Post-exposure Prophylaxis (PEP)

Introduction

I. Definition of the Prevention Area

Antiretroviral post-exposure prophylaxis (PEP)--short-term antiretroviral therapy initiated soon after known or suspected exposure to HIV--aims to prevent the establishment of HIV infection in an exposed person.

PEP has become the standard of care to prevent acquisition of HIV infection after occupational exposure to blood or other bodily fluids of people infected with HIV. There is less of a consensus regarding the administration of PEP after nonoccupational exposure. While PEP is part of the package of post-sexual assault care in most countries, the use of nonoccupational PEP, outside of rape or isolated incidents of exposure, is more controversial--particularly when the HIV status of the source case is unknown. The World Health Organization (WHO) and the U.S. Department of Health and Human Services offer guidelines for nonoccupational PEP.

II. Epidemiological Justification for the Prevention Area

Each day, new HIV infections occur among health care workers, sexual assault victims, and other individuals following known or suspected exposure to HIV in blood or genital secretions. PEP is generally considered appropriate for people with occasional high-risk exposure to HIV (such as health care workers exposed to bodily fluids of patients with HIV or people sexually assaulted by a person with documented HIV infection). It may also be appropriate following occasional accidental exposure in serodiscordant partnerships (such as when a condom breaks during sex). In other cases of possible exposure, PEP may not be warranted unless there is a strong likelihood that the source of the exposure is HIV-positive.

Evidence suggests that a simple, relatively nontoxic and effective antiretroviral PEP regimen could prevent some of these new HIV infections. Although the degree of protection offered by PEP cannot be established in placebo-controlled trials because of ethical issues, studies of people who had a known exposure to HIV and were administered PEP suggest that PEP is about 80 percent effective in preventing establishment of HIV infection. Data from macaque studies suggest that PEP is protective when administered as soon as possible after exposure and that the effect degrades over time. Thus, in order to be effective, PEP should ideally begin within 48 hours of exposure and at least within 72 hours, and PEP should continue for 28 days. Cases of seroconversion despite PEP have been documented after occupational and nonoccupational exposure to HIV.

III. Core Programmatic Components

Successful implementation of occupational or nonoccupational PEP depends on the following: 1) identification (usually self-identification) of people at risk of exposure; 2) counseling PEP candidates on the implications of seroconversion and, if they are not infected with HIV, on risk reduction to lower the odds of recurrent exposure; 3) informed determination of the exposure risk on a case-by-case basis, including HIV testing of the source, if possible; 4) HIV testing of the PEP candidate before and after completion of PEP; 5) selection of an appropriate PEP regimen; 6) initiation of PEP within at least 72 hours of exposure; and 7) completion of a 28-day PEP course.

IV. Current Status of Implementation Experience

WHO strongly advises national authorities to establish PEP guidelines, especially in countries with a high HIV prevalence. Studies of individuals who have undergone PEP regimens suggest which antiretroviral combinations may be most tolerable as PEP. Tenofovir and emtricitabine have attracted research attention as PEP agents because of their tolerability, once-daily administration as a single pill, and high concentration in the female genital tract. Whether three-drug regimens hold an advantage over two-drug regimens remains uncertain, but U.S. health authorities recommend a three-drug regimen. As with any antiretroviral use, PEP poses some risk of resistance.

Despite the cost of PEP, it has been successfully implemented in low-income countries, such as Kenya (for occupational and nonoccupational exposures) and Malawi (for sexually exposed children). An analysis of four studies suggests that PEP could be cost-effective when following exposure to blood and/or body fluids known to contain HIV. PEP has been used in children and adolescents after sexual assault in both high- and low-income settings. Some work indicates higher toxicity rates and worse adherence in children and adolescents than in adults.

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Antiretroviral Agents Used by HIV-Uninfected Persons for Prevention: Pre- and Postexposure Prophylaxis

Grant, R. M. Clinical Infectious Diseases (2010), Vol. 50 Suppl. 3, pp. S96-101.

The author reviews the range of biomedical prevention therapies from prevention of mother-to-child transmission to pre-exposure prophylaxis (PrEP) and PEP. The author also discusses issues that challenge research on new prophylactic approaches and individual and societal barriers that affect provision and use. PEP is not commonly offered where resources are scarce because questions about treatment efficacy and regimen safety prevail. The author also considers issues that have been raised with respect to PrEP (a daily oral dose of a single ARV or in combination) and microbial (ARV in gel form) prevention approaches for high-risk populations. A concern raised is that prevention options like these confer safety from HIV and may lead individuals to believe that they can engage in risky sexual behavior. Clinical trials currently underway will provide answers to some of these concerns and will help inform decisions by implementers and policymakers in determining what programs are offered in resource-poor locales. The author cautions that community acceptance and support for biomedical approaches like these are critical to adherence and successful outcomes.

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Narrative Review: Antiretroviral Therapy to Prevent the Sexual Transmission of HIV-1

Cohen, M. S., Gay, C., Kashuba, A. D. M., et al. Annals of Internal Medicine (2007), Vol. 146 No. 8, pp. 591-601.

This summary focuses on the findings of prevention studies for PrEP and PEP within the larger literature review covered by the article. The rationale for PEP is based on a series of studies conducted with rhesus and macaque monkeys that provide the critical parameters of treatment--namely, beginning ARVs not later than 72 hours after exposure and continuing with the regimen for 28 days. The limitations of animal studies for PEP reflect shortcomings of studies conducted with humans. Rigorous trials have not been carried out because they require very large samples and are prohibitively expensive or face ethical dilemmas. Therefore, studies use small samples and do not address long-term patient outcomes. In fact, only one study with humans has proven that PEP is effective in preventing HIV. This was a retrospective case control study of medical accidents with sharps (n = 679). An 81 percent reduction in risk was registered when ZDV (or another ARV drug) was administered to workers who were exposed. Protocols and guidelines used worldwide are based on this research and the series of animal studies. The authors discuss a number of potentially harmful consequences if widespread use of ART for prevention is adopted, including increased high risk behaviors on the part of people who believe themselves to be safe, emergence of drug resistance strains, and provision of ARVs to those with low probability for HIV transmission.

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National HIV/AIDS Clinicians' Consultation Center

University of California, San Francisco. (2010).

This U.S.-based center hosts a PEP hotline for providers seeking clinical guidance related to the treatment occupational exposure to HIV.

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