Autonomic neuropathy and prolongation of QT interval in human immunodeficiency virus infection

Villa, Antonio; Foresti, Valeriano; Confalonieri, Franco

doi:10.1007/bf01845498

Cited by 66 publications

(55 citation statements)

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“…The reason for this association is unclear, but could reflect the influence of chronic infection or cumulative exposure to anti-HIV drugs on the heart and the autonomic nervous system. Villa et al [7]. have reported greater QTc interval duration in HIVinfected patients with asymptomatic autonomic neuropathy than in HIV-infected patients without neurological disorder.…”

Section: Discussionmentioning

confidence: 96%

Relationship between HIV protease inhibitors and QTc interval duration in HIV‐infected patients: a cross‐sectional study

Charbit

Rosier

Bollens

et al. 2008

Brit J Clinical Pharma

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WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • The risks of torsade de pointes and QTc prolongation in HIV patients have been reported. • Authors have shown that four protease inhibitors (PIs) blocked human ether‐a‐go‐go‐related gene (hERG), the current that underlies QTc prolongation and drug‐induced proarrhythmia, and have also reported cases of torsades and suggested that PIs were responsible for these adverse events. • This earlier paper has had a major impact on the perception of the arrhythmogenic risk associated with PIs, and regulatory agencies in Europe and the USA have modified the labelling of PIs accordingly. WHAT THIS STUDY ADDS • The present study provides alternative explanations for QTc prolongation in a cohort of HIV patients and reports ECG abnormalities found in such patients. • It does not confirm that PIs play a significant role in QTc interval prolongation in HIV patients. • In contrast, it shows that QTc prolongation is related to common causes and to the duration of HIV infection rather than to anti‐HIV treatments. AIMS QTc interval prolongation and torsades de pointes have been reported in HIV‐infected patients. Protease inhibitors (PIs) are suspected to contribute to this adverse reaction. However, many factors can prolong QTc interval. We examined factors influencing QTc duration in HIV‐infected patients. METHODS Unselected HIV‐infected patients (n = 978) were enrolled in this prospective, single‐centre cross‐sectional study. Variables related to infection and treatments were collected. A digital electrocardiographic record was recorded in each patient and QT interval duration was measured and corrected using both Bazett's (QTcB) and Fridericia's (QTcF) formula. Results were analysed with a multivariable linear model. RESULTS After excluding arrhythmias and complete bundle branch blocks, QT interval was measured in 956 patients. The mean (SD) QTcB was 418 ms (23) and QTcF was 405 ms (20). QTc was found prolonged (>450 ms in women and >440 ms in men) in 129 [13.5%; 95% confidence interval (CI) 11.5, 15.8] and 38 (4%; 95% CI 2.9, 5.4) patients using Bazett and Fridericia corrections, respectively. On multivariable analysis, incomplete bundle branch block, ventricular hypertrophy, signs of ischaemic cardiopathy, female gender, White ethnic origin and age were significantly associated with QTc prolongation. The only HIV variable independently associated with QTc prolongation was the duration of infection (P = 0.023). After adjustment, anti‐HIV treatment, in particular PI (P = 0.99), was not associated with QTc prolongation. CONCLUSIONS Although PIs block in vitro hERG current, they are not independently associated with QTc interval prolongation. Prolonged QTc interval in HIV‐infected patients is primarily associated with factors commonly known to prolong QT and with the duration of HIV infection.

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Section: Discussionmentioning

confidence: 96%

Relationship between HIV protease inhibitors and QTc interval duration in HIV‐infected patients: a cross‐sectional study

Charbit

Rosier

Bollens

et al. 2008

Brit J Clinical Pharma

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“…As many HIV-infected patients who have cardiovascular risk factors and/or underlying cardiovascular diseases, and who are therefore at increased risk for malignant ventricular arrhythmias, may desire to use ATV as part of their antiviral therapy, this information is of relevance. Acquired long QT syndrome, drug-induced QT prolongation, TdP and increased risk for cardiovascular disease have also been reported in HIV-infected patients [5][6][7][8][9][10][11][12][13][28][29][30]. This study was prompted by early concerns that ATV might prolong the QTc.…”

Section: Discussionmentioning

confidence: 99%

“…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]. The prolongation of the QTc may increase the risk for malignant ventricular arrhythmias and sudden cardiac death, especially in patients with underlying cardiovascular disease [14][15][16][17].…”

Section: Introductionmentioning

confidence: 99%

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A prospective evaluation of the effect of atazanavir on the QTc interval and QTc dispersion in HIV‐positive patients

et al. 2006

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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...

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“…QT prolongation has been reported with a prevalence as high as 65% in patients with HIV and autonomic neuropathy (17,20,26). In addition, some antiretroviral agents have been associated with corrected QT interval (QTc) prolongation (1,2,22,23).…”

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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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Autonomic neuropathy and prolongation of QT interval in human immunodeficiency virus infection

Cited by 66 publications

References 32 publications

Relationship between HIV protease inhibitors and QTc interval duration in HIV‐infected patients: a cross‐sectional study

Relationship between HIV protease inhibitors and QTc interval duration in HIV‐infected patients: a cross‐sectional study

A prospective evaluation of the effect of atazanavir on the QTc interval and QTc dispersion in HIV‐positive patients

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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