Time-to-Tuberculosis disease diagnosis after completion of Tuberculosis preventive therapy among people living with HIV on Antiretroviral Therapy in Eastern Uganda: A retrospective cohort study
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Abstract
Background
Tuberculosis (TB) remains a leading cause of morbidity and mortality among people living with HIV (PLHIV), who face a 12-fold higher risk of active TB reactivation than HIV-negative individuals. TB preventive therapy (TPT) is an effective intervention, yet TB/HIV co-infection persists at 40–45%, raising questions about the durability of a single course of TPT. This study assessed the time from TPT completion to TB diagnosis and predictors of early TB reactivation.
Methods
We conducted a retrospective case-only cohort study using routine data from Uganda’s electronic medical record system, TB registers, and patient files at three TASO Centres of Excellence (Soroti, Mbale, Tororo). PLHIV on antiretroviral therapy (ART) diagnosed with TB after completing TPT between 2022–2024 were included. Participant characteristics and time to TB diagnosis were summarised descriptively; predictors of early TB were identified using logistic regression.
Results
Among 670 participants, most were female (464, 69.3%) with mean age 51.6 years (SD 14.5). Newly diagnosed TB accounted for 638 (95.2%), including bacteriologically confirmed pulmonary TB (535, 79.9%), clinically diagnosed TB (123, 18.4%), and extrapulmonary TB (12, 1.8%). Overall, 548 (82.8%) participants were virally suppressed, with most on Dolutegravir-based regimens (641, 95.7%). Early TB occurred in 144 (21.5%), with average time to diagnosis 2.6 years. Multivariable analysis showed care at TASO Soroti was protective (aOR = 0.104, p < 0.001), while clinically diagnosed TB (aOR = 1.91, p = 0.007), shorter ART duration (<5 years: aOR = 3.07, p = 0.001; 5–10 years: aOR = 1.74, p = 0.018), and viral suppression (aOR = 1.87, p = 0.014) increased odds of early TB.
Conclusions
TB can occur soon after TPT completion, with one in five PLHIV developing early disease particularly those with shorter ART duration despite viral suppression. Strengthening TB screening, continuous monitoring, and repeat TPT for high-risk groups may improve prevention.
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This Zenodo record is a permanently preserved version of a PREreview. You can view the complete PREreview at https://prereview.org/reviews/20277934.
Summary
This preprint examines the time from completion of tuberculosis preventive therapy to later TB diagnosis among people living with HIV on ART in Eastern Uganda. The study uses routine program data from three TASO Centres of Excellence in Mbale, Soroti, and Tororo and includes 670 people who developed TB after completing TPT. I think this is an important and useful study because it addresses a practical TB/HIV program question in a high-burden setting.
Main contribution
The main contribution is that the paper describes the timing and characteristics of TB cases occurring after TPT completion. The comparison across Mbale, Soroti, and Tororo is also useful because it may point to …
This Zenodo record is a permanently preserved version of a PREreview. You can view the complete PREreview at https://prereview.org/reviews/20277934.
Summary
This preprint examines the time from completion of tuberculosis preventive therapy to later TB diagnosis among people living with HIV on ART in Eastern Uganda. The study uses routine program data from three TASO Centres of Excellence in Mbale, Soroti, and Tororo and includes 670 people who developed TB after completing TPT. I think this is an important and useful study because it addresses a practical TB/HIV program question in a high-burden setting.
Main contribution
The main contribution is that the paper describes the timing and characteristics of TB cases occurring after TPT completion. The comparison across Mbale, Soroti, and Tororo is also useful because it may point to facility-level differences in screening, follow-up, diagnosis, or local TB exposure.
Strengths
A major strength is the good use of routine program data from electronic medical records, TB registers, and patient files. The operational definitions are clear, and the descriptive epidemiology is easy to follow. I also like the size of the study: 670 post-TPT TB cases is a meaningful real-world sample for programmatic analysis. The high proportion of bacteriologically confirmed TB cases also strengthens the validity of the findings. The paper has a clear policy implication because it supports continued TB screening after TPT completion and raises the question of repeat or extended TPT for higher-risk groups.
Major comments
One point that could be clarified is the study design and framing. I may be misunderstanding the authors' intent, but it is not fully clear whether the study is meant to estimate TB risk after TPT or to describe people who developed TB after TPT. Since the analysis only includes people who already developed TB after completing TPT, it cannot estimate TB risk or TPT failure rates among all PLHIV who completed TPT.
The paper is strongest as a description of timing and characteristics among post-TPT TB cases. I suggest the authors make this distinction clearer in the abstract, discussion, and conclusion to avoid overinterpreting the findings.
The definition of early TB as diagnosis within 1.5 years after TPT completion also needs more explanation. The authors should explain why this cutoff was chosen. The finding that viral suppression was associated with higher odds of early TB should also be interpreted carefully, since this may reflect better clinic engagement, more frequent screening, or unmeasured confounding rather than a biological increase in TB risk.
Minor comments
The limitations section should more directly mention the case-only design. Some language around "TPT durability" should be softened because the study does not include all people who completed TPT. The site differences, especially the lower odds of early TB at Soroti, are interesting and could be discussed more clearly in relation to program quality, diagnostic practices, or local TB transmission.
Overall assessment
Overall, I think this is a useful preprint with real public health value for TB/HIV programs in Eastern Uganda and similar settings. I like the use of routine program data, the large sample, the clear operational definitions, and the comparison across the three TASO sites. The main improvement would be to frame the conclusions more carefully around what the study design can actually show.
Competing interests
The author declares that they have no competing interests.
Use of Artificial Intelligence (AI)
The author declares that they used generative AI to come up with new ideas for their review.
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