Near-death PEP follows questionable exposure

CDC warns against use of nevirapine

Following life-threatening liver problems in two health care workers, public health officials are warning against the use of the drug nevirapine (NVP) for post-exposure prophylaxis (PEP) for occupational HIV exposures. Moreover, the cases underscore that powerful PEP drugs should not be administered unless the severity of exposure warrants, an epidemiologist with the Centers for Disease Control and Prevention advises Hospital Infection Control.

Elise Beltrami, MD, medical epidemiologist in the CDC division of healthcare quality promotion, questioned the use of a PEP regimen in the case of a 38-year-old male physician who developed fulminant hepatitis after taking NVP, zidovudine, and lamivudine.

"The physician was hospitalized in intensive care [following] a mucous membrane exposure to body fluids that were not bloody," she says. "If you look at our guidelines, we might not even recommend PEP in that situation."

The CDC is planning to issue an update on PEP issues in the coming months that will expand upon the point, Beltrami says.

"We are very much going to emphasize that people really have to look at the exposure," she says. "We know people are taking PEP for urine exposures and things that we know don’t carry a risk of transmission."

The two cases were reported by the CDC on Jan. 5, 2001.¹ The other case involved a 43-year-old female phlebotomist who required a liver transplant after developing fulminant hepatitis and end-stage hepatic disease. She was on a three-drug PEP regimen that included NVP, zidovudine, and lamivudine.

Carefully weigh risks and benefits

"She had a needlestick exposure, so it sounds certainly like PEP was warranted in that case," Beltrami says. "The take-home message really should be for all who prescribe PEP to weigh the risks and the benefits. For nevirapine, probably the risk outweighs the benefit."

Indeed, NVP is not recommended for basic or expanded PEP regimens, the CDC stated in reporting the cases. Severe, life-threatening, and fatal cases of hepatotoxicity and skin reactions have occurred among HIV-infected patients treated with NVP, the CDC added.

However, the agency stated that the data on the safe and effective use of single-dose NVP to prevent perinatal HIV transmission, and a theoretical advantage of more rapid activity (i.e., NVP does not require phosphorylation for activation) have prompted clinicians to include NVP in PEP regimens following HIV exposures.

"We have found serious adverse events with other regimens as well," Beltrami says. "The concern in this case was we have never seen a health care worker need a liver transplant. We have never seen health care workers hospitalized in critical condition.

Off the map

"[But] PEP period is off-label. None of these drugs are labeled [by the FDA] for post-exposure prophylaxis use. In our recommendations we have certain regimens that are basically recommended for PEP. Sometimes clinicians will use other regimens in special circumstances where there is resistance or the health care worker can’t tolerate the recommended drug," she adds.

Including the two case reports of fulminant hepatitis, the FDA is aware of 22 cases of serious adverse events related to NVP taken for PEP from March 1997 through September 2000. Twelve occurred in the United States. In the HIV PEP registry, which collected data on occupational HIV PEP use from October 1995 through March 1999, six cases of serious adverse events related to PEP were reported among 492 registered participants. Those included a severe skin reaction that occurred in one of 11 health care workers taking a regimen that included NVP.

Other NVP uses OK

The findings do not apply to NVP use in other settings, the CDC emphasized. Single-dose NVP remains one of the regimens recommended for prevention of perinatal HIV transmission. No serious toxicity has been reported among mothers and infants using this regimen. In addition, combination antiretroviral regimens containing NVP may continue to be used in HIV-infected persons after weighing the risks and benefits and monitoring adverse reactions, the CDC recommended.

Reference

1. Centers for Disease Control and Prevention. Serious adverse events attributed to nevirapine regimens for postexposure prophylaxis after HIV exposures —- worldwide, 1997-2000. MMWR 2001; 49:1,153-1,156.