Abacavir Use and Risk of Acute Myocardial Infarction and Cerebrovascular Events in the Highly Active Antiretroviral Therapy Era

Background. Some studies have suggested that exposure to antiretroviral therapy (ART) with abacavir is associated with an increased risk of acute myocardial infarction (AMI). Methods. Using the Veterans Health Administration’s Clinical Case Registry we calculated the risk of AMI and cerebrovascular events (CVA) associated with the cumulative use of abacavir and other nucleoside combinations. We also evaluated the impact of pre-existing chronic kidney disease on the selection of abacavir versus tenofovir in the last recorded ART regimen, and on highly active antiretroviral therapy–associated AMI and CVA risks. Results. A total of 19,424 human immunodeficiency virus–infected patients contributed 76,376 patient-years of follow. After adjusting for age, hypercholesterolemia, hypertension, type 2 diabetes, and smoking, the hazard ratio (HR) for each year of abacavir use was 1.18 (95% confidence interval [CI], .92–1.50; P 5 .191) for AMI and 1.16 (95% CI, .98–1.37; P 5 .096) for CVA. Abacavir use was more common among patients with prior chronic kidney disease than was tenofovir use (12.46% versus 7.15%; P 5 .0001), and chronic kidney disease was associated with a significantly higher risk of AMI (HR, 2.41; 95% CI, 1.73–3.36), and CVA (HR, 1.80; 95% CI, 1.44–2.24). Compared with patients who received neither tenofovir nor abacavir, patients who received tenofovir had lower risk of AMI (HR, 0.16; 95% CI, .08–.33; P 5 .0001) and CVA (HR, 0.22; 95% CI, .15–.32; P 5 .001). Use of abacavir was associated with lower risk of CVA (HR, 0.60; 95% CI, .45–.79). Conclusions. We observed no association between cumulative or current abacavir use and AMI or CVA. Abacavir use was more common than was tenofovir use among patients with prior chronic kidney disease, and chronic kidney disease independently predicted higher rates of AMI and CVA. In the potent antiretroviral therapy (ART) era, the overall increase in survival of human immunodeficiency virus (HIV)–infected patients has been associated with a shift in the underlying causes of death among such patients to fewer AIDS-related deaths and more deaths that are not AIDS-related. Several database analyses and observational cohort studies have reported a higher incidence of cardiovascular disease (CVD) among HIV-infected patients than among HIV-negative controls [1–5]. CVD now account for 8%–22% of deaths among HIV-infected patients, and this percentage appears to be increasing