Rifampicin‑only resistant TB linked to higher early death, especially with HIV

Tuberculosis remains a leading infectious killer worldwide, and drug resistance makes treatment harder. Most cases of rifampicin-resistant disease are also resistant to isoniazid, a pattern called MDR/RR-TB, but in some places rifampicin mono-resistant tuberculosis (RmR-TB) — resistance to rifampicin with continued susceptibility to isoniazid — is common. Curious about whether RmR-TB carries a different risk of death than the more familiar multidrug-resistant form, researchers led a large individual patient data meta-analysis. Corresponding author Anna Jazza and collaborators gathered detailed participant-level data from tens of thousands of people treated for drug-resistant tuberculosis to compare outcomes. The study focused on patients who had drug susceptibility test results for at least rifampicin, isoniazid, and fluoroquinolones and who began TB treatment, and it followed patients through a two-year treatment period. The goal was to estimate mortality during treatment for RmR-TB compared with MDR-TB, and to see whether HIV status changed that relationship.

The analysis brought together records on thousands of people: the study initially involved 16,651 individuals with confirmed drug-resistant tuberculosis, and among 16,568 patients classified for analysis there were 2,878 (17.4%) with RmR-TB, 11,236 (67.8%) with MDR-TB, 2,384 (14.4%) with pre-XDR-TB, and 70 (0.4%) with XDR-TB. The team used mixed-effects logistic regression to estimate odds of death during the two-year treatment window, adjusting for age, sex, history of TB, disease site, and HIV status. They found that during the first four months of treatment the cumulative incidence of mortality was higher among patients with RmR-TB compared with those with MDR-TB, pre-XDR-TB and XDR-TB. Overall, 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). Mortality was lower for RmR-TB than for pre-XDR or XDR-TB. Although HIV status did not significantly modify the effect (p-value interaction = 0.362), the higher odds of mortality were observed only among RmR-TB patients with HIV co-infection (aOR 1.17; 95% CI:1.03–1.33).

These results confirm a counterintuitive pattern seen in smaller studies: rifampicin monoresistance is not necessarily a milder form of drug-resistant TB when it comes to survival. By using individual patient data and statistical adjustment for key factors, the study strengthens evidence that RmR-TB deserves close clinical and programmatic attention. The finding that the excess mortality associated with RmR-TB was concentrated among people living with HIV highlights the intersection of two major public health problems and suggests that HIV co-infection identifies a particularly vulnerable subgroup. While RmR-TB patients fared better than those with pre-XDR or XDR-TB, the unexpectedly high early mortality among RmR-TB — especially in the first four months of treatment — underlines the importance of robust drug susceptibility testing for rifampicin, isoniazid and fluoroquinolones and careful clinical management of co-infected patients. Anna Jazza and colleagues’ work calls attention to the need to recognize RmR-TB as a distinct and potentially serious category in treatment planning and surveillance.