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Evidence for a relationship between polysubstance use, depression, and adherence to antiretroviral therapy (ART) is limited. The objectives of this study were to examine the associations of depression, illicit drug, and alcohol use with adherence to ART. People living with HIV (PLHIV) from the Miami Adult Studies on HIV cohort were asked about the number of doses of their ART medication missed to assess ART adherence. Harmful alcohol drinking was evaluated using the Alcohol Use Disorders Identification Test and illicit substance use assessed with self-report and urine screen. The Center for Epidemiologic Studies Depression Scale was used to assess depression symptoms. Of 391 PLHIV, 16.6% missed at least one dose (range:1–4) in the past four days. Cocaine/crack, opiate use, and depression were significantly independently associated with a greater mean number of doses missed. The mean number of doses missed was significantly greater among participants who used alcohol in combination with cocaine/crack, marijuana, and tobacco compared to non-users. In conclusion, polysubstance use increased the risk for poor ART adherence among PLHIV. The use of cocaine/crack or opiates individually and depressive symptoms also promote poor ART adherence. An integrated approach targeting substance disorders and depression may help achieve better ART adherence.

Polysubstance use and adherence to antiretroviral treatment in the Miami Adult Studies on HIV (MASH) cohort