HIV protease inhibitors associated with hepatic cytolysis

Before initiating protease inhibitor treatment in HIV-infected patients, clinicians should assess patients’ liver enzyme levels and viral co-infections, according to a report in the December issue of Antimicrobial Agents and Chemotherapy. Dr. Catherine Leport, of Hopital Pitie Salpetriere, Paris, and other members of the APROCO Study Group recruited 1080 HIV-infected patients who initiated protease inhibitor treatment at 1 of 47 French AIDS centres. Serological status was determined for 613 patients. Forty-five tested positive for hepatitis B surface antigen and 159 were hepatitis C virus seropositive.

Severe cytolysis developed in 23 patients, including 16 infected with hepatitis C and 5 infected with hepatitis B, the investigators report. Median time from initiation of protease inhibitor to alanine aminotransferase greater than 5 times the upper limit of normal was 95 days. In multivariate analysis, positivity for hepatitis C antibodies was associated with a hazard ratio of 7.95, and positivity for hepatitis B surface antigen with a hazard ratio of 6.67. The investigators observed “no association between severe cytolysis and the type of protease inhibitor or the response at month 1 in terms of CD4+ cell count and plasma HIV RNA level.”

The researchers note that in previous phase III trials, patients with abnormal liver enzyme levels were commonly excluded, precluding the detection of this adverse event and its risk factors. Dr. Leport and her colleagues emphasize the need to monitor severe adverse events after expanded use of protease inhibitors in unselected population samples.

COMMENT

Given the potential difficulties of managing hepatic cytolysis clinicians should assess patients’ liver enzyme levels and viral co-infections before initiating protease inhibitor treatment.