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 an 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 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.

Extended-release naltrexone reduces alcohol consumption among released prisoners with HIV disease as they transition to the community

“…Therefore, evaluating the effect of XR-NTX on alcohol consumption among PLH after being released from incarceration is a major public health priority. Previously, we provided preliminary evidence on the high acceptance of XR-NTX (Springer, 2012; Springer et al, 2014), correlates of retention on XR-NTX one month after release (Krishnan et al, 2015; Springer et al, 2015), as well as the hepatic safety among this population (Vagenas et al, 2014), suggesting it may be effectively implemented within the CJS. Key findings from this study are the lack of difference in alcohol consumption using Bayesian modeling, yet a number of new findings did emerge.…”

“…The study protocol and methods have previously been described extensively (Springer et al, 2014), along with preliminary safety (Vagenas et al, 2014) and early post-release retention data (Springer et al, 2015). Briefly, Project INSPIRE is a prospective, double-blinded randomized, placebo-controlled trial of XR-NTX among incarcerated PLH with AUDs who were transitioning to the community from September 2010 and February 2015.…”

Design and methods of a double blind randomized placebo-controlled trial of extended-release naltrexone for HIV-infected, opioid dependent prisoners and jail detainees who are transitioning to the community

“…Concerns regarding hepatic safety of XR-NTX have been expressed prior to initiating this intervention given the impact of cART on liver function and the high rate of Hepatitis C virus co-infection. New evidence, however, now provides assurances of XR-NTX safety in HIV-infected patients on cART [68, 69]. Given the consequences of relapse to opioid use after release from the correctional system, XR-NTX can prevent relapse, and prevent the spiral of poor care leading to increased HIV risk behaviors, poor adherence to cART, and possible risk of infecting those in the community.…”

Medications for Treatment of Opioid Use Disorder among Persons Living with HIV

“…This study suggests the risk of hepatotoxicity is minimal in HIV-infected participants treated with naltrexone, and that there are no adverse immunologic or virologic effects of treatment. The safety of extended-released naltrexone (XR-NTX) is further demonstrated in PLH randomized to XR-NTX following release from prison, who experienced no change in hepatic enzymes compared to those receiving placebo in two double-blind, placebo-controlled randomized trials in PLH with alcohol use disorders and those with opioid use disorders [41], nor in the completed trials themselves [12, 42, 43]. HIV/HCV co-infection has no effect on XR-NTX hepatic safety [44].…”