HIV-Tat Exacerbates the Actions of Atazanavir, Efavirenz, and Ritonavir on Cardiac Ryanodine Receptor (RyR2).

The incidence of sudden cardiac death (SCD) in people living with HIV infection (PLWH), especially those with inadequate viral suppression, is high and the reasons for this remain incompletely characterized. The timely opening and closing of type 2 ryanodine receptor (RyR2) is critical for ensuring rhythmic cardiac contraction-relaxation cycles, and the disruption of these processes can elicit Ca waves, ventricular arrhythmias, and SCD. Herein, we show that the HIV protein Tat (HIV-Tat: 0-52 ng/mL) and therapeutic levels of the antiretroviral drugs atazanavir (ATV: 0-25,344 ng/mL), efavirenz (EFV: 0-11,376 ng/mL), and ritonavir (RTV: 0-25,956 ng/mL) bind to and modulate the opening and closing of RyR2.