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HIV Prevention Knowledge Base

A Collection of Research and Tools to Help You Find What Works in Prevention

Biomedical Interventions: Oral Pre-exposure Prophylaxis (PrEP) for HIV Prevention

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:

  • Educating health workers and at-risk populations
  • Producing, distributing, and providing ARVs for PrEP
  • Recruiting risk candidates who may not wish to disclose risk factors with sensitivity
  • Providing individual education and counseling and adherence support
  • Testing for HIV before PrEP is provided
  • Selecting the regimen
  • Following up regularly to assess safety, toxicity, HIV status, and potential resistance
  • Identifying and costing service delivery approaches.

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.