Initial Management of an Exposure
Initial management of a potential exposure to HIV should include immediate decontamination of the region involved in the exposure (washing with soap and water for percutaneous injuries or using saline irrigation for splashes to the eye), followed by immediate evaluation for possible antiretroviral PEP.[,] Subsequent steps should include reporting the incident to the appropriate health care facility supervisor, performing baseline testing on the exposed health care worker for the blood-borne pathogen(s) in question, and, if PEP is initiated, baseline chemistry and hematology testing; these steps, however, should not interfere with timely wound site decontamination and administration of the first dose of the antiretroviral PEP medications. Because many antiretroviral agents, especially the protease inhibitors, have potential interactions with other medications, it is important to obtain information regarding any current medications the health care worker is taking. In addition, it is important to determine if the health care worker has a history of renal disease, since tenofovir, which is routinely used as part of the PEP regimen, can potentially cause nephrotoxicity. The initial assessment of the exposure should also include evaluation for the potential risk of transmission of other blood-borne pathogens, such as hepatitis B virus or hepatitis C virus. The following discussion, however, will only address the evaluation and management of occupational exposure to HIV.
Selection of Postexposure Prophylaxis Antiretroviral Therapy
The prior 2005 U.S. Public Health Service guidelines for the management of occupational exposures to HIV classified PEP regimens as either "basic" two-drug regimens or "expanded" three-drug regimens and the regimens. In contrast, the 2013 guidelines for the management of occupational exposures to HIV, recommends that all postexposure prophylaxis antiretroviral regimens should consist of at least 3 drugs, thereby eliminating the prior stratification of basic and expanded regimens. The 2013 guidelines classify the recommended regimens as either preferred or alternative (Figure 1). In addition the 2013 guidelines provide recommendations regarding use of medications that require expert consultation, medications generally not recommended, and those that should not be given (Figure 2). All recommended regimens consist of a dual nucleoside reverse transcriptase inhibitor (NRTI) backbone combined with an anchor drug(s) from one of the following classes: integrase inhibitor, protease inhibitor boosted with ritonavir (Norvir), or a non-nucleoside reverse transcriptase inhibitor. The regimen of tenofovir-emtricitabine plus raltegravir (Isentress) was selected as the preferred regimen because of its potency, convenient dosing schedule, and favorable side effect profile. In addition, tenofovir has been shown to be effective in preventing SIV in monkeys when administered after they were exposed to SIV.[,]
Timing and Duration of PEP
The question of how long after the exposure will PEP provide benefit remains unknown with certainty. Animal models of PEP have suggested efficacy of PEP wanes with time following the exposure. Specifically, these data suggest that PEP is substantially less effective if initiated more than 24 to 36 hours after the exposure and may be ineffective if administered after 72 hours.[,,,] Similar studies involving human subjects have not been performed for obvious ethical reasons. A review of cases in which PEP failed to prevent HIV transmission in health care personnel did not establish a cut-off time, since most of these individuals received PEP within a few hours of their exposure. Similarly, a retrospective case-control study published in 1997 that demonstrated the efficacy of zidovudine (Retrovir) PEP in reducing the risk of seroconversion did not identify a cut-off time for PEP efficacy. An interesting case report published in 2000 suggested that PEP may have some efficacy in humans even if administered beyond 48 hours. Taking all available data into consideration, the U.S. Public Health Service Guidelines recommend prompt initiation of PEP, preferably within 2 hours, but the guidelines do not rule out consideration of PEP even if more than 72 hours have elapsed since the exposure. If greater than 72 hours have elapsed after the exposure, expert consultation is recommended. In addition, the guidelines state that if PEP is delayed for more than 72 hours, the likelihood of benefit may not outweigh the inherent risk of antiretroviral therapy, but using PEP could be considered if the exposure represented an extremely high risk of transmission. For exposures involving a known HIV-infected source patient, the exposed health care worker should take a 28-day course of PEP, regardless of which regimen is selected. Animal studies suggest better efficacy with 28 days of PEP when compared with shorter duration of therapy, particularly when the regimen is started within 24 hours (Figure 3). The recommended duration of PEP for a mucocutaneous exposure is also 28 days.
During the initial evaluation of the exposure, it is important to determine whether initial management decisions should involve expert consultation; the 2013 U.S. Public Health Service guidelines outline specific circumstances for which expert consultation is advised:
- Delayed exposure report (eg. longer than 72 hours)
- Unknown source (eg. needle in sharps disposal)
- Known or suspected pregnancy in exposed person
- Exposed person breast-feeding
- Known or suspected ARV drug resistance in source patient
- Serious medical illness in exposed persons
- Toxicity occurring in exposed person taking PEP regimen Timing of PEP
Exposure Involving a Patient with Drug-Resistant HIV
For any health care worker who suffers an occupational exposure that involves a patient with highly-resistant HIV, expert consultation is strongly recommended. Prompt expert consultation is particularly important given the availability of multiple medications that have activity against many highly drug-resistant strains of HIV, particuarly dolutegravir (Tivicay), darunavir (Prezista) boosted with ritonavir, etravirine (Intelence), and enfuvirtide (Fuzeon). Appropriate use of a combination of medications in the setting of drug-resistant HIV should ideally be guided by recent resistance tests from the HIV-infected source patient. Obtaining resistance testing on the HIV-infected patient at the time of the exposure would not provide useful information in this setting, since it would take a minimum of several weeks to obtain the result from a genotype or phenotype test.
Adverse Effects and Antiretroviral PEP Medications
The management of PEP medication adverse effects may play an important role in helping the health care provider complete the full 28-day course of PEP therapy. Several studies that primarily involved use of older antiretroviral medications have documented high rates of medication-related adverse effects among health care workers taking PEP.[,] The current recommended regimen of tenofovir-emtricitabine plus raltegravir is usually well tolerated, but if any non-serious symptoms develop that may jeopardize completion of therapy, they should be promptly addressed and managed. Several medications are not recommended for use either because of potential severe toxicity or poor efficacy. Multiple cases of severe hepatotoxicity associated with use of nevirapine (Viramune) for PEP have been reported and this drug is contraindicated for use in PEP. Efavirenz (Sustiva) is much less likely to cause hepatotoxicity than nevirapine, but is infrequently used in this setting because of the neuropsychiatric side effects that often occur during the first weeks of therapy and the significant rates of efavirenz-resistant HIV. The use of abacavir (Ziagen), or any fixed-dose combination drug that contains abacavir (Epzicom, Trizivir), is not recommended because of its potential to cause a hypersensitivity reaction. The most side effects associated with protease inhibitor use consist of nausea and diarrhea. The protease inhibitor booster ritonavir can cause significant drug-drug interactions. Atazanavir (Reyataz) is generally well tolerated, though it commonly causes indirect hyperbilirubinemia, which occasionally results in overt jaundice or scleral icterus.
Follow-Up and Laboratory Testing of the Health Care Worker
Follow-up testing and evaluation of a health care worker following an exposure is recommended regardless of whether PEP is initiated (Figure 4). Baseline HIV antibody testing should be performed and at 6 weeks, 3 months, and 6 months after the initial exposure; if a 4th generation HIV combination antigen-antibody tests is used, then follow-up HIV testing can occur at weeks 6 and 16. Because of the potential for false-positive results, HIV RNA testing is not recommended as a means to screen for seroconversion, unless the health care worker develops clinical symptoms that suggest acute HIV infection. Rare cases of documented failure with the use of combination antiretroviral therapy for postexposure prophylaxis have been reported and thus health care workers should be educated regarding the signs and symptoms of acute HIV infection. If PEP is administered, laboratory testing (CBC, renal panel, and hepatic aminotransaminase levels) to monitor for toxicity should be performed at baseline, after two weeks of PEP, and as indicated for evaluation of signs and symptoms of potential medication toxicity.
Counseling the Health Care Worker
Counseling of the exposed health care worker is an important component of the exposure event. The psychological impact of an exposure can be significant, and professional counseling may be necessary with some individuals, regardless of the level of risk involved. In addition, counseling and management of PEP medication adverse effects plays a very important role in helping the health care provider complete the full 28-day course of PEP therapy. Measures to prevent secondary transmission of HIV should also be recommended during the follow-up period, particularly for the first 12 weeks following the exposure. These measures include barrier protection with sexual activity, and refraining from donating blood or other bodily fluids. Cessation of breast-feeding may be advisable for a woman who suffers a high-risk exposure and thus could transmit HIV to her infant. Health care providers are advised that they may continue working in their normal capacity during the follow-up period. Prompt evaluation of any acute illness that develops in the follow-up period should be encouraged, both to rule out possible acute HIV seroconversion and to assess the possibility of a serious adverse medication reaction. If a health care worker acquires HIV from an occupational exposure, expert consultation is indicated for counseling, consideration for immediate antiretroviral therapy, and to determine the advisability of continuing work in the same capacity.
Resources for Expert Consultation
Clinician Consultation Center: Postexposure/PEP Consultation
Phone: (888) 448-4911
Description: Expert consultation regarding occupational exposures to HIV, hepatitis B, or hepatitis C available to clinicians 9 am-2 am EST, 7 days/week