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The present research was supported by the Consejo Nacional de Investigaciones Científicas y Técnicas, the Buenos Aires University School of Medicine, and the Agencia Nacional de Promoción Científica y Tecnológica (Argentina). The authors have no conflicts of interest to declare.

Objectives: Owing to advances in antiretroviral therapy (ART), we re-examined minimum ART adherence levels necessary to achieve sustained HIV-1 viral load (VL) suppression among people with HIV who use drugs (PHIV-PWUD). Design and methods: We used data from ACCESS, a community-recruited prospective cohort of PHIV-PWUD in Vancouver, Canada. We calculated adherence using the proportion of days of ART dispensed in the year before each VL measurement. We used generalized linear mixed-effects models to identify adherence- and ART regimen-related correlates of VL suppression (<200 copies/ml). We employed probit regression models and generated dose–response curves to estimate the minimum adherence level needed to produce VL suppression in 90% of measures, stratified by regimen and calendar-year. Results: Among 837 ART-exposed PHIV-PWUD recruited between 1996 and 2017, the overall estimated adherence level necessary to achieve 90% VL suppression was 93% (95% confidence interval [CI]: 90–96). This differed by regimen: 69% (95% CI: 45–92) for integrase inhibitor (INSTI)-, 96% (95% CI: 92–100) for boosted protease inhibitor (bPI)-, and 98% (95% CI: 91–100) for non-nucleoside reverse transcriptase inhibitor-based regimens. In multivariable analysis, INSTI-based regimens were positively associated with VL suppression (vs. bPIs), while un-boosted PIs and other regimens were negatively associated. We observed a decreasing temporal trend of estimated adherence necessary for 90% VL suppression, dropping to 64% (95% CI: 50–77) during 2016–2017. Conclusion: Although high levels of ART adherence were necessary to achieve consistent VL suppression, the minimum necessary adherence levels decreased over time. Overall, INSTI-based regimens performed the best, suggesting that they should be preferentially prescribed to PHIV-PWUD.