Pre-exposure prophylaxis (PrEP) refers to the use of antiretroviral (ARV) medication by HIV-negative persons prior to HIV exposure, with the goal of preventing HIV infection. The use of prophylactic medications is standard practice for the prevention of many other infections (such as malaria), but it is experimental for the prevention of HIV. The success of ARV drugs in preventing HIV transmission from mothers to infants and in decreasing seroconversion when given to adults shortly after HIV exposure stimulated interest in the concept of PrEP. Encouraging results of animal studies increased hopes that PrEP will prove to be an effective HIV prevention tool. This method could be particularly useful for women who are unable to negotiate safer sex, and for uninfected partners in serodiscordant relationships.
Initially, the lack of a safe ARV drug with simple dosing was the main limitation to the study of PrEP in humans. Two ARV drugs now used in HIV treatment, tenofovir and emtricitabine, meet those criteria and are being tested in clinical trials as PrEP. Some of the first clinical trials were stopped in response to community protests about trial design, conduct, and safety. Now, seven studies with broad international support are under way or will begin enrolling in 2009. Approximately 19,000 people in 11 countries will be enrolled in the trials to determine the safety and efficacy of daily PrEP with tenofovir alone and in combination with emtricitabine. The studies include men who have sex with men (MSM), injection drug users (IDUs), serodiscordant couples, and women at high risk for acquiring HIV. Two trials, one with IDUs in Thailand and the other with MSM in the United States, will be completed in 2009. The other studies are expected to be completed by 2012.
These trials will determine whether PrEP is safe and how much it can minimize the risk of HIV infection, but numerous questions will remain about its implementation outside of the research context. Will intermittent use of the drugs be effective? Who will bear the costs? How should the health and safety of PrEP users be monitored? Will people taking PrEP engage in riskier sex because they feel protected against HIV? PrEP should be implemented in combination with other effective prevention methods, such as behavioral counseling, but how can this best be done?
Because PrEP is still in a study phase, full program implementation likely remains years away. Governmental and nonprofit organizations therefore have an opportunity to prepare for the trial results and to begin addressing the outstanding questions about PrEP for the populations with which they work. If clinical trials demonstrate efficacy of PrEP, as many expect they will, the demand for its provision may increase rapidly. Policymakers, program planners, and public health workers should prepare for this possibility.
Updated: December 2009
Read these summaries of the research providing the evidence-base that supports the prevention approach
Summary of Research Articles |
Reports and Briefs
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Tenofovir Disoproxil Fumarate for Prevention of HIV Infection in Women: A Phase 2, Double-Blind, Randomized, Placebo-Controlled Trial
Peterson, L., et al. PLoS Clinical Trials (2007), Vol. 2, pp. 327.
This is the only completed clinical trial to date on the use of tenofovir PrEP in humans. The trial was designed to assess safety and preliminary efficacy of PrEP with daily tenofovir in HIV-negative women at high risk for HIV infection. However, due to premature closures of the study sites in Cameroon and Nigeria- efficacy could not be assessed. A total of 936 HIV-negative women were randomized to tenofovir or placebo. Tenofovir was not associated with increased adverse events compared to the placebo. Two women on tenofovir and eight women on placebo were diagnosed with new HIV infections during the trial, but the difference was not statistically significant. All women received standard of care prevention counseling. The average number of sexual partners in the past month decreased from 21 at baseline to 14 during follow-up. Condom use increased from 52 percent at baseline to 95 percent at the twelfth month follow-up. This study demonstrated that tenofovir is safe for HIV-negative women, but the assessment of its efficacy was inconclusive.
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Potential Impact of Antiretroviral Chemoprophylaxis on HIV-1 Transmission in Resource-Limited Settings
Abbas, U.L., Anderson, R.M., & Mellors, J.W. PLoS ONE (2007), Vol. 2, pp. e875.
Clinical trials are evaluating the efficacy of PrEP, but will not specifically assess its public health impact. A mathematical model was used to simulate the effects of PrEP on an HIV-1 epidemic in sub-Saharan Africa with optimistic, neutral and pessimistic scenarios. The optimistic scenario assumed 90 percent efficacy of PrEP, 75 percent coverage of the general HIV-uninfected population and no change in sexual behavior among persons taking the medication. With these assumptions, the model predicted a 74 percent decline in cumulative new HIV infections after ten years. If PrEP were instead targeted to the highest risk groups (16 percent of the population), the model estimated a 28.8 percent decline in new infections. This risk-targeted approach could avert 2.7 to 3.2 million new HIV-1 infections in southern sub-Saharan Africa over a 10-year period. The neutral scenario predicted a 6.8 percent decrease in new HIV infections with a risk-targeted strategy; and the pessimistic scenario predicted a 0.8 percent decrease. The projected decreases would be partially offset; however, if persons on PrEP increased risky sexual behavior or discontinued the drugs. For instance, in an optimistic scenario, if tenofovir were used, the cost per HIV infection averted with the risk-targeted strategy was $638 per person per year; $1,160 in a neutral scenario, and $2,494 in a pessimistic scenario. These results suggested that PrEP could be cost-effective if efficacy and adherence were high, long-term use were sustained, and sexual disinhibition were prevented.
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The Impact of Pre-Exposure Prophylaxis (PrEP) on HIV Epidemics In Africa And India: A Simulation Study
Vissers, D.C., et al. PLoS ONE (2008), Vol. 3, pp. e2077.
This mathematical modeling (simulation) study estimated the potential effect of PrEP in India, Botswana, and Kenya among sex workers and their clients. Although this model used a similar scenario as did Abbas et al in their model, Vissers et al predicted a smaller impact of PrEP in sub-Saharan Africa (0.14 averted HIV infections per person per year (pppy) of PrEP compared to 0.33 averted HIV infections pppy). The predicted impact of PrEP in southern India was much lower than that in sub-Saharan Africa. In the former, levels of condom use during commercial sex acts are relatively high, so any level of behavioral disinhibition (lower rates of condom use) could substantially decrease or even negate the impact of PrEP in that region.
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Knowledge and Use of Preexposure and Postexposure Prophylaxis among Attendees of Minority Gay Pride Events, 2005 through 2006
Voetsch, A.C., et al. Journal of Acquired Immune Deficiency Syndromes (2007), Vol. 46, pp. 378-380.
Although still in the clinical trial stage, information about PrEP has spread through the public; and the popular press has reported that some men who have sex with men are engaging in “street” use of PrEP. Randomly selected minority men who identified as gay or bisexual were surveyed at gay pride events in several U.S .cities. Of these, approximately one-fifth of survey respondents had heard of using antiretroviral drugs to prevent HIV, either as PrEP or as post-exposure prophylaxis (PEP). However, only one of 397 (0.3 percent) HIV-negative respondents had ever used PrEP and one of 60 (1.7 percent) HIV-positive respondents had ever given ART to a partner to use as PrEP.
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The Acceptability of Pre-Exposure Prophylaxis (Prep) For HIV Prevention in Lima, Peru
Cunningham, W., et al. AIDS-XVII International AIDS Conference (2008), Abstract no. WEPE0260.
Hypothetical scenarios were presented to 42 people at risk for acquiring HIV in order to identify which attributes of PrEP would be most acceptable to potential users. The scenarios varied by out-of-pocket costs, PrEP effectiveness, drug side effects, duration of administration, frequency of use, clinic type dispensing the drug and profession of the provider. Participants prioritized cost, followed by effectiveness and side effects. Acceptability was highest in a scenario with low out-of-pocket costs ($10/month), the drug’s effectiveness was 95 percent and there were no side effects.
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Antiretroviral Resistance Is Not an Important Risk of the Oral Tenofovir Prophylaxis Trial in Botswana: A Simple Mathematical Modeling Approach
Smith, D., et al. Presented at the XVI International AIDS Conference, Toronto, Canada (2006).
The risk of development of antiretroviral resistance in persons who seroconvert while taking PrEP is often cited as a concern in PrEP implementation deliberations. This mathematical simulation study estimated the risk of being infected with a tenofovir-resistant virus among participants in a PrEP trial in Botswana. Even with conservative assumptions, the simulation trial estimated that less than one of the 46 people expected to seroconvert would have a tenofovir-resistant virus. Many more resistance mutations would likely develop in HIV-infected patients being treated in Botswana outside of the trial.
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Cost-effectiveness Analysis of ART for Pre-exposure Prophylaxis
Hill, A., Youle, M. & Boucher, C. Paper presented at the 14th Conference on Retroviruses and Opportunistic Infections, Los Angeles, CA (2007), No. 901.
High drug costs may be a substantial obstacle to PrEP program implementation in many countries. This study used the lowest published costs of antiretroviral medications to estimate the cost of PrEP per person per year and to compare it to the cost of lifetime treatment of one case of HIV in sub-Saharan Africa. PrEP’s cost ranges from $50 (for intermittent lamivudine) to $850 (for tenofovir, lamivudine and lopinavir-ritonavir) per person per year. Depending on the scenario, PrEP’s cost-effectiveness varies widely and could be improved by lowering drug manufacturing costs and by targeting only those populations at highest risk for HIV infection. In countries with annual HIV seroconversion rates of at least one percent, using PrEP with 80 percent efficacy at a cost of less than US$50 per year, would be more cost-effective than treating one case of HIV infection.
Read these summaries of promising interventions
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Anticipatory Planning for PrEP Rollout in Malawi Based on Country Priorities
Mack, N., et al. AIDS-XVII International AIDS Conference (2008), Abstract no. WEPE0261.
Key informant interviews in Malawi found that the country “was committed to increasing safer sex behaviors as its primary HIV prevention method and would not support widespread, long-term use of PrEP for HIV prevention.” PrEP programs in Malawi would need to be targeted to highest-risk groups for HIV infection, such as sex workers and men with sexually transmitted infections. The authors recommend that plans for roll-out of PrEP be in line with country-specific HIV/AIDS prevention strategies; that plans be initiated early, and that appropriate stakeholders be closely involved in planning.
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Criteria for Drugs Used in Pre-Exposure Prophylaxis Trials against HIV Infection
Derdelinckx, I., et al. PLoS Medicine (2006), Vol. 3, pp. e454.
This paper proposes criteria for deciding which medications should be used as PrEP. Drug safety is a critical consideration since PrEP is given to individuals for long-term prevention rather than treatment. 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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The Abandoned Trials of Pre-Exposure Prophylaxis for HIV: What Went Wrong?
Singh, J.A. & Mills, E.J. PLoS Med (2005), Vol. 2 No. 9, pp. e234.
Activist groups protested against several trials of PrEP, and in some cases, succeeded in halting clinical studies. The most dramatic protest was in 2004, against a trial of tenofovir among Cambodian sex workers. Protestors alleged that study leaders had not adequately included sex workers in the study design; that the trial did not provide sufficient prevention counseling or HIV pre- and post-test counseling; and that the study did not provide medical services or insurance for those who seroconverted during the study or who experienced adverse events related to the trial drug. Protestors argued that the safety of the long-term use of tenofovir for individuals who were HIV-negative had not been established. Two other trials, one in Cameroon and the other in Nigeria, were also halted. The former was stopped because of reports that some study participants had been intentionally infected with HIV; the latter ended because the study team was unable to maintain adequate quality controls.
Adapt and use these program materials, including tools, curricula, and models
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PrepWatch
AIDS Vaccine Advocacy Coalition
Reports, updates, and news related to PrEP: A two-page summary of ongoing PrEP clinical trials, including a table that summarizes the participating countries, study populations, and funding sources for each trial.
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Pre-Exposure Prophylaxis (PrEP) for HIV Prevention: A Fact Sheet for Advocates
AIDS Vaccine Advocacy Coalition
This Fact Sheet provides essential information on pre-exposure prophylaxis (PrEP) for HIV prevention.
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Fact Sheet: CDC’s Trials of Pre-Exposure Prophylaxis for HIV Prevention
U.S. Centers for Disease Control and Prevention
An overview of rationale for CDC trials in Botswana and Thailand with discussion of future directions.
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Questions and Answers: CDC’s Clinical Studies of Pre-Exposure Prophylaxis for HIV Prevention
U.S. Centers for Disease Control and Prevention
Answers to frequently asked questions about clinical trials of PrEP.
Link to important additional materials and websites
Promote HIV chemoprophylaxis research, don't prevent it
Grant, R.M., et al. AIDS, Science (2005), Vol. 309, pp. 2170-1.
View Article
Preexposure Prophylaxis for HIV: Unproven Promise and Potential Pitfalls
Liu, A.Y., Grant, R.M., & Buchbinder, S.P. Journal of the American Medical Association (2006), Vol. 296, pp. 863-865.
View Article
Pre-exposure prophylaxis for HIV infection: what if it works?
Paxton, L.A., Hope, T., & Jaffe, H.W. The Lancet (2007), Vol. 370, pp. 89-93
View Article
