From 6 to 30 percent of HIV-infected patients treated with antiretroviral therapy (ART) develop significantly increased blood levels of liver enzymes, an indicator of liver toxicity. In some studies, high-dose ritonavir (RTV) has been associated with an increased risk of liver toxicity compared with other antiretroviral regimens. However, RTV is no longer recommended as first-line treatment and is increasingly being co-administered at lower doses with other protease inhibitors (PIs).
Used this way, RTV-boosted ART (lopinavir, indinavir, and saquinavir) is not associated with significantly increased risk of liver toxicity over unboosted PI-based ART (indinavir, nalfinavir) among HIV-infected patients coinfected or uninfected with hepatitis C virus. Thus, other medication-related factors, for example, medication efficacy and non-liver toxicity, should guide individual treatment decisions, according to researchers at the Schools of Medicine and Public Health at Johns Hopkins University.
In a study that was supported in part by the Agency for Healthcare Research and Quality (HS07809), the researchers compared the incidence of liver enzyme elevations before and during ART among 1,161 HIV-infected adults (with and without hepatitis B and/or C coinfection). The subjects—who had never previously been treated with PIs—received RTV-boosted and unboosted PI-based ART.
The incidence of severe liver toxicity (elevations of three to more than five times the pretreatment liver enzyme levels) was: nelfinavir, 11 percent; lopinavir/RTV (200 mg/day), 9 percent; indinavir, 13 percent; indinavir/RTV (200-400 mg/day), 12.8 percent; and saquinavir/RTV (800 mg/day), 17.2 percent. The risk of liver toxicity was significantly greater among individuals who had chronic viral hepatitis. However, the majority of HCV-infected patients taking PI-based ART did not develop significant liver toxicity.
See "Hepatotoxicity associated with protease inhibitor-based antiretroviral regimens with or without concurrent ritonavir," by Mark S. Sulkowski, M.D., Shruti H. Mehta, M.P.H., Richard E. Chaisson, M.D., and others, in AIDS 18, pp. 2277-2284, 2004.
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