<p>Flow diagram of included patients and outcomes.</p>

Tuberculosis (TB) comorbidities and multimorbidity - the presence of two or more concurrent diseases or health conditions - are major contributors to TB incidence and mortality. We investigated the prevalence and associated mortality of TB comorbidities and multimorbidity in South Africa. We conducted a prospective cohort study of adults ≥15 years with bacteriologically-confirmed pulmonary TB, nested within a trial in two provinces of South Africa. We investigated five TB key comorbidities (HIV, undernutrition, diabetes, smoking and alcohol use), and assessed all-cause mortality over 15 months using Cox regression. TB comorbidity was defined as TB with one comorbidity, and TB multimorbidity as TB with two or more comorbidities. Of 1997 participants, 1896 (95%) had mortality data available at 15 months. Median age was 38 (IQR 29–48) years, 1203/1997 (60%) were male, 86·2% (95% CI 84·6-86·6) had TB comorbidity and 47·5% (45·3-49·7) had TB multimorbidity. TB comorbidity peaked in participants aged 40–49 years (93% [90–95]), was more prevalent in men vs women (90%[88–91] vs 81%[78–84], p < 0·001), and in urban vs rural areas (88%[86–90] vs 84%[81–86], p = 0·005). Mortality was higher for participants with TB multimorbidity with two (16·0%[13·0-18·8], HR 1·88[1·20-2·95], p = 0·006) and three or more (19·9%[14·9-24·6], HR 2·58[1·56-4·24], p < 0·001) TB key comorbidities than those with no comorbidities (11·2%[7·17-15·0]) or TB comorbidity (10·6% [8·32-12·8]). The joint population attributable fraction for the TB key comorbidities on mortality was 60·0% (49·6-69·2%). TB comorbidities and multimorbidity are highly prevalent and significantly associated with mortality. People with TB should be offered screening and management of comorbidities to reduce their risk of death.