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 (I 2 ) 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%, I 2 = 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.