The Care of Persons with Recent Sexual Exposure to HIV

Approximately 41 000 new HIV infections occur annually in the United States; about half are caused by sexual transmission [1]. Until recently, patients had little motivation to seek medical care soon after sexual exposure to HIV. However, evidence that postexposure treatment with zidovudine is associated with a significant decrease in risk for occupational HIV infection [2, 3] has led to the recommendation that prophylaxis be considered for persons with sexual exposures [4-7]. Physicians in primary care settings, emergency departments, and sexually transmitted disease clinics must be prepared to evaluate, treat, and counsel patients with recent sexual exposure to HIV. Several tasks should be accomplished during the initial visit (Table 1). First, appropriate candidates for postexposure prophylaxis should be identified and offered antiretroviral treatment. Second, HIV testing must be performed to identify persons who are already infected and need long-term antiretroviral therapy. Finally, interventions to prevent future transmission of HIV must be initiated [8, 9]. Table 1. Assessment of Persons with a Recent Sexual Exposure to HIV Rationale for Postexposure Treatment The theory underlying the use of postexposure prophylaxis is that antiretroviral treatment instituted immediately after exposure to HIV may abort infection by inhibiting local HIV replication and allowing the host's immune defenses to eradicate the virus inoculum. Although no direct evidence shows that postexposure treatment prevents infection after sexual exposure, this is biologically plausible given the efficacy of treatment after transcutaneous occupational exposure and the similarities between the immune responses to transcutaneous and transmucosal exposures [10-12]. Identification of Candidates for Treatment Identification of candidates for postexposure treatment requires assessment of the type of sexual exposure, the HIV status of the patient and the patient's partner, the patient's attitude toward safer sex, and the length of time since the exposure (Table 1). Type of Sexual Exposure Few studies have assessed the per-episode risk for HIV infection with specific sexual practices [13-16]. The probability is highest with unprotected receptive anal intercourse (0.008 to 0.032) [13]. The risk is higher with receptive vaginal intercourse (0.0005 to 0.0015) than with insertive vaginal intercourse (0.0003 to 0.0009) [14-16]. No per-contact estimates of risk with insertive anal intercourse or with oral intercourse have been published, although seroconversion as a result of oral sex has been documented [17-19]. Even for sexual acts for which the average per-exposure risk has been quantified, the average risk may not apply to a specific encounter. In some cases, HIV infections result from few contacts; in others, HIV infection does not occur despite many contacts [15, 16]. Many source and host factors influence the likelihood of HIV infection [20]. HIV Status of the Patient Preventive treatment is given on the basis of the assumption that the patient is not already HIV infected. Many persons at risk have never been tested [21, 22], however, and others will have had unsafe sex since 6 months before their last negative test result. For these reasons, an HIV antibody test should be done during the initial visit. With conventional HIV assays, most infected persons will have detectable antibodies 4 to 6 weeks after exposure and almost all will seroconvert by 6 months [23]. If the patient reports having had multiple exposures in the recent past, an HIV viral load test should be performed to detect primary HIV infection [19]. Testing for HIV should not prevent the immediate initiation of prophylaxis. Rapid HIV tests are extremely sensitive but are not specific enough to definitively diagnose pre-existing HIV infection [24, 25]. Patients found to be HIV infected at baseline should be prescribed an optimal drug regimen for primary or long-standing HIV infection [26]. Assessment of Sexual Partner (Source of Infection) The HIV status of the sexual partner may not be known if he or she has never been tested or has engaged in unsafe behaviors since 6 months before the last negative test result. If the partner is willing to be tested, treatment can be started and then stopped if the partner's HIV antibody test result is negative. If the partner is unavailable or unwilling to be tested, treatment decisions should be based on the likelihood that the partner is HIV infected. Factors to consider include the partner's HIV risk behaviors and the prevalence of HIV and AIDS in the partner's community [1]. If the partner is HIV infected, additional information, including stage of illness and results of recent HIV viral load tests, can improve treatment decisions. Persons with advanced disease [2] and high viral loads are more likely to transmit HIV. Because the correlation between plasma and genital fluid viral titer varies [27, 28], transmission may still occur even if the source has a nondetectable serum viral load. A history of antiretroviral treatment can identify cases in which drug resistance is more likely so that the prophylactic regimen can be adjusted [29]. Care of the source patient should include counseling on how future risks can be avoided, both with the partner who has presented for care and with other partners. Several probable cases of HIV transmission during rape have been reported [30, 31], and postexposure prophylaxis of HIV infection should always be considered and recommended when it is indicated [32, 33]. Patient Attitude toward Safer Sex Many motivated persons diligently practice safer sex but are accidentally exposed to HIV when a condom breaks. Reported per-episode failure rates with condoms are high (0.9% to 4.5%) [34, 35]. In contrast, some persons may seek postexposure prophylaxis in the hope that it will enable them to maintain high-risk behaviors without being infected. Between these two extremes, patients present with various risk histories. Some have an isolated episode of unsafe sex while high on substances. Others may have many unsafe exposures with partners of unknown HIV status but seek care because of exposure to HIV through a partner who is known to be infected. Because it is difficult to assess a patient's motivation for practicing safer sex in the short time frame necessary to initiate postexposure treatment, clinicians should err on the side of offering treatment for an exposure but should emphasize the importance of safer sexual behavior in the future. Recommendations for Postexposure Prophylaxis We recommend postexposure prophylaxis after unprotected receptive and insertive anal and vaginal intercourse with a partner who is or is likely to be HIV infected (Table 2). Prophylaxis should also be offered for receptive fellatio with ejaculation, although the lack of per-contact estimate for this behavior makes it more difficult to weigh the benefits against the risks. We do not recommend prophylaxis after other sexual exposures, such as cunnilingus or receptive fellatio without ejaculation, unless factors are present that increase the likelihood of transmission (such as exposure to menstrual blood). We recommend treating only isolated exposures or exposures in a patient who is willing to practice safer behaviors in the future. Finally, immediate treatment is optimal, and treatment should be initiated within 72 hours (the cut-off suggested for occupational exposures [6]). Table 2. Recommendations for Postexposure Prophylaxis Treatment Regimen Until further data are available, the treatment regimen should be modeled after that used for occupational exposures (Table 3) [36, 37]: zidovudine and lamivudine for 4 weeks. An alternative regimen is stavudine and didanosine, but zidovudine is the only drug for which efficacy data in the setting of postexposure treatment are currently available. Addition of a protease inhibitor may be indicated if the source patient has advanced HIV disease or is known to have a high HIV viral load (>50 000 copies/mL). Addition of a protease inhibitor should also be considered if the source partner has been previously treated with one or both of the nucleoside analogues in the recommended two-drug regimens. If the partner is experienced with numerous antiretroviral drugs, individualization of the regimen is necessary. The importance of adhering to the regimen must be emphasized. Table 3. Treatment Protocol for Postexposure Prophylaxis Of the available protease inhibitors, nelfinavir or indinavir should be used. Although there is more experience with indinavir, this drug must be taken on an empty stomach; this requirement may decrease compliance. Indinavir use is also often complicated by kidney stones or other urologic symptoms [38], although this can be minimized by having patients drink at least 48 ounces of fluid a day. Nelfinavir commonly causes diarrhea, which is usually well controlled with over-the-counter diarrheal medications. Some HIV experts routinely prescribe triple therapy for prophylaxis after sexual exposure. We do not favor this as a routine approach because use of a third drug increases the risk for side effects, complicates the regimen (which may decrease adherence), and increases the cost of treatment. Although triple therapy is more effective than two nucleoside analogues in reducing viral replication in HIV-infected persons [39], the same may not apply to prophylaxis. Persons with long-standing HIV infection have billions of viral particles in their bodies; in contrast, the viral inoculum immediately after sexual exposure is very small and a single drug may therefore be effective. However, patients who have had multiple exposures and do not seek care until close to the 72 hour cut-off will probably have higher viral loads. Transmission of HIV strains that are resistant to zidovudine [40, 41], didanosine [42], or lamivudine have been documented [43], but transmission of resistance from part