Agencies urge caution in use of PEP agents
Revised CDC guidelines to offer few changes
A revised bloodborne pathogen guideline from the Centers for Disease Control and Prevention (CDC) will clarify the recommendations on post-exposure prophylaxis (PEP). The main message: The risk of HIV transmission needs to be carefully weighed against the toxicity of PEP agents.
The guideline on management of occupational exposure to bloodborne pathogens, which is due for release this spring, will include an algorithm for PEP. (For an excerpt of the guidelines in PDF format, click here.) The original guideline was published in 1996 and updated in 1998. The CDC also will address the use of newer PEP agents.
"There’s no evidence that we need to change our guidelines," says Elise Beltrami, MD, medical epidemiologist at CDC’s division of healthcare quality promotion. "But we need to emphasize the fundamental of weighing the risk and benefit of what you’re doing."
Reports of severe toxicity with a PEP agent that has been occasionally used in triple-drug therapy placed added scrutiny on PEP recommendations. In January, the CDC and the Food and Drug Administration (FDA) issued a joint report on severe adverse events related to nevirapine.1 That followed brief reports in the Journal of the American Medical Association of two health care workers who suffered severe toxic effects to nevirapine during PEP, including a 43-year-old phlebotomist who developed acute hepatic failure, lapsed into a coma, and required a liver transplant.2
In its MedWatch reports, the FDA had 22 other cases of serious adverse events related to nevirapine taken for PEP from March 1997 through September 2000. The most common events involved hepatotoxicity and skin reaction; in four cases, patients experienced both.
"NVP is not recommended for basic or expanded PEP regimens," according to the Morbidity and Mortality Weekly Report (MMWR).
Nevirapine’s addition to some PEP regimens followed its success in other uses. It has been used safely and effectively as a single dose to prevent perinatal HIV transmission, and it has more rapid activity than other PEP agents. But the benefits of using nevirapine in HIV-infected patients and to prevent perinatal transmission are very different from its use in healthy, occupationally exposed individuals, experts say. In fact, one of the cases reported by CDC and FDA involved a 38-year-old physician who was splashed with a patient’s body fluid. "It wasn’t even clear there was blood in the body fluid," notes Beltrami. The physician suffered from severe hepatitis caused by the nevirapine.
In addition to presenting a danger to liver function, nevirapine can cause skin hypersensitivity reactions that actually resemble symptoms of seroconversion illness associated with acute HIV infection, notes David K. Henderson, MD, deputy director for clinical care at the Warren G. Magnuson Clinical Center of the National Institutes of Health in Bethesda, MD.
Those effects are even more troubling when the PEP wasn’t necessary to begin with. PEPline, a national advice hotline based at San Francisco General Hospital, advised callers in 58% of consultations to stop or not start PEP. (See Hospital Employee Health, January 2001.) "These reports of toxicity are of great concern," says David Bangsberg, MD, MPH, director of the Epidemiology and Prevention Interventions Center at the hospital and co-director of PEPline. "We believe that nevirapine should not be used as standard post-exposure prophylaxis, except under extraordinary circumstances and only in the context of expert consultation."
Henderson notes that the severe toxicity can occur even on a short course of nevirapine. "[The report] provides a reminder for everyone involved in this business that these are not benign drugs."
To make it easier for employee health professionals to reference information on PEP and management of occupational exposures, the revised CDC guidelines will adopt a more user-friendly format, says Beltrami.
The CDC also has combined its recommendations related to HIV, hepatitis B, and hepatitis C into one document. A review of the current literature on occupational exposures provided the background for the upcoming guideline and indicated no significant departure from current practice.3 The review includes the following information about managing hepatitis C exposures:
• No PEP is recommended for HCV exposure.
• Health care workers exposed to HCV should receive baseline testing and follow-up testing at four to six months for antibodies to HCV and alanine aminotransferase elevations. Tests for HCV RNA can be performed at four to six weeks if an earlier result is desired.
• A positive test for HCV antibodies should be confirmed with supplemental testing.
• There are no reported cases of HCV transmission from infected surgeons or dentists to patients in the United States. The CDC does not recommend restriction of health care workers with hepatitis C from performing invasive procedures.
[Adverse reactions to PEP agents should be reported to the FDA MedWatch program, HF-2, FDA, 5600 Fishers Lane, Rockville, MD 20857. Telephone: (800) 332-1088. Fax: (800) 332-0178. Web site: www.FDA.gov/medwatch. For expert consultation on the use of PEP, contact PEPline (24 hours a day) at (888) 448-4911 or the CDC’s occupational exposure information line (Monday-Friday, 9 a.m. to 5 p.m. EST) at (404) 639-6425.]
References
1. Centers for Disease Control and Prevention and Food and Drug Administration. Serious adverse events attributed to nevirapine regiments for postexposure prophylaxis after HIV exposures Worldwide, 1997-2000. MMWR 2001; 49:1,153-1,156.
2. Johnson S, Baraboutis J, Sha BE, et al. Adverse effects associated with use of nevirapine in HIV postexposure prophylaxis for 2 health care workers. JAMA 2000; 284:2,722-2,723.
3. Beltrami EM, Williams IT, Shapiro CN, Chamberland ME. Risk and management of bloodborne infections in health care workers. Clinical Microbiology Reviews 2000; 13:385-407.
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