Occupational Postexposure Prophylaxis

Background

Health care personnel (HCP) and other individuals working in medical, public safety, sanitation, and laboratory settings are at risk of occupational exposure to HIV. Although avoiding exposure to HIV is the only reliable way of preventing HIV infection, postexposure prophylaxis (PEP), can reduce the risk of HIV infection in exposed HCP. PEP is defined as antiretroviral (ARV) therapy that is initiated soon after exposure to HIV with the intention of preventing HIV infection.

This chapter examines the general issues involved with PEP in occupational settings. The information is based on 2013 U.S. Public Health Service (USPHS) guidelines for occupational PEP (see "References," below). For information on PEP for nonoccupational HIV exposures (such as sexual exposure), see chapter Nonoccupational Postexposure Prophylaxis. Note that other bloodborne pathogens, particularly hepatitis B virus (HBV) and hepatitis C virus (HCV), also may be transmitted through occupational exposure; it is important to consider these potential infections when assessing occupational exposures. For information on the management of occupational exposures to HBV and HCV, refer to the 2001 USPHS PEP guidelines (see "References," below). In addition, the National Clinicians' Post-Exposure Prophylaxis Hotline (PEPline) is available for telephone consultation at 888-HIV-4911 (888-448-4911).

The risk of HIV infection after exposure depends on several factors that are related to the exposure itself and to the source patient (see below). To make sound PEP recommendations, the clinician must assess the risk of HIV infection from the particular exposure. After this, the clinician and the exposed worker must discuss the possible benefit of PEP (given the risk of HIV transmission from the injury) in relation to the willingness of the exposed worker to adhere to a 28-day course of ARV medicines, the potential toxicity of the regimen, and drug interactions. HCP who are pregnant at the time of their exposure must weigh the risk of fetal exposure to HIV against the potential teratogenic and other risks of the ARV drugs (it should be noted that pregnancy is not a contraindication to PEP, and that a number of ARVs are recommended for use during pregnancy, based on safety and efficacy data) (see chapter Reducing Maternal-Infant HIV Transmission).

The efficacy of PEP is related to the specific PEP regimen, the timing of PEP, and the exposed worker's level of adherence to the PEP regimen. PEP is most likely to be effective if it is started within hours of an exposure, and outcomes may be compromised as the time from exposure increases. Nevertheless, it may be reasonable to offer PEP up to 72 hours after exposure. Adherence to PEP is strongly affected by factors such as the tolerability of the ARVs, the number of pills in the regimen, and the frequency of dosing. As current guidelines emphasize, it is very important to select a PEP regimen that is expected to be tolerated and that is convenient to take; any side effects or adherence difficulties should be managed promptly. The guidelines recommend the use of 3 (or more) PEP drugs for all exposures. Although the optimal duration of PEP is not known; studies support ARV treatment for 28 days.

In the work setting, HIV infection may occur through percutaneous injuries (e.g., needlesticks) or mucocutaneous exposures (e.g., mucous membrane or nonintact skin exposure) to blood or other potentially infectious body fluids. The risk of HIV seroconversion after occupational exposure with an HIV-contaminated hollow-bore needle is best described as 0.3%, on average. Another way of describing this to an exposed HCP is that, without PEP, HIV transmission occurs about once in 300 instances of needlestick from a known HIV-infected source patient. In a retrospective case-control study of HCP with percutaneous exposure to HIV, the following exposure and source patient factors were associated with an increased risk of HIV transmission:

  • Large-gauge (<18-gauge) hollow-bore needle
  • Deep injury
  • Visible blood on the device
  • Procedure with needle in a blood vessel
  • Terminal AIDS in the source patient
  • High HIV viral load of the source patient

The factor described as "terminal AIDS in the source patient" is considered a surrogate for a source patient with a high HIV viral load (this study was done prior to the routine use of HIV viral load assays); high HIV viral load is known to be a substantial risk factor for HIV transmission. On the other hand, although an undetectable HIV viral load is thought to indicate a low risk of HIV transmission, transmission still is possible, and cases of perinatal and sexual transmission from sources with undetectable serum HIV RNA have been reported.

Compared with percutaneous injury, exposure of infectious body fluids to mucous membranes (e.g., eye or mouth) or to skin with an obvious impairment of integrity (e.g., abrasion or wound) typically involves a lower risk of HIV transmission (the transmission risk for mucous membrane exposure to HIV is approximately 1 in 1,000, and less than 1 in 1,000 for cutaneous exposure). However, mucocutaneous exposures that involve large volumes of blood or other infectious fluid from an HIV-infected patient with a high HIV RNA level or prolonged duration of contact are considered increased-risk exposures.

S: Subjective

An HCP reports possible exposure to HIV through a needlestick injury or mucocutaneous exposure.

Ideally, the HCP should immediately decontaminate the injured or exposed skin with soap and water, or flush the exposed mucous membranes with copious amounts of water or saline. The HCP should report the exposure immediately to appropriate authorities in the health care institution (e.g., the institution's needlestick hotline).

Take a thorough history of the specific exposure, including the type of exposure, the type and amount of body fluid involved, the point of entry or exposure, the time it occurred, the HIV status of the source patient (if known), and HIV risk factors of the source patient (if HIV status is not known).

A: Assessment

Assess potential exposure to HIV (and to HBV and HCV). Consider the HIV status of the source and the characteristics of the exposure in deciding whether PEP should be offered. The guidelines recommend the use of PEP following percutaneous or mucous membrane exposures to potentially infectious body fluids. They note that PEP should be offered even in the case of an exposure to a source patient with an undetectable HIV viral load. Consult with experts if there is uncertainty about whether a particular exposure poses sufficient risk to warrant PEP.

P: Plan

Laboratory Testing

For the exposed HCP

  • Perform a baseline HIV antibody test.
  • Test for other infections transmitted through occupational exposure, particularly hepatitis B (HBV surface antigen, surface antibody, core antibody), and hepatitis C (HCV antibody).
  • Obtain complete blood count (CBC), creatinine and estimated glomerular filtration rate (GFR), and hepatic transaminases at baseline, before treatment with ARV medications.
  • For women who may be pregnant, perform a pregnancy test.

For the source person

  • The institution should perform appropriate testing of the source person for bloodborne pathogens (e.g., HIV, HBV, and HCV) if the person's status is unknown.
  • The use of rapid or expedited HIV tests makes it possible to render quick decisions about the need for HIV PEP, and the 4th-generation Ag/Ab tests identify most cases of HIV during the window period of acute HIV infection (see chapter Expedited HIV Testing).
  • Although a positive expedited test result requires confirmation before the individual is diagnosed as HIV infected, for the purposes of PEP, it should be considered a true positive until proven otherwise, and the exposed worker should be counseled accordingly. If, upon further testing, the source patient is determined to be HIV uninfected, PEP should be discontinued. A negative expedited test result is considered reliable unless the source has signs or symptoms of acute HIV (see chapters Expedited HIV Testing and Early HIV Infection).
  • PEP should not be delayed (beyond 1-2 hours) while source patient HIV testing is under way.

Treatment

A regimen consisting of at least 3 ARV drugs is recommended for all occupational HIV exposures (the U.S. guidelines no longer recommend evaluation of the severity of exposure to determine the number of drugs in a PEP regimen). Recommendations for PEP regimens are based on expert opinion and largely follow the principles of HIV treatment regimens, but the PEP guidelines place particular emphasis on optimizing the tolerability and convenience of the regimen to facilitate adherence for 28 days.

Considerations in choosing the medications for a PEP regimen include:

  • Possible ARV adverse effects
  • Dosing schedule
  • Drug-drug interactions with other medications the HCP may be taking
  • The likelihood that the source patient's virus is resistant to 1 or more ARV medications

Provide counseling about the potential risks and benefits of PEP drugs, including possible adverse effects, drug-drug interactions, and the importance of close adherence. Recommended regimens are shown in Table 1; select one that is likely to be effective, tolerable, and convenient. Note that although these regimens are potent in treating HIV infection, their efficacy as prophylaxis has not been demonstrated. Consultation with experts is recommended (see "Expert Consultation," below).

These recommendations are drawn from the 2013 guidelines for occupational PEP; consult the most recently updated version of the guidelines for current information.

Table 1. Antiretroviral Regimens for Occupational Postexposure Prophylaxis of HIV Infection
Adapted from Updated U.S. Public Health Service Guidelines for the Management of Occupational Exposures to Human Immunodeficiency Virus and Recommendations for Postexposure Prophylaxis (2013). Accessed December 1, 2013.
Preferred Regimen
  • Raltegravir 400 mg BID + tenofovir 300 mg/emtricitabine 200 mg QD (Truvada)
Alternative Regimens

(combine 1 drug or drug pair from left column with 1 NRTI pair from right column)

  • Raltegravir 400 mg BID
  • Darunavir 800 mg QD + ritonavir 100 mg QD
  • Etravirine 200 mg BID
  • Rilpivirine 25 mg QD
  • Atazanavir 300 mg QD + ritonavir 100 mg QD
  • Lopinavir/ritonavir 400/100 mg BID

+

  • Tenofovir + emtricitabine (Truvada), 1 tablet QD
  • Tenofovir 300 mg QD + lamivudine 300 mg QD
  • Zidovudine + lamivudine (Combivir), 1 tablet BID
  • Zidovudine 300 mg BID + emtricitabine 200 mg QD
 

OR

 
  • Elvitegravir/cobicistat/tenofovir/emtricitabine (Stribild) (complete regimen; no additional NRTIs needed)

Refer to the appendix in the updated PEP guidelines for more complete information on the advantages, and disadvantages of the various ARV agents available for PEP, and to the adult and adolescent ARV treatment guidelines (reference below) for more information about ARV adverse effects and drug-drug interactions.

Certain ARVs generally are not recommended for PEP because of elevated risk of toxicities; these include nevirapine (which is contraindicated as PEP), abacavir (testing for HLA- B*5701 must be done), didanosine, enfuvirtide, and tipranavir. Efavirenz may have a higher rate of significant adverse effects than other listed agents. Additionally, efavirenz should not be used with women who are in the first trimester of pregnancy or who may become pregnant while on PEP, because of possible teratogenicity. Some "alternative" ARVs may be considered for use based on consultation with experts.

If the source person is known or suspected to have infection with HIV that is resistant to ARV medications, seek expert consultation in selecting an appropriate PEP regimen. However, PEP should not be delayed while consultation is being solicited, and it is possible to adjust regimens based on expert advice.

Begin ARV prophylaxis as soon as possible after the exposure occurs, preferably within a few hours and no later than 72 hours postexposure. Treatment should be continued for 28 days unless the source person is determined to be HIV uninfected.

Provide counseling about the efficacy of PEP, including timely initiation of PEP medications, the importance of adherence to the regimen for 28 days, and management of common adverse effects. Counsel exposed workers to avoid possible transmission of HIV, e.g., by using use latex barriers with their sex partners, avoiding breast feeding if possible, avoiding pregnancy, and avoiding blood/tissue donations, until transmission of HIV infection has been ruled out.

Follow-Up

Exposed workers should be reevaluated within 72 hours after exposure to review any available new information about the exposure and the source person as well as test results. For HCP taking PEP, early reevaluation offers the opportunity for further education and counseling, including assessment and support of PEP adherence and evaluation and management of any side effects. In addition to health education counseling, many exposed workers need emotional support during their follow-up visits.

For persons on PEP, monitoring for adherence and adverse effects should be conducted again at 2 weeks. Blood testing (e.g., CBC, creatinine and electrolytes, liver function tests, others as indicated) should be done to monitor for PEP toxicity, as indicated by the particular ARV regimen.

PEP is discontinued after 4 weeks, and monitoring for ARV toxicity generally should not be repeated unless there is a need to recheck an abnormal result.

Follow-up HIV antibody testing should be done at 6 weeks, 3 months, and 6 months after the exposure. If a 4th-generation HIV Ag/Ab assay is used, the final HIV test can be done at 4 months rather than 6 months. Follow-up for 12 months is recommended for HCP who acquired hepatitis C via exposure to a source who was coinfected with HIV and HCV.

Symptoms of acute HIV infection such as fever, rash, and lymphadenopathy (see chapter Early HIV Infection) may occur in HCP who are infected with HIV through occupational exposure. Exposed HCP should be counseled about the symptoms of acute HIV infection and instructed to return for reevaluation as soon as possible if symptoms develop. If symptoms consistent with acute HIV appear within 4-6 weeks after an occupational exposure, the HCP should be evaluated immediately; an HIV RNA test should be performed if acute HIV infection is suspected. If an HCP is found to be infected with HIV, that individual should be referred immediately to an HIV specialist for further evaluation and care.

Expert Consultation

Consultation with experts in PEP and in ARVs is recommended for assistance with managing all occupational exposures. This is particularly important if the source person is known or suspected to have ARV-resistant virus or if there are unusual or perplexing elements about the case (e.g., if the exposed HCP is pregnant or breast feeding, has significant medical illness, or takes medications that may interact with PEP ARVs). Consultation on the treatment of occupational exposures to HIV and other bloodborne pathogens is available to the clinician managing the exposed person on the National Clinicians' Post-Exposure Prophylaxis Hotline (PEPline) at 888-HIV-4911 (888-448-4911). This service is available 7 days a week, at no charge (additional information is available on the PEPline website at www.nccc.ucsf.edu).

Prophylaxis Against HBV and HCV

Prophylaxis against HBV is recommended for patients with potential exposure to HBV who do not have immunity against HBV. Give hepatitis B immune globulin (HBIG) as a 0.06 mL/kg IM injection and initiate the vaccination series. For patients who received the vaccination series but did not develop protective antibodies (HBV sAb+), give HBIG at the time of the postexposure workup and initiate revaccination; consider repeat of HBIG in 1 month. For patients with immunity to HBV, no treatment is indicated.

For HCV, no prophylactic treatments are recommended. After potential exposure, perform a baseline HCV antibody test. If the source is known to have HCV infection, consider alanine aminotransferase (ALT) and HCV viral load testing at 4-6 weeks. HCV antibody testing should be repeated at 4-6 months. If HCV seroconversion occurs (indicated by ALT elevation, detectable HCV viral load, or confirmed positive HCV antibody test result), refer the patient to a hepatitis C expert because early treatment of HCV may be indicated.

Addendum: Workplace Obligations

The health care institution has certain obligations to an exposed employee.* The institution should do the following:

  • Evaluate the circumstances of the exposure, the type of fluid, and possible entry points.
  • Evaluate the source patient.
  • Perform baseline HIV antibody testing of the exposed HCP.
  • Counsel the exposed HCP about the possible risks and benefits of PEP.
  • Offer or recommend PEP as soon as possible after the exposure, preferably within the first several hours.
  • Counsel the HCP about avoiding secondary transmission to others (safer sex and other risk-reduction practices, as indicated).
  • Support and maintain the confidentiality of the HCP.
  • For an HCP who is taking PEP, monitor for medication toxicity and adherence, and check for drug-drug interactions with other medications the HCP may be taking.
  • Repeat HIV testing at 6 weeks, 3 months, and 6 months (if a 4th-generation HIV Ag/Ab assay is used, the final HIV test can be performed at 4 months).
  • Report the exposure as required by federal and state regulations (including U.S. Occupational Safety and Health Administration requirements).

The PEP guidelines recommend that health care institutions have a formal mechanism for consultation about occupational HIV exposures, appropriate initial lab testing for source patients and exposed HCP, counseling for exposed HCP, availability of initial PEP regimens (e.g., starter packs), and a mechanism for outpatient follow-up. The protocols should be readily available to emergency department providers and others who manage exposure incidents.

* Legal issues vary from state to state. In many states, institutions and clinics have no obligation toward nonemployees or students who are exposed to HIV in their settings. In such situations, clinical supervisors or school or university officials often are the first contact for notification. However, everyone working in a health care setting should be familiar with the procedures and financial responsibilities for HIV exposure management to avoid delays in HIV PEP treatment.

Patient Education

  • Persons who have possible exposures to HIV in the work setting should contact the PEP service of their employer or a qualified medical provider as soon as possible after the exposure, or they should go to an emergency department. Although PEP may be effective if it is started within 72 hours of exposure, the sooner medications are initiated, the better the chance for preventing HIV transmission.
  • PEP medications should be taken as directed for the full 28-day course. Adherence to PEP medications is essential for successful treatment.
  • PEP recipients should be advised to contact their providers if they experience uncomfortable side effects. Providers may prescribe medications to alleviate the side effects, or they may prescribe different PEP medications.
  • Until HIV infection has been ruled out, exposed workers should be advised to use latex or polyurethane barriers to prevent transmission of HIV to their sex partners, to avoid pregnancy, and to avoid breast feeding if possible.
  • Exposed HCP should be counseled about the symptoms of primary HIV infection and instructed to contact their care providers immediately if symptoms develop.

References

  • Bassett IV, Freedberg KA, Walensky RP. Two drugs or three? Balancing efficacy, toxicity, and resistance in postexposure prophylaxis for occupational exposure to HIV. Clin Infect Dis. 2004 Aug 1;39(3):395-401.
  • Do AN, Ciesielski CA, Metler RP, et al. Occupationally acquired human immunodeficiency virus (HIV) infection: national case surveillance data during 20 years of the HIV epidemic in the United States. Infect Control Hosp Epidemiol. 2003 Feb;24(2):86-96.
  • Gerberding JL. Clinical practice. Occupational exposure to HIV in health care settings. N Engl J Med. 2003 Feb 27;348(9):826-33.
  • Kuhar DT, Henderson DK, Struble KA, et al.; U.S. Public Health Service Working Group. Updated U.S. Public Health Service Guidelines for the Management of Occupational Exposures to Human Immunodeficiency Virus and Recommendations for Postexposure Prophylaxis. Infect Control Hosp Epidemiol. 2013 Sep;34(9):875-92.
  • Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Department of Health and Human Services. Accessed December 1, 2013.
  • U.S. Department of Health and Human Services. Updated U.S. Public Health Service Guidelines for the Management of Occupational Exposures to HBV, HCV, and HIV and Recommendations for Postexposure Prophylaxis. MMWR Recomm Rep. 2001 Jun 29;50(RR11);1-42.
  • Wang SA, Panlilio AL, Doi PA, et al. Experience of healthcare workers taking postexposure prophylaxis after occupational HIV exposures: findings of the HIV Postexposure Prophylaxis Registry. Infect Control Hosp Epidemiol. 2000 Dec;21(12):780-5.
  • Zenner D, Tomkins S, Charlett A, et al. HIV prone occupational exposures: epidemiology and factors associated with initiation of post-exposure prophylaxis. J Epidemiol Community Health. 2009 May;63(5):373-8.