Risk for HIV Transmission in Nonoccupational Exposures
Sexual and injection-drug use (IDU) exposures to HIV can pose a risk of HIV transmission similar to or even exceeding that associated with typical occupational percutaneous (needlestick) injuries (Figure 1).[,] The risk of HIV transmission associated with sexual exposures varies considerably by exposure type, with receptive anal intercourse considered to confer the greatest risk.[,] Mucosal disruption in either the source or the exposed individual likely increases the risk of HIV transmission, as might occur with traumatic intercourse, or if either partner has genital ulcerative disease. Hence, the risk of HIV transmission presumably increases in the setting of aggressive sexual activity or after a violent sexual assault. The risk of HIV transmission also correlates with factors related to the HIV-infected partner. Several studies have documented a greater risk of transmission in persons with advanced HIV disease and those with higher serum HIV RNA levels.[,] To better determine the risk of the exposure, the initial evaluation of a patient with possible nonoccupational exposure to HIV should therefore attempt to document the HIV status of the source partner, time and type of exposure, the presence of genital disease or other lesions in any individual involved in the exposure, whether a condom was use for part or all of the sexual encounter. Information regarding the source patient's HIV RNA level and drug-resistance testing can be useful, but this information is not usually available. In addition, if possible, the source patient should undergo testing for HIV, hepatitis C virus, and hepatitis B virus, if the status for these infections is unknown.
Rationale for Providing Nonoccupational PEP
The justification for offering PEP after nonoccupational exposures to HIV derives from the established efficacy of PEP following occupational exposures to HIV, the efficacy of postnatal prophylaxis for infants born to HIV-infected mothers,[,] and animal studies.[,,,,,,] In one animal study, investigators demonstrated the benefit of tenofovir PEP in reducing the likelihood of seroconversion after intravenous inoculation of simian immunodeficiency virus (SIV), with the best results achieved if given within 24 hours and if given for 28 days (Figure 2). Although data are relatively scarce regarding the efficacy of PEP following sexual exposure in human subjects, results of small observational studies further support the efficacy of PEP in this setting.[,,] A cohort study involving 200 men who have sex with men (MSM) in Brazil found that recipients of nonoccupational PEP following sexual exposures had a seroconversion rate of 0.7 per 100 person-years, as compared with 4.1 per 100 person-years for individuals in this cohort who did not receive nonoccupational PEP. Similarly, an observational study of 325 female survivors of sexual assault in Brazil documented 4 seroconversions among 145 women who did not receive nonoccupational PEP compared with no seroconversions among the 180 women who received nonoccupational PEP. Earlier reports from observational studies in British Columbia, Australia, France, Switzerland, and the United States failed to document any seroconversions among more than 900 recipients of PEP following sexual exposures. A report from San Francisco described HIV seroconversion in 7 (1%) of 702 persons who received nPEP during the years 1997 to 1999 for high-risk sexual exposures, with subject receiving a dual nucleoside reverse transcriptase inhibitor (NRTI) regimen; among the 7 persons with HIV seroconversion, all 7 had engaged in receptive anal intercourse, and the median time for starting PEP was 45.5 hours after the exposure occurred.
Guidelines for Initiating Nonoccupational PEP
In 2005, the Department of Health and Human Services (DHHS) and CDC jointly published guidelines that provided detailed recommendations regarding the use of nonoccupational PEP following nonoccupational exposure to HIV. Unfortunately, the 2005 nonoccupational PEP guidelines have not been updated and as of April, 10, 2015, no subsequent federal guidelines on nonoccupational PEP have been issued. The 2005 guidelines endorse the use of nonoccupational PEP if the exposed individual seeks care within 72 hours of the exposure and the risk of transmission is deemed substantial (Figure 3). These guidelines define a substantial exposure risk as contact of an area of the body known to be associated with acquisition of HIV (vagina, rectum, eye, mouth, or other mucous membrane, non-intact skin, or percutaneous contact) with a body substance known to transmit HIV (blood, semen, vaginal secretions, rectal secretions, breast milk, or any body fluid that is visibly contaminated with blood) when the source is known to have HIV infection. Body fluids not considered to pose substantial risk include urine, nasal secretions, saliva, sweat, or tears, as long as none of these secretions is contaminated with blood. Exposure to blood via the sharing of contaminated needles or syringes is considered a substantial exposure risk. If an exposure associated with a substantial risk of transmission has occurred, but the HIV status of the source patient is not known, the recommendation is to evaluate on a case-by-case basis, ideally in consultation with an expert. For persons who present with a history that represents no substantial risk for HIV or if they seek care when more than 72 hours have elapsed since the exposure, nonoccupational PEP is not routinely recommended; in some circumstances where more than 72 hours have elapsed since the exposure, clinicians may consider use of nonoccupational PEP if the potential benefit of the medications is deemed to outweigh the risk for medication-related adverse effects. Specific recommendations regarding bite injuries, or percutaneous injuries with a needle discarded in a public setting are beyond the scope of this discussion and should be evaluated on a case-by-case basis with expert consultation.
Recommendations for Nonoccupational PEP Antiretroviral Regimens
The clinician performing the evaluation should carefully weigh the risks and benefits of nonoccupational PEP and discuss these issues in detail with the exposed individual. If, after this discussion, the clinician believes that nonoccupational PEP is indicated and the exposed individual is amenable to initiating PEP, a three-drug antiretroviral therapy regimen should be started as soon as possible and continued for 28 days. In our opinion, the recommended antiretroviral regimens in the 2005 DHHS/CDC guidelines (Figure 4) are outdated and do not meet the current standard of care in clinical practice. Most notably, the use of efavirenz (Sustiva) is problematic since this medication is often very poorly tolerated in the initial weeks of therapy and significant rates of efavirenz resistance now exist in the population of persons infected with HIV. The 2013 U.S. Public Health Services guidelines for the management of occupational exposures to HIV recommends using a three-drug PEP regimen consisting of tenofovir-emtricitabine (Truvada) plus raltegravir (Isentress), primarily based on potency, convenient dosing schedule, and favorable side effect profile. In recent years, many clinics and centers that provide antiretroviral therapy for nonoccupational PEP have transitioned from using regimens recommended in the 2005 nonoccupational PEP guidelines to tenofovir-emtricitabine plus raltegravir (the regimen recommended in the 2013 occupational PEP guidelines).[,,] In addition, the International Antiviral Society-USA publication on HIV Prevention in Clinical Care Settings recommends considering use of the regimen tenofovir-emtricitabine plus raltegravir for nonoccupational postexposure prophylaxis for HIV-related sexual and parenteral exposures. In the situation whereby a patient could not take tenofovir-emtricitabine plus raltegravir, expert consultation should be obtained. Several studies have shown relatively poor adherence with nonoccupational PEP, particularly in patients who have suffered a sexual assault.
Potential Toxicity of PEP Antiretroviral Therapy
Appropriately selected antiretroviral therapy administered for a 28-day course for nonoccupational PEP carries a low risk of serious toxicity. The most commonly used regimen, tenofovir-emtricitabine plus raltegravir, is generally very well tolerated and has minimal risk of serious toxicity. Because tenofovir can potentially cause nephrotoxicity, a baseline serum creatinine should be obtained on any patient who will receive nonoccupational PEP. As is the case for PEP following occupational exposures, nevirapine (Viramune) is contraindicated in PEP regimens for nonoccupational exposures because of the unacceptably high risk of serious liver and skin toxicity when this agent is administered to relatively immunocompetent individuals.[,,] Mild to moderate side effects that may occur with nonoccupational PEP regimens include nausea, diarrhea, abdominal discomfort, fatigue, and malaise; these side typically resolve rapidly after discontinuing PEP. If mild to moderate side effects impair adherence, a different antiretroviral agent can be substituted for the offending agent. Because PEP is administered for only 28 days, toxicities that have been associated with long-term administration of antiretroviral therapy, such as lipodystrophy or persistent insulin resistance, are considered highly unlikely, and have not been documented to date among recipients of PEP for either occupational or nonoccupational exposures to HIV.
Effect of Offering PEP on Subsequent High-Risk Behavior
Concerns have been raised that offering PEP following sexual exposures to HIV may promote unsafe sexual behaviors if individuals in the community perceive that nonoccupational PEP can be used as a substitute for safe sexual practices. Investigators from the San Francisco Department of Public Health attempted to assess this risk in a pilot feasibility study. The study included 397 participants who received antiretroviral PEP following an act of unprotected sexual intercourse or injection drug use within the preceding 72 hours if the exposure likely involved a significant risk of HIV transmission. Among those enrolled, 375 had had sexual exposures, most of whom were men who have sex with men (MSM). When appropriate, PEP was offered, and behavioral counseling was also included in the initial and subsequent follow-up visits. At 6 months following presentation for nonoccupational PEP, most participants reported that their level of unsafe sexual behavior had decreased significantly. This reduction in unsafe sexual behavior persisted at 12 months of follow-up, and rates of sexually transmitted diseases did not increase (Figure 5). Multiple other studies have also shown that availability of PEP for sexual exposures does not increase unsafe sexual behaviors.[,,,]
Initial Laboratory Evaluation and Follow-Up Testing
Patients who undergo evaluation for nonoccupational exposure to HIV will need baseline and follow-up laboratory monitoring (Figure 6). The initial evaluation of the exposed individual should include baseline serology tests (HIV, HBV, and HCV), screening for other sexually transmitted infections (chlamydia, gonorrhea, and syphilis), and routine blood work (complete blood count with differential, hepatic transaminase levels, blood urea nitrogen, and creatinine). In addition, a pregnancy test should be performed on women of reproductive age, and emergency contraception should be considered for women who sustained vaginal exposure with semen. If the exposed individual initiates PEP, monitoring of hematologic, hepatic, and renal parameters should be performed 2 to 3 weeks after starting therapy. Follow-up testing for HIV, hepatitis B virus, and hepatitis C virus should be performed if the possibility of transmission of these agents exists. Most experts strongly recommend against performing HIV RNA testing of the exposed individual as part of the standard laboratory monitoring, especially considering false positive results can occur when the HIV viral load assay is used to screen for HIV infection in asymptomatic patients.
Evaluation for Possible Primary HIV Infection
Persons who have sustained a potential exposure to HIV should be educated regarding the signs and symptoms associated with primary HIV infection (acute retroviral syndrome). The development of signs or symptoms compatible with primary HIV infection should prompt immediate clinical evaluation, preferably by a clinician with HIV expertise. Patients with acute HIV generally have a negative or indeterminate HIV serology but a very high HIV RNA level. In the setting of suspected acute retroviral syndrome, HIV RNA testing would be appropriate, but caution should be exercised in interpreting any detectable HIV RNA level less than 10,000 copies/mL. For a detailed discuss regarding primary HIV infection see the case Acute (Primary) HIV Infection.
Counseling regarding prevention of HIV acquisition and transmission is indicated for all individuals who have had a sexual or drug exposure to HIV. If the exposed individual had a consensual sexual encounter, that individual should receive counseling regarding sexual behavioral risk reduction, and the counseling should emphasize that avoiding exposures to HIV is clearly a more effective means to prevent HIV acquisition than receiving PEP following an exposure. Intensive counseling and follow-up is warranted for all victims of sexual assault. Counseling should also be offered for individuals who may be unsettled about the possibility, even if remote, of acquiring HIV infection as a consequence of their exposure. For individuals who have anticipated continued high-risk behavior, counseling should include discussion regarding potential use of preexposure prophylaxis (PrEP) in the future, assuming they do not contract HIV from the current exposure.