Estimating the effect of hepatitis C infection on multidrug-resistant tuberculosis treatment outcomes under hypothetical interventions on regimen composition and adherence

Hepatitis C virus (HCV) infection is associated with unfavorable multidrug- and rifampicin-resistant (MDR/RR) tuberculosis (TB) outcomes. We examined whether this association would decrease in settings where no participants were lost-to-follow-up or where all adhered to regimens comprised of priority TB drugs. We analyzed data from 1530 participants with HCV testing in the endTB observational cohort (NCT03259269). We estimated the relative risk of death, treatment failure, and loss-to-follow-up comparing participants with and without HCV, using inverse probability weighting to adjust for confounding. We then estimated relative risks of HCV on death and failure in weighted pseudopopulations representing hypothetical interventions eliminating loss-to-follow-up and ensuring adherence to strong MDR/RR-TB regimens. The unadjusted risk difference comparing participants with and without HCV was 14.1% (95% confidence interval [CI] 8.0%, 20.1%), decreasing to 11.0% (95%CI, 3.0%, 19.1%) after weighting. In pseudopopulations without loss-to-follow-up or with adequate adherence to strong regimens, the risk differences were 7.7% (95% CI, 0.8%, 16.2%) and 7.0% (95% CI, -1.6%, 17.3%), respectively. Adjustment for baseline confounders attenuated the association between HCV and unfavorable outcomes, suggesting these factors partly explain the disparity. Further attenuation after eliminating loss-to-follow-up suggests that improving treatment retention in MDR/RR-TB care may reduce outcome disparities among patients with HCV.