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Many antiretroviral agents are associated with hepatotoxicity, which can limit treatment options for HIV-infected patients. Although the risk for drug-related hepatotoxicity is known to be higher among patients coinfected with HIV and hepatitis C virus (HCV) than among those with HIV monoinfection, whether effective treatment of chronic HCV infection reduces this risk remains unclear. Now, investigators report results of a retrospective study of 132 HIV/HCV-coinfected patients in Spain who had completed a full course of interferon-based anti-HCV therapy before they received antiretroviral therapy (ART).
Forty-three patients (33%) achieved a sustained virologic response (SVR), defined as an undetectable HCV RNA for 6 months after treatment withdrawal and thereafter. The rate of hepatotoxicity during ART was 9.3% among the 43 patients with an SVR, versus 37.5% among the 89 patients without an SVR (P<0.001). Likewise, the proportion of patients with grade 3 or 4 alanine-transaminase elevations was greater among those without an SVR (27.3% vs. 6.9%; P=0.007). In logistic regression analysis, the only variables independently associated with hepatotoxicity were lack of an SVR (odds ratio, 6.1; 95% confidence interval, 1.8–37.5) and receipt of a dideoxynucleoside (didanosine or stavudine) (OR, 3.6; 95% CI, 1.2–10.4).
Labarga P et al. Hepatotoxicity of antiretroviral drugs is reduced after successful treatment of chronic hepatitis C in HIV-infected patients. J Infect Dis 2007 Sep 1; 196:670-6.
Cooper CL. De-“Liver”-ing HIV/hepatitis C virus–coinfected patients from antiretroviral hepatotoxicity. J Infect Dis 2007 Sep 1; 196:656-8.
Comment
The prospect of reducing ART-associated hepatotoxicity argues in favor of treating HCV prior to HIV in coinfected patients with high CD4-cell counts for whom delaying ART initiation is safe. As an editorialist points out, many patients present late in their disease, with low CD4-cell counts and their first AIDS-defining opportunistic infection. For such patients, HIV treatment must come first. More data are needed to determine whether preemptive HCV therapy is appropriate for patients who fall in between these two extremes (e.g., CD4 counts of 200–350 cells/mm3). For now, the fact that only a minority of patients achieve an SVR after HCV therapy suggests that ART should not be delayed for patients in this “gray zone.”