Association of incomplete adherence to antiretroviral therapy with cardiovascular events and mortality in virologically suppressed persons with HIV: the Swiss HIV cohort study

Background: Incomplete antiretroviral therapy (ART) adherence, even if sufficient to maintain viral suppression, is associated with enhanced inflammation in persons with HIV (PWH). However, its clinical implications remain unknown. Methods: PWH enrolled in the Swiss HIV Cohort Study without a history of cardiovascular disease (CVD) who initiated ART between 2003 and 2018 and had viral suppression ( /=6 months were evaluated. The association between incomplete self-reported ART adherence (>/=1 or >/=2 missed doses in the last month) and (1) any CVD event (myocardial infarction, revascularization, cerebral hemorrhage, stroke, and/or death due to CVD event) or (2) non-CVD-related death was evaluated using adjusted Cox proportional hazards models. Results: A total of 6971 PWH (74% male) were included in the analysis (median age [interquartile range {IQR}], 39 [32-47] years). The median (IQR) follow-up was 8 (4-11) years, with 14 (8-23) adherence questionnaires collected per participant. In total, 205 (3%) participants experienced a CVD event, and 186 (3%) died a non-CVD-related death. In an adjusted competing risk model where missing data were imputed, missing >/=1 ART dose showed an increased, but not statistically significant, risk for CVD events (hazard ratio [HR], 1.23; 95% CI, 0.85-1.79; P = .28). Non-CVD-related mortality showed a statistically significantly increased risk with missing >/=1 ART dose (HR, 1.44; 95% CI, 1.00-2.07; P = .05) and missing >/=2 ART doses (HR, 2.21; 95% CI, 1.37-3.57; P = .001). Conclusions: Incomplete ART adherence was significantly associated with an increased risk for non-CVD-related mortality in PWH with virologic suppression. This highlights the potential role of nonadherence to ART as a driver of non-AIDS clinical outcomes.