Toxicité des antirétroviraux chez les patients co-infectés par les virus VIH et VHC

The introduction of HAART (Highly Active Antiretroviral Therapy) has deeply modified the epidemiologic data on HIV infection. Consequently, chronic hepatotoxicities, particularly those related to HCV, became a leading cause of morbidity and mortality amongst co-infected HIV-HCV patients. They became a major factor to be considered before starting and conducting a HAART regimen. Due to the epidemiology of these two infections and referring to several huge randomised prospective clinical trials recently reported, understanding the antiretroviral toxicity is a true challenge in the follow-up of co-infected patients. It includes: i) understanding the intrinsec toxicities of each antiretroviral class, particularly drugs-related hepatotoxicities; then ii) the incidences of those treatments in co-infected patients, with or without anti-HCV bitherapy; and iii) the pathogenic reciprocal interactions between HIV and HCV and between anti-HIV and anti-HCV treatments. Four mechanisms of drug-related liver toxicity have been recognized: i) direct drug toxicity; ii) immune reconstitution; iii) hypersensitivity reactions with liver involvement; and iv) mitochondrial toxicity. The benefit-risk ratio notion must be strongly evaluated and the therapeutic strategy must include, for each patient, a strict monitoring of biochemichal (liver parameters, hemogram, amylasemia, lipasemia, evaluation of liver fibrosis index) and clinical (weight, lipodystrophy) parameters. A better pharmacological knowledge, a global view and the development of new drugs with less hepatotoxicity, like fusion inhibitors, would increase the quality of life of co-infected patients. Liver transplantation could be a hope for patients with severe hepatic failure.