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Case 5: Discussion

Risk for HIV Transmission in Nonoccupational Exposures

Although the use of postexposure prophylaxis (PEP) following occupational exposures to HIV has been widely accepted for years, the use of PEP following nonoccupational sexual or injection drug use (IDU) exposures has been more controversial, and only recently did the CDC formally endorse the use of nonoccupational PEP. Sexual and 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)[1,2. The risk of HIV transmission associated with sexual exposures varies considerably by exposure type, with receptive anal intercourse considered to confer the greatest risk[1,2]. 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 a violent sexual assault.

The risk of HIV transmission may also depend on 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 high serum HIV RNA levels[1]. The initial evaluation of a patient with possible nonoccupational exposure to HIV should therefore attempt to document the exact time and type of exposure, the presence of genital disease or other lesions in either individual, and the HIV status and disease stage of the source partner. In addition, if possible, the source patient should undergo baseline evaluation that consists of HIV serology testing (if this individual's HIV status is not known), screening for other sexually transmitted diseases (chlamydia, gonorrhea, and syphilis), and serologic tests for hepatitis B and C viruses[2]. Other information regarding the source patient's HIV status, such as CD4 count, viral load, and resistance test results, can also be useful if available quickly, but in most situations they do not contribute significantly to decision-making regarding PEP.

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[3], the efficacy of post-natal prophylaxis for infants born to HIV-infected mothers[2,4], animal models of SIV transmission[5,6], and animal PEP studies[7,8,9,10]. In one particularly notable animal study, investigators inoculated the vaginal mucosal area of macaques with HIV-2 and found that a 28-day course of subcutaneous PMPA (tenofovir), initiated 12 hours or 36 hours following the exposure, prevented seroconversion in all 8 of these animals, whereas seroconversion occurred in 3 of 4 control macaques who did not receive PEP. In addition, separate studies have shown that PEP with tenofovir reduces the likelihood of seroconversion after intravenous inoculation of simian immunodeficiency virus (SIV)[11,12].

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[13,14,15]. A cohort study involving 200 men who have sex with men (MSM) in Brazil found that recipients of 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 had similar exposures but did not receive PEP. Similarly, an observational study of 325 female survivors of sexual assault in S?o Paolo, Brazil documented four seroconversions among 145 women who did not receive PEP compared with no seroconversions among the 180 women who received PEP[2]. 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[2]. A more recent unpublished report from the San Francisco group has described 7 HIV seroconversions among persons who received PEP; all 7 had receptive anal intercourse, and the median time for starting PEP was 45.5 hours after the exposure occurred[16].

Recommendations for Initiating Nonoccupational PEP

Recently, the Department of Health and Human Services (DHHS) and CDC jointly published guidelines that provide detailed recommendations regarding the use of PEP following nonoccupational exposure to HIV[2]. The guidelines endorse the use of PEP if the exposed individual seeks care within 72 hours of the exposure and the risk of transmission is deemed substantial (Figure 2). 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. 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.

Nonoccupational PEP Antiretroviral Regimens

The clinician performing the evaluation should carefully weigh the risks and benefits of PEP and discuss these with the exposed individual. If, after this discussion, the clinician believes that PEP is indicated and the exposed individual is amenable to initiating PEP, a three-drug highly active antiretroviral therapy (HAART) regimen should be started as soon as possible and continued for 28 days (Figure 3)[2]. A two-drug (dual-nucleoside reverse transcriptase inhibitor) regimen should be considered if the clinician and patient have concerns regarding adherence and toxicity related to the three-drug regimen. In some circumstances, special care must be taken in designing the PEP regimen if the source patient has known or suspected antiretroviral-resistant HIV; consultation with an expert in PEP is recommended in this setting.

Potential Toxicity of PEP Antiretroviral Therapy

Appropriately selected HAART regimens administered for a 28-day course of PEP appear to carry a low risk of serious toxicity. 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[17,18]. Mild to moderate side effects of PEP regimens are common and include gastrointestinal problems (nausea, diarrhea, abdominal discomfort), fatigue, and malaise. In addition, the most common laboratory abnormalities that develop consist of suppression of blood cell lines from zidovudine (Retrovir), increased indirect bilirubin caused by indinavir (Crixivan) or atazanavir (Reyataz), and dyslipidemia. These side effects and laboratory abnormalities resolve after discontinuing PEP. More serious adverse effects, such as nephrotoxicity or hepatotoxicty, rarely occur. 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 HAART, 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 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[14]. 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 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 4). Other studies have also suggested that the availability of PEP for sexual exposures does not appear to increase unsafe sexual behaviors[13,19,20].

Initial Laboratory Evaluation and Follow-Up Testing

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) (Figure 5)[2]. 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 (Figure 5). If the exposed individual initiates PEP, monitoring of hematologic, hepatic, and renal parameters should be performed 2-3 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 (Figure 5). 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[21].

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 Case 1 in the section Initial Evaluation.

Prevention Counseling

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.

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  • The following link will open in a new window.
    Figure 1. Estimated Per-Act Risk for Acquisition of HIV, by Exposure Route#

    #These estimates of risk of transmission from sexual exposure assume no condom use.
    The risk for blood transfusion is approximately 9,000 per 10,000 exposures to blood contaminated with HIV.
    *Refers to oral intercourse performed on a man.
    This figure reproduced and modified from Smith DK, Grohskopf LA, Black RJ, et al. Antiretroviral postexposure prophylaxis after sexual, injection-drug use, or other nonoccupational exposure to HIV in the United States: recommendations from the U.S. Department of Health and Human Services. MMWR 2005;54(No. RR-2):1-20.


    Figure 1
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    Figure 2. DHHS Recommendations for Antiretroviral Postexposure Prophylaxis for Nonoccupational Exposure to HIV

    *Substantial risk for HIV exposure is defined in these guidelines as exposure 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.
    +Negligible risk is defined in these guidelines as exposure OF vagina, rectum, eye, mouth, or other mucous membrane, nonintact skin, intact skin, or percutaneous contact WITH urine, nasal secretions, saliva, sweat, or tears (if not visibly contaminated with blood), REGARDLESS of the known or suspected HIV status of the source.
    From: Smith DK, Grohskopf LA, Black RJ, et al. Antiretroviral postexposure prophylaxis after sexual, injection-drug use, or other nonoccupational exposure to HIV in the United States: recommendations from the U.S. Department of Health and Human Services. MMWR 2005;54(No. RR-2):1-20.


    Figure 2
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    Figure 3. DHHS Recommended Antiretroviral Regimens for Postexposure Prophylaxis for Nonoccupational Exposure to HIV

    *Do not use efavirenz for pregnant women or women with pregnancy potential (women with child bearing potential implies women who want to conceive or those who are not using effective contraception).
    †Low-dose (100-400 mg) Ritonavir

    From: Smith DK, Grohskopf LA, Black RJ, et al. Antiretroviral postexposure prophylaxis after sexual, injection-drug use, or other nonoccupational exposure to HIV in the United States: recommendations from the U.S. Department of Health and Human Services. MMWR 2005;54(No. RR-2):1-20.


    Figure 3
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    Figure 4. Change in High Risk Sexual Activity and STD Rates 12 Months after Receipt of Antiretroviral Medications for Potential Sexual Exposure to HIV

    High risk sexual acts were defined as contact with a high-risk partner that consisted of either unprotected receptive or insertive anal or vaginal intercourse, or oral intercourse with receipt of ejaculate.

    Data from: Martin JN, Roland ME, Neilands TB, et al. Use of postexposure prophylaxis against HIV infection following sexual exposure does not lead to increases in high-risk behavior. AIDS. 2004;18:787-92.


    Figure 4
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    Figure 5. Recommended Laboratory Evaluation following Potential Sexual Exposure to HIV

    High risk sexual acts were defined as contact with a high-risk partner that consisted of either unprotected receptive or insertive anal or vaginal intercourse, or oral intercourse with receipt of ejaculate.

    Data from: Martin JN, Roland ME, Neilands TB, et al. Use of postexposure prophylaxis against HIV infection following sexual exposure does not lead to increases in high-risk behavior. AIDS. 2004;18:787-92.


    Figure 5