Severity and Number of Substances Used are Independently Associated with Antiretroviral Therapy Adherence Over Time among People with HIV in the Current Treatment Era.

Substance use is associated with decreased antiretroviral therapy (ART) adherence among people with HIV (PWH). Adherence plays a significant role in mediating the negative effects of substance use on HIV suppression and is a principal modifiable patient-level factor in improving HIV suppression and reducing ART drug resistance. Understanding substance use and ART adherence, particularly with rapidly changing substance use epidemiology and ART regimens, is vital to improving HIV care. Among 10,557 PWH (2010-2021) from 8 academic clinical sites nationally we examined longitudinal associations of substance use severity and number of substances used (measured using AUDIT-C and modified ASSIST) with patient-reported ART adherence (visual analog scale). Alcohol (68% any use, 18% unhealthy use [AUDIT-C > 4 men, > 3 women]), marijuana (33%), and methamphetamine (9%) use were most reported. Polysubstance use was common (32%). Both higher severity substance use and higher number of substances used were associated with lower ART adherence. Severity of methamphetamine use had the strongest dose-response association with ART adherence (low severity [ASSIST 1-3]: -3.05%, 95% CI: -4.23%, -1.87%; moderate [ASSIST 4-26]: -6.20%, 95% CI: -7.08%, -5.33%; high [ASSIST > 26]: -10.77%, 95% CI: -12.76%, -8.78%). Severe substance use, especially methamphetamine, and higher number of illicit drugs used were associated with declines in adherence at levels that were likely clinically meaningful in the modern era of ART. Findings support integrating substance use care with HIV care and potential benefits of harm reduction strategies for improving adherence such as encouraging lower levels of substance use and fewer number of substances used.