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

Alexander R Bazazi, Gabriel J Culbert, Martin P Wegman, Robert Heimer, Adeeba Kamarulzaman, Frederick L Altice, Alexander R Bazazi, Gabriel J Culbert, Martin P Wegman, Robert Heimer, Adeeba Kamarulzaman, Frederick L Altice

Abstract

Introduction: Mortality is elevated after prison release and may be higher in people with HIV and opioid use disorder (OUD). Maintenance with opioid agonist therapy (OAT) like 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, mostly related to HIV. 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: Postrelease mortality in this sample of men with HIV and OUD was extraordinarily high, and most deaths were likely of infectious etiology. No effect of prerelease methadone on postrelease mortality was observed, which may be due to study limitations or an epidemiological context in which inadequately treated HIV, and not inadequately treated OUD, is the main cause of death after prison release.

Trial registration: NCT02396979. Retrospectively registered 24/03/2015.

Keywords: HIV; Methadone; Mortality; Opioid use disorder; Prison.

Conflict of interest statement

FLA reports Speakers Bureau: Simply Speaking HIV, Gilead Sciences, Merck, Clinical Care Options (role: speaker); Grants: NIH, NIDA, HRSA, SAMHSA, Gilead Foundation (role: PI); Advisory Board: Merck, Gilead (role: member/consultant). None these conflicts are related to this research. ARB, GJC, MPW, RH, and AK have no competing interests to declare.

© 2022. The Author(s).

Figures

Fig. 1
Fig. 1
Participant flow diagram. *Reasons for exclusion not mutually exclusive. **All post randomization withdrawals and deaths occurred shortly after screening and before intervention receipt
Fig. 2
Fig. 2
Unadjusted and adjusted probability of survival. Left panel showing unadjusted probability of survival, Kaplan–Meier survival curves. Right panel showing Kaplan–Meier survival curves adjusted for baseline covariates using inverse probability weighting

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