Clinical

Etravirine does not appear to be hepatotoxic

Last Updated: 2008-11-06 14:11:40 -0400 (Reuters Health)

By Martha Kerr

SAN FRANCISCO (Reuters Health) - Longer term follow-up of the recently approved non-nucleoside reverse transcriptase inhibitor (NNRTI) etravirine (Intelence; Tibotec Therapeutics) for the treatment of HIV infection shows that etravirine does not appear to cause elevations in serum alanine transaminase levels (ALT) or other signs of hepatotoxicity, researchers announced here at the annual meeting of the American Association for the Study of Liver Diseases.

Other NNRTIs, in particular nevirapine, have been associated with significant liver toxicity, said principal investigator Dr. Jacob Lalezari of Quest Clinical Research in San Francisco, California, as he presented results of a pooled analysis of the DUET-1 and DUET-2 trials.

FDA approved etravirine in January as a component of HIV therapy that includes a protease inhibitor, based largely on the results of DUET-1 and DUET-2.

Dr. Lalezari presented the 48-week data on etravirine's effect on liver function in 599 patients in DUET-1 and 604 patients in DUET-2 who were randomized to either etravirine or placebo in addition to combination therapy that included a protease inhibitor. Patients were treatment-experienced and two-thirds had two or more resistance mutations to other NNRTIs and/or protease inhibitors.

Overall adverse events "were not different between the etravirine and placebo arms of the study," with the exception of rash with the NNRTI. After a median of 52 weeks of treatment, there were 39 events in the etravirine arm and 37 in the placebo arm.

Elevations in liver enzymes were rare and "evenly split between the arms and generally asymptomatic regardless of regimen," Dr. Lalezari reported.

Among the 139 patients co-infected with hepatitis B or C, there were four treatment-related hepatic adverse events in patients receiving etravirine and three such events in patients on placebo, which "were likely attributable to hepatitis" itself.

"The appropriate patient profile is still emerging" for treatment with etravirine, but the lack of hepatotoxicity "is one less thing to worry about," Dr. Lalezari said after presenting his findings.