Programmatic effectiveness of tuberculosis preventive treatment for people with HIV in six high-tuberculosis-burden...

In randomised clinical trials (RCTs), tuberculosis preventive treatment (TPT) reduced tuberculosis incidence and mortality among people with HIV; however, real-world impact has not been evaluated since antiretroviral therapy (ART) was expanded to all people with HIV regardless of CD4 cell count. This study aimed to determine the programmatic effectiveness of TPT on reducing tuberculosis incidence and all-cause mortality among people with HIV initiating ART.

This prospective cohort study emulated six RCTs using individual-level data from electronic health records in Haiti, Kenya, Nigeria, Uganda, Ukraine, and Zimbabwe to estimate TPT effectiveness among people with HIV initiating ART between Jan 1, 2018, and Dec 31, 2021 (Haiti, Kenya, Nigeria, and Ukraine) or Dec 31, 2022 (Uganda and Zimbabwe). In each country, we created cohorts of newly enrolled people with HIV initiating ART, regardless of age. We excluded people diagnosed with tuberculosis 6 months before to 30 days after ART start. De-identified extracted data for each patient included visit-level data for selected study variables between the date of enrolment into HIV care and Dec 31, 2023 (Haiti, Kenya, Nigeria, and Ukraine) or Dec 31, 2024 (Uganda and Zimbabwe). Target trial emulation was used to define a hypothetical randomised trial of TPT initiation during an 8-week grace period compared with no TPT initiation. TPT effectiveness was summarised using adjusted hazard ratios (HRs) for tuberculosis and all-cause mortality estimated using an inverse propensity weighting approach, with weights adjusted for confounders including age and sex (time-fixed) and CD4 cell count, viral load, clinical stage, ART initiation, and ART adherence (time-varying). The six countries were pooled in a meta-analysis using inverse-variance weighting with effect heterogeneity assessed using I².

We included 235 424 people with HIV: 69 936 people from Haiti, 65 936 from Uganda, 57 851 from Ukraine, 24 099 from Zimbabwe, 9549 from Kenya, and 8053 from Nigeria. In 235 424 people, 147 667 (62·7%) were aged 25-44 years, 133 582 (56·7%) were female, 101 842 (43·3%) were male, 104  277 (44·3%) had clinical stage 1, and 138 914 (59·0%) were on dolutegravir-based regimens. The adjusted HR for tuberculosis ranged from 0·35 (95% CI 0·28-0·43) in Haiti to 0·60 (0·36-0·91) in Kenya. The pooled HR for tuberculosis was 0·39 (0·34-0·43) with minimal variation across countries (I²=0%, 95% CI 0-75). The adjusted HR for mortality ranged from 0·25 (95% CI 0·20-0·30) in Uganda to 0·69 (0·53-0·96) in Zimbabwe. The pooled HR for mortality was 0·55 (0·51-0·58) with significant variation across countries (I²=96%, 95% CI 93-97).

TPT was effective in reducing tuberculosis incidence and mortality in people with HIV across various epidemiological contexts and risk groups. In an era of universal test-and-treat and new ART regimens, these data reinforce support for TPT as essential in HIV care.

Gates Foundation.

For the French and Ukrainian translations of the abstract see Supplementary Materials section.