Antiretroviral Therapy and Cardiovascular Risk in People with HIV in the United States - An Updated Analysis

Background Several antiretroviral therapy (ART) medications have been associated with increased cardiovascular risk, but less is known about the safety of modern ART. We sought to compare the risk of major adverse cardiac events (MACE) among different ART regimens. Methods Using insurance claims databases from 2008-2020, we identified adults <65 years who newly initiated ART. We compared nucleoside reverse transcriptase inhibitor (NNRTI)-based regimens to protease inhibitors (PI)- and integrase inhibitors (INSTI)-based regimens. We used propensity score-weighted Kaplan-Meier functions to estimate the 6, 12, 18, 24, 36, and 48-months risk and risk differences (RD) of MACE. Results Among 37,935 ART initiators (median age 40 years, 23% female, 26% Medicaid-insured), 45% started INSTI-, 16% PI-, and 39% NNRTI-based regimens. MACE occurred in 418 individuals (1.1%) within 48 months after ART initiation. Compared to NNRTI initiators, the risk of MACE was higher at 12 months [RD 0.50, 95% CI (0.14, 0.99)], 18 months [RD 0.53, 95% CI (0.11, 1.06)], and 24 months [RD 0.62, 95% CI (0.04, 1.29)] for PI initiators, and at 12 [RD 0.20, 95% CI (0.03, 0.37)] and 18 months [RD 0.31, 95% CI (0.06, 0.54)] for INSTI initiators; the precision of estimates was limited for longer duration of follow-up. Conclusions Among ART initiators, PI-based and INSTI-based regimens were associated with higher short-term risk of MACE compared to NNRTI-based regimens. The pattern of association between INSTIs and PIs with excess risk of MACE was similar.