Co-infection with hepatitis B and/or C, rather than the use of particular antiretrovirals, is the main factor predicting the risk of developing liver toxicity after starting HAART, according to researchers at the National AIDS Therapy Evaluation Centre (NATEC) in the Netherlands.
They evaluated 394 patients who started a protease inhibitor-containing regimen between July 1996 and February 1998 at Amsterdam's Academic Medical Centre, and found that 18% developed liver enzyme elevations to more than five times the upper limit of normal. Cases occurred after a median of 25 weeks on the HAART regimen, and people with either hepatitis C (OR 2.46) and hepatitis B co-infection (OR 2.78) were significantly more likely to experience liver enzyme elevation
They also experienced the fastest onset of liver enzyme elevation (90% of all cases occurred between 12 and 42 weeks after starting the HAART regimen).
Modification of treatment did not affect the likelihood that liver enzyme levels would subsequently decline in those who experienced elevation, suggesting that treatment adjustment on PI-containing regimen may not be necessary, but those who did modify treatment generally experienced greater declines in ALT and AST levels.
There was no evidence that specific protease inhibitors or nucleoside analogues were associated with an increased risk of liver toxicity, but the study did not collect data on the use of NNRTIs.
Reference
Den Brinker M et al. Hepatitis B and C virus co-infection and the risk for hepatotoxicity of highly active antiretroviral therapy in HIV-1 infection. AIDS 14: 2895-2902, 2000.