Differential Effects of Substance Use on HIV Care and Symptom Outcomes: A Longitudinal Analysis Among People with HIV.

Among people with HIV (PWH), those with suboptimal antiretroviral therapy (ART) adherence face heightened risk for poor clinical outcomes. Substance use is a critical barrier in this population, yet most research treats substance use as a homogeneous risk factor. This study examined the differential effects of specific substances on HIV-related outcomes among PWH with suboptimal ART adherence. Using data from a randomized controlled trial conducted in New York City and Birmingham, AL ( = 300; July 20, 2023 to May 7, 2024), we tested whether baseline use of 10 substance classes predicted ART adherence self-efficacy, self-reported ART adherence, HIV self-management, and symptom distress at 6 and 12 months. Linear regression models were estimated across multiply imputed datasets, adjusting for intervention assignment, site, sociodemographic, and baseline outcomes. Results indicated that baseline cocaine use was significantly associated with lower self-reported adherence at 6 months ( = -5.03, < 0.050), methamphetamine use predicted poorer HIV self-management at 12 months ( = -2.92, < 0.050), hallucinogen use predicted lower adherence self-efficacy at 12 months ( = -20.26, < 0.050), and inhalant use was associated with greater HIV symptom distress at 6 months ( = 8.33, < 0.050). No significant associations were observed for cannabis, heroin, prescription opioids, stimulants, sedatives, or other substances. Findings highlight the importance of moving beyond generalized models of substance use in HIV care to account for the unique ways different substances affect HIV care and symptom outcomes. Tailoring interventions to substance-specific risk profiles may improve outcomes for PWH.