Several antiretroviral therapy (ART) classes have been associated with increased myocardial infarction (MI) risk. No studies have examined cardiovascular disease (CVD) in people living with HIV (PLWH) on integrase strand transfer inhibitors (INSTI). We examine the risk of CVD in PLWH on INSTI-based regimens.
Using Truven Health Analytics MarketScan® databases for commercially insured and Medicaid covered adults, we identified PLWH newly initiated on ART between Jan 1, 2008 and Dec 30, 2015. New users were those without ART claims in the 6 months prior to study inclusion. The primary outcome, major adverse cardiac event (MACE), was a composite of acute MI, ischemic stroke, coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI) assessed through Dec 30, 2016. We excluded PLWH with MACE events 6 months prior to the first stable regimen start. We identified cardiac outcomes and covariates associated with risk of cardiac events using ICD-9-CM diagnosis and procedure codes and CPT-4 codes. Calendar-time specific inverse-probability-weighted Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for association between INSTI use and MACE. Propensity score models included potential predictors of CVD and INSTI use. Censoring occurred for the earliest of MACE events during the first 6 months of a stable regimen, 90 days post-ART switch, health plan disenrollment, death and study end.
20,459 new ART initiators were identified. 5,128 (25%) PLWH initiated INSTI-based regimens (raltegravir 33%, elvitegravir 49%, dolutegravir 18%). 11,191 (55%) initiated non-nucleoside reverse transcriptase inhibitors and 4,145 (20%) protease inhibitors. Median duration of follow-up was 561 (348, 985) days. Mean age was 40.6 years, 79% were male, and 17% were Medicaid insured. Hypertension was present in 9.5% of INSTI users vs 7.4% non-users; lipid lowering treatment in 19.8% vs 17.9%; diabetes in 6% vs 4.8% and smoking in 13.5% vs 10.2%. 161 MACE events occurred; acute MI 11 (0.21%) vs 55 (0.36%), stroke 14 (0.27%) vs 48 (0.31), CABG 1 (0.02%) vs 6 (0.04%), PCI 5 (0.1%) vs 21 (0.14%) of INSTI users vs. non-users. INSTI-based ART was associated with significantly lower risk of MACE events (HR 0.57; 95% CI 0.45, 0.73) compared to non-INSTI based regimens.
INSTI-based regimens were associated with a 43% decreased risk of CVD in this cohort. Validation of these findings in cohorts with longer follow up is needed.