https://orcid.org/0000-0001-9958-8462
Figures
Abstract
Background
Clinical trials have shown the protective efficacy of tuberculosis preventive treatment (TPT) for averting disease and death from tuberculosis among people living with HIV/AIDS (PLHIV). TPT has been recommended for PLHIV since the 1980s. However, tuberculosis is still the first cause of death in PLHIV.
Objective
We aimed to summarize the evidence related to the real-world effectiveness of TPT on tuberculosis incidence among PLHIV.
Method
This is a systematic review and meta-analysis of observational cohort studies. The search was carried out in PubMed (via MEDLINE), Embase, LILACS, Scopus and Web of Science databases. Free and controlled vocabulary was used for the searches, with no restrictions on language or publication period. Studies reporting hazard ratios (HR) for tuberculosis incidence among PLHIV who received TPT were pooled using random-effects meta-analysis models. Meta-regression was performed to assess whether study-level characteristics accounted for heterogeneity, as evaluated by Cochran’s I² statistic. Study quality was appraised using the Newcastle-Ottawa Scale. This study was registered with PROSPERO (CRD42024586273).
Results
Among 8,330 screened studies, 34 were included, with nine contributing to the meta-analysis. TPT was associated with a 63% reduction in tuberculosis incidence risk (HR = 0.37, 95% CI: 0.28–0.48; I² = 43%). Children exhibited consistent stronger protection (82% risk reduction, HR = 0.18, 0.09–0.37; I² = 0%) than adults (56% reduction, HR = 0.44, 0.37–0.53; I² = 21%).
Conclusion
In real world conditions, TPT significantly and substantially reduces tuberculosis incidence in PLHIV, with consistent evidence of stronger protective effects in children. Despite some heterogeneity among adult studies, the pooled evidence confirms the protective effectiveness previously observed in clinical trials. These findings reinforce the global recommendation for broad implementation of TPT among PLHIV.
Citation: Silva Júnior JNdB, Leal GdC, Ferreira QR, Andrade LKdA, Ballestero JGdA, Santos VS, et al. (2025) Effectiveness of tuberculosis preventive treatment on disease incidence among people living with HIV/AIDS: A systematic review and meta-analysis. PLoS One 20(8): e0330208. https://doi.org/10.1371/journal.pone.0330208
Editor: Sreenivas Achuthan Nair, Stop TB Partnership, UNOPS, SWITZERLAND
Received: February 9, 2025; Accepted: July 28, 2025; Published: August 26, 2025
Copyright: © 2025 Silva Júnior et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Data Availability: All relevant data are within the manuscript and its Supporting information files.
Funding: This study was financed by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior—Brazil (CAPES)—Finance Code 001 (PROGRAMA PROEX—Auxílio no. 1603/2024—Process number: 88881.973889/2024-01) and the Conselho Nacional de Desenvolvimento Científico and Tecnológico—Brazil (CNPq) (Research productivity scholarship—Process number: 306469/2025-1) awarded to PFP. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript."
Competing interests: The authors have declared that no competing interests exist.
Introduction
Acquired immunodeficiency syndrome (AIDS) and tuberculosis are two of the leading infectious causes of global morbidity and mortality. In 2023, approximately 10.8 million people fell ill with tuberculosis, resulting in 1.25 million deaths, including 161,000 among people living with the human immunodeficiency virus (PLHIV) [1]. That same year, tuberculosis regained its position as the leading cause of death from a single infectious agent in the world, after three years being overtaken by the coronavirus disease (COVID-19), and was responsible for almost twice as many deaths as HIV/AIDS [1].
The combination of tuberculosis and HIV/AIDS can be lethal due to the synergistic interaction between the two diseases, which amplifies mutual severity. HIV-induced immunosuppression compromises the cellular immune response, increasing susceptibility to primary infection and reactivation of tuberculosis infection (TBI) [2]. This interaction significantly reduces the survival of PLHIV, especially those with low CD4 T-lymphocyte counts and in settings with a high burden of infectious diseases [3,4].
During the 1980s, the World Health Organization (WHO) and other institutions recommended using isoniazid for preventing tuberculosis, especially in areas with a high prevalence of the disease and population at high risk to develop tuberculosis disease [5]. WHO currently recommends shorter rifampicin-based regimens for tuberculosis preventive treatment (TPT), but isoniazid remains an option [6] From the perspective of the Sustainable Development Goals (SDG), in 2015, the WHO declared that achieving the goal of eliminating tuberculosis would only be possible with the broad expansion of TPT alongside continuing to detect and treat persons with tuberculosis [5]. However, the development of tuberculosis disease among PLHIV remains a global concern [7].
HIV-induced immunosuppression increases the risk of reactivation, even after preventive treatment for tuberculosis has been administered. It is estimated that the risk of progression from TBI to tuberculosis disease among PLHIV is 14–18 times higher than in the general population [1]. Non-adherence to antiretroviral therapy (ART) and the presence of comorbidities or coinfections can further compromise the effectiveness of TPT [7,8].
Understanding the impact of TPT on tuberculosis incidence among PLHIV is crucial not only to addressing the gaps in the global response to tuberculosis-HIV co-infection, but also to advancing the goal of eliminating tuberculosis as a public health problem.
Systematic reviews that consolidate global evidence provide critical support for developing more targeted policies and interventions for tuberculosis control [8]. While previous reviews on TPT among PLHIV have focused mainly on clinical trials [9–11], these may not reflect long-term outcomes or real-world implementation challenges. Moreover, some reviews did not specifically assess tuberculosis incidence among PLHIV who received TPT, or were limited to evidence from a single country, such as the cohort-based review by Geremew et al. [12], whereas the present study adopts a global perspective.
To evaluate the sustained benefits of TPT, this systematic review aimed to summarize the evidence related to the effectiveness of TPT on the incidence of tuberculosis among PLHIV in cohort studies.
Methods
Search strategy and selection criteria
This is a systematic review and meta-analysis of cohort studies whose protocol was registered in the PROSPERO (CRD42024586273), based on the guidelines included in the Joanna Briggs Institute Manual for Evidence Synthesis [13], the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) [14] and Meta-Analyses Of Observational Studies in Epidemiology (MOOSE) [15]. The PRISMA Checklist is available at S1 Table.
The research question, the objective of the study and the descriptors use the mnemonic combination PECO, where P (Population) is PLHIV; E (Exposure) is TPT; C (Control) is PLHIV not undergoing tuberculosis preventive treatment and O (Outcome) is the incidence of tuberculosis. In other words, the guiding question of this review was: What is the summarized evidence related to the effectiveness of TPT on the incidence of tuberculosis among PLHIV?
Different combinations of search terms related to HIV, TPT and tuberculosis disease incidence were used. The Boolean operator ‘OR’ was used within each group and the Boolean operator ‘AND’ among the groups. Table 1 displays the descriptors used according to the application of their respective acronym.
The search was carried out on September 1, 2024 in the following databases: PubMed via Medical Literature Analysis and Retrieval System Online (MEDLINE), Excerpta Medica Database (EMBASE), Latin American and Caribbean Literature in Health Sciences (LILACS), SciVerse Scopus (SCOPUS) and Web of Science, accessed via the journal portal of the Coordination for the Improvement of Higher Education Personnel (CAPES). These databases were selected due to their extensive coverage and relevance to the subject under investigation, to enhance the representativeness and validity of the evidence incorporated into this review. The detailed search strategies tailored to each of the defined databases are provided in the Supporting Information (S2 Table).
Inclusion and exclusion criteria
Eligible studies included prospective or retrospective cohorts of PLHIV who received or not TPT and were monitored for subsequent tuberculosis incidence, irrespective of language and publication year.
We excluded studies based on the following criteria (details on the reason for exclusion of each article considered for full reading are provided in S3 Table): other types of study (reviews, case reports, clinical trials, cross-sectional studies, or other non-cohort designs); conference abstracts (conference abstracts were excluded due to limited methodological detail and unavailability of full data); subject-obstacle (studies that did not clearly involve PLHIV, or that did not assess tuberculosis incidence as an outcome after TPT initiation); and gray literature (documents from the gray literature, including reports, dissertations, and other non–peer-reviewed sources).
Duplicates were removed and two authors (JNBSJ and GCL) independently selected the studies by reading the titles and abstracts of the studies identified, using the Rayyan QCRI [16].
If there were disagreements in the evaluations of the articles, a third author (QRF) was consulted. The final sample was selected by reading all the material. In cases where multiple publications of a study or cohort were identified, the publications with the most recent data were included. Deepl platform was used to translate abstracts from languages other than Portuguese and English, to guarantee the eligibility of the titles selected.
Data extraction
Using a standardized data extraction form, four authors (JNBSJ, GCL, QRF and LKAA) extracted information from the studies (first author, year of publication, country of study, period of analysis, study setting, objective, study population, eligibility criteria for TPT and effectiveness of TPT on the incidence to active tuberculosis).
The information extracted from the studies was organized in a Google Sheets spreadsheet, ensuring online accessibility and allowing collaboration among the authors in real time. All steps and information extracted from the studies underwent double validation (JNBSJ and GCL).
Meta-analysis and statistical analysis
Studies reporting hazard ratios (HRs) for tuberculosis incidence among PLHIV who received TPT were pooled using random-effects meta-analysis models, prioritizing the most adjusted estimates when available. Effect measures were log-transformed (logHR) to ensure distributional symmetry and to allow proper combination of effect sizes. The meta-analysis was conducted using the restricted maximum likelihood (REML) method to estimate between-study heterogeneity (τ²). This model was selected due to the expected clinical and methodological variability among the study populations. The pooled HR and its 95% confidence interval (CI) were calculated, and heterogeneity was assessed using the I² statistic.
Studies were stratified by age group (adults and children) to explore potential sources of heterogeneity, as per protocol. Subgroup differences were tested using the Q-test for heterogeneity between groups. In addition, meta-regression analyses were performed to formally assess whether the effect of TPT on tuberculosis incidence varied by age group and ART use. The age group variable (children vs. adults) showed a statistically significant interaction with the estimated effect size.
A forest plot was constructed to visualize the pooled effect, and a funnel plot was used to assess potential publication bias through visual inspection. Due to the inclusion of subgroups in the meta-analysis model, Egger’s regression test was not applied, as it is not appropriate for models including subgroups. All statistical analyses were conducted using R (version 4.5.0) with the meta and metafor packages.
Assessment of the methodological quality of the studies included in the review
To evaluate the methodological quality of the included studies, we used the Newcastle-Ottawa Scale (NOS) [17]. This tool, commonly applied in cohort studies, assesses three domains: selection of the exposed and non-exposed cohorts (maximum of four stars), comparability of the cohorts (maximum of two stars), and assessment of outcomes (maximum of three stars), with one star awarded for each item adequately fulfilled. Two authors (QRF and LKAA) independently conducted the quality assessment, and any discrepancies were resolved through consultation with a third author (JNBSJ). No studies were excluded based on the methodological quality assessment. Detailed information regarding this evaluation is available in the Supporting Information (S4 Table), presenting the full results.
Results
The search across the selected databases yielded a total of 8,330 documents. After excluding duplicates, we included 34 [18–51] studies published between 1999 and 2024. The flowchart of the steps taken to include the studies can be seen in Fig 1. Table 2 presents the information and synthesis of the main results of the studies selected for this systematic review.
The 34 articles were published between 1999 and 2024, with 82% conducted in Sub-Saharan Africa: Ethiopia contributed with 13 studies [18,23,27,29,31–34,37,40,42,44,45], South Africa with five [24,26,39,49,50], Kenya with three [21,41,46], Tanzania with three [25,35,41], Uganda with two [22,41], Botswana with one [47] and Zambia with one [20]. In addition, Brazil contributed with three studies [19,28,43] and Spain with one [48], the United States with one [51], Hong Kong with one [36], India with one [30], and Indonesia with one [38] contributed with 1 study each. S1 Fig (Supplementary Information) shows the geographical distribution of the studies. Only one study [18] reported a cohort using rifapentine + isoniazid, in addition to isoniazid alone, all other cohorts used isoniazid TPT. Their settings feature a variety of ART or HIV centers, ranging from clinics to hospitals, reference centers, and specialized health units. All reported a risk reduction of TB, although with varying degrees of effect.
The random-effects meta-analysis included 13 studies evaluating the protective effect of the intervention in tuberculosis incidence, 11 conducted in adults and two in children. The forest plot visually displays a pooled HR of 0.36 (95% CI: 0.27–0.48), indicating a consistent protective effect across most studies, despite substantial heterogeneity (I² = 87.7%, τ² = 0.1613, p < 0.001).
Influence analysis identified four outlier studies: Saito et al. [41] (Cook’s d = 0.13), Golub et al. [50] (Cook’s d = 0.03), Atey et al. [32] (Cook’s d = 0.009), and Russom et al. [24] (Cook’s d = 0.29). After excluding these studies, heterogeneity was substantially reduced (I² = 43%, τ² = 0.0488), with a resulting 63% reduction in the risk of tuberculosis incidence following preventive treatment (HR = 0.37, 95% CI: 0.28–0.48). Although the studies by Maokola et al. [25] and Frigati et al. [49] demonstrated high influence, their exclusion did not meaningfully change the overall pooled HR (Fig 2).
Subgroup analysis
There were stronger protective effects in children compared to adults (p = 0.01, Fig 2). Among adults, seven studies indicated a median risk reduction of 56% (pooled HR: 0.44; 95% CI: 0.37–0.53), with low between-study heterogeneity (I² = 21.3%). The study by Maokola et al. [25] in Tanzania contributed the largest weight to the analysis (32.0%) and reported a consistent 52% risk reduction (HR: 0.48; 95% CI: 0.40–0.58). In contrast, Beshaw et al. [29] in Ethiopia demonstrated the most pronounced protective effect (92% reduction, HR: 0.08; 95% CI: 0.02–0.37), although with lower precision, accounting for 3.1% of the weight. Such variability may reflect regional differences in intervention implementation or underlying population characteristics (Fig 2).
In children, the two available studies demonstrated a markedly higher protective effect, with a pooled hazard ratio of 0.18 (95% CI: 0.09–0.37), corresponding to an 82% reduction in the risk of tuberculosis. Kebede et al. [27] in Ethiopia reported an 87% reduction (HR: 0.13; 95% CI: 0.04–0.42), while Frigati et al. [49] in South Africa observed a 78% reduction (HR: 0.22; 95% CI: 0.09–0.53). The complete homogeneity between pediatric studies (I² = 0%) reinforces the robustness of this protective effect (Fig 2).
No significant difference in the protective effect of TPT was found among studies according to ART use (p > 0.05) in the meta-regression analysis.
Quality of the studies included in the review
The methodological quality scores using the NOS [17] ranged from three to eight points, with a maximum possible score of nine. The majority of studies (n = 33) were classified as having a moderate or low risk of methodological or reporting bias (S4 Table).
Specifically, 18 studies [18,19,22,24,25,30–33,36,37,39–41,43–46] scored seven or eight points and were therefore classified as having a low risk of bias. Sixteen studies [20,21,23,26,27,29,34,35,38,42,47–51] scored four, five, or six points and were considered to have a moderate risk of bias, while only one study was classified as having a high risk of bias [28], with a score of 3/9 (S4 Table).
Fig 3 shows the funnel plot of the 9 studies included in the meta-analysis. Visually, no evident asymmetry was observed among the points, suggesting a low likelihood of publication bias.
Each blue dot represents a study included in the meta-analysis. The vertical dashed line indicates the pooled hazard ratio (log-transformed), and the diagonal lines represent the 95% confidence limits expected in the absence of bias.
Discussion
This systematic review and metanalysis of observational cohort studies reinforces the effectiveness of TPT in real-world settings, showing a 60% overall risk reduction, ranging from 50 to 92%. Our study corroborates the findings of previous meta-analyses that have evaluated the efficacy of TPT in reducing the incidence of active tuberculosis among PLHIV, using data solely from mathematical models [10] and clinical trials [11]. Additionally, our global results align with the protective effect observed in Ethiopian programmatic settings [12], who reported a 74% TB risk reduction among PLHIV receiving ART with IPT. This consistency across diverse contexts strengthens the case for TPT’s broad applicability beyond controlled research environments. To our knowledge, our study is the first to explore age-specific differences on a global scale.
The consistency of the protective effect of TPT, even in the presence of initial heterogeneity across studies reinforces the robustness of this review’s findings. Through sensitivity analysis, four studies with high statistical impact were identified and excluded, without compromising the direction or magnitude of the estimated association. This stability suggests that despite contextual and methodological variations across studies, the benefit of TPT remains clear and reproducible, reinforcing its relevance for practice in diverse settings.
The risk of rapid incidence to active tuberculosis is higher in children than in adults, mainly in children under five [52], raising special concern in this age group. The greater magnitude of TPT protective effect found in children living with HIV in the present review may be due to the higher initial risk but also to earlier intervention, lower burden of comorbidities, or better treatment adherence when supervised, as suggested in household contacts [53].
Strong protection in high-burden countries such as Ethiopia and South Africa support the hypothesis of more intense protection in higher-risk populations. However, there was great heterogeneity in the effect even among the high-burden countries. According to previous studies, this variability may be attributed to differences in study design, populations assessed, TPT implementation strategies, ART adherence, and individual immunological profiles, including hemoglobin levels, CD4 + T cell counts, and viral load, rather than differences between countries alone [19,54]. It was beyond the scope of the current study to analyze the reasons for heterogeneity.
Operational challenges, such as difficulties in ruling out active tuberculosis before starting TPT, fear of adverse reactions, limited adherence to guidelines and lack of drugs, have been noted as possible barriers to the effective implementation of TPT [20,21,46,55]. These limitations may partially explain the heterogeneity observed and suggest that the protective effect of TPT could be even greater in the absence of such restrictions.
In our meta-analysis, no significant association was found between tuberculosis incidence and ART use among individuals who underwent TPT. This suggests that the protective effect of TPT persists regardless of ART status. Nonetheless, this finding should be interpreted with caution, as only a few studies included participants not on ART or clearly reported ART status as an inclusion criterion [44,45].
Our review also points out the lack of knowledge on TPT protection in low-burden settings, and to the paucity of comparison of the effectiveness of different TPT regimens. Apart from one study [18], all others were cohorts of isoniazid TPT.
One of the limitations of this review is the residual heterogeneity among studies involving adults (I² = 21.3%), which may reflect differences in eligibility criteria, TPT regimens, or the quality of active tuberculosis screening. Furthermore, the smaller number of pediatric studies limits more detailed subgroup analyses and points to the need for additional research focused on children. Factors such as immune status and interaction with ART should be investigated in future studies to optimize prevention strategies.
This study not only contributes to the understanding of the dynamics associated with tuberculosis-HIV co-infection, but also provides subsidies to improve global strategies for the prevention and control of tuberculosis among PLHIV, with an emphasis on an integrated and evidence-based approach. Additionally, the consistency of the findings, even after the exclusion of influential studies in the sensitivity analysis, reinforces the robustness and reliability of the estimated effect.
Conclusion
This systematic review and meta-analysis of cohort studies provides evidence of the effectiveness of TPT in reducing the incidence of active tuberculosis among PLHIV, with conmore pronounced benefits observed in children. Although some variability was observed among adult studies, the overall findings confirm the protective benefit previously demonstrated in clinical trials and show the feasibility of this strategy. These results reinforce global recommendations for broad implementation and scale up of TPT among PLHIV and highlight the importance of age-specific strategies.
Finally, the expanded implementation of TPT, particularly among pediatric populations, may contribute significantly to global tuberculosis elimination goals.
Supporting information
S1 Fig. Geographical distribution of included studies.
https://doi.org/10.1371/journal.pone.0330208.s005
(PDF)
References
- 1.
World Health Organization. Global Tuberculosis Report 2024. Genebra: WHO. 2024. https://www.who.int/teams/global-tuberculosis-programme/tb-reports/global-tuberculosis-report-2024
- 2. Barr DA, Kerkhoff AD, Schutz C, Ward AM, Davies GR, Wilkinson RJ, et al. HIV-Associated Mycobacterium tuberculosis Bloodstream Infection Is Underdiagnosed by Single Blood Culture. J Clin Microbiol. 2018;56(5):e01914-17. pmid:29444831
- 3.
World Health Organization. Tuberculosis. WHO. https://www.who.int/news-room/fact-sheets/detail/tuberculosis. 2023
- 4. Tancredi MV, Sakabe S, Waldman EA. Mortality and survival of tuberculosis coinfected patients living with AIDS in São Paulo, Brazil: a 12-year cohort study. BMC Infect Dis. 2022;22(1).
- 5.
World Health Organization. Guidelines for intensified tuberculosis case-finding and isoniazid preventive therapy for people living with HIV in resource-constrained settings. Genebra: WHO. 2011. https://iris.who.int/bitstream/handle/10665/44472/9789241500708_annexes_eng.pdf?sequence=2&isAllowed=y
- 6.
World Health Organization. WHO consolidated guidelines on tuberculosis. Module 1: prevention – tuberculosis preventive treatment. 2 ed. Genebra: WHO. 2024.
- 7. Sharan R, Bucşan AN, Ganatra S, Paiardini M, Mohan M, Mehra S, et al. Chronic Immune Activation in TB/HIV Co-infection. Trends Microbiol. 2020;28(8):619–32. pmid:32417227
- 8. van Geuns D, Arts RJW, de Vries G, Wit FWNM, Degtyareva SY, Brown J, et al. Screening for tuberculosis infection and effectiveness of preventive treatment among people with HIV in low-incidence settings. AIDS. 2024;38(2):193–205. pmid:37991008
- 9. Akolo C, Adetifa I, Shepperd S, Volmink J. Treatment of latent tuberculosis infection in HIV infected persons. Cochrane Database Syst Rev. 2010;2010(1):CD000171. pmid:20091503
- 10. Uppal A, Rahman S, Campbell JR, Oxlade O, Menzies D. Economic and modeling evidence for tuberculosis preventive therapy among people living with HIV: A systematic review and meta-analysis. PLoS Med. 2021;18(9):e1003712. pmid:34520463
- 11. Ross JM, Badje A, Rangaka MX, Walker AS, Shapiro AE, Thomas KK, et al. Isoniazid preventive therapy plus antiretroviral therapy for the prevention of tuberculosis: a systematic review and meta-analysis of individual participant data. The Lancet HIV. 2021;8(1):e8–15.
- 12. Geremew D, Endalamaw A, Negash M, Eshetie S, Tessema B. The protective effect of isoniazid preventive therapy on tuberculosis incidence among HIV positive patients receiving ART in Ethiopian settings: a meta-analysis. BMC Infect Dis. 2019;19(1):405. pmid:31077133
- 13. Moola S, Munn Z, Tufunaru C, Aromataris E, Sears K, Sfetc R, et al. Systematic reviews of Aetiology and risk. JBI Manual for Evidence Synthesis. JBI. 2024.
- 14. Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021;:n71.
- 15. Stroup DF. Meta-analysis of Observational Studies in Epidemiology A Proposal for Reporting. JAMA. 2000;283(15):2008.
- 16. Ouzzani M, Hammady H, Fedorowicz Z, Elmagarmid A. Rayyan—a web and mobile app for systematic reviews. Syst Rev. 2016;5(1).
- 17. Zeng X, Zhang Y, Kwong JSW, Zhang C, Li S, Sun F, et al. The methodological quality assessment tools for preclinical and clinical studies, systematic review and meta-analysis, and clinical practice guideline: a systematic review. J Evid Based Med. 2015;8(1):2–10. pmid:25594108
- 18. Ajema AT, Simachew Y, Meshesha MD, Gari T. Time to tuberculosis development and its predictors among HIV-positive patients: A retrospective cohort study. PLoS One. 2024;19(2):e0298021. pmid:38346004
- 19. Mulatu G, Gembe M, Chalchisa J, Teklu T, Yismaw W, Dereje D, et al. Isoniazid Preventive Therapy Uptake and Its Effect on Tuberculosis Incidence Among People Living with HIV in Illubabor and Buno Bedelle Zones, South-West Ethiopia, 2022: A Retrospective Cohort Study. HIV AIDS (Auckl). 2023;15:649–62. pmid:37954622
- 20. Nyangu S, Kagujje M, Mwaba I, Luhanga D, Hambwalula R, Maliko S, et al. Breakthrough TB among people living with HIV on TB preventive therapy. Public Health Action. 2022;12(4):153–8. pmid:36561906
- 21. Onyango DO, van der Sande MAB, Yuen CM, Mecha J, Matemo D, Oele E, et al. Drop-offs in the isoniazid preventive therapy cascade among children living with HIV in western Kenya, 2015-2019. J Int AIDS Soc. 2022;25(8):e25939. pmid:35927793
- 22. Kazibwe A, Oryokot B, Mugenyi L, Kagimu D, Oluka AI, Kato D, et al. Incidence of tuberculosis among PLHIV on antiretroviral therapy who initiated isoniazid preventive therapy: A multi-center retrospective cohort study. PLoS One. 2022;17(5):e0266285. pmid:35576223
- 23. Geremew D, Geremew H, Tamir M, Adem M, Tegene B, Bayleyegn B. Tuberculosis and isoniazid prophylaxis among adult HIV positive patients on ART in Northwest Ethiopia. PLoS One. 2022;17(4):e0266803. pmid:35452463
- 24. Russom M, Woldu HG, Berhane A, Jeannetot DYB, Stricker BH, Verhamme K. Effectiveness of a 6-Month Isoniazid on Prevention of Incident Tuberculosis Among People Living with HIV in Eritrea: A Retrospective Cohort Study. Infect Dis Ther. 2022;11(1):559–79.
- 25. Maokola WM, Ngowi BJ, Mahande MJ, Todd J, Robert M, Msuya SE. Impact of Isoniazid Preventive Therapy on Tuberculosis incidence among people living with HIV: A secondary data analysis using Inverse Probability Weighting of individuals attending HIV care and treatment clinics in Tanzania. PLoS One. 2021;16(7):e0254082. pmid:34255776
- 26. Mandalakas AM, Hesseling AC, Kay A, Du Preez K, Martinez L, Ronge L, et al. Tuberculosis prevention in children: a prospective community-based study in South Africa. Eur Respir J. 2020;57(4):2003028.
- 27. Kebede F, Kebede B, Kebede T, Agmasu M. Effect of Isoniazid Preventive Therapy on the Incidence of Tuberculosis among Seropositive Children Attending HIV/AIDS Care in Two General Hospitals, Northwest Ethiopia, 2021. J Trop Med. 2021;2021:9996953. pmid:34545289
- 28. Vieira de Souza CT, Benamor Teixeira M de L, Fragoso da Silveira Gouvêa MI, Milnor J, De Lima Filho JB, De Souza Borges Quintana M, et al. Tuberculosis incidence in patients with human immunodeficiency virus, treated with isoniazid for latent tuberculosis infection. Rev Patol Trop. 2021;50(3):201–11.
- 29. Beshaw MA, Balcha SA, Lakew AM. Effect of Isoniazid Prophylaxis Therapy on the Prevention of Tuberculosis Incidence and Associated Factors Among HIV Infected Individuals in Northwest Ethiopia: Retrospective Cohort Study. HIV AIDS (Auckl). 2021;13:617–29. pmid:34135640
- 30. Padmapriyadarsini C, Sekar L, Reddy D, Chitra A, Poornagangadevi N, Selvaraj M, et al. Effectiveness of isoniazid preventive therapy on incidence of tuberculosis among HIV-infected adults in programme setting. Indian J Med Res. 2020;152(6):648–55. pmid:34145105
- 31. Aemro A, Jember A, Anlay DZ. Incidence and predictors of tuberculosis occurrence among adults on antiretroviral therapy at Debre Markos referral hospital, Northwest Ethiopia: retrospective follow-up study. BMC Infect Dis. 2020;20(1):245. pmid:32216747
- 32. Atey TM, Bitew H, Asgedom SW, Endrias A, Berhe DF. Does Isoniazid Preventive Therapy Provide Better Treatment Outcomes in HIV-Infected Individuals in Northern Ethiopia? A Retrospective Cohort Study. AIDS Res Treat. 2020;2020:7025738. pmid:32411454
- 33. Mengesha Y, Ahmed M. Assessment of Isoniazid Preventive Therapy Outcome Among People Living with HIV in a Referral Hospital, Northeast Ethiopia. Integr Pharm Res Pract. 2020;9:127–33. pmid:32983945
- 34. Yirdaw KD, Teklu AM, Mamuye AT, Zewdu S. Breakthrough tuberculosis disease among people with HIV - Should we be worried? A retrospective longitudinal study. PLoS One. 2019;14(2):e0211688. pmid:30716126
- 35. Sabasaba A, Mwambi H, Somi G, Ramadhani A, Mahande MJ. Effect of isoniazid preventive therapy on tuberculosis incidence and associated risk factors among HIV infected adults in Tanzania: a retrospective cohort study. BMC Infect Dis. 2019;19(1):62. pmid:30654753
- 36. Wong NS, Leung CC, Chan KCW, Chan WK, Lin AWC, Lee SS. A longitudinal study on latent TB infection screening and its association with TB incidence in HIV patients. Sci Rep. 2019;9(1):10093. pmid:31300686
- 37. Ahmed A, Mekonnen D, Shiferaw AM, Belayneh F, Yenit MK. Incidence and determinants of tuberculosis infection among adult patients with HIV attending HIV care in north-east Ethiopia: a retrospective cohort study. BMJ Open. 2018;8(2):e016961. pmid:29437750
- 38. Satiavan I, Hartantri Y, Werry B, Nababan Y, Wisaksana R, Alisjahban B. Effect of isoniazid preventive therapy on tuberculosis incidence in people living with HIV-AIDS at Hasan Sadikin hospital. IOP Conf Ser: Earth Environ Sci. 2018;125:012006.
- 39. Maharaj B, Gengiah TN, Yende-Zuma N, Gengiah S, Naidoo A, Naidoo K. Implementing isoniazid preventive therapy in a tuberculosis treatment-experienced cohort on ART. Int J Tuberc Lung Dis. 2017;21(5):537–43. pmid:28399969
- 40. Semu M, Fenta TG, Medhin G, Assefa D. Effectiveness of isoniazid preventative therapy in reducing incidence of active tuberculosis among people living with HIV/AIDS in public health facilities of Addis Ababa, Ethiopia: a historical cohort study. BMC Infect Dis. 2017;17(1):5. pmid:28049455
- 41. Saito S, Mpofu P, Carter EJ, Diero L, Wools-Kaloustian KK, Yiannoutsos CT, et al. Implementation and Operational Research: Declining Tuberculosis Incidence Among People Receiving HIV Care and Treatment Services in East Africa, 2007-2012. J Acquir Immune Defic Syndr. 2016;71(4):e96–106. pmid:26910387
- 42. Ayele HT, van Mourik MSM, Bonten MJM. Effect of isoniazid preventive therapy on tuberculosis or death in persons with HIV: a retrospective cohort study. BMC Infect Dis. 2015;15:334. pmid:26269094
- 43. Aquino DS de, Moura LCRV, Maruza M, Silva AP da, Ximenes RA de A, Lacerda HR, et al. Factors associated with treatment for latent tuberculosis in persons living with HIV/AIDS. Cad Saude Publica. 2015;31(12):2505–13. pmid:26872227
- 44. Assebe LF, Reda HL, Wubeneh AD, Lerebo WT, Lambert SM. The effect of isoniazid preventive therapy on incidence of tuberculosis among HIV-infected clients under pre-ART care, Jimma, Ethiopia: a retrospective cohort study. BMC Public Health. 2015;15:346. pmid:25886730
- 45. Yirdaw KD, Jerene D, Gashu Z, Edginton ME, Kumar AMV, Letamo Y, et al. Beneficial effect of isoniazid preventive therapy and antiretroviral therapy on the incidence of tuberculosis in people living with HIV in Ethiopia. PLoS One. 2014;9(8):e104557. pmid:25105417
- 46. Masini EO, Sitienei J, Weyeinga H. Outcomes of isoniazid prophylaxis among HIV-infected children attending routine HIV care in Kenya. Public Health Action. 2013;3(3):204–8. pmid:26393030
- 47. Sibanda T, Tedla Z, Nyirenda S, Agizew T, Marape M, Miranda AG, et al. Anti-tuberculosis treatment outcomes in HIV-infected adults exposed to isoniazid preventive therapy in Botswana. Int J Tuberc Lung Dis. 2013;17(2):178–85. pmid:23317952
- 48. Martínez-Pino I, Sambeat MA, Lacalle-Remigio JR, Domingo P. Incidence of tuberculosis in HIV-infected patients in Spain: the impact of treatment for LTBI. int j tuberc lung dis. 2013;17(12):1545–51.
- 49. Frigati LJ, Kranzer K, Cotton MF, Schaaf HS, Lombard CJ, Zar HJ. The impact of isoniazid preventive therapy and antiretroviral therapy on tuberculosis in children infected with HIV in a high tuberculosis incidence setting. Thorax. 2011;66(6):496–501. pmid:21460373
- 50. Golub JE, Pronyk P, Mohapi L, Thsabangu N, Moshabela M, Struthers H, et al. Isoniazid preventive therapy, HAART and tuberculosis risk in HIV-infected adults in South Africa: a prospective cohort. AIDS. 2009;23(5):631–6. pmid:19525621
- 51. Gourevitch MN, Hartel D, Selwyn PA, Schoenbaum EE, Klein RS. Effectiveness of isoniazid chemoprophylaxis for HIV-infected drug users at high risk for active tuberculosis. AIDS. 1999;13(15):2069–74. pmid:10546859
- 52. Carvalho ACC, Cardoso CAA, Martire TM, Migliori GB, Sant’Anna CC. Epidemiological aspects, clinical manifestations, and prevention of pediatric tuberculosis from the perspective of the End TB Strategy. J Bras Pneumol. 2018;44(2):134–44. pmid:29791553
- 53. Martinez L, Seddon JA, Horsburgh CR, Lange C, Mandalakas AM, TB Contact Studies Consortium. Effectiveness of preventive treatment among different age groups and Mycobacterium tuberculosis infection status: a systematic review and individual-participant data meta-analysis of contact tracing studies. Lancet Respir Med. 2024;12(8):633–41. pmid:38734022
- 54. Turinawe G, Asaasira D, Kajumba MB, Mugumya I, Walusimbi D, Tebagalika FZ, et al. Active tuberculosis disease among people living with HIV on ART who completed tuberculosis preventive therapy at three public hospitals in Uganda. PLoS One. 2024;19(11):e0313284. pmid:39527556
- 55. Van Ginderdeuren E, Bassett J, Hanrahan C, Mutunga L, Van Rie A. Health system barriers to implementation of TB preventive strategies in South African primary care facilities. PLoS One. 2019;14(2):e0212035. pmid:30763378