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. Data from the iPrEx, Partners PrEP, and TDF2 studies have shown that daily oral tenofovir/emtricitabine (TDF/FTC) (marketed as Truvada) use is safe and effective for reducing risk of infection in heterosexual men and women, men who have sex with men, and transgender women. Data from these studies formed the basis of Gilead’s application to the US Food and Drug Administration for approval of TDF/FTC as PrEP (Gilead is the manufacturer and patent holder for TDF/FTC). Trial data show that TDF/FTC reduces HIV transmission risk for people who take it correctly and consistently.
Epidemiological Justification for the Prevention Area
A safe, effective, and acceptable oral prevention regimen would be another tool for HIV-prevention programs. Three placebo-controlled clinical trials have shown significant reduction in HIV acquisition among HIV-negative persons who received and took an ARV pill daily, as shown in the following:
Trial Study Drug Population Results iPrEX TDF/FTC Men who have sex with men, transgender 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)
TDF2 TDF/FTC Men and women; Botswana Risk reduced by 62%
One placebo-controlled trial that included prophylaxis with TDF–FTC (FemPrEP) and the oral TDF arm of the VOICE trial did not significantly reduce the rate of HIV infection and was associated with increased rates of side effects, as compared with placebo. Despite substantial counseling efforts, drug adherence appeared to be low.
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 work to understand the interaction between the behavioral and biomedical aspects of these results, and the implications for PrEP.
Core Programmatic Components
Roll-out of ARV PrEP has not started, but programs will 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 sensitive risk factors.
- Providing individual education, counseling, and adherence support.
- HIV testing before PrEP provision.
- Regimen selection.
- Regular follow-up to assess safety, toxicity, HIV status, and potential resistance.
- Identifying and costing service delivery approaches.
Successful implementation will depend on involvement of national ministries of health, normative agencies, donors, provider organizations, and community groups.
Current Status of Implementation Experience
Guidelines for prescribing and using PrEP are available from a range of groups, including state health departments in the US, the US Centers for Disease Control (CDC) and national-level clinician groups as well as guidelines on international demonstration projects from the World Health Organization. In the US the Food and Drug Administration (FDA) has approved daily Truvada for HIV prevention, and some communities in the US are exploring how it might best be delivered.
Outside the US, Truvada as PrEP is not approved by local regulators and in most cases remains inaccessible outside research studies. The optimal approach to PrEP is being studied in the United States. Attention is increasingly focused on questions such as: 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 balance using ARVs for PrEP with providing ARVs for treatment?