Treatment outcomes and post-treatment mortality among people with multidrug/rifampicin-resistant tuberculosis in Sierra Leone: a national cohort study

Abstract

**Background:** Evidence on biosocial factors driving adverse outcomes in multidrug/rifampicin-resistant tuberculosis (MDR/RR-TB) can inform design of person-centred interventions. We evaluated treatment outcomes, post-treatment mortality, and their associated risk factors among people with multidrug/rifampicin-resistant tuberculosis (MDR/RR-TB) in Sierra Leone.

**Methods:** We did a national cohort study of people with MDR/RR-TB in Lakka Hospital, Freetown, 2017-2022. Treatment was with WHO-recommended short (9-11 month) or long (18-24 month) regimens, with adverse treatment outcome (death or loss to follow-up before or during treatment, or treatment failure) following WHO definitions. Participants with treatment success had 12-months follow-up to ascertain post-treatment mortality. We used directed acyclical graph-informed logistic regression to investigate biosocial factors associated with adverse treatment outcome and post-treatment mortality.

**Findings:** We recruited 739 people with MDR/RR-TB, median age 34-years (IQR: 25-45), 70% (517/739) male and 22% (160/734) HIV-positive. 22% (161/739) had adverse treatment outcome, with 18% (134/739) dying before or during treatment. Adverse treatment outcome was associated with age ≥45-years versus 25-44-years (adjusted odds ratio \[aOR\] = 1.9; 95% confidence interval: 1.1-3.2); unemployment (aOR = 2.9; 1.8-4.8); HIV (aOR = 1.8; 1.1-2.7); chronic lung disease (aOR = 1.7; 1.0-2.9); renal impairment (aOR = 4.8; 1.8-12.9); underweight (aOR = 1.6; 1.1-2.4); and long regimen (aOR = 2.0; 1.3-3.2). Among those with treatment success, 9.9% (57/578) had post-treatment mortality. This was associated with HIV (aOR = 2.0, 1.0-3.9), smoking (aOR = 2.7, 1.3-5.5), chronic lung disease (aOR = 2.2, 1.1-4.7), previous loss-to-follow-up (aOR = 3.1, 1.1-8.7) and severe TB on their original chest radiography (aOR = 2.4, 1.2-4.5).

**Interpretation:** Adverse outcomes, including death after treatment success, were common among people with MDR/RR-TB in Sierra Leone and associated with modifiable risk factors, highlighting the urgent need for holistic, person-centred biosocial interventions for people with MDR/RR-TB throughout and beyond treatment.

**Funding:** Medical Research Council-MR/Y503216/1; Medical Research Foundation-MRF-131-0006-RG-KHOS-C0942.