Updated U.S. Public Health Service Guidelines for the Management of Occupational Exposures to HVB, HCV and HIV and Recommendations for Postexposure Prophylaxis [MMWR 2001; 50: RR-11]: The long awaited updated guidelines for occupational exposures to bloodborne pathogens has arrived in the June 29, 2001 issue of MMWR. Highlights are summarized below:

The relative risks of transmission of the three major bloodborne viruses with a sharps injury from an infected source are summarized below:

Post-exposure prophylaxis for HBV: The most significant change is the recommendation that health care workers who have the 3 dose HBV vaccine series should be tested at 1-2 months after the 3rd dose for anti-HBs levels; if < 10 mIU/ml they should ungergo a second 3 dose series. With regard to managing exposures, risk assumes a source with positive serology for HBsAg. The most efficient source of transmission is blood due to the high HBV titers compared with other body fluids. Nevertheless, most HBV-infected healthcare workers do not have a history of percutaneous injury, and HBV can survive in dried blood at room temperature in the environment for up to one week. Thus, other mechanisms of transmission may apply in the healthcare setting. With regard to interventions, the use of HBIG or HBV vaccine is each 70-75% effective in preventing HBV transmission. Both HBV vaccine and HBIG appear relatively safe from side effects and can be used in pregnancy. The rate of anaphylaxis with HBV vaccine is estimated at 1/600,000 vaccine doses and is rare with HBIG, although has been reported. HBIG provides 75% protection when given up to one week following post-exposure prophylaxis for up to one week. The utility of HBIG when started over seven days after exposure is not known. HBV, when indicated, should be given within 24 hours and should be administered at a separate site when given simultaneously with HBIG. Details of the recommendations are summarized as follows:

HBV Postexposure Prophylaxis
Vaccination status: HCW	Features of Source
	HBsAg positive	Source unknown
Unvaccinated	HBIG* x vaccine series (3 doses)	HBV vaccine (3 doses)
Vaccinated
Responder	No Rx	No Rx
Non responder	HBIG x 1 + vaccine series or HBIG x 2	Rx as source positive if high risk
Antibody status unknown	Test for anti-HBs Anti-HBs >10 mIU/mL no Rx Anti-HBs <10 mIU/mL HBIG x 1 + booster	Test for anti-HBs Anti-HBs >10 mIU/mL - no Rx Anti-HBs <10 mIU/mL - booster vaccine dose and recheck titer in 1-2 mo
*HBIG=Hepatitis B Immune Globulin; dose is 0.06 mL/kg IM. Should be given as soon as possible and within 7 days. Responder defined by antibody to HBsAg of >10 mIU/mL. HBIG + the vaccine series is preferred for non-responders who did not complete the 3 dose series; HBIG x 2 doses is preferred if there were 2 vaccine series and no response.

HCV Postexposure Prophylaxis: The reported risk from an HCV-infected source is 1.8% with a range of 0-7% in various reports. The following recommendations are made:

• Anti-HCV testing of the source
• The exposed healthcare worker should have baseline anti-HCV and ALT tests; follow-up testing at 4-6 months should include anti-HCV and ALT. Testing for HCV RNA (to detect acute infection prior to seroconversion) may be performed at 4-6 weeks.
  
• All positive results for anti-HCV should be confirmed as with the RIBA
• Post-exposure IG is not recommended because this has not proven effective in primate studies, no protective antibody response has been identified after HCV infection, and the ACIP has concluded that IG for HCP postexposure prophylaxis is not indicated.
• Antiviral agents (interferon with or without ribavirin) are not recommended because no trials have been done to show effectiveness, available data suggests that infection must be established before interferon can be effective, and the drugs are not FDA-approved for this indication (and they have extensive side effects).

HIV Postexposure Prophylaxis: The new recommendations represent a rather radical departure from prior recommendations and are summarized as follows:

• PEP should be started as soon as possible; if the delay exceeds 36 hours, expert consultation is called for.
• Prophylaxis should be continued for four weeks if tolerated.
• The exposed person should be reevaluated within 72 hours as additional information about the source is obtained -- serologic status, viral load, current treatment, any resistance test results, or information other factors that would modify recommendations.
• EIA should be used to monitor for seroconversion, and this test should be performed for at least six months post-exposure. Viral load tests are not recommended in the health care worker unless there is an illness compatible with the acute retroviral syndrome.
• If PEP is given, the healthcare worker should be monitored for drug toxicity at baseline and at two weeks with a CBC, renal function tests, and hepatic function tests. For those receiving IDV, the tests should include urinalysis.
• Healthcare workers are "asked to commit to behavioral measures, e.g. sexual abstinence or condom use... for several weeks to two months." The greatest risk is during the first 6-12 weeks post-exposure.
• Female healthcare workers with known or possible pregnancy should be treated as anyone else, except for the selection of drugs, which should involve a discussion with her provider on benefit and risks. Efavirenz and the combination of d4T and ddI should be avoided.

Specific recommendations for post-exposure prophylaxis are provided in the following two tables, one for percutaneous injuries and the second for exposures to mucous membranes or non-intact skin:

Drug selection: There is now an expanded menu with multiple options for two drug and three drug combinations. Two drug combinations include three dual nucleoside combinations. The three drug regimens for higher risk exposures include two nucleosides plus abacavir, a PI or an NNRTI other than nevirapine. In fact, the only FDA-approved antiretroviral agents that are not listed are ddC (which is not mentioned) and nevirapine which is contraindicated. The specific recommendations are provided below:

Recommended Regimens*
2 drug combinations:

• AZT + 3TC
• 3TC + d4T
• d4T + ddI

3 drug combinations:

• 2 nucleosides (above list) + indinavir, nelfinavir, efavirenz, abacavir, ritonavir, Fortovase, amprenavir, delavirdine or lopinavir

* Decisions should be made based in part on information about the source including antiretroviral therapy, response to therapy including viral load and any data on HIV resistance testing. Decisions should not delay initiation of PEP and modifications can made.

Recommended resources for additional information by telephone or Internet:

Occupational Exposure Management Resources

• National Clinician's Post-exposure Prophylaxis Hotline (HRSA, AETC, CDC) (available at all times): 888-448-4911 or http://www.ucsf.edu/hivcntr
• Needlestick (UCLA): http://www.needlestick.mednet.ucla.edu
• Hepatitis Hotline: 888-443-7232 or http://www.cdc.gov/hepatitis
• CDC Reporting (Occupationally acquired HIV and PEP failures): 800-893-0485
• FDA: Unusual or severe toxicity of antiretrovirals: 800-332-1088 or http://www.fda.gov/medwatch
• HIV/AIDS Treatment Information: http://www.hivatis.org

Comment: With regard to HIV, the new guidelines include some profound changes from the prior recommendations. First, the complicated algorithms from the old guidelines proved cumbersome in application and, fortunately, have been replaced with simplified charts. Secondly, the choice of antiretroviral agents has been expanded substantially to include three pairs of nucleosides in the two drug regimen as well as the use of ABC, EFV, DLV or any PI. The only agents that are FDA-approved and not included are ddC, which is not mentioned, and nevirapine, which is contraindicated due to hepatotoxicity previously reported in healthcare workers. It is clear that the panel understood the complexities of drug selection which is the result of revolutionary changes in the field regarding drug selection, which is now tailored to individual circumstances based on tolerance and anticipated or proven resistance in the source strain. It is important for those selecting these regimens to be particularly aware of the hypersensitivity reactions associated with ABC and the mental status changes noted with efavirenz; both reactions are most likely to occur early in the course of therapy, which is the only time that healthcare workers will be exposed to the drugs. It is anticipated that some of the guidelines will prove frustrating to interpret due to ambiguity of the definitions. For example, a low risk patient is described as one with a viral load <1,500 c/ml, and a high risk patient is one with "a high viral load." Similarly, for surface exposures, the two categories are "small volume," described as a few drops, and "large volume," which is described as "a major blood splash." Thus, the majority of exposures will probably fall in a middle category that is not provided for or defined. Nevertheless, these decisions have always been based on subjective interpretation, and most will find the guidelines to be easier to follow, especially with expert assistance that is readily available through multiple sources, including the National Clinicians Postexposure Prophylaxis Hotline at 888-448-4911.
posted 7/6/2001

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