Rate and risk factors of liver toxicity in patients receiving antiretroviral therapy

Background: The benefit of highly active antiretroviral therapy (HAART) may be limited by the development of liver toxicity. The prevalence and risk factors of this complication using different antiretroviral drug combinations are not well known. Patients and Method: Clinical charts of HIV-infected patients, previously naive for antiretroviral drugs, starting HAART between January 1997 and January 2000 were reviewed. Liver toxicity was scored according to increases in liver enzymes. Results: HIV infection had been acquired by intravenous drug use in 36 (40%) of 91 subjects recruited in the study. The rest had been infected through homosexual (38%) or heterosexual contact (22%). Overall, 43 patients (47%) were coinfected with hepatitis C (42%) and/or B (8%) viruses. Antiretroviral therapy included protease inhibitors (PI) plus two nucleosides in 48 individuals and non-nucleosides in 50. Baseline characteristics were similar across the different treatment groups. Liver toxicity was recorded in 30 (31%) subjects, and it was severe in 10 (11%). Cytolysis was the predominant pattern (28), while only one case of cholestasis and one with a mixed pattern were recorded. Coinfection with hepatitis B and/or C viruses was associated with liver toxicity (RR: 10.36; 95% CI, 1.38-77.56; p = 0.03) as was a high alcohol intake (RR: 3.35; 95% CI, 2.43-4.62; p = 0.01). No differences in the rate of hepatotoxicity were found when comparing PI and non-nucleoside containing regimens. The development of isolated hyperbilirubinemia (27%) was strongly associated with the use of indinavir (RR: 3.61; 95% CI, 1.81-7.21; p < 0.001). Conclusions: Liver toxicity occurs in about one third of HIV-infected patients after initiating HAART, regardless of the drugs used, yet it is commonly mild and transient. A high alcohol intake and a coinfection with HCV/HBV constitute the most important predictive factors.