Acute myocardial infarction associated with abacavir and tenofovir based antiretroviral drug combinations in the United States

Abstract

Introduction Although 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. Methods Using 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. Results Over 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. Conclusion The 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.

Vascular dysfunction and body mass index in African adults with HIV

“…Decreases in nitric oxide result in decreased vascular compliance. In contrast, Dorjee, Desai [54] reported that while some ART regimens such as abacavir and tenofovir based drug combinations have been associated with increased cardiovascular risk, tenofovir and emtricitabine-efavirenz were associated with a lower risk of acute myocardial infarction [54]. However, more studies are needed to validate these findings.…”

Direct and indirect cardiovascular and cardiometabolic sequelae of the combined anti-retroviral therapy on people living with HIV

“…The incidence of coronary heart disease rose noticeably with exposure to cART, especially those containing protease inhibitors compared to those that contained non-nucleoside reverse transcriptase inhibitors (relative risk of 1.16 vs 1.05 respectively). Dorjee et al (2021) ( Dorjee et al, 2021 ) further found that tenofovir-emtricitabine-raltegravir is associated with an increased risk of acute myocardial infarction. However, this association was heavily questioned as these PLHIV were found to have an adverse cardiovascular disease risk prior to receiving cART.…”

Factors influencing left ventricular diastolic dysfunction on echocardiography of people living with HIV in Kunming, China

“…The occurrence of cardiovascular disease (CVD) in PLWH is of great concern. Recently, the number of patients with HIV-related CVD, 6 particularly atherosclerosis, 7 myocardial infarction, 8 and heart failure, 9 has been increasing globally. Risk factors for CVD in PLWH include common risk factors for CVD, ART, inflammatory response, and immune dysfunction caused by HIV infection.…”