Oral Pre-exposure Prophylaxis (PrEP) for HIV Prevention

Introduction

I. Definition of the Prevention Area

Pre-exposure prophylaxis (PrEP) aims to prevent acquisition of HIV through use of antiretroviral (ARV) agents before potential exposure to HIV. Several trials of daily oral PrEP have been completed, and other trials of daily and intermittent use of oral PrEP and injectable agents are underway. The primary strategy being tested involves daily use of one (tenofovir [TDF]) or two (TDF/emtricitabine [FTC]) oral ARV drugs.

II. Epidemiological Justification for the Prevention Area

A safe, effective, and acceptable oral prevention regimen could provide another tool for HIV prevention programs. Three placebo-controlled clinical trials have shown significant reduction in HIV acquisition among HIV-negative persons who received an ARV pill to take daily, as shown in the following:

Trial

Study Drug

Population

Results

iPrEX

TDF/FTC

Men who have sex with men, transgendered women;
Brazil, Ecuador, Peru, South Africa, Thailand, United States

Risk reduced by 44%; higher protection (73%) among most consistent users

Partners PrEP

TDF and TDF/FTC

Serodiscordant heterosexual couples;
Uganda, Kenya

Risk reduced by: 67% (TDF)
75% (TDF/FTC)

TDF2

TDF/FTC

Men and women; Botswana

Risk reduced by 62%

One placebo-controlled trial (FemPrEP) and the oral TDF arm of the VOICE trial were stopped early when data reviews determined that they would be unlikely to answer the study question. (VOICE continues to evaluate daily oral TDF/FTC.). Both trials studied the impact of PrEP in African women.

Data from all these trials suggest that effectiveness is strongly correlated with adherence and that thus far the incidence of acquiring drug-resistant HIV is low. The FemPrEP trial data strongly suggest that the lack of effectiveness was due mainly to women in the trial not taking the tablets consistently. Researchers are continuing to work to understand the interaction between the behavioral and biomedical aspects of these results, and the implications for PrEP.

III. Core Programmatic Components

Roll-out of ARV PrEP has not started, but programs would involve the following components:

Successful implementation would depend on active involvement of national ministries of health, normative agencies, donors, provider organizations, and community groups.

IV. Current Status of Implementation Experience

PrEP is not yet being rolled out in programs largely due to the cost of the approach in large populations and concerns about adverse effects in HIV-negative individuals, yet the optimal approach is being explored through implementation science studies. For example, iPrEX-OLE is exploring implementation questions with iPrEX trial participants; implementation studies are also beginning in the United States. Attention is increasingly focused on implementation questions. Will PrEP need to be taken every day? Will intermittent dosing be effective, less costly, and easier to use? What is the best way to provide PrEP (e.g., service setting, packaging, pricing)? Which groups or individuals should be prioritized? Will side effects prove tolerable to healthy people? Will PrEP promote emergence of resistant HIV? Will people taking PrEP engage in riskier behaviors, offsetting PrEP's benefits? Will PrEP be safe and effective for women who are pregnant or wish to conceive? How can the global health community best balance using ARVs for PrEP with providing ARVs for treatment?

The Centers for Disease Control and Prevention has issued interim guidance for PrEP among men who have sex with men in the United States while formal guidance is developed. Gilead Sciences, the pharmaceutical company that sponsors TDF and TDF/FTC, submitted data to the U.S. Food and Drug Administration requesting a labeling change that approves TDF/FTC as PrEP to reduce the risk of HIV acquisition among adults. The request is being considered under priority review. Efforts to build on completed and ongoing trials are important to understand how best to utilize this potentially important new tool for HIV prevention.

What we know

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Putting it into practice

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Tools and Curricula

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Learn more

PrEP Using Daily Oral TDF/FTC or TDF in Women (and Men): What the Science Tells Us in March 2012

AIDS Vaccine Advocacy Coalition. (2012).

This one-page brief, aimed at advocates, summarizes the implications of concluded and ongoing clinical trials and other research on pre-exposure prophylaxis (PrEP), including new information presented at the 2012 Conference on Retroviruses and Opportunistic Infections. It states that PrEP using a daily oral tenofovir (TDF) or TDF/emtricitabine (FTC) tablet reduces the risk of HIV in women and men, and summarizes the information to support this statement. It provides brief descriptions of information to support additional conclusions from PrEP research to date, underscoring that adherence is critical to effectiveness, that risk perception appears to contribute to an individual's willingness and ability to adhere to the daily regimen, and that regular HIV testing is and will remain critical to addressing resistance. Finally, the brief identifies pregnant women and adolescents as among the key groups where more data are needed.

pdf View Report outside link (PDF, 222 KB)


Partners PrEP Study Demonstrates that PrEP Significantly Reduces HIV Risk: Key Messages

University of Washington, International Clinical Research Center. (2011).

This document lists "key messages" prepared by the study team in anticipation of the release of results from the Partners PrEP study. Randomization was stopped early at the recommendation of the trial's independent Data Safety and Monitoring Board due to overwhelming evidence of effectiveness, and results were announced at the International AIDS Conference in July 2011, just a week later. This document provides an overview of the trial, its conduct, the trial findings, and their implications for pre-exposure prophylaxis in these and other populations.

pdf View Report outside link (PDF, 64 KB)


PrEP Implementation Policy Forum: Developing Country-level Preparation and Capacity for PrEP Implementation

International AIDS Society. (2007).

This report contains proceedings of a policy forum focused on country-level preparedness for pre-exposure prophylaxis (PrEP). It outlines approaches for translating research into policy and deriving lessons from implementation planning for male circumcision for HIV prevention. Ministry of Health representatives from several key countries emphasized that country-level preparedness will be predicated on the evidence, defining target populations, cost and financing, and addressing stigma and integration into existing health systems. The report also addresses designing global and national PrEP guidelines and affordability and availability of PrEP drugs. It concludes with 10 "Key Take Home Messages" to consider in preparing for PrEP implementation.

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Criteria for Drugs Used in Pre-exposure Prophylaxis Trials against HIV Infection

Derdelinckx, I., Wainberg, M. A., Lange, J. M., et al. PLoS Medicine (2006), Vol. 3, p. e454.

This paper proposes criteria for deciding which medications should be used for pre-exposure prophylaxis (PrEP). Drug safety is a critical consideration because PrEP is given to healthy individuals for long-term prevention. Drugs used for PrEP must be potent against HIV, easy to use, cost-effective, and have a high barrier to resistance. Theoretically, drugs that interfere with HIV replication before the virus enters the host cell are preferable. An ideal PrEP drug would also have a unique resistance profile and not be used in treatment of established HIV infection, but such a medication does not yet exist.

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