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The association of methadone use with physical function and frailty among persons who inject drugs
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24 December 2025
Future research should also investigate the impact of MMT on muscle mass or muscle quality, and the impact of other opioid agonist therapies, such as buprenorphine, on frailty and physical function. . we underscore the importance of early screening and intervention for frailty and physical function among individuals receiving such treatment and the integration of clinical models designed to intervene and prevent further progression of aging-related conditions [30]. The incorporation of a geriatric-based approach to care at outpatient treatment clinics may help attenuate or prevent complications associated with aging, such as hospitalization, loss of independence and decreased quality of life [13]. Additionally, our findings encourage the consideration of more optimized long-term strategies for managing substance use disorders.
Abstract
Background and Aims
Persons who inject drugs (PWID) experience a high burden of early-onset frailty, primarily due to multifactorial causes such as infections (human immunodeficiency virus [HIV], hepatitis C virus [HCV]), substance use, and polypharmacy. Methadone, although an effective treatment for opioid use disorder, has demonstrated toxicity across several body systems that may impact or accelerate the aging process. Therefore, the purpose of this analysis was to determine the association of methadone use with frailty and physical function among PWID.
Design
This study performed a retrospective analysis from the AIDS Linked to IntraVenous Experience (ALIVE) longitudinal cohort between 2005 and 2020, using multivariable mixed effect logistic regression, adjusting for demographics, body mass index, substance use, HIV, and comorbidities. Our study population is from the AIDS Linked to the Intravenous Experience (ALIVE) cohort. This community-based cohort, initiated in 1988, recruits people with a history of injection drug use.
Setting
Baltimore, Maryland, United States.
Participants
Adult participants (≥18 years) were recruited into the ALIVE cohort if they reported a history of or current injection drug use. Our study included 2153 participants with 13 909 person-years of follow-up.
Measurements
Methadone usage, whether prescribed or non-medical, was self-reported by participants during study follow-up. The primary outcome measurement was frailty as defined by the Fried frailty phenotype. Physical function was measured using grip strength and 4-m gait speed.
Findings
At baseline, 883 were currently using methadone. Median age was 48 (interquartile range: 42, 53) years; 81% were Black, 34% female, 80% had incomes <$5000, and 31% were living with HIV. Methadone use was associated with 25% higher odds of frailty (95% confidence interval [CI]: 1.09, 1.43). This difference suggested that the odds of frailty among individuals using methadone at age 50 were comparable to those not using methadone at age 54. Methadone use was associated with lower average grip strength [-0.71 kg (95% CI: -0.94, -0.48)], but not slower gait speed. About 25% of the participants reported three or more comorbidities, and those that were on methadone had a higher proportion of having more comorbidities.
Current use of opiates (OR = 1.18, 95% CI = 1.10-1.38), having HIV (OR = 1.28, 95% CI = 1.05-1.56), having three or more comorbidities (OR = 1.95, 95% CI = 1.63-2.32) and having severe depression (OR = 3.08,
95% CI = 2.69-3.52) were also related to higher risk of frailty, when considering frailty as two categories (robust vs frail).
Conclusions
Among persons who inject drugs, those using methadone appear to be more likely to experience frailty at an earlier age compared with those not using methadone. Early screening for frailty and other geriatric conditions may be warranted among individuals with active methadone use in this population.
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