Why HIV Infection Prolongs QTc Interval

HIV-positive patients experience sudden death more often than the general population, but scant evidence connects HIV severity and highly active antiretroviral therapy (HAART) regimens.

HAART reduces HIV-related complications and death, but with the HIV population aging and with HAART’s propensity to cause drug-induced disease, HIV-infected individuals are more likely to have metabolic, renal, and cardiovascular disease than ever before. Previous research suggested that HIV and HAART may prolong corrected QT (cQT) interval, leading to torsade de pointes, ventricular tachycardia, and ventricular fibrillation. Viral infection of the heart, autonomic neuropathy, and protease inhibitors are possible mechanisms.

Now, a team of Italian researchers has found advanced HIV infection prolongs cQT independent of HAART. They analyzed ECG findings of 351 consecutively enrolled HIV patients retrospectively. The primary endpoint was prevalence of long cQT (>470 ms in women and >450 ms in men). The secondary endpoints were predictors of cQT prolongation, and the association between HAART and HIV severity with long cQT.

Prolonged cQT was a common finding (7.4%) and associated with low CD4-positive cell count nadir. It was unassociated with traditional cardiovascular risk factors.

Past studies have linked low CD4 count and progression to AIDS with general cardiovascular disease. Animal studies have found HIV infection reduces potassium outward channels on mouse myocardium. Protease inhibitors, except atazanavir, block hERG channels, which can prolong QT interval. HIV experts have consistently contended that protease inhibitors’ ability to control HIV infection outweighs this proarrhythmic effect.

The study’s authors recommend monitoring HIV patients closely, especially if they have a low CD4-positive cell count or severe disease. Providers may use a Holter ECG or implanted loop recorder to determine arrhythmic burden throughout the day. Prudent management includes avoiding cQT prolonging medications and administering beta blockers to reduce arrhythmia risk.

Disease severity, as evidenced by low CD4-positive cell count, is the only predictor of prolonged cQT interval in HIV patients.

Reference

Gili S, et al. Prevalence and predictors of long corrected QT interval in HIV-positive patients: a multicenter study. J Cardiovasc Med. 2016;17:000-000.