A retrospective cohort study of liver toxicity in hepatitis B and C HIV co-infected patients in the HIV Ontario observational database (HOOD)
Phillips, E., Raboud, J. and Saskin, R. (2003) A retrospective cohort study of liver toxicity in hepatitis B and C HIV co-infected patients in the HIV Ontario observational database (HOOD). In: 2nd IAS Conference on HIV Pathogenesis and Treatment, 13 - 16 July 2003, Paris, France.
Objectives: To identify risk factors for significant hepatic dysfunction among HIV-hepatitis B (hepB) or hepatitis C (hepC) co-infected patients related to antiretroviral (ART) exposure. Methods: All HOOD patients that were chronic carriers of hepB or hepC were identified. ART medication and laboratory adverse event data were obtained through bi-annual chart reviews. Results: 404 HIV co-infected patients were identified (hepC(n=317); hepB(n=104); both hepC/hepB(n=17). 243 (60%) and 249 (62%) of these patients had ever had grade 3 or 4 elevations in ALT and AST respectively versus 676 (41%) and 673 (41%) (p<.001 and p<.001) of those with HIV not co-infected. The median (IQR) duration of infection with hepC and/or hepB at the time of initial identification of elevations in transaminases(AST/ALT) was 842 days (260,1780). The median (IQR) time after starting any ART to the development of Grade 3 or 4 hepatic dysfunction was 896 days (216,1680). Grade 3 or 4 elevations in AST/ALT were significantly associated with ever taking: a boosted PI (72% vs 59%, p=.01), ritonavir (70% vs 51%, p=.0001), ddI (66% vs 56%, p=.03) and a trend with ever taking d4T (63% vs 54%, p=.06) but not with taking a nelfinavir based regimen without previous exposure to ritonavir, d4T and/or ddI(61% vs 62%, p=.96). Patients who had ever had grade 3 or 4 elevations in ALT/AST also had exposure to higher median numbers of all types of ARTs (6 vs 5, p<.001), nucleoside reverse transcriptase inhibitors (4 vs 3, p=.001), nonnucleoside reverse transcriptase inhibitors (1 vs 0, p=.004) and PIs (2 vs 1, p=.002). Conclusions: A high proportion of HIV patients co-infected with hepB and hepC have serious elevations in transaminases which may be related to both type and cumulative exposure to ART. Patients exposed to boosted PI regimens, ddI and d4T appear to be at heightened risk and patients on nelfinavir-based regimens without previous exposure to other PIs or ddI/d4T at lower risk for serious hepatotoxicity.
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