Although people with hepatitis C have a four-fold higher risk of developing liver toxicity on HAART, almost 90% do not suffer any significant liver problems as a result of their anti-HIV treatment, according to a new US study from Johns Hopkins School of Medicine. The findings challenge the view amongst many doctors and people with HIV that protease inhibitors are especially difficult to tolerate if you are co-infected with hepatitis C. However, the study also confirms the view that ritonavir is responsible for a much higher rate of liver toxicity among all patients.
Researchers looked at 298 patients who had started a new regimen between January 1996 and January 1998, 71% of whom received protease inhibitors. 52% had hepatitis C infection. 10.4% of all individuals developed serious liver toxicity (defined as grade 3 or 4 elevation of ALT and AST, adopted from ACTG standard measures) after a median of 188 days, but 30% of ritonavir users developed severe toxicity. Ritonavir accounted for half of all severe toxicity cases although only 50 of 298 patients were receiving the drug. Rates of severe toxicity were similar in those who used saquinavir in combination with ritonavir.
Co-infection with hepatitis C made no difference to the rate of severe toxicity in ritonavir users, but severe toxicity in people taking non-PI containing regimens (usually two NAs) only occurred in individuals co-infected with hepatitis C (p=0.06). Individuals with hepatitis C taking PIs other than ritonavir were 60% more likely to develop severe toxicity than those without hepatitis C, but this trend was not statistically significant and only 8.1% of HIV/HCV co-infected individuals experienced severe toxicity on PIs other than ritonavir.
A CD4 increase of more than 50 cells after starting PI therapy or a baseline CD4 count below 200 were also associated with an increased risk of severe toxicity regardless of HCV status. These findings suggest either an immune restoration effect or that CD4 increase in this context is a surrogate for superior drug absorption and hence increased risk of liver toxicity.
Severe hyperbilirubinemia (another marker of liver toxicity) was seen in ten (3.4%) individuals, and was associated with indinavir treatment (RR 2.3, non-significant). All but two cases occurred in individuals with hepatitis C or B.
Twenty-five out of 31 individuals with severe toxicity stopped therapy, but six continued with no significant consequnces, and there were no deaths attributed to drug-related liver toxicity.
Reference
Sulkowski MS et al. Hepatotoxicity associated with antiretroviral therapy in adults infected with human immunodeficiency virus and the role of hepatitis C or B virus infection. Journal of the American Medical Association 283 (1), January 5 2000.