title: Impact of HAART exposure and associated lipodystrophy on advanced liver fibrosis in HIV/HCV-coinfected patients.
abstract: The impact of antiretroviral drug exposure and associated lipodystrophy and/or insulin resistance (IR) on advanced liver fibrosis in HIV/HCV-coinfected patients is not fully documented. We determined the prevalence of advanced liver fibrosis (defined by hepatic stiffness ≥9.5 kPa) and associated factors, focusing on the impact of highly active antiretroviral therapy and its major adverse effects (lipodystrophy and IR), in 671 HIV/HCV-coinfected patients included in the ANRS CO13 HEPAVIH cohort. One hundred ninety patients (28.3%) had advanced liver fibrosis. In univariate analysis, advanced liver fibrosis was significantly associated with male sex, higher body mass index, HCV infection through intravenous drug use, a lower absolute CD4 cell count, a longer history of antiretroviral treatment, longer durations of protease inhibitors, non-nucleoside reverse transcriptase inhibitors and NRTI exposure, lipodystrophy, diabetes, and a high homeostasis model assessment method (HOMA) value. The only antiretroviral drugs associated with advanced liver fibrosis were efavirenz, stavudine and didanosine. In multivariate analysis, male sex (OR 2.0, 95% CI 1.1-3.5; P = 0.018), HCV infection through intravenous drug use (OR 2.0, 95% CI 1.1-3.6; P = 0.018), lipodystrophy (OR 2.0, 95% CI 1.2-3.3; P = 0.01), median didanosine exposure longer than 5 months (OR 1.7, 95% CI 1.0-2.8; P = 0.04) and a high HOMA value (OR 1.1, 95% CI 1.0-1.2; P = 0.005) remained significantly associated with advanced liver fibrosis. Mitochondrial toxicity and IR thus appear to play a key role in liver damage associated with HIV/HCV-coinfection, and this should be taken into account when selecting and optimizing antiretroviral therapy. Antiretroviral drugs with strong mitochondrial toxicity (e.g. didanosine) or a major effect on glucose metabolism should be avoided.
authors.affiliation: INSERM, U897, ISPED, Université Victor Segalen, Bordeaux, France.
authors.forename: M A
authors.initials: MA
authors.lastname: Loko
authors.forename: F
authors.initials: F
authors.lastname: Bani-Sadr
authors.forename: M
authors.initials: M
authors.lastname: Winnock
authors.forename: K
authors.initials: K
authors.lastname: Lacombe
authors.forename: P
authors.initials: P
authors.lastname: Carrieri
authors.forename: D
authors.initials: D
authors.lastname: Neau
authors.forename: P
authors.initials: P
authors.lastname: Morlat
authors.forename: L
authors.initials: L
authors.lastname: Serfaty
authors.forename: F
authors.initials: F
authors.lastname: Dabis
authors.forename: D
authors.initials: D
authors.lastname: Salmon
mesh_terms: D000328:Adult; D000480:Alkynes; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects; D000998:Antiviral Agents / Q000009:adverse effects* / Q000627:therapeutic use; D048588:Benzoxazines / Q000009:adverse effects / Q000627:therapeutic use; D018791:CD4 Lymphocyte Count; D060085:Coinfection / Q000188:drug therapy*; D003521:Cyclopropanes; D016049:Didanosine / Q000009:adverse effects / Q000627:therapeutic use; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy*; D006526:Hepatitis C / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D007333:Insulin Resistance; D008060:Lipodystrophy / Q000139:chemically induced*; D008103:Liver Cirrhosis / Q000188:drug therapy* / Q000209:etiology; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000187:drug effects; D012737:Sex Factors; D018119:Stavudine / Q000009:adverse effects / Q000627:therapeutic use
chemical_list: D000480:Alkynes; D000998:Antiviral Agents; D048588:Benzoxazines; D003521:Cyclopropanes; D018119:Stavudine; C098320:efavirenz; D016049:Didanosine