Protease Inhibitor-Associated QT Interval Prolongation

OBJECTIVE: To evaluate the literature on protease inhibitor (Pp associated QT interval prolongation and risk for torsade de pointes in patients infected by HIV. DATA SOURCES: Primary literature was identified through MEDLINE (1950-August 2011) and EMBASE (1980-August 2011), using the following search terms: antiretroviral agents, HIV, protease inhibitors, QTc, QT prolongation, and torsade de pointes. STUDY SELECTION AND DATA EXTRACTION: English-language case reports of antiretroviral therapy associated QT interval prolongation, studies of healthy volunteers, or studies that evaluated the impact of Pls on QT interval in patients infected with HIV were reviewed and selected. Article bibliographies and conference abstracts were also reviewed. DATA SYNTHESIS: Several case reports, as well as in vitro data, have implicated Pis as a potential cause of QT interval prolongation and/or torsade de pointes. Saquinavir, therapeutically boosted with the potent CYP3A4 inhibitor ritonavir, was the only PI shown to be associated with significant QT interval prolongation in studies with healthy volunteers. While 1 case control study in HIV-infected patients found that nelfinavir or efavirenz, a nonnucleoside reverse transcriptase inhibitor, increased the risk of QT interval prolongation, larger prospective studies have not demonstrated any significant increase in QT interval following exposure to Pls. Similar risk factors for QT interval prolongation seen in non HIV-infected patients, such as older age, female sex, ethnicity, cardiac conditions, diabetes mellitus, and concomitant use of other QT interval prolonging medications, especially methadone, were risk factors identified in studies of HIV-infected patients. CONCLUSIONS: Pls do not appear to independently predispose patients to QT interval prolongation. However, other risk factors (both HIV-related and non HIV-related) may increase the risk of QT interval prolongation. Available data suggest that baseline and follow-up electrocardiogram monitoring are unnecessary precautions, but may be considered in patients who are initiating PI therapy and are on multiple medications with proarrhythmic potential and/or have multiple comorbidities, increasing the risk.