Reuters 23 May 2001

A comprehensive retrospective review of more than 10,000 adult AIDS patients participating in 21 different AIDS Clinical Trials Group (ACTG) studies "confirms suspicions all of us have had," Dr. Raymond T. Chung, told Reuters Health. Namely, that antiretroviral therapy is associated with a high rate of severe hepatotoxicity, regardless of drug class or combination.

Dr. Chung of Massachusetts General Hospital in Boston presented the findings to the Digestive Disease Week annual meeting, which is in full swing here in Atlanta. The researchers evaluated data for AIDS patients, enrolled in ACTG studies between 1991 and 2000. The subjects were taking a variety of drug combinations including one or more nucleoside reverse transcriptase inhibitors (NRTIs), nonnucleoside reverse transcriptase inhibitors (NNRTIs) and protease inhibitors (PIs).

"In that period of time, therapies have clearly improved from the standpoint of controlling HIV disease," Dr. Chung said. Nevertheless, regardless of drug class or combination of therapy, "there appeared to be an across-the-board high rate of hepatotoxicity, defined as elevations in liver enzymes to greater than five times the upper limit of normal."

Overall, 10% of patients developed grade 3 and 4 hepatotoxicity and 23% of them had to discontinue therapy permanently. According to the data, 2.5% of all deaths in the study period were liver related.

NNRTI-containing regimens, especially those including nevirapine and efavirenz, were particularly hard on the liver, with high rates of discontinuation. In November, the US Food and Drug Administration issued an alert for nevirapine based on reports of liver toxicity.

Dr. Chung said that it would be useful to look at baseline pretreatment variables, such as coinfection, metabolic status and liver enzyme status, which may have predicted the development of liver toxicity. "The idea would be to single out those patients who require close monitoring or, potentially, management of their metabolic or viral conditions prior to starting HAART.