HIV and body mass index are associated with prolonged corrected QT interval among people with drug-resistant tuberculosis on bedaquiline-containing regimen in Uganda

Objectives

People with drug-resistant tuberculosis (DR-TB) on bedaquiline-containing regimens are at risk for a prolonged corrected QT (QTc) interval but this problem is understudied in low-resource countries. We determined the magnitude and risk factors for QTc interval prolongation among people with DR-TB on bedaquiline-containing regimens at three referral hospitals in Uganda.

Methods

Using retrospectively collected data, we designed a matched case-control study, with cases as participants with prolonged QTc interval and controls as those with normal QTc interval in 1:1. QTc interval prolongation was defined as an increase in QTc interval by 60 milliseconds in electrocardiogram from the baseline or ≥500 milliseconds during follow-up for men and women. Factors associated with cases compared with controls were identified using a multivariable conditional regression analysis at a 5% significance level, reported using odds ratio (OR) and the 95% confidence interval (CI).

Results

Of 153 participants, 39 (25.5%) had a prolonged QTc interval. We matched 30 participants with prolonged QTc interval (cases) with 30 participants with normal QTc interval (controls). Cases and controls were similar in several sociodemographic and clinical characteristics but different regarding the baseline body mass index (BMI), baseline weight, and HIV infection. Increasing BMI (adjusted OR 1.29, 95% CI 1.02-1.63) and HIV infection (adjusted OR 0.27, 95% CI 0.08-0.96) were associated with the cases compared with the controls.

Conclusions

We found a relatively high prevalence of QTc interval prolongation among people with DR-TB on a bedaquiline-containing regimen compared with the prevalence in healthy individuals, with a higher likelihood in those with increasing BMI and a lower likelihood in those with HIV. We recommend routine anthropometric measurements to identify individuals with DR-TB at a high risk for QTc interval prolongation. In addition, tuberculosis/HIV treatment guidelines for people with DR-TB on bedaquiline-containing regimens should include risk assessment for prolonged QTc intervals.