Risk of Cardiovascular Events Among Patients Initiating Efavirenz-Containing Versus Efavirenz-Free Antiretroviral Regimens

In the United States, there are an estimated 1.2 million people living with human immunodeficiency virus (HIV) infection [1]. These individuals face a number of health issues including increased risk for cardiovascular (CV) disease. Several analyses have evaluated the incidence of myocardial infarction (MI) among HIV-positive (HIV+) individuals, with reported rates ranging from 3.5 per 1000 people to 11.1 per 1000 people [2]. Compared with similarly aged HIV-negative (HIV−) people, HIV+ people had MI rates that were 1.5 to 2 times greater [3]. Human immunodeficiency virus-positive infection has also been associated with increased risk for ischemic stroke [4]. Although antiretroviral (ARV) therapy—the current standard of care for the treatment of HIV infection—reduces HIV-related morbidity and mortality [5], associations between the use of certain ARVs and increased risk for CV events have been reported. Two nucleoside reverse-transcriptase inhibitors (NRTIs), abacavir and didanosine, have been linked to increases in MI, although the pathway through which these medications affect MI risk is unknown [6–8]. In addition, several analyses have found that HIV+ patients treated with protease inhibitors (PIs), specifically indinavir and lopinavir, had greater risk of experiencing a CV event, including MI and coronary artery disease [2, 8, 9]. It has been hypothesized that the increase in risk associated with these PIs is due in part to dyslipidemia resulting from PI use [10]. Efavirenz (EFV), a non-NRTI (NNRTI), has been associated with hyperlipidemia in some patients with HIV [11]. Although abnormal lipid levels are known to be associated with increased risk of MI [12], the association between EFV use and CV disease is unclear. Two large studies have found no association with EFV use and MI but did not examine other CV outcomes [7, 9], although another analysis reported an increase in the risk of incident CV events associated with NNRTI use [13]. Therefore, the objective of this analysis was to compare incidence rates (IRs) and hazards of CV events between patients initiating EFV-containing vs EFV-free ARV regimens in 2 real-world databases. The CV events evaluated in this analysis included MI, stroke, percutaneous coronary intervention (PCI), coronary artery bypass graft (CABG), and a composite of any of the aforementioned CV events.