidence Risk Scores in a Cohort of Black and White Men Who Have Sex With Men in the South.2017
Preexposure prophylaxis guidelines have low sensitivity for identifying seroconverters in a sample of young Black MSM in Chicago.2018
Prediction of HIV acquisition among men who have sex with men.2009
Development of a clinical screening index predictive of incident HIV infection among men who have sex with men in the United States.2012
A Brief Screening Tool to Assess the Risk of Contracting HIV Infection Among Active Injection Drug Users.-- Not Found --
Daily and Nondaily Oral Preexposure Prophylaxis in Men and Transgender Women Who Have Sex With Men: The Human Immunodeficiency Virus Prevention Trials Network 067/ADAPT Study.2018
The acceptability and feasibility of an HIV preexposure prophylaxis (PrEP) trial with young men who have sex with men.2013
Patterns and correlates of PrEP drug detection among MSM and transgender women in the Global iPrEx Study.2014
Estimating efficacy in a randomized trial with product nonadherence: application of multiple methods to a trial of preexposure prophylaxis for HIV prevention.2015
Retention in care outcomes for HIV pre-exposure prophylaxis implementation programmes among men who have sex with men in three US cities.2016
Medication Adherence in a Nationwide Cohort of Veterans Initiating Pre-exposure Prophylaxis (PrEP) to Prevent HIV Infection.2018
Adherence to Pre-Exposure Prophylaxis for HIV Prevention in a Clinical Setting.2016
High interest in preexposure prophylaxis among men who have sex with men at risk for HIV infection: baseline data from the US PrEP demonstration project.2015
HIV protective efficacy and correlates of tenofovir blood concentrations in a clinical trial of PrEP for HIV prevention.2014
Uptake of pre-exposure prophylaxis, sexual practices, and HIV incidence in men and transgender women who have sex with men: a cohort study.2014
Daily oral tenofovir and emtricitabine-tenofovir preexposure prophylaxis reduces herpes simplex virus type 2 acquisition among heterosexual HIV-1-uninfected men and women: a subgroup analysis of a randomized trial.2014
Randomized trial of clinical safety of daily oral tenofovir disoproxil fumarate among HIV-uninfected men who have sex with men in the United States.2013
Accuracy of Self-Report and Pill-Count Measures of Adherence in the FEM-PrEP Clinical Trial: Implications for Future HIV-Prevention Trials.2015
The impact of adherence to preexposure prophylaxis on the risk of HIV infection among people who inject drugs.2015
Tenofovir-based preexposure prophylaxis for HIV infection among African women.2015
Antiretroviral prophylaxis for HIV prevention in heterosexual men and women.
Antiretroviral prophylaxis for HIV infection in injecting drug users in Bangkok, Thailand (the Bangkok Tenofovir Study): a randomised, double-blind, placebo-controlled phase 3 trial.2013
Preexposure chemoprophylaxis for HIV prevention in men who have sex with men.2010
On-Demand Preexposure Prophylaxis in Men at High Risk for HIV-1 Infection.2015
Antiretroviral preexposure prophylaxis for heterosexual HIV transmission in Botswana.
Preexposure prophylaxis for HIV infection among African women.2012
Safety, adherence and acceptability of intermittent tenofovir/emtricitabine as HIV pre-exposure prophylaxis (PrEP) among HIV-uninfected Ugandan volunteers living in HIV-serodiscordant relationships: a randomized, clinical trial.
Safety and adherence to intermittent pre-exposure prophylaxis (PrEP) for HIV-1 in African men who have sex with men and female sex workers.2012
Pre-exposure prophylaxis to prevent the acquisition of HIV-1 infection (PROUD): effectiveness results from the pilot phase of a pragmatic open-label randomised trial.2016
Tenofovir disoproxil fumarate for prevention of HIV infection in women: a phase 2, double-blind, randomized, placebo-controlled trial.2007
Plasma Tenofovir Levels to Support Adherence to TDF/FTC Preexposure Prophylaxis for HIV Prevention in MSM in Los Angeles, California.2017
Preexposure Prophylaxis for HIV Infection Integrated With Municipal- and Community-Based Sexual Health Services.2016
Safety and Feasibility of Antiretroviral Preexposure Prophylaxis for Adolescent Men Who Have Sex With Men Aged 15 to 17 Years in the United States.2017
An HIV Preexposure Prophylaxis Demonstration Project and Safety Study for Young MSM.2017

Downloadable Data Content

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