QT interval prolongation in patients receiving bedaquiline-based regimens for drug-resistant tuberculosis in Sub-Saharan Africa: A systematic review and meta-analysis.

BACKGROUND

Drug-resistant tuberculosis (DR-TB) is a major public health challenge in Sub-Saharan Africa (SSA), worsened by high HIV prevalence and limited healthcare infrastructure. Bedaquiline, a cornerstone DR-TB treatment, is linked to QT interval prolongation, a risk factor for life-threatening arrhythmias. This systematic review and meta-analysis estimated the incidence of QT prolongation in bedaquiline-treated DR-TB patients in SSA.

METHODS

Following PRISMA guidelines, we searched PubMed, Embase, Cochrane Library, Web of Science, and African Journals Online (2013-2024). Studies reporting QT intervals in DR-TB patients receiving bedaquiline in SSA were included (QTc > 450 ms men/>460 ms women). A random-effects model with Freeman-Tukey transformation estimated pooled incidence. Subgroup and sensitivity analyses explored heterogeneity (I2) and bias, with funnel plots assessing publication bias. Data were analyzed using Stata 18.0.

RESULTS

From 616 records, 23 studies (6673 bedaquiline-exposed patients) were included; 19 studies with 6158 patients contributed to the meta-analysis. Pooled incidence of QTc prolongation (>450 ms in men or >460 ms in women) was 15.0% (95% CI 9.0-22.0%, I2 = 97.1%). RCTs reported higher incidence (35.6%) than observational studies (13.1%; p = 0.001). HIV co-infection (prevalence 26.4%) showed a non-significant trend toward higher incidence (22.0% vs 11.0%, p = 0.07) and QT-prolonging drugs (52.8%) increased risk.

CONCLUSION

QT prolongation is significant in SSA's bedaquiline-treated DR-TB patients, necessitating enhanced ECG monitoring and integrated TB-HIV care.