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Abstract
INCIDENCE OF HEPATOTOXICITY AND MORTALITY IN 21 ADULT ANTIRETROVIRAL TREATMENT TRIALS
REISLER R, LIOU S, SERVOSS J, ROBBINS G, THEODORE D, MURPHY R, CHUNG R
Background: The use of antiretroviral therapy (ART) for HIV has been associated with severe hepatotoxicity and death. We therefore sought to quantify the incidence of hepatotoxicity and mortality in a multicenter HIV cohort receiving diverse ART regimens. Methods: We retrospectively analyzed 21 adult AIDS Clinical Trials Group (AACTG) studies, which enrolled 9,003 patients into arms that included single and double NRTIs, triple regimens including NRTIs, NNRTIs, and PIs. Severe hepatotoxicity was defined as Grade 3 or 4 elevations (>5xULN) of AST, ALT, or total bilirubin on therapy. Results: A high rate of Grade 3/4 hepatotoxicity (10%) was found in all treatment regimens (12% single agent NRTI, 7.9% double agent NRTI, 8.6% PI (-) triple agent, 12% PI (+) triple agent). Of all patients with Grade 3/4 hepatotoxicity, 23% permanently discontinued ART (27% single Rx, 24% double Rx, 22% PI (-) triple Rx, 9.3% PI (+) triple Rx). Of the NNRTI regimens, those utilizing NVP or EFV were significantly more likely to be associated with Grade 3/4 hepatotoxicity (DEL vs NVP, OR= 2.7, 95% CI 1.6-4.7, p= 0.003; DEL vs EFV, OR 2.5, 95% CI 1.2-5.5, p= 0.01). The NNRTI regimens also led to a high rate of discontinuation among those with Grade 3/4 toxicity: 24% NVP, 33% EFV, 24% DEL. The overall and the hepatic-related death rates were 15% and 0.3% respectively. Of all deaths, 2.5% (35/1384) were hepatic-related. The NNRTI regimens had a low hepatic-associated death rate, (0.8% of all deaths). Conclusions: In a large U.S. HIV cohort (1) there is a high rate of severe ART hepatotoxicity irrespective of class. (2) in all groups except PI-containing triple regimens, severe hepatotoxicity led to frequent permanent treatment discontinuation. (3) of reported deaths, there was a significant hepatic-associated mortality. (4) among NNRTIs, there was a high rate of hepatotoxicity, particularly with NVP and EFV, with high rates of discontinuation; mortality was infrequent.
The 1st. IAS Conference on HIV Pathogenesis and Treatment
Abstract no.
43
Suggested Citation
"REISLERR, et al.
INCIDENCE OF HEPATOTOXICITY AND MORTALITY IN 21 ADULT ANTIRETROVIRAL TREATMENT TRIALS.
Oral Presentation:
The 1st. IAS Conference on HIV Pathogenesis and Treatment
:
Abstract no.
43"
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