Abstract
BACKGROUND: Despite effective antiretroviral therapy (ART), serious non-AIDS events (SNAEs), including cardiovascular disease and death, remain prevalent among people with HIV (PWH). Imperfect ART adherence despite viral suppression may contribute to this risk, underscoring the need to clarify the relationship between adherence, viral load dynamics, and SNAE development. METHODS: We performed an analysis of deidentified data of participants in the prospective observational Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections (ACTG) A5001 and A5322 studies. The baseline was defined as the time at the first viral suppression to <200 copies/mL after treatment initiation. Antiretroviral therapy adherence was assessed using the periodically administered ACTG self-report questionnaire and dichotomized as >90% versus ≤90% adherence. Data were primarily analyzed using inverse probability of censoring weights modeling. RESULTS: Among 2940 participants followed for a median of 6.2 years, 237 SNAEs occurred, comprising 103 deaths and 134 cardiovascular events. Nearly all participants (95.9%) remained virally suppressed to <200 copies/mL over the full duration of follow-up. Adherence to ART >90% showed a protective effect on the development of all SNAEs: adjusted hazard ratio (aHR) 0.612 (95% confidence interval .390-.961). When only the development of the first SNAE was considered, the association remained substantially similar: aHR 0.641 (95% confidence interval .400-1.027). CONCLUSIONS: Adherence to ART >90% compared to ≤90% reduces SNAE risk even in virally suppressed PWH, underscoring the need for continued adherence support to improve long-term health outcomes for PWH.