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 (when someone working in a healthcare setting is exposured to materials infected with HIV). There is less of a consensus regarding the administration of PEP after nonoccupational exposure (potential exposure to HIV outside the workplace (such as from sexual assault, or during episodes of unprotected sex or needle-sharing injection drug use). 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 rationale for nonoccupational PEP rests on evidence from animal studies, studies of prophylaxis to prevent mother-to-child transmission of HIV, and evidence from studies of PEP after occupational exposure to blood or other bodily fluids infected with HIV. The World Health Organization (WHO) and the U.S. Department of Health and Human Services offer guidelines for nonoccupational PEP. WHO strongly advises national authorities to establish PEP guidelines, especially in countries with a high HIV prevalence.
Epidemiological Justification for the Prevention Area
Each day, new HIV infections occur among health care workers, survivors of sexual assault, and other individuals following known or suspected exposure to HIV in blood or genital secretions. A simple, relatively nontoxic, effective antiretroviral PEP regimen could prevent some of these new HIV infections. PEP is 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.
The degree of protection offered by PEP cannot be established in placebo-controlled trials because case-controlled reports favoring PEP make such trials unethical. Furthermore, trials comparing two effective PEP regimens would require a large sample size to detect a statistically significant difference. Enrolling such a study would be logistically difficult, given that participants would need to be identified, screened, and initiated on treatment within the very narrow window of 72 hours following exposure.
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.
Current Status of Implementation Experience
Data from studies of people who have used 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, to be effective, PEP should ideally begin within 48 hours of exposure and at least within 72 hours, and should continue for 28 days. Cases of seroconversion despite PEP have been documented after occupational and nonoccupational exposure to HIV.
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 drug, 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.