This prospective cohort study used target trial emulation across 235,424 people with HIV initiating ART in six high-TB-burden countries (Haiti, Kenya, Nigeria, Uganda, Ukraine, Zimbabwe) between 2018–2022, comparing TB incidence and all-cause mortality over 2 years in those who started TPT (isoniazid, 6-month) within 8 weeks of HIV care enrollment vs. those who never received TPT.
TPT initiation within 8 weeks was associated with a 61% reduction in TB incidence (pooled HR 0.39, 95% CI 0.34–0.43; I²=0%) and a 45% reduction in all-cause mortality (pooled HR 0.55, 95% CI 0.51–0.58; I²=96%) across all six countries. Country-specific TB HRs ranged from 0.35 (Haiti) to 0.60 (Kenya); mortality HRs ranged from 0.25 (Uganda) to 0.69 (Zimbabwe). Benefits were consistent across children <15 years, all WHO clinical stages, and dolutegravir-based regimens.
- Heavy reliance on EMR data with substantial missing CD4 counts (up to 100% in Haiti) and unverified TPT adherence/completion data, making results conservative for full-course effectiveness. - Unmeasured confounding by indication (e.g., healthier patients may have preferentially received TPT), provider preferences, drug supply gaps, and COVID-19 disruptions could not be fully adjusted for. - Nigeria was underpowered (n=8,053 vs. target ~18,000), limiting country-specific conclusions; contact with drug-resistant TB cases was unavailable as a covariate.
Start TPT as early as possible after HIV care enrollment—benefit was greatest within 2 weeks but still significant within 8 weeks—for all people with HIV, including children, those with early-stage disease, and those on dolutegravir-based ART. These real-world data across 235,000 patients confirm TPT should remain a standard, non-negotiable part of HIV care in high-TB-burden settings.
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