Mortality in HIV and tuberculosis patients following implementation of integrated HIV-TB treatment: Results from an open-label cluster-randomized trial

BACKGROUND: HIV-TB treatment integration reduces mortality. Operational implementation of integrated services is challenging. This study assessed the impact of quality improvement (QI) for HIV-TB integration on mortality within primary healthcare (PHC) clinics in South Africa. METHODS: -tests and cox-proportional hazards model. (Clinicaltrials.gov, NCT02654613, registered 01 June 2015, trial closed). FINDINGS: Overall, 21 379 participants were enrolled between December 2016 and December 2018 in intervention and control arm clinics: 1329 and 841 HIV-TB co-infected (10·2%); 10 799 and 6 611 people living with Human Immunodeficiency Virus (HIV)/ acquired immunodeficiency syndrome (AIDS) (PLWHA) only (81·4%); 1 131 and 668 patients with TB only (8·4%), respectively. Average cluster sizes were 1657 (range 170-5782) and 1015 (range 33-2027) in intervention and control arms. By 12 months, 6529 (68·7%) and 4074 (70·4%) were alive and in care, 568 (6·0%) and 321 (5·6%) had completed TB treatment, 1078 (11·3%) and 694 (12·0%) were lost to follow-up, with 245 and 156 deaths occurring in intervention and control arms, respectively. Mortality rates overall [95% confidence interval (CI)] was 4·5 (3·4-5·9) in intervention arm, and 3·8 (2·6-5·4) per 100 person-years in control arm clusters [mortality rate ratio (MRR): 1·19 (95% CI 0·79-1·80)]. Mortality rates among HIV-TB co-infected patients was 10·1 (6·7-15·3) and 9·8 (5·0-18·9) per 100 person-years, [MRR: 1·04 (95% CI 0·51-2·10)], in intervention and control arm clusters, respectively. INTERPRETATION: HIV-TB integration supported by a QI intervention did not reduce mortality in HIV-TB co-infected patients. Demonstrating mortality benefit from health systems process improvements in real-world operational settings remains challenging. Despite the study being potentially underpowered to demonstrate the effect size, integration interventions were implemented using existing facility staff and infrastructure reflecting the real-world context where most patients in similar settings access care, thereby improving generalizability and scalability of study findings. FUNDING: Research reported in this publication was supported by South African Medical Research Council (SAMRC), and UK Government's Newton Fund through United Kingdom Medical Research Council (UKMRC).