Treating drug-resistant tuberculosis in an era of shorter regimens: Insights from rural South Africa

Background. Progressive interventions have recently improved programmatic outcomes in drug-resistant tuberculosis (DR-TB) care in South Africa (SA). Amidst these, a shorter regimen was introduced in 2017 with weak evidence, and has shown mixed results. Outcomes still fall short of national targets, and the coronavirus disease 2019 pandemic has undermined progress to date. Objectives. To describe the outcomes of participants treated for DR-TB using a shorter, compared with a longer, regimen in a deeply rural SA setting, and to explore other factors affecting these outcomes. Methods. This retrospective cohort study describes outcomes in short and long DR-TB treatment regimens, over 5 years, at two rural treatment sites in SA. Characteristics were analysed for outcome correlates using multivariable logistic regression models. Results. Of 282 treatment episodes, 62% were successful, with higher success in shorter (69%) compared with longer regimens (58%). Mortality was approximately 21% in both groups. Characteristics included high proportions of HIV co-infection (61%). Injectables (adjusted odds ratio (aOR) 3.00, 95% confidence interval (CI) 1.48 - 6.09), bedaquiline (aOR 3.16, 95% CI 1.36 - 7.35), increasing age (aOR 0.97, 95% CI 0.95 - 0.99) and HIV viraemia defined as final HIV-RNA viral load >1 000 copies/mL (aOR 0.16, 95% CI 0.07 - 0.37) were all significantly and independently associated with treatment success. Injectables (aOR 0.22, 95% CI 0.08 - 0.57), bedaquiline (aOR 0.05, 95% CI 0.01 - 0.19), increasing age (aOR 1.09, 95% CI 1.05 - 1.13), extra-pulmonary TB (aOR 8.15, 95% CI 1.62 - 41.03) and HIV viraemia (aOR 9.20, 95% CI 3.22 - 26.24) were all significantly and independently associated with mortality. Conclusion. In a rural context, treating DR-TB amid limited resources and a high burden of HIV co-infection, we found that after considering controls, a short regimen was no different to a longer regimen in terms of success or mortality. Therefore, by alleviating burdens on multiple stakeholders, a short regimen is likely to be favourable for rural patients, clinicians, and healthcare systems. Besides other previously described correlates of outcomes, HIV viraemia emerged as a novel marker for reliably predicting poor outcomes in DR-TB with HIV co-infection, and a pragmatic target for intervention.