An evaluation of hepatic enzyme elevations among HIV-infected released prisoners enrolled in two randomized placebo-controlled trials of extended release naltrexone

Abstract

Extended-release naltrexone (XR-NTX), an approved treatment for opioid or alcohol dependence, is a once-monthly injectable formulation of naltrexone. Hepatotoxicity concerns have limited its use, necessitating further investigation. This study aims to examine hepatic enzyme levels in participants of 2 randomized placebo-controlled trials (RCTs) of XR-NTX. Hepatic transaminases were measured in 85 patients enrolled in RCTs of XR-NTX among HIV-infected prisoners, transitioning to the community and receiving treatment for either dependence on alcohol (52.9%), opioids (44.7%) or both (16.5%). Baseline characteristics included HCV co-infection (55.7%), antiretroviral therapy (81%), mental illness (39%) and receiving psychiatric medications (34.1%). Levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and gamma glutamyl transferase (GGT) were not statistically different between persons randomized to placebo (N=24) and XR-NTX (N=61) arms. These results confirm that XR-NTX is safe to use among opioid and alcohol dependent HIV-infected released prisoners receiving ART with high rates of co-morbid HCV infection and mental illness.

Trial registration: ClinicalTrials.gov NCT01246401 NCT10177310.

Keywords: Alcohol; Co-morbidities; HIV/AIDS; Hepatotoxicity; Naltrexone; Opioids; Prisoners.

Copyright © 2014 Elsevier Inc. All rights reserved.

Figures

Figure 1

Hepatic Enzyme Elevations (HEE) among participants in the XR-NTX and placebo arms, comparing NIH/DAIDS1 definitions of HEE: Grades 1, 2: elevations up to 5x ULN2; Grades 3, 4: elevations ≥5x ULN. 1 Division of AIDS 2 Upper Limit of Normal

Figure 2

Kaplan-Meier curves depicting liver enzyme (AST, ALT, GGT) levels over time, for placebo and naltrexone arms. A) HEE >5xULN (DAIDS Grades 3, 4) were censored; B) HEE of two DAIDS Grades magnitude were censored.