Acute hepatitis developed in 2.6% of Dutch patients starting a nevirapine-containing HAART regimen, according to a report in the October 17th edition of the journal AIDS. Nevirapine was considered by the investigators to be the most likely cause of liver injury in all the patients, and liver function rapidly returned to normal in all cases when therapy with nevirapine was stopped.
Doctors at the Slotervaal Hospital in Amsterdam wished to determine the characteristics of patients who developed hepatic abnormalities within twelve weeks of starting a nevirapine-containing HAART regimen. Accordingly, between 1999 and 2001 data including demographic details, use of anti-HIV drugs, baseline liver function and viral load were gathered on the 306 individual who commenced therapy with an anti-HIV drug regimen including nevirapine.
A total of eight patients (2.6%) developed acute hepatitis in a median of 24 days (range 20 – 25 days) after starting therapy with nevirapine. All the patients were white, six were men, four were antiretroviral naïve at baseline, and four had received previous anti-HIV therapy with a protease inhibitor-containing regimen that had suppressed HIV viral load to below 200 copies/mL.
Transaminases (liver enzymes) peaked a median of 28 days after starting nevirapine. Rash developed in five patients.
Anti-HIV therapy was discontinued completely by five patients, with the remaining three individuals replacing nevirapine for another anti-HIV drug. Transaminase levels returned to normal in all individuals within a median of 44.5 days (range 28.8 to 46.3 days), and clinical symptoms disappeared in seven patients within 15 days and in the remaining patient 37 days after stopping nevirapine.
The investigators were unable to identify any specific risk factors amongst the eight patients for acute hepatitis after commencing nevirapine therapy. CD4 cell counts ranged from 230 cells/mm3, HIV-treatment histories differed, only one patient was infected with hepatitis B (and none with hepatitis C), and liver function was normal at baseline in all but this one individual.
”The reason for development of this hepatic reaction is not clear…as no specific factor that applied to all the patients in this group could be identified”, conclude the investigators. They recommend that transaminase levels should be monitored in all patients immediately therapy with nevirapine is started.
An editorial accompanying this article in the same issue of AIDS emphasises the importance of checking both short- and long-term markers of liver toxicity in HAART-treated individuals. These tests are “simple” to perform and should be performed frequently, the editorial stresses. This reinforces a warning in the European product information that patients taking nevirapine should be closely monitored during the first eight weeks of therapy because of the risk of hepatic side-effects.
Further information on this website
Nevirapine - overview
The liver - factsheet
de Matt MMR et al. Case series of acute hepatitis in a non-selected group of HIV-infected patients in nevirapine-containing antiretroviral treatment. AIDS 17: 2209 – 2214, 2003.
Manfredi R. HIV infection, antiretroviral therapy, and hepatic function. Emerging epidemiological, pathogenetic, and clinical issues, and their consequences on disease management. AIDS 17: 2253 – 2256, 2003.