Association between exposure to Efavirenz and substrates of dysrhythmia in HIV‐infected young adults

Abstract

Background: Dysrhythmia and sudden cardiac arrest occur more likely in HIV patients than healthy subjects. Thus, we need to examine dysrhythmias adverse effects of medications including Efavirenz as early as possible especially in young subjects.Hypothesis: Efavirenz might have contributed to increased risk of developing common types of dysrhythmia in young HIV infected patients.Methods: We performed a retrospective cohort study among 62 patients on Efavirenz and 38 controls. All participants were under 40 years old without cardiovascular disease. Total significant dysrhythmia in 24-hour ECG monitoring was the primary endpoint determined as the composite of high premature ventricular contraction (PVC) (>500 beats per 24 hours), high premature atrial contraction (PAC) (>500 bp24h), sinus pause, atrioventricular blocks, ventricular tachycardia, prolonged QTc, and low heart rate variability (HRV). Modified composite dysrhythmia consisted of low HRV (SD of normal-to-normal [SDNN]), high PVC and prolonged QT.Results: Mean heart rate, Efavirenz regimen, male gender, and CD4 count predicted total dysrhythmia. Odds ratios were 1.108, 2.90, 4.36, and 0.96, respectively. The incidence of total dysrhythmia, high PVC, high PAC, low HRV(SDNN), and prolonged QTc were 54.8%, 41.85%, 9.71%, 45.2%, and 12.9% in patients on Efavirenz against 42.11%, 31.64%, 0%, 34.2%, and 7.91% in controls, respectively (p-values: .031, .001, <.0001, .063, and .043 respectively). Modified composite dysrhythmia was also more frequent in Efavirenz group than that of control group (69.42% vs. 52.60%, respectively p = .032).

Prevention of heart failure, tachyarrhythmias and sudden cardiac death in HIV

“…Risk factors for prolonged QT in PLWH include male sex [66 ▪ ], Asian race [66 ▪ ], high HIV viral load [63,65,66 ▪ ], lower CD4 count [63,65], ART use [69 ▪ ], and increased inflammatory biomarker levels [64,68]. The data correlating specific ART classes and QT prolongation are conflicting but support increased risk with older generation protease inhibitors, efavirenz, and rilpivirine [65,70]. Few studies have examined longitudinal changes in QT intervals.…”

An overview of genetic variants regarding efavirenz‐related dysthymias in HIV‐infected patients: Response to a letter to the editor

“… 1 We found that chronic exposure to efavirenz (EFV) may be associated with increased premature ventricular contraction (PVC), premature atrial contraction (PAC) as well as decreased heart rate variability (HRV) in young human immunodeficiency virus (HIV) patients. 2 The impact of underlying genetic risk factors on the development of dysrhythmias has been partially understood. Given this fact, in conjunction with the genetic predisposition of patients who receive EFV, some issues might be addressed.…”

Efavirenz, dysrhythmia and HIV

“…We would like to share ideas on “Association between exposure to Efavirenz and substrates of dysrhythmia in HIV‐infected young adults.” 1 Hosseini et al concluded, “ patients with Efavirenz had higher prevalence of frequent PVC, frequent PAC, total significant dysrhythmia, Low HRV and prolonged QTc than controls .” 1 The Efavirenez is widely mentioned for effect on cardiac rhythm. An important determinant is underlying genetic factors.…”

“…CYP2B6*6*6 allele carrier is associated with cardiac rhythm problem in person with HIV receiving Efavirenez. 2 It is interesting to assess background genetic factors in case and control group in the report by Hosseini et al 1 In a previous report from Iran, CYP2B6*6 was common in Iran population 3 and it might be an explanation for the high frequency of cardiac dysrhythmia among HIV cases receiving Efavirenez in the study by Hosseini et al…”