Progression of liver fibrosis may be speeded by nevirapine

Treatment with nevirapine may be associated with more rapid progression of liver fibrosis in HCV/HIV coinfected persons, according to research published in the March 26^th edition of AIDS.

Data from a cohort of 152 HIV/HCV coinfected people with a known or estimated date of HCV infection were evaluated. All had undergone liver biopsy, a majority (109/152) after 1996. None had been treated for hepatitis C and 47/152 had never been treated for HIV.

Several variables that are associated with fibrosis were analysed. The investigators considered age at HCV infection, route of transmission, duration of infection, age and ALT levels at liver biopsy, alcohol intake, HCV genotype and viral load. Data regarding HIV, nadir CD4 cell count and CD4 cell count at biopsy, clinical AIDS, use of antiretroviral agents prior to biopsy and the duration of antiretroviral therapy were included in the statistical analysis.

Fibrosis scores of F0 to F2, which indicate no liver scarring to moderate scarring, were grouped as non-advanced fibrosis. F3 and F4, indicating serious liver scarring to cirrhosis, were categorized as advanced fibrosis. The fibrosis progression rate was estimated by using a model that assumes that no fibrosis is present on the day of HCV infection, and that fibrosis progresses at a constant rate thereafter. For example, a person who has a fibrosis score of F2 ten years after infection has a fibrosis progression rate of 0.2. The cut-off level for fibrosis progression was established at 0.2 per year, because a rate >0.2 per year translates into progression by at least one stage after five years.

There were several significant differences between HAART recipients and those who were not receiving HAART prior to liver biopsy. The median nadir CD4 cell count was predictably lower among those who had received HAART (231 vs. 390) than among the non-HAART group. The median age at biopsy was significantly higher among those who received HAART (38 vs. 30), and their duration of HCV infection was significantly greater (15.5 years vs. 9 years).

Nevirapine use was significantly associated with a fibrosis progression rate >0.2, yet it is difficult to tease out the drug’s actual contribution to accelerated fibrosis progression. Although treatment with nevirapine in people coinfected with HIV and hepatitis B or C is associated with an increased risk of serious liver enzyme elevations and hence liver damage, fibrosis does not always progress at a constant rate. The 14/46 individuals in the nevirapine group with advanced fibrosis may have already had advanced fibrosis before they started the drug. Members of this group were older, and aging has been associated with more rapid fibrosis progression. Longer duration of HCV infection may have contributed to their liver damage. More advanced HIV disease may have accelerated fibrosis progression as well; 25% of the HAART group had clinical AIDS (vs. 6.5% of the non-HAART group).

Although nevirapine’s influence on fibrosis progression remains unclear, it does not appear to be the optimal therapy for coinfected persons, the authors concluded.