Tuberculosis preventive treatment and the risk of incident tuberculosis and death in children living with HIV in Namibia: a national cohort study

Background Tuberculosis (TB) preventive treatment (TPT) reduces TB risk in people with HIV, but evidence in children remains limited. Namibia has offered isoniazid-based TPT to children living with HIV (CLHIV) since 2005. We assessed the effect of TPT on incident TB and all-cause mortality in a nationwide cohort. Methods In this retrospective cohort study, we linked national electronic HIV-care records (2002–2024) to electronic TB registers for children aged < 15 years at HIV-care enrolment. Outcomes were incident TB and all-cause mortality. We estimated Mantel–Haenszel incidence/mortality rate ratios (IRR or MRR) stratified by antiretroviral therapy (ART) exposure, and fitted flexible parametric survival models with TPT coded as a time-varying covariate (pre-TPT, during-TPT, post-TPT), adjusting for sex, age-group, WHO HIV stage, ART, and cotrimoxazole. E-values quantified robustness to unmeasured confounding. Findings Of 24,355 CLHIV (12,911 [53.1%] female), 14,783 (60.7%) received TPT. Over 202,415 person-years, TB incidence was 0.72 per 100 person-years on TPT vs. 1.56 without (IRR 0.48, 95% CI 0.44–0.53), and mortality was 0.32 vs. 1.03 (MRR 0.31, 0.27–0.36). Adjusted hazard ratios were 0.60 (0.46–0.77) during TPT and 0.58 (0.51–0.65) post-TPT for incident TB, and 0.28 (0.16–0.49) during TPT for mortality. Protection was strongest in children initiating TPT after age 6 years. Interpretation Programmatic TPT approximately halved TB incidence and substantially reduced mortality in CLHIV. Protection against TB persisted beyond treatment, whereas mortality benefit attenuated after completion, likely reflecting survivor bias. Findings support WHO guidance, including caution regarding routine TPT in infancy. Funding This study received no external funding.