Abstract
IntroductionAlthough individual antiretroviral drugs have been shown to be associated with elevated cardiovascular disease (CVD) risk, data are limited on the role of antiretroviral drug combinations. Therefore, we sought to investigate CVD risk associated with antiretroviral drug combinations.MethodsUsing an administrative health-plan dataset, risk of acute myocardial infarction (AMI) associated with current exposure to antiretroviral drug combinations was assessed among persons living with HIV receiving antiretroviral therapy (ART) across the U.S. from October 2009 through December 2014. To account for confounding-by-indication and for factors simultaneously acting as causal mediators and confounders, we applied inverse probability of treatment weighted marginal structural models to longitudinal data of patients.ResultsOver 114,417 person-years (n = 73,071 persons) of ART exposure, 602 cases of AMI occurred at an event rate of 5.26 (95% CI: 4.86, 5.70)/1000 person-years. Of the 14 antiretroviral drug combinations studied, persons taking abacavir-lamivudine-darunavir had the highest incidence rate (IR: 11/1000; 95% CI: 7.4–16.0) of AMI. Risk (HR; 95% CI) of AMI was elevated for current exposure to abacavir-lamivudine-darunavir (1.91; 1.27–2.88), abacavir-lamivudine-atazanavir (1.58; 1.08–2.31), and tenofovir-emtricitabine-raltegravir (1.35; 1.07–1.71). Tenofovir-emtricitabine-efavirenz was associated with reduced risk (0.65; 0.54–0.78). Abacavir-lamivudine-darunavir was associated with increased risk of AMI beyond that expected of abacavir alone, likely attributable to darunavir co-administration. We did not find an elevated risk of AMI when abacavir-lamivudine was combined with efavirenz or raltegravir.ConclusionThe antiretroviral drug combinations abacavir-lamivudine-darunavir, abacavir-lamivudine-atazanavir and tenofovir-emtricitabine-raltegravir were found to be associated with elevated risk of AMI, while tenofovir-emtricitabine-efavirenz was associated with a lower risk. The AMI risk associated with abacavir-lamivudine-darunavir was greater than what was previously described for abacavir, which could suggest an added risk from darunavir. The results should be confirmed in additional studies.
Highlights
Individual antiretroviral drugs have been shown to be associated with elevated cardiovascular disease (CVD) risk, data are limited on the role of antiretroviral drug combinations
Antiretroviral medications are universally prescribed in combinations, but to date few studies have systematically evaluated the risk of cardiovascular disease associated with exposure to antiretroviral drug combinations; most CVD risk assessments have been made for individual drugs [9]
We investigated the relationship between receipts of various antiretroviral drug combinations containing agents from four major drug classes, including nucleos(t)ide reverse transcriptase inhibitors (NRTI), non-nucleoside reverse transcriptase inhibitors (NNRTI), protease inhibitors (PI), and integrase strand transfer inhibitors (InSTI), used in the treatment of HIV infection and the subsequent risk of acute myocardial infarction (AMI)
Summary
Individual antiretroviral drugs have been shown to be associated with elevated cardiovascular disease (CVD) risk, data are limited on the role of antiretroviral drug combinations. We sought to investigate CVD risk associated with antiretroviral drug combinations. As ART options expand and costs of treatment decline, understanding the toxicities associated with the use of antiretroviral agents is needed to improve health outcomes of PLHIV. Antiretroviral medications are universally prescribed in combinations, but to date few studies have systematically evaluated the risk of cardiovascular disease associated with exposure to antiretroviral drug combinations; most CVD risk assessments have been made for individual drugs [9]
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