Longitudinal Effect of Antiretroviral Therapy on Markers of Hepatic Toxicity: Impact of Hepatitis C Coinfection

Abstract

To characterize longitudinal hepatic toxicity of antiretroviral therapy in HIV-infected women with and without hepatitis C virus (HCV) infection, we measured alanine and aspartate aminotransferase values among women initiating highly active antiretroviral therapy (HAART). For 312 HIV/HCV coinfected women who received HAART for a mean of 1.8 years, the prevalence of elevated aminotransferase levels >3 times and >5 times the upper limit of normal (ULN) was low (<12% and <4%, respectively), and the prevalence of elevated aminotransferase levels declined over time. When we analyzed trends in aminotransferase levels according to type of HAART received among HCV-infected and uninfected women, we found that mean aminotransferase levels declined among 539 women receiving therapy with protease inhibitors (decreases of 5.34%-4.23% of the ULN per year; P values for trend of.007-.06), but mean values among 128 women receiving therapy with nonnucleoside reverse-transcriptase inhibitors remained stable (from decreases of 1.65% to increases of 7.57% of the ULN per year; P values of.19-.71). Our findings lend support to assertions that antiretroviral therapy is safe for women with HCV infection.

Hepatotoxicity of antiretrovirals: Incidence, mechanisms and management

“…If the patient is taking an antiretroviral with higher hepatotoxic potential, substitution of that particular drug is an available option. Regarding the continuation of the same regimen, spontaneous decrease of transaminases levels has been reported [77]. However, the elevation of transaminases can persist, and the long-term consequences are unknown.…”

Hepatic Steatosis in Human Immunodeficiency Virus

“…In a recent large study of almost 6000 HIV patients, the prevalence of abnormal ALT and AST in subjects without HCV was 55% and 76% respectively (9). Most clinical studies on hepatoxicity of HAART have focused on patients with severe liver enzyme elevations (defined as ≥ 5x the upper limit of normal (ULN) (5; 10–12). However, the majority of patients with abnormal liver enzymes have mild to moderate enzyme elevations (1.25 to 5 × ULN), and there are few studies with histologic data in these individuals.…”

The Prevalence and Risk Factors for Abnormal Liver Enzymes in HIV-Positive Patients without Hepatitis B or C Coinfections

“…Because the main focus on liver disease in patients with HIV has been on coinfection with hepatitis C virus (HCV) and hepatitis B virus (HBV), there has been little attention to other causes of liver diseases in the absence of HCV and HBV [9,10]. Furthermore, most clinical studies on hepatoxicity have focused on those with severe liver enzyme elevations (defined as ‡5· the upper limit of normal (ULN) [5,[11][12][13]. However, the majority of patients with abnormal liver chemistries have mild to moderate liver enzyme elevations (1.25-4· ULN).…”