PHS Recommendations for the Management of Health-Care Worker Exposures to HIV: Part 2

October 1, 1998

Health-care organizations should make available to their workers a system that includes written protocols for prompt reporting, evaluation, counseling, treatment, and follow-up of occupational exposures that may place health-care workers at

Health-care organizations should make available to their workers a system that includes written protocols for prompt reporting, evaluation, counseling, treatment, and follow-up of occupational exposures that may place health-care workers at risk for acquiring any blood-borne infection, including human immunodeficiency virus (HIV). Employers also are required to establish exposure-control plans, including postexposure follow-up for their employees, and to comply with incident reporting requirements mandated by the Occupational Safety and Health Administration. Access to clinicians who can provide postexposure care should be available during all working hours, including nights and weekends.

Antiretroviral agents for postexposure prophylaxis should be available for timely administration (ie, either by providing access to postexposure prophylaxis drugs on site or creating links with other facilities or providers to make them available off-site). Persons responsible for providing postexposure counseling should be familiar with evaluation and treatment protocols and the facility’s procedures for obtaining drugs for postexposure prophylaxis.

Health-care workers should be educated to report occupational exposures immediately after they occur, particularly because postexposure prophylaxis is most likely to be effective if implemented as soon after the exposure as possible. Health-care workers who are at risk for occupational exposure to HIV should be taught the principles of postexposure management, including options for postexposure prophylaxis as part of job orientation and ongoing job training.

Exposure Report

If an occupational exposure occurs, the circumstances and postexposure management should be recorded in the health-care worker’s confidential medical record (usually on a form the facility designates for this purpose). Relevant information includes:

Date and time of exposure

Details of the procedure being performed, including where and how the exposure occurred, and if the exposure was related to a sharp device, the type of device and how and when in the course of handling the device the exposure occurred

Details of the exposure, including the type and amount of fluid or material and the severity of the exposure (eg, for a percutaneous exposure, depth of injury and whether fluid was injected; or for a skin or mucous-membrane exposure, the estimated volume of material and duration of contact and the condition of the skin [eg, chapped, abraded, or intact])

Details about the exposure source (ie, whether the source material contained HIV or other blood-borne path-ogen[s]), and if the source is an HIV-infected person, the stage of disease, history of antiretroviral therapy, and viral load, if known

Details about counseling, postexposure management, and follow-up.

Exposure Management

Treatment of an Exposure Site: Wounds and skin sites that have been in contact with blood or body fluids should be washed with soap and water; mucous membranes should be flushed with water. There is no evidence that the use of antiseptics for wound care or expressing fluid by squeezing the wound further reduces the risk for HIV transmission. The use of antiseptics is not, however, contraindicated. The application of caustic agents (eg, bleach) or the injection of antiseptics or disinfectants into the wound is not recommended.

Assessment of Infection Risk: After an occupational exposure, the source-person and the exposed health-care worker should be evaluated to determine the need for HIV postexposure prophylaxis. Follow-up for hepatitis B virus and hepatitis C virus infections also should be conducted in accordance with previously published Centers for Disease Control (CDC) recommendations.

Evaluation of Exposure: The exposure should be evaluated for potential to transmit HIV based on the type of body substance involved and the route and severity of the exposure. Exposures to blood, fluid containing visible blood, or other potentially infectious fluid (including semen; vaginal secretions; and cerebrospinal, synovial, pleural, peritoneal, pericardial, and amniotic fluids) or tissue through a percutaneous injury (ie, needle-stick or other penetrating sharps-related event) or through contact with a mucous membrane are situations that pose a risk for blood-borne transmission and require further evaluation (Figure 1).

In addition, any direct contact (ie, personal protective equipment either was not used or was ineffective in protecting skin or mucous membranes) with concentrated HIV in a research laboratory or production facility is considered an exposure that requires clinical evaluation to assess the need for postexposure prophylaxis.

For skin exposures, follow-up is indicated if it involves direct contact with a body fluid listed above and there is evidence of compromised skin integrity (eg, dermatitis, abrasion, or open wound). If the contact is prolonged or involves a large area of intact skin, however, postexposure follow-up may be considered on a case-by-case basis or if requested by the health-care worker.

For human bites, the clinical evaluation must consider possible exposure of both the bite recipient and the person who inflicted the bite. HIV transmission only rarely has been reported by this route. If a bite results in blood exposure to either person involved, postexposure follow-up, including consideration of postexposure prophylaxis, should be provided.

Evaluation and Testing of an Exposure Source: The person whose blood or body fluids are the source of an occupational exposure should be evaluated for HIV infection. Information available in the medical record at the time of exposure (eg, laboratory test results, admitting diagnosis, or past medical history) or from the source person may suggest or rule out possible HIV infection.

Examples of information to consider when evaluating an exposure source for possible HIV infection include laboratory documentation (eg, prior HIV testing results or results of immunologic testing [eg, CD4+ count]), clinical symptoms (eg, acute syndrome suggestive of primary HIV infection or undiagnosed immunodeficiency disease), and history of possible HIV exposures (eg, injecting-drug use, sexual contact with a known HIV-positive partner, unprotected sexual contact with multiple partners [heterosexual and/or homosexual], or receipt of blood or blood products before 1985).

If the source is known to have HIV infection, available information about this person’s stage of infection (ie, asymptomatic or AIDS), CD4+ T-cell count, results of viral load testing, and current and previous antiretroviral therapy, should be gathered for consideration in choosing an appropriate postexposure prophylaxis regimen.

If this information is not immediately available, initiation of postexposure prophylaxis, if indicated, should not be delayed; changes in the postexposure prophylaxis regimen can be made after postexposure prophylaxis has been started, as appropriate.

If the HIV serologic status of the source person is unknown, the source person should be informed of the incident and, if consent is obtained, tested for serologic evidence of HIV infection. If consent cannot be obtained (eg, patient is unconscious), procedures should be followed for testing source persons according to applicable state and local laws. Confidentiality of the source person should be maintained at all times.

Human immunodeficiency virus-antibody testing of an exposure source should be performed as soon as possible. Hospitals, clinics, and other sites that manage exposed health-care workers should consult their laboratories regarding the most appropriate test to use to expedite these results. An FDA-approved rapid HIV-antibody test kit should be considered for use in this situation, particularly if testing by enzyme immunoassay cannot be completed within 24 to 48 hours.

Repeatedly reactive results by enzyme immunoassay or rapid HIV-antibody tests are considered highly suggestive of infection, whereas a negative result is an excellent indicator of the absence of HIV antibody. Confirmation of a reactive result by Western blot or immunofluorescent antibody is not necessary for making initial decisions about postexposure management but should be done to complete the testing process.

If the source is HIV seronegative and has no clinical evidence of acquired immunodeficiency syndrome (AIDS) or symptoms of HIV infection, no further testing of the source is indicated. It is unclear whether follow-up testing of a source who is HIV negative at the time of exposure, but recently (ie, within the last 3 to 6 months) engaged in behaviors that pose a risk for HIV transmission, is useful in postexposure management of health-care workers; health-care workers who become infected generally seroconvert before repeat testing of a source would normally be performed.

If the exposure source is unknown, information about where and under what circumstances the exposure occurred should be assessed epidemiologically for risk for transmission of HIV. Certain situations, as well as the type of exposure, may suggest an increased or decreased risk; an important consideration is the prevalence of HIV in the population group (ie, institution or community) from which the contaminated source material is derived.

For example, an exposure that occurs in a geographic area where injecting-drug use is prevalent or in an AIDS unit in a health-care facility would be considered epidemiologically to have a higher risk for transmission than one that occurs in a nursing home for the elderly where no known HIV-infected residents are present. Exposure to a blood-filled hollow needle or visibly bloody device also suggests a higher-risk exposure than exposure to a needle that was most likely used for giving an injection. Decisions regarding appropriate management should be individualized based on the risk assessment. HIV testing of needles or other sharp instruments associated with an exposure, regardless of whether the source is known or unknown, is not recommended. The reliability and interpretation of findings in such circumstances are unknown.

Clinical Evaluation and Baseline Testing of Exposed Health-care Workers: Exposed health-care workers should be evaluated for susceptibility to blood-borne pathogen infections. Baseline testing (ie, testing to establish serologic status at the time of exposure) for HIV antibody should be performed. If the source person is seronegative for HIV, baseline testing or further follow-up of the health-care worker normally is not necessary. If the source person has recently engaged in behaviors that are associated with a risk for HIV transmission, baseline and follow-up HIV-antibody testing (eg, 3 and/or 6 months postexposure) of the health-care worker should be considered. Serologic testing should be made available to all workers who are concerned that they may have been exposed to HIV.

For purposes of considering HIV postexposure prophylaxis, the evaluation also should include information about medications the health-care worker may be taking and any current or underlying medical conditions or circumstances (ie, pregnancy, breast feeding, or renal, or hepatic disease) that may influence drug selection. Pregnancy testing should be offered to all nonpregnant women of childbearing age.

HIV Postexposure Prophylaxis

The following recommendations apply to situations in which a health-care worker has had an exposure to a source person with HIV or in which information suggests that there is a likelihood that the source person is HIV-infected. These recommendations are based on the risk for HIV infection after different types of exposure and limited data regarding efficacy and toxicity of postexposure prophylaxis.

Because most occupational HIV exposures do not result in the transmission of HIV, potential toxicity must be carefully considered when prescribing postexposure prophylaxis. When possible, these recommendations should be implemented in consultation with persons having expertise in antiretroviral therapy and HIV transmission.

Explaining Postexposure Prophylaxis to Health-care Workers: Recommendations for chemoprophylaxis should be explained to health-care workers who have sustained occupational HIV exposures (Figure 1). For exposures for which postexposure prophylaxis is considered appropriate, workers should be informed that:

Knowledge about the efficacy and toxicity of drugs used for postexposure prophylaxis is limited.

Only zidovudine has been shown to prevent HIV transmission in human.

There are no data to address whether adding other antiretroviral drugs provides any additional benefit for postexposure prophylaxis, but experts recommend combination drug regimens because of increased potency and concerns about drug-resistant virus.

Data regarding toxicity of antiretroviral drugs in persons without HIV infection or in pregnant women are limited for zidovudine and not known regarding other antiretroviral drugs

Any or all drugs for postexposure prophylaxis may be declined by the health-care worker.

Health-care workers who have HIV occupational exposures for which postexposure prophylaxis is not recommended should be informed that the potential side effects and toxicity of taking postexposure prophylaxis outweigh the negligible risk of transmission posed by the type of exposure.

Factors in Selection of a Postexposure Prophylaxis Regimen: Selection of the postexposure prophylaxis regimen should consider the comparative risk represented by the exposure and information about the exposure source, including history of and response to antiretroviral therapy based on clinical response, CD4+ T-lymphocyte counts, viral load measurements, and current disease stage. Most HIV exposures will warrant only a two-drug regimen, using two nucleoside analogue reverse transcriptase inhibitors, usually zidovudine (Retrovir) and lamivudine (Epivir). The addition of a third drug, usually a protease inhibitor (ie, indinavir [Crixivan] or nelfinavir [Viracept]), should be considered for exposures that pose an increased risk for transmission or where resistance to the other drugs used for postexposure prophylaxis is known or suspected.

Timing of Postexposure Prophylaxis Initiation: Postexposure prophylaxis should be initiated as soon as possible. The interval within which postexposure prophylaxis should be started for optimal efficacy is not known. Animal studies have demonstrated the importance of starting postexposure prophylaxis within hours after an exposure.

To assure timely access to postexposure prophylaxis, an occupational exposure should be regarded as an urgent medical concern and prophylaxis started as soon as possible after the exposure (ie, within a few hours rather than days). If there is a question about which antiretrovirals to use, or whether to use two or three drugs, it is probably better to start zidovudine and lamivudine immediately than to delay postexposure prophylaxis administration.

Although animal studies suggest that postexposure prophylaxis probably is not effective when started later than 24 to 36 hours postexposure, the interval after which there is no benefit from postexposure prophylaxis for humans is undefined. If appropriate for the exposure, postexposure prophylaxis should, therefore, be started, even when the interval since exposure exceeds 36 hours. Initiating therapy after a longer interval (eg, 1 to 2 weeks) may be considered for exposures that represent an increased risk for transmission; even if infection is not prevented, early treatment of acute HIV infection may be beneficial.

The optimal duration of postexposure prophylaxis is unknown. Because 4 weeks of zidovudine appeared protective in health-care workers, postexposure prophylaxis probably should be administered for 4 weeks, if tolerated.

Postexposure Prophylaxis if Serologic Status of Source Person is Unknown: If the source person’s HIV serologic status is unknown at the time of exposure (including when the source is HIV negative but may have had a recent HIV exposure), use of postexposure prophylaxis should be decided on a case-by-case basis, after considering the type of exposure and the clinical and/or epidemiologic likelihood of HIV infection in the source (Figure 1). If these considerations suggest a possibility for HIV transmission and HIV testing of the source is pending, it is reasonable to initiate a two-drug postexposure prophylaxis regimen until laboratory results have been obtained and later modify or discontinue the regimen accordingly.

Postexposure Prophylaxis if Exposure Source is Unknown: If the exposure source is unknown, use of postexposure prophylaxis should be decided on a case-by-case basis. Consideration should include the severity of the exposure and the epidemiologic likelihood that the health-care worker was exposed to HIV.

Postexposure Prophylaxis for Pregnant Health-Care Workers: If the health-care worker is pregnant, the evaluation of risk and need for postexposure prophylaxis should be approached as with any other health-care worker who has had an HIV exposure. The decision to use any antiretroviral drug during pregnancy should, however, involve discussion between the woman and her health-care provider regarding the potential benefits and potential risks to her and her fetus.

Follow-up of Health-care Workers Exposed to HIV

Postexposure Testing: Health-care workers with occupational exposure to HIV should receive follow-up counseling, postexposure testing, and medical evaluation regardless of whether they receive postexposure prophylaxis HIV-antibody testing should be performed for at least 6 months postexposure (eg, at 6 weeks, 12 weeks, and 6 months). It is unclear whether an extended follow-up period (eg, 12 months) is indicated in certain circumstances.

Although rare instances of delayed HIV seroconversion have been reported, the infrequency of this occurrence does not warrant adding to health-care workers’ anxiety by routinely extending the duration of postexposure follow-up. Circumstances for which extending the duration of follow-up have been suggested include the use of highly potent antiretroviral regimens (ie, more than two drugs) because of theoretical concerns that HIV seroconversion could be delayed, or simultaneous exposure to HIV.

Data are insufficient for making a general recommendation in these situations. This should not preclude a decision to extend follow-up in an individual situation based on the clinical judgment of the health-care worker’s health-care provider, however. HIV testing should be performed on any health-care worker who has an illness that is compatible with an acute retroviral syndrome, regardless of the interval since exposure. HIV-antibody testing with enzyme immunoassay should be used to monitor for seroconversion.

The routine use of direct virus assays (eg, HIV p24 antigen enzyme immunoassay or polymerase chain reaction for HIV RNA) to detect infection in exposed health-care workers generally is not recommended. Although direct virus assays may detect HIV infection a few days earlier than enzyme immunoassay, the infrequency of health-care worker seroconversion and increased costs of these tests do not warrant their routine use in this setting. Also, HIV RNA is approved for use in established HIV infection; its reliability in detecting very early infection has not been determined.

Monitoring and Management of Postexposure Prophylaxis Toxicity

If postexposure prophylaxis is used, drug-toxicity monitoring should be performed at baseline and again 2 weeks after starting postexposure prophylaxis. Clinical judgment, based on medical conditions that may exist in the health-care worker and any toxicity associated with drugs included in the postexposure prophylaxis regimen, should determine the scope of testing. Minimally these tests should include a complete blood count and renal and hepatic chemical function studies.

Monitoring for evidence of hyper-glycemia should be included for health-care workers whose regimen includes any protease inhibitors; if the health-care worker is receiving indinavir, monitoring for crystalluria, hematuria, hemolytic anemia, and hepatitis also should be included. If toxicity is noted, modification of the regimen should be considered after expert consultation; further diagnostic studies may be indicated.

Health-care workers who fail to complete the recommended regimen often do so because of the side effects they experience (eg, nausea and diarrhea). These symptoms often can be managed without changing the regimen by prescribing antimotility and antiemetic agents or other medications that target the specific symptoms. In other situations, modifying the dose interval (ie, administering a lower dose of drug more frequently throughout the day, as recommended by the manufacturer) may help promote adherence to the regimen.

Counseling and Education

Although HIV infection following an occupational exposure occurs infrequently, the emotional impact of the exposure often is substantial. In addition, health-care workers are given seemingly conflicting information. Although health-care workers are told that there is a low risk for HIV transmission, a 4-week regimen of postexposure prophylaxis is recommended and they are asked to commit to behavioral measures (ie, sexual abstinence or condom use) to prevent secondary transmission, all of which influence their lives for several weeks to months. Access to persons who are knowledgeable about occupational HIV transmission and who can deal with the many concerns an HIV exposure may raise for the health-care worker is, therefore, an important element of postexposure management.

Health-care workers who are exposed to HIV should be advised to use the following measures to prevent secondary transmission during the follow-up period, especially during the first 6 to 12 weeks after the exposure when most HIV-infected persons are expected to seroconvert: (1) use sexual abstinence or condoms to prevent sexual transmission and to avoid pregnancy; and (2) refrain from donating blood, plasma, organs, tissue, or semen.

If the exposed health-care worker is breast-feeding, she should be counseled about the risk for HIV transmission through breast milk, and discontinuation of breast feeding should be considered, especially following high-risk exposures. If the health-care worker chooses to receive postexposure prophylaxis, temporary discontinuation of breast-feeding while she is taking postexposure prophylaxis should be considered to avoid exposing the infant to these agents. Nucleoside analog reverse transcriptase inhibitors are known to pass into breast milk; it is not known whether this also is true for protease inhibitors.

There is no need to modify a health-care worker’s patient-care responsibilities to prevent transmission to patients based solely on an HIV exposure. If HIV seroconversion is detected, the health-care worker should be evaluated according to published recommendations for HIV-infected health-care workers.

Exposed health-care workers should be advised to seek medical evaluation for any acute illness that occurs during the follow-up period. Such an illness, particularly if characterized by fever, rash, myalgia, fatigue, malaise, or lymphadenopathy, may be indicative of acute HIV infection but also may be due to a drug reaction or another medical condition.

Exposed health-care workers who choose to take postexposure prophylaxis should be advised of the importance of completing the prescribed regimen. Information should be provided about potential drug interactions and the drugs that should not be taken with postexposure prophylaxis, the side effects of the drugs that have been prescribed [see oncology 12(9):1342-1343, 1998] measures to minimize these effects, and the methods of clinical monitoring for toxicity during the follow-up period. They should be advised that the evaluation of certain symptoms should not be delayed (eg, back or abdominal pain, pain on urination or blood in the urine, or symptoms of hyperglycemia [ie, increased thirst and/or frequent urination]).

Recommendations for Selecting Drugs for Postexposure Prophylaxis

The selection of a drug regimen for HIV postexposure prophylaxis must strive to balance the risk for infection against the potential toxicity of the agent(s) used. Because postexposure prophylaxis is potentially toxic, its use is not justified for exposures that pose a negligible risk for transmission (Figure 1). Also, there is insufficient evidence to recommend a highly active regimen for all HIV exposures. Two regimens for postexposure prophylaxis are, therefore, provided (Table 1): (1) a "basic" two-drug regimen that should be appropriate for most HIV exposures; and (2) an "expanded" three-drug regimen that should be used for exposures that pose an increased risk for transmission (Figure 1) or where resistance to one or more antiretroviral agents is known or suspected.

When possible, the regimens should be implemented in consultation with persons having expertise in antiretroviral treatment and HIV transmission.

Situations That Require Special Consideration

Resistance of the Source Virus to Antiretroviral Drugs: It is unknown whether drug resistance influences transmission risk; transmission of drug-resistant HIV has been reported and is therefore a theoretical concern when choosing postexposure prophylaxis regimens, however. If the source-person’s virus is known or suspected to be resistant to one or more of the drugs included in the postexposure prophylaxis regimen, the selection of drugs to which the source person’s virus is unlikely to be resistant is recommended.

If the resistance is to one class of antiretroviral drugs, the addition to the basic postexposure prophylaxis regimen of a drug from another class might be considered (eg, addition of a protease inhibitor when a source patient has not been treated with a protease inhibitor but has virus resistance to one or more nucleoside analog reverse transcriptase inhibitors). It is strongly recommended that prophylaxis be started regardless of the resistance status of the source virus; if resistance is known or suspected, a third or fourth drug may be added to the regimen until consultation with an expert in the treatment of HIV infection or disease can be obtained.

Known or Suspected Pregnancy in the Health-Care Worker: Pregnancy should not preclude the use of optimal postexposure prophylaxis regimens, and postexposure prophylaxis should not be denied to a health-care worker solely on the basis of pregnancy. As discussed previously, an occupationally exposed pregnant health-care worker must, however, be provided with full information about what is known and not known regarding the potential benefits and risks associated with use of the antiretroviral drugs to her and her fetus in order to make an informed decision regarding the use of postexposure prophylaxis.

The choice of antiretroviral drugs to use for postexposure prophylaxis in pregnant health-care workers is complicated by the potential need to alter dosing because of physiologic changes associated with pregnancy and the potential for short- or long-term effects on the fetus and newborn. Thus, considerations that should be discussed with a pregnant health-care worker include:

The potential risk for HIV transmission based on the type of exposure;

The stage of pregnancy (the first trimester being the period of maximal organogenesis and risk for terato-genesis); and

What is known about the pharmacokinetics, safety, and tolerability of the drug or combination of drugs during pregnancy.

Postexposure Registries

Health-care providers in the US are encouraged to enroll health-care workers who receive postexposure prophylaxis in a confidential registry developed by ODO, Glaxo Wellcome and Merck & Co., to assess toxicity; telephone (888) 737-4448 ([888] PEP-4HIV), or write the HIV postexposure prophylaxis Registry, 1410 Commonwealth Drive, Suite 215, Wilmington, NC 28405. Unusual or serious and unexpected toxicity from antiretroviral drugs should be reported to the manufacturer and/or FDA, telephone (800) 332-1088.

Health-care providers also should report instances of prenatal exposure to antiretroviral agents to the Antiretroviral Pregnancy Registry. The registry is an epidemiologic project to collect observational, nonexperimental data on antiretroviral drug exposure during pregnancy to assess potential teratogenicity. Referrals should be directed to the Antiretroviral Pregnancy Registry, 1410 Commonwealth Drive, Suite 215, Wilmington, NC 28405; telephone (800) 258-4263 or (800) 722-9292, ext. 39437; fax (800) 800-1052.

A protocol has been developed to evaluate HIV seroconversion in a health-care worker who received postexposure prophylaxis These events can be reported to the CDC, telephone (404) 639-6425.

Resources for Consultation

Clinicians who seek consultation on HIV postexposure prophylaxis for assistance in managing an occupational exposure should access local experts in HIV treatment as much as possible. In addition, the "National Clinicians’ Postexposure Prophylaxis Hotline (PEP-Line)" has been created to assist clinicians with these issues; telephone (888) 448-4911. Other resources and registries include the HIV Postexposure Prophylaxis Registry, the Antiretroviral Pregnancy Registry, FDA, and CDC (Table 2).

Administrative Considerations

Effective implementation of the elements of postexposure management detailed in these recommendations may require various types of expertise. The assessment of the severity of an exposure generally requires clinical train-

ing and experience (ie, medical or nursing). However, the assessment, of HIV infection risk and initiation of a basic postexposure prophylaxis regimen necessitates knowledge or experience in clinical epidemiology, infection control, occupational health, or the clinical treatment of patients with HIV.

Decisions about HIV postexposure prophylaxis are particularly complex if protease inhibitors are used or there is concern about drug-resistant virus. Thus, expert consultation when prescribing postexposure prophylaxis is strongly encouraged. Postexposure prophylaxis protocols should list the names of readily available resources for consultation and could include policies that require infectious disease evaluation before prescribing an expanded antiretroviral regimen. These efforts should not, however, delay initial implementation of postexposure prophylaxis where it is appropriate.