Role of antiretroviral treatment in prolonging QTc interval in HIV-positive patients

Chinello, Pierangelo; Lisena, Francesco Paolo; Angeletti, Claudio; Boumis, Evangelo; Papetti, Federica; Petrosillo, Nicola

doi:10.1016/j.jinf.2006.11.001

Cited by 42 publications

(49 citation statements)

References 25 publications

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“…The ORs of presenting a QTc interval prolongation among patients taking nelfinavir with or without AZT were 12.66 (95% CI, 2.33-68.69) and 3.94 (95% CI, 0.79-19.70), respectively. 57 These findings support the concept of a multiple-hit hypothesis for causing QTc prolongation.…”

Section: Electrophysiology Of Ventricular Repolarizationsupporting

confidence: 70%

“…The evidence so far suggests that QT prolongation does not seem to be a class effect. Lopinavir, nelfinavir, ritonavir, and saquinavir have been shown to block HERG channels and cause QTc prolongation, 57 whereas on the other hand, atazanavir did not show statistically significant QTc prolongation at 1-month follow up from baseline. 58 These observations lead to the conclusion that there are individual differences between various drugs from the same group and further studies are needed to clarify this issue.…”

Section: Electrophysiology Of Ventricular Repolarizationmentioning

confidence: 91%

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HIV Protease Inhibitors Induced Prolongation of the QT Interval: Electrophysiology and Clinical Implications

Singh

Arora²,

Jawad³

2010

American Journal of Therapeutics

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In recent years, there have been considerable advancements in our understanding of the role of ionic channels in mediating cardiac repolarization. Advances in ion channel cloning have generated great interest in the diagnosis and understanding of electrophysiological processes involved in ventricular repolarization, particularly the QT interval prolongation and abnormal T- and T/U-wave morphology associated with torsades de pointes. Unfortunately, a number of drugs are being increasingly recognized to alter the repolarization and, thus, increase the propensity for various cardiac arrhythmias, especially polymorphic ventricular tachycardia, syncope, and even ventricular fibrillation and sudden death. Recently, HIV protease inhibitors have been shown to cause prolongation of ventricular repolarization. This review focuses on electrophysiological mechanisms underlying drug-induced QTc prolongation in relation to protease inhibitors and its clinical implications.

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Section: Electrophysiology Of Ventricular Repolarizationsupporting

confidence: 70%

Section: Electrophysiology Of Ventricular Repolarizationmentioning

confidence: 91%

HIV Protease Inhibitors Induced Prolongation of the QT Interval: Electrophysiology and Clinical Implications

Singh

Arora²,

Jawad³

2010

American Journal of Therapeutics

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“…In a recent case-control study conducted at our institute, we were able to demonstrate an association between the administration of efavirenz or nelfinavir and the development of QT interval prolongation in HIV-infected individuals [17]. Moreover, we provided evidence that the risk of QT prolongation increased when efavirenz or nelfinavir therapy was combined with zidovudine therapy.…”

Section: Acknowledgmentsmentioning

confidence: 55%

QT Interval Prolongation and Antiretroviral Treatment: Another Point of Interest

Chinello

Petrosillo

2007

Clinical Infectious Diseases

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“…However, in a case study of a patient with recurrent syncope and polymorphic ventricular tachycardia, efavirenz was found to mediate QTc prolongation, with the potential to produce life-threatening arrhythmia (6). Furthermore, a study by Chinello and colleagues reported an increased risk of prolonged QTc interval among patients taking efavirenz (7).…”

Section: Discussionmentioning

confidence: 99%

No Effect of a Single Supratherapeutic Dose of Lersivirine, a Next-Generation Nonnucleoside Reverse Transcriptase Inhibitor, on Corrected QT Interval in Healthy Subjects

Vourvahis

Wang

Ndongo

et al. 2012

Antimicrob Agents Chemother

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The objective of this study was to investigate the effect of a supratherapeutic dose of lersivirine (LRV) on corrected QT (QTc) interval using Fridericia's equation (QTcF) in healthy subjects. In this randomized, single-dose, placebo-and active-controlled 3-way crossover study, healthy adult males (n ‫؍‬ 48) were randomized to receive LRV (2,400 mg), moxifloxacin (400 mg), or placebo for each treatment period. Triplicate 12-lead electrocardiogram measurements were performed, PK samples were collected, and vital signs were measured. Adverse event monitoring and safety laboratory testing were performed. All subjects were white (mean age, 39 years; body mass index [BMI], 25.6 kg/m 2 ) and completed the study. Following LRV administration, the upper bound of the 90% confidence interval (CI) for time-matched adjusted mean differences to placebo QTcF at each time point postdose was below the regulatory threshold of 10 ms, satisfying the criteria for a negative thorough QT/QTc study. The highest upper bound of QTcF 90% CI occurred at 6 h for LRV (3.32 ms; 90% CI, 1.47 to 5.17 ms). The study was deemed adequately sensitive as the lower bound of the 90% CI for the adjusted mean QTcF differences between moxifloxacin and placebo at the moxifloxacin historical T max of 3 h was >5 ms (15.29 ms; 90% CI, 13.44 to 17.14 ms). There was no statistically significant relationship between LRV exposure and placebo-adjusted change from baseline QTcF or clinically significant changes in QRS complex, pulse rate (PR) interval, heart rate, or blood pressure. LRV (2,400 mg) did not prolong the QTcF interval, and no clinically relevant electrocardiogram or vital sign changes were observed in healthy subjects.

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Role of antiretroviral treatment in prolonging QTc interval in HIV-positive patients

Cited by 42 publications

References 25 publications

HIV Protease Inhibitors Induced Prolongation of the QT Interval: Electrophysiology and Clinical Implications

HIV Protease Inhibitors Induced Prolongation of the QT Interval: Electrophysiology and Clinical Implications

QT Interval Prolongation and Antiretroviral Treatment: Another Point of Interest

No Effect of a Single Supratherapeutic Dose of Lersivirine, a Next-Generation Nonnucleoside Reverse Transcriptase Inhibitor, on Corrected QT Interval in Healthy Subjects

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