Background Multidrug resistant or rifampicin-resistant tuberculosis (MDR/RR-TB) poses a significant global public health challenge. While most people with RR-TB have MDR-TB (resistance to isoniazid and rifampicin), rifampicin mono-resistant tuberculosis (RmR-TB, rifampicin resistance, isoniazid susceptibility) is prevalent in certain regions. We aimed to compare mortality between patients with RmR-TB and MDR-TB and assess potential effect modification by HIV status during treatment. Methods We conducted an individual patient data meta-analysis involving 16,651 individuals with confirmed drug-resistant tuberculosis, all of whom had drug susceptibility test results for at least rifampicin, isoniazid, and fluoroquinolones and had initiated TB treatment. Mixed-effects logistic regression was used to estimate mortality during two-year treatment, adjusting for age, sex, history of TB, disease site, and HIV status. Stratified analyses explored effect modification by HIV status. Results Among 16,568 patients, 2878 (17.4%) were classified as having RmR-TB, 11,236 (67.8%) as MDR-TB, 2384 (14.4%) as pre-XDR-TB, and 70 (0.4%) as XDR-TB. During the first four months of treatment, the cumulative incidence of mortality was higher among patients with RmR-TB compared to those with MDR-TB, pre-XDR-TB and XDR-TB. Patients with RmR-TB had 14% higher odds of mortality compared to patients with MDR-TB (32.2% vs 23.7%; aOR 1.14; 95% CI: 1.02–1.27), but a lower mortality compared to patients with pre-XDR or XDR-TB. Although HIV status did not significantly modify the effect (p-value interaction = 0.362), the odds of mortality was only higher among RmR-TB patients with HIV co-infection (aOR 1.17; 95% CI:1.03–1.33). Conclusion Using a large individual patient data meta-analysis, this study confirmed the counterintuitive finding of prior smaller studies that the odds of mortality are higher among patients with RmR-TB compared to MDR-TB. While HIV co-infection was not an effect modifier, the higher odds of mortality were only observed among RmR TB patients living with HIV.

The authors have declared no competing interest.

This study did not receive any funding

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