Southwestern Medical Center at Dallas,and 6 Veterans Affairs North Texas Health Care System, Dallas, TX, USA Background Atazanavir (ATV), an HIV protease inhibitor (PI) that may be preferred for the treatment of HIV-infected patients with cardiovascular comorbidities because of its favourable effects on plasma lipids, has been associated with cardiac rhythm disturbances.
ObjectiveTo quantify the effect of ATV on corrected QT (QTc) and QTc dispersion (QTd), markers of the potential for cardiac dysrhythmia, in patients switching from other PIs to ATV.
MethodsIn this prospective, single-centre, open-label study, 12-lead electrocardiograms were performed for subjects at baseline, 2 h after the first dose of ATV, and 1 month after initiation of ATV.
ResultsTwenty-one patients (19 received ritonavir-boosted ATV) completed the study. There was a trend towards an increase in the QTc at 2 h after the first dose [mean AE standard deviation 3.19 AE 8.0 ms; 95% confidence interval (CI) À 0.47 to 6.85 ms; P 5 0.084]. There was no difference between QTc values at baseline and at 1 month ( À 1.5 AE 8.75 ms; 95% CI À 5.50 to 2.46; P 5 0.43). There was a nonsignificant decrease in the QTd between baseline and 2 h ( À 5.1 AE 15.19 ms; 95% CI À 13.22 to 2.96; P 5 0.197) and between baseline and 1 month ( À 0.61 AE 15.04 ms; 95% CI À 8.1 to 6.87; P 5 0.865). A significant increase in the PR interval (7.4 AE 10.7 ms; 95% CI 2.5 to 12.25 ms; P 5 0.005) was observed at 1 month.
ConclusionsThe use of ATV did not result in increases in the QTc interval or QTd. However, PR interval monitoring may be warranted in patients with underlying heart block or those treated with atrioventricular nodal blocking agents.
IntroductionAtazanavir (ATV) is the newest protease inhibitor (PI) approved for use in highly active antiretroviral therapy (HAART). Recent studies suggest that this PI may not be associated with the dyslipidaemia commonly seen with other PIs, and thus ATV may be an alternative for HIVpositive patients experiencing this adverse drug effect [1,2]. However, ATV has been associated with atrioventricular (AV) block, bradycardia and prolongation of the corrected QT (QTc) interval in some patients [3,4]. Acquired long-QT syndrome, drug-induced QT prolongation, and torsades de pointes (TdP) have also been previously reported in HIV-infected patients [5][6][7][8][9][10][11][12][13]
Methods
PatientsThis was a prospective, single-centre, open-label study.Patients were enrolled in the study from November 2003 to December 2004. Patients were included in the study if they were being treated with HAART at the HIV Clinic at the Dallas Veterans Affairs (VA) Medical Center, were418 years of age, had a documented diagnosis of HIV, were able to give informed consent, were capable of attending ambulatory care services, and were deemed appropriate candidates for the addition of ATV to their HAART regimen. Patients were excluded if they were hospitalized, required to take oral antacids within 2 h of ATV administration, histamine receptor antagonists an...