Impact of Prerelease Methadone on Mortality Among People with HIV and Opioid Use Disorder After Prison Release: Results from a Randomized and Participant Choice Open-Label Trial in Malaysia

Abstract

Introduction: Mortality is elevated after prison release and may be higher in people with HIV and opioid use disorder (OUD). Opioid agonist therapy (OAT) with methadone or buprenorphine reduces mortality in people with OUD and may confer benefits to people with OUD and HIV leaving prison. Survival benefits of OAT, however, have not been evaluated prospectively in people with OUD and HIV leaving prison. Methods:This study prospectively evaluated mortality after prison release and whether methadone initiated before release increased survival after release in a sample of men with HIV and OUD (n=291). We linked national death records to data from a controlled trial of prerelease methadone initiation conducted from 2010 to 2014 with men with HIV and OUD imprisoned in Malaysia. Vital statistics were collected through 2015. Allocation to prerelease methadone was by randomization (n=64) and participant choice (n=246). Cox proportional hazards models were used to estimate treatment effects of prerelease methadone on postrelease survival. Results: Overall, 62 deaths occurred over 872.5 person-years (PY) of postrelease follow-up, a crude mortality rate of 71.1 deaths per 1000 PY (95% confidence interval [CI] 54.5–89.4). Most deaths were of infectious etiology. In a modified intention-to-treat analysis, the impact of prerelease methadone on postrelease mortality was consistent with a null effect in unadjusted (hazard ratio [HR] 1.3, 95% CI 0.6–3.1) and covariate-adjusted (HR 1.2, 95% CI 0.5–2.8) models. Predictors of mortality were educational level (HR 1.4, 95% CI 1.0–1.8), pre-incarceration alcohol use (HR 2.0, 95% CI 1.1–3.9), and lower CD4+ T-lymphocyte count (HR 0.8 per 100-cell/mL increase, 95% CI 0.7–1.0). Conclusions: Mortality after prison release in this sample of men with HIV and OUD was extraordinarily high and unaffected by prerelease methadone. Treatment of OUD alone may be insufficient to reduce mortality in settings where inadequately treated HIV is the main cause of death after prison release. Trial registration number: NCT02396979. Retrospectively registered 24/03/2015.

Association of Opioid Agonist Treatment With All-Cause Mortality and Specific Causes of Death Among People With Opioid Dependence

“…Characteristics of observational studies are presented in eAppendix 4 (eTables 7-15 in the Supplement). Cohorts ranged from 110 to 306 786 participants and included people from Europe (20 of 36 studies [58%]; 278 977 people), Australia (6 studies [17%]; 103 715 people), Asia (5 studies [14%]; 311 658 people), and North America (5 studies [14%]; 110 631 people). Seventeen studies (47%) concluded follow-up in 2010 or later.…”

“…Sixteen studies (44%) used OAT registry data. Mortality data during and after OAT were stratified by methadone treatment for 28 of 36 studies (78%) and by buprenorphine treatment for 8 of 36 studies (22%) . Type of OAT was unspecified in 6 of 36 studies (17%) …”

“…Three studies reported mortality after release from prison for people who initiated OAT during incarceration, compared with those who had opioid dependence and were incarcerated but had not received OAT. All-cause (RR, 0.24; 95% CI, 0.15-0.37) and drug-related (RR, 0.19; 95% CI, 0.10-0.37) mortality was lower during the first 4 weeks after release from prison for people who left incarceration still receiving OAT compared with those who were released but were not receiving OAT.…”

“…Nineteen observational studies conducted multivariable analyses adjusting for a range of potential confounders on all-cause (and in some cases overdose-related) mortality (Table 4). There was minimal change in the RRs after controlling for confounding, regardless of the variables included (eTable 21 in the Supplement).…”