Uptake and completion of Tuberculosis Preventive Therapy among people living with HIV on Antiretroviral Therapy in Uganda, 2020–2023

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The country has implemented several initiatives to scale up TPT including the integration of TPT into HIV care services. The WHO target for both initiation and completion of TPT among PLHIV in care is 90% by 2035. We described trends and spatial distribution of TPT uptake and completion, and reasons for non-completion among PLHIV in Uganda to track progress towards meeting the targets. Methods We extracted and analyzed national and subnational aggregated data on TPT among PLHIV on Antiretroviral Therapy (ART) as reported through the District Health Information System Version 2 (DHIS2) from January 2020 to December 2023. TPT eligibility, initiation, and completion rates were calculated. Reasons for failure to complete TPT were categorized as loss to follow-up, TB diagnosis, stopping due to side effects, and death while on TPT. We analyzed trends using the Mann-Kendall test and described spatial distribution by region over time. P-values of < 0.05 were considered statistically significant. Results By June 2023, 1,330,693 PLHIV on ART were eligible for TPT, of which 87% (1,157,703) had been initiated and 92% (1,065,086) of the initiated had completed TPT treatment. Between January 2020 and December 2023, uptake of TPT increased from 21% of eligible PLHIV to 89% and completion increased from 91–96%. Of the 92,617 (8%) ART clients who did not complete their TPT regimen, 29,435 (37%) were lost to follow-up, 2,356 (3%) died, and 1,589 (2%) were diagnosed with TB. Conclusion Uganda is close to achieving the WHO TPT initiation target and has already met the target for TPT completion among PLHIV. It is important for the Ministry of Health to maintain the high initiation rates of TPT among PLHIV who are newly enrolled in care. Tuberculosis People Living with HIV TB Preventive Therapy Uganda Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Introduction Tuberculosis (TB) continues to be the primary cause of illness and death among people living with HIV (PLHIV) worldwide [ 1 ]. Individuals living with HIV are at high risk of developing TB disease due to their weakened immune response [ 2 ]. They face the same level of exposure to TB infection in their communities as the general population [ 3 , 4 ]. Globally, in 2022, 6.3% (0.67 million) of TB cases were attributed to HIV, and 167,000 TB deaths occurred among PLHIV [ 5 – 7 ]. The World Health Organization's (WHO) End TB Strategy calls for a reduction in TB cases and TB deaths by 90% and 95% respectively, by 2035, which are the targets adopted by Uganda [ 8 ]. The aim is to eradicate TB as a disease of public health concern by 2050, with a key strategy being Tuberculosis Preventive Therapy (TPT). In Uganda, TPT involves providing anti-TB drugs to individuals without symptoms or signs of active TB disease, irrespective of whether tuberculin skin test or interferon-gamma release assay test has been performed [ 1 , 9 , 10 ]. This intervention is highly effective in lowering the occurrence and fatality rates of TB among PLHIV. TPT is estimated to reduce the likelihood of developing active TB disease by about 60% and the risk of TB-related mortality by up to 37% among PLHIV [ 10 ]. The WHO recommends TPT for all PLHIV as part of a comprehensive package of HIV care, along with antiretroviral therapy (ART), and regular screening for TB symptoms [ 11 ]. The WHO End TB Strategy calls for 90% TPT coverage among PLHIV and close contacts of infectious TB patients by 2035 [ 12 , 13 ]. Uganda adopted the WHO recommendations and guidelines for TPT and has implemented several initiatives to scale up TPT among PLHIV since 2015 [ 14 ]. These include integrating TPT into HIV care services, introducing new TPT regimens such as rifapentine-based 3HP, conducting mass campaigns to increase awareness and demand for TPT, and using digital technologies to monitor and support TPT adherence and completion [ 15 , 16 ]. As a result, the country has achieved remarkable progress in increasing TPT coverage among PLHIV, from 0.6% in 2016 to 88.8% in 2022 [ 17 ]. The decision by the Ministry of Health to initiate or expand testing for TB infection required preparedness of medical services. Many individuals who may be eligible for Tuberculosis preventive therapy (TPT) needed to access this important intervention readily. It would be beneficial for referral pathways and health services to be thoughtfully planned or reorganized, allowing for timely testing and proper linkage to treatment for target populations based on their test results [ 18 ]. The cascade of care is a model for evaluating patient retention across sequential stages of care required to achieve a successful treatment outcome [ 19 ]. This approach was first used to evaluate HIV care and has since been applied to other interventions, including TPT [ 19 ]. A TPT cascade involves a multistep process that requires the coordination of healthcare workers across various locations. Potential losses can occur at the various stages of the cascade. In this study, we described the TPT cascade and assessed the trends of TPT uptake, completion, and the temporal distribution of loss to follow-up among PLHIV on antiretroviral therapy in Uganda from 2020 to 2023 to inform programming. Methods Study design and data sources We conducted a descriptive analysis using TPT surveillance data from all the health facilities across Uganda that report through the District Health Information System version 2 (DHIS2). DHIS2 is a web-based platform that collects routine health service data from all public and private health facilities. The variables include information on HIV testing, care, and treatment services, as well as TB screening, diagnosis, treatment, and prevention [ 20 ]. Health facilities report this data to the district health offices through a monthly report, which is then aggregated and submitted to the Ministry of Health. Uganda’s health facilities are classified into seven levels based on the services they provide and the size of their catchment area [ 21 ]. The classification starts at a Village Health Team (VHT) level then ascends to Health Center II up to the National Referral Hospital level. TB and HIV care is provided at five levels: health centers III and IV, general hospitals, regional referral hospitals, and national referral hospitals. The study population included all PLHIV who were enrolled in HIV care services and eligible for TPT according to the national guidelines [ 22 ]. Study variables We abstracted national level semi-annual aggregated data for a total of 8 data points from January 2020 to December 2023. The key TPT variables abstracted included the number of ART patients who were eligible for TPT, the number of ART patients who were initiated on TPT, the number of ART patients who completed their TPT regimen, the number of ART patients on TPT who were lost to follow-up, the number of TPT patients who stopped TPT due to side effects, the number of ART patients who died while on TPT, and the number of ART patients who developed TB while on TPT. As per the national guidelines, TPT uptake was defined as the initiation of any TPT regimen, while completion was defined as receiving the full course of the prescribed TPT regimen. Data Analysis TPT uptake was calculated by dividing the number of eligible ART clients initiated on TPT in a semi-annual period by the number of all eligible ART clients in that semi-annual period. TPT completion was calculated by dividing the number of ART clients expected to complete and completed TPT in that semi-annual period by the number of all ART clients expected to complete TPT in that semi-annual period. Loss to follow-up was calculated by dividing the number of ART clients expected to complete in each period but were lost to follow-up by the total number of ART clients expected to complete in that period. To calculate the TPT cascade, we first calculated the proportion of PLHIV on ART who were eligible for TPT by dividing the number of eligible individuals by the total number of PLHIV on ART. Then we calculated the proportion of those eligible who had initiated TPT, and from those who had initiated, we calculated the proportion of individuals who completed their TPT regimen. We used time-series plot to describe temporal trends of TPT uptake, completion, and loss to follow-up over time. The data was analyzed in STATA version 14, and the Mann-Kendall test was utilized to determine the significance of trends at a level of 0.05. We also used the Quantum Geographic Information System (QGIS) to conduct spatial analysis to visualize and describe spatial patterns and variations of TPT loss to follow up among PLHIV across regions in Uganda. Results TPT cascade among HIV patients on ART, Uganda, 2020‒2023 Between January 2020 and December 2023, a total of 1,441,254 PLHIV had been enrolled on ART, of which 1,330,693 (92.3%) were eligible for TPT. Among those eligible, 87.0% (1,157,703) were initiated on TPT, and 92.0% (1,065,086) of those initiated completed their full dose of TPT (Fig. 1 ). Overall, 80.0% of the total eligible individuals were able to progress through all steps of the TPT care cascade and complete their TPT. Trends in Tuberculosis Preventive Therapy uptake and completion among HIV patients on Antiretroviral Therapy, Uganda, 2020‒2023 Overall, between January 2020 and December 2023, TPT uptake increased from 29% of eligible PLHIV to 89%, an increase of 60% (p = 0.004), and completion increased from 91–96%, an increase of 5% (p = 0.02), with the greatest increases for both uptake and completion occurring between July 2020 and June 2021. Between January 2020 and December 2020, TPT completion dropped from 91–87%, but then went back up to 92% in January 2021, remaining at that level through the end of the year. The uptake of TPT remained level at 64% throughout the entire 2021 period (Fig. 2 ). Regional distribution of Tuberculosis Preventive Therapy uptake among HIV patients on ART, Uganda, 2020‒2023 Overall, from January 2020 to December 2023, uptake of TPT in Uganda varied across regions, ranging from a low of 69% in the Tooro subregion to a high of 98% in the Bunyoro subregion (Fig. 3 ). Loss to follow-up, death, and discontinuation of Tuberculosis Preventive Therapy among HIV patients on Antiretroviral Therapy, Uganda, 2022‒2023 During the study period, 92,617 (8%) ART clients on TPT did not complete their course of TPT. Of this number, 43,956 (48%) had no documented reasons. Of the 48,661 (52.5%) who had documented reasons, 29,435 (61%) were lost to follow-up; 15,281 (31%) stopped due to side effects, 2,356 (5%) died, and 1,589 (3%) developed TB before TPT completion (Fig. 4 ). Temporal-spatial patterns of loss to follow-up among patients on Antiretroviral Therapy and Tuberculosis Preventive Therapy by region, Uganda, 2020‒2023 In Fig. 5 , the darker the area, the higher the rate of loss to follow-up. We observed that over the study period, loss to follow-up was decreasing. Most (7/15) of the regions started at a rate of more than 40 per 1,000 TPT patients, and 3 years later, only one region was still at a greater than 40 per 1,000 rates. Kampala subregion experienced the highest decline in loss to follow-up, decreasing from as high as 98 per 1,000 in January 2020 to 0 per 1,000 in June 2023, whereas the Lango subregion experienced the least decline in loss to follow-up, going from 65 per 1,000 in January 2020 to 22 per 1,000 in June 2023. This denotes an improving trend in the reduction of loss to follow-up of ART patients initiated on TPT. Discussion Our assessment revealed approximately 80% of all PLHIV on ART eligible for TPT successfully passed through all stages of the TPT cascade and finished their treatment. The uptake (initiation) of TPT among all eligible patients on ART was 87%, with a completion rate of 92% among those who began the treatment. Both uptake and completion rates showed significant improvement from 2020 to 2023, nearing the targeted 90% mark for both indicators. Among those who did not complete the treatment, over one-third were lost to follow-up, with the Mideastern region (Tooro) experiencing the highest rate of loss to follow-up during the study period. The TPT care cascade results are similar to findings from other studies, which found that over 70% of all PLHIV on ART eligible for TPT progressed through all steps of the care cascade and completed the treatment [ 17 , 23 ]. The loss registered at initiation can be attributed to inadequate counseling techniques used to educate clients who did not have TB to otherwise accept TPT [ 24 , 25 ]. Another study found that the lockdown during the COVID-19 outbreak in Uganda greatly affected access and utilization of healthcare services; this may have had a major impact on the number of clients who initiated TPT in that year [ 26 ]. The higher uptake rates in our study could be explained by the fact that guidelines on the initiation of TPT are clear and integrated within the HIV prevention and treatment guidelines. In another study done in Thailand and Vietnam, two settings where integration had not yet been implemented, TPT uptake rates were low (75%), and this was attributed to delays in initiating TPT [ 27 ]. Although TPT uptake improved during the same period, this fell short of the national and global target of 90%. Studies have suggested that challenges with uptake may be related to clinicians’ fears, beliefs, and lack of sufficient information on TPT [ 30 ]. Additional studies may be needed to understand the causes of low TPT uptake in poorly performing regions. The TPT completion surpassed the national and global target of 90% with regional variations ranging from 68–94%. This was consistent with a 2022 study done in Uganda on TPT, which showed a national TPT completion of 94% [ 17 , 28 ]. This achievement could be attributed to the enhanced integration of HIV and TB management among PLHIV by the Ministry of Health. In a systematic review and meta-analysis of studies from multiple country programs serving similar populations, an overall completion rate of 59.8% was registered, attributed to the integration of TB and HIV care [ 23 ]. Commodity availability and implementing partners' support for TPT demand creation among the beneficiaries made this possible [ 14 , 29 ]. Despite the regional level reduction in loss to follow-up, we did not find significant differences in the proportion of patients lost to follow-up over the three and half years of the study. A 2022 study on factors contributing to pulmonary TB treatment lost to follow-up in Low-Middle income countries demonstrated that treatment illiteracy and insufficient pre-treatment counseling were the most important factors associated with LTFU [ 31 ]. This same study suggested that enhancing pre-screening and pre-treatment counseling could help reduce LTFU. The regional loss to follow-up varied, influenced not only by cultural differences and healthcare perceptions but also by a range of other factors such as socioeconomic status, access to healthcare services, and levels of education. For instance, a study conducted in Kenya highlighted that healthcare perceptions can significantly hinder the uptake of TPT, contributing to increased loss to follow-up [ 32 ]. However, it is essential to consider that these perceptions may interact with other barriers, creating a complex landscape that affects patient engagement and retention in care. In our study, we observed many clients who did not complete treatment because of TPT side effects, a finding similar to a 2023 study in Uganda on treatment outcomes for drug-resistant TB patients, where a high frequency of adverse events led to persisting discontinuation of treatment [ 33 ]. To address the persistent issue of anti-TB drug side effects, several measures have been proposed elsewhere and one such is nanomedicine, which is an emerging research area that offers the potential of effective drug delivery using nanoparticles and a reduction in drug doses. A study done in 2023 explored the progress of this research and found that this technology offers a slow, sustained, and controlled release of anti-TB drugs and provides the advantages of low doses, reduced side effects, and improved patient compliance [ 34 ]. Our findings have implications for TB prevention and control programs in Uganda and other similar settings. First, the study demonstrates that initiation and completion of TPT can improve over time, implying that 100% coverage of TPT is feasible. Secondly, addressing the issues that lead to high loss to follow-up of PLHIV on TPT could help the programs achieve 100% completion rates. Study limitations The study has some limitations to consider when interpreting the results. First, we used secondary data from the DHIS2, which may have issues of completeness and accuracy since the reporting rates were at 93%. The unreported 7% could introduce bias or inaccuracies, affecting the overall reliability of the findings. Secondly, it was not possible to do age and sex disaggregation because this was aggregated data. This prevented us from studying the differences within the population. Conclusion Despite marked improvements in TPT uptake and completion among PLHIV over three years, a proportion of patients discontinued treatment prematurely, which may impact the long-term efficacy of TPT and delay progress toward End TB strategy goals. Understanding the reasons for non-return to clinics can significantly enhance interventions. These insights enrich the evidence base on TPT implementation among PLHIV in Uganda and similar settings, supporting efforts to accelerate TB elimination through prevention. We recommend a similar study on specific factors associated with high TPT uptake in our setting to inform program implementation. Abbreviations ART Antiretroviral Therapy DHIS2 District Health Information System version 2 HC Health Center LTFU Loss to follow-up HIV Human Immunodeficiency Virus MoH Ministry of Health TB Tuberculosis TPT TB preventive therapy US CDC United States Centers for Disease Control and Prevention WHO World Health Organization Declarations Ethical considerations We used TPT surveillance data from the DHIS2 that are routinely collected and reported by health facilities as part of the national health information system. Ministry of Health Uganda gave the administrative clearance to use the TPT data. The data are aggregated and anonymized and do not contain any personal identifiers of the patients or health workers as such it was determined to be non-research. The office of the Center for Global Health, US Center for Disease Control and Prevention determined that this activity was not human subject research, with its primary intent being for public health practice or disease control. In agreement with the International Guidelines for Ethical Review of Epidemiological Studies by the Council for International Organizations of Medical Sciences (1991). This activity was reviewed by the U.S. CDC and was conducted in a manner consistent with applicable federal law and CDC policy. §§See, e.g., 45 C.F.R. part 46, 21 C.F.R. part 56; 42 U.S.C. § 241(d); 5 U.S.C. § 552a; 44 U.S.C. § 3501 et seq. Consent for publication Not applicable Competing interests: The authors declare that they have no competing interests. Funding and disclaimer: This publication has been supported by the President's Emergency Plan for AIDS Relief (PEPFAR) through the U.S. Centers for Disease Control and Prevention (CDC) under the terms of GH001353-01 through Makerere University School of Public Health to the Uganda Public Health Fellowship Program, Ministry of Health. The findings and conclusions in this report are those of the author(s) and do not necessarily represent the official position of the funding agencies. Author Contribution IS: participated in the conception, design, analysis, and interpretation of the study and wrote the draft manuscript; MN, SW, BK, and DL supported the concept development. CN, LB, and DL reviewed the report, reviewed the drafts of the manuscript for intellectual content, and made multiple edits and recommendations to the drafts; ARA and DL reviewed the final manuscript to ensure intellectual content and scientific integrity. All authors read and approved the final manuscript. Acknowledgments The authors would like to thank the Ministry of Health and the AIDS Control Program for their permission and support in accessing the data utilized in this project. We would also like to thank the US Centers for Disease Control and Prevention (CDC) for their technical support. Data Availability The datasets upon which our findings are based belong to the Ugandan Public Health Fellowship Program and Ministry of Health Uganda. For confidentiality reasons, the datasets are not publicly available. However, the data sets can be made available upon reasonable request from the corresponding author (Innocent Ssemanda, Email: [email protected] ) and with permission from the Uganda Public Health Fellowship Program and Ministry of Health Uganda. References (WHO), W.H.O. Tuberculosis profile Report: WHO Western Pacific Region 2022 [cited 2024 24-April-2024]; Available from: https://worldhealthorg.shinyapps.io/tb_profiles/?_inputs_&group_code=%22WPR%22&entity_type=%22group%22&lan=%22EN%22. Komrower, D. and M. Thillai, Tuberculosis and HIV co-infection. Clin Tuberc A Pract Handb, 2015: p. 157-70. Komrower, D. and M. Thillai, Tuberculosis and HIV co-infection. Clinical Tuberculosis: A Practical Handbook, 2015. 157 . 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-5314078","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":371135994,"identity":"6a778bdc-88e1-4e1b-bc96-c09d40dd91a6","order_by":0,"name":"Innocent 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Health","correspondingAuthor":false,"prefix":"","firstName":"Alex","middleName":"Riolexus","lastName":"Ario","suffix":""},{"id":371136011,"identity":"e9e0a8f9-0158-4ac5-8d31-07308c82a0e5","order_by":8,"name":"Daniel Kadobera","email":"","orcid":"","institution":"Uganda National Institute of Public Health","correspondingAuthor":false,"prefix":"","firstName":"Daniel","middleName":"","lastName":"Kadobera","suffix":""},{"id":371136012,"identity":"a60c66f1-c4d8-40ce-bd84-2a058b5d629a","order_by":9,"name":"Deus Lukoye","email":"","orcid":"","institution":"U.S. Centers for Disease Control and Prevention","correspondingAuthor":false,"prefix":"","firstName":"Deus","middleName":"","lastName":"Lukoye","suffix":""}],"badges":[],"createdAt":"2024-10-22 19:23:12","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5314078/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5314078/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":68364708,"identity":"b701815b-fa81-4677-919f-60d63860ddf0","added_by":"auto","created_at":"2024-11-06 12:58:33","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":16004,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eTuberculosis Preventive Therapy cascade among HIV patients on Antiretroviral Therapy, 2020‒2023\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-5314078/v1/bd9755c1db6c9981c8f78607.png"},{"id":68364705,"identity":"7c86a010-4c0c-482e-a8a6-c6bf2c8bdfe1","added_by":"auto","created_at":"2024-11-06 12:58:33","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":29064,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eTrends in Tuberculosis Preventive Therapy uptake and completion among HIV patients on Antiretroviral Therapy, Uganda, 2020‒2023\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-5314078/v1/04d438648539af8e2e44eca2.png"},{"id":68364706,"identity":"e09616eb-58c3-46f6-8fde-b1178d627293","added_by":"auto","created_at":"2024-11-06 12:58:33","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":116623,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eRegional distribution of Tuberculosis Preventive Therapy uptake among HIV patients on Antiretroviral Therapy, 2020‒2023\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-5314078/v1/0b9b1398c074e38fc3a04da4.png"},{"id":68365005,"identity":"451ceb7d-b3a2-4041-bc6d-e970419517f6","added_by":"auto","created_at":"2024-11-06 13:06:33","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":22875,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eReasons for non-completion of Tuberculosis Preventive Therapy among HIV patients on Antiretroviral Therapy, Uganda, 2022‒2023\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"4.png","url":"https://assets-eu.researchsquare.com/files/rs-5314078/v1/4808a7ca3dd2929f45cb940f.png"},{"id":68364709,"identity":"258ab9a9-9040-4f7c-9957-9f6213b7fffc","added_by":"auto","created_at":"2024-11-06 12:58:33","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":166034,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eTemporal distribution of loss to follow-up among patients on Antiretroviral Therapy and Tuberculosis Preventive Therapy by region, Uganda, 2020‒2023\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"5.png","url":"https://assets-eu.researchsquare.com/files/rs-5314078/v1/020b01265b36fdb3f54bc8c9.png"},{"id":75394714,"identity":"e2f510c9-9bfd-4338-b0c4-e0b26b541380","added_by":"auto","created_at":"2025-02-04 06:16:59","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1320832,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5314078/v1/46294290-5589-46c2-b742-a519a291fab6.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Uptake and completion of Tuberculosis Preventive Therapy among people living with HIV on Antiretroviral Therapy in Uganda, 2020–2023","fulltext":[{"header":"Introduction","content":"\u003cp\u003eTuberculosis (TB) continues to be the primary cause of illness and death among people living with HIV (PLHIV) worldwide [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Individuals living with HIV are at high risk of developing TB disease due to their weakened immune response [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. They face the same level of exposure to TB infection in their communities as the general population [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Globally, in 2022, 6.3% (0.67\u0026nbsp;million) of TB cases were attributed to HIV, and 167,000 TB deaths occurred among PLHIV [\u003cspan additionalcitationids=\"CR6\" citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe World Health Organization's (WHO) End TB Strategy calls for a reduction in TB cases and TB deaths by 90% and 95% respectively, by 2035, which are the targets adopted by Uganda [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. The aim is to eradicate TB as a disease of public health concern by 2050, with a key strategy being Tuberculosis Preventive Therapy (TPT). In Uganda, TPT involves providing anti-TB drugs to individuals without symptoms or signs of active TB disease, irrespective of whether tuberculin skin test or interferon-gamma release assay test has been performed [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. This intervention is highly effective in lowering the occurrence and fatality rates of TB among PLHIV. TPT is estimated to reduce the likelihood of developing active TB disease by about 60% and the risk of TB-related mortality by up to 37% among PLHIV [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. The WHO recommends TPT for all PLHIV as part of a comprehensive package of HIV care, along with antiretroviral therapy (ART), and regular screening for TB symptoms [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. The WHO End TB Strategy calls for 90% TPT coverage among PLHIV and close contacts of infectious TB patients by 2035 [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eUganda adopted the WHO recommendations and guidelines for TPT and has implemented several initiatives to scale up TPT among PLHIV since 2015 [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. These include integrating TPT into HIV care services, introducing new TPT regimens such as rifapentine-based 3HP, conducting mass campaigns to increase awareness and demand for TPT, and using digital technologies to monitor and support TPT adherence and completion [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. As a result, the country has achieved remarkable progress in increasing TPT coverage among PLHIV, from 0.6% in 2016 to 88.8% in 2022 [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe decision by the Ministry of Health to initiate or expand testing for TB infection required preparedness of medical services. Many individuals who may be eligible for Tuberculosis preventive therapy (TPT) needed to access this important intervention readily. It would be beneficial for referral pathways and health services to be thoughtfully planned or reorganized, allowing for timely testing and proper linkage to treatment for target populations based on their test results [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. The cascade of care is a model for evaluating patient retention across sequential stages of care required to achieve a successful treatment outcome [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. This approach was first used to evaluate HIV care and has since been applied to other interventions, including TPT [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. A TPT cascade involves a multistep process that requires the coordination of healthcare workers across various locations. Potential losses can occur at the various stages of the cascade. In this study, we described the TPT cascade and assessed the trends of TPT uptake, completion, and the temporal distribution of loss to follow-up among PLHIV on antiretroviral therapy in Uganda from 2020 to 2023 to inform programming.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy design and data sources\u003c/h2\u003e \u003cp\u003eWe conducted a descriptive analysis using TPT surveillance data from all the health facilities across Uganda that report through the District Health Information System version 2 (DHIS2). DHIS2 is a web-based platform that collects routine health service data from all public and private health facilities. The variables include information on HIV testing, care, and treatment services, as well as TB screening, diagnosis, treatment, and prevention [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. Health facilities report this data to the district health offices through a monthly report, which is then aggregated and submitted to the Ministry of Health. Uganda\u0026rsquo;s health facilities are classified into seven levels based on the services they provide and the size of their catchment area [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. The classification starts at a Village Health Team (VHT) level then ascends to Health Center II up to the National Referral Hospital level. TB and HIV care is provided at five levels: health centers III and IV, general hospitals, regional referral hospitals, and national referral hospitals. The study population included all PLHIV who were enrolled in HIV care services and eligible for TPT according to the national guidelines [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e].\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eStudy variables\u003c/h3\u003e\n\u003cp\u003eWe abstracted national level semi-annual aggregated data for a total of 8 data points from January 2020 to December 2023. The key TPT variables abstracted included the number of ART patients who were eligible for TPT, the number of ART patients who were initiated on TPT, the number of ART patients who completed their TPT regimen, the number of ART patients on TPT who were lost to follow-up, the number of TPT patients who stopped TPT due to side effects, the number of ART patients who died while on TPT, and the number of ART patients who developed TB while on TPT. As per the national guidelines, TPT uptake was defined as the initiation of any TPT regimen, while completion was defined as receiving the full course of the prescribed TPT regimen.\u003c/p\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eData Analysis\u003c/h2\u003e \u003cp\u003eTPT uptake was calculated by dividing the number of eligible ART clients initiated on TPT in a semi-annual period by the number of all eligible ART clients in that semi-annual period. TPT completion was calculated by dividing the number of ART clients expected to complete and completed TPT in that semi-annual period by the number of all ART clients expected to complete TPT in that semi-annual period. Loss to follow-up was calculated by dividing the number of ART clients expected to complete in each period but were lost to follow-up by the total number of ART clients expected to complete in that period.\u003c/p\u003e \u003cp\u003eTo calculate the TPT cascade, we first calculated the proportion of PLHIV on ART who were eligible for TPT by dividing the number of eligible individuals by the total number of PLHIV on ART. Then we calculated the proportion of those eligible who had initiated TPT, and from those who had initiated, we calculated the proportion of individuals who completed their TPT regimen.\u003c/p\u003e \u003cp\u003eWe used time-series plot to describe temporal trends of TPT uptake, completion, and loss to follow-up over time. The data was analyzed in STATA version 14, and the Mann-Kendall test was utilized to determine the significance of trends at a level of 0.05. We also used the Quantum Geographic Information System (QGIS) to conduct spatial analysis to visualize and describe spatial patterns and variations of TPT loss to follow up among PLHIV across regions in Uganda.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eTPT cascade among HIV patients on ART, Uganda, 2020‒2023\u003c/h2\u003e \u003cp\u003eBetween January 2020 and December 2023, a total of 1,441,254 PLHIV had been enrolled on ART, of which 1,330,693 (92.3%) were eligible for TPT. Among those eligible, 87.0% (1,157,703) were initiated on TPT, and 92.0% (1,065,086) of those initiated completed their full dose of TPT (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Overall, 80.0% of the total eligible individuals were able to progress through all steps of the TPT care cascade and complete their TPT.\u003c/p\u003e \u003cp\u003e \u003cb\u003eTrends in Tuberculosis Preventive Therapy uptake and completion among HIV patients on Antiretroviral Therapy, Uganda, 2020‒2023\u003c/b\u003e \u003c/p\u003e \u003cp\u003eOverall, between January 2020 and December 2023, TPT uptake increased from 29% of eligible PLHIV to 89%, an increase of 60% (p\u0026thinsp;=\u0026thinsp;0.004), and completion increased from 91\u0026ndash;96%, an increase of 5% (p\u0026thinsp;=\u0026thinsp;0.02), with the greatest increases for both uptake and completion occurring between July 2020 and June 2021. Between January 2020 and December 2020, TPT completion dropped from 91\u0026ndash;87%, but then went back up to 92% in January 2021, remaining at that level through the end of the year. The uptake of TPT remained level at 64% throughout the entire 2021 period (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eRegional distribution of Tuberculosis Preventive Therapy uptake among HIV patients on ART, Uganda, 2020‒2023\u003c/h2\u003e \u003cp\u003eOverall, from January 2020 to December 2023, uptake of TPT in Uganda varied across regions, ranging from a low of 69% in the Tooro subregion to a high of 98% in the Bunyoro subregion (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cb\u003eLoss to follow-up, death, and discontinuation of Tuberculosis Preventive Therapy among HIV patients on Antiretroviral Therapy, Uganda, 2022‒2023\u003c/b\u003e \u003c/p\u003e \u003cp\u003eDuring the study period, 92,617 (8%) ART clients on TPT did not complete their course of TPT. Of this number, 43,956 (48%) had no documented reasons. Of the 48,661 (52.5%) who had documented reasons, 29,435 (61%) were lost to follow-up; 15,281 (31%) stopped due to side effects, 2,356 (5%) died, and 1,589 (3%) developed TB before TPT completion (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cb\u003eTemporal-spatial patterns of loss to follow-up among patients on Antiretroviral Therapy and Tuberculosis Preventive Therapy by region, Uganda, 2020‒2023\u003c/b\u003e \u003c/p\u003e \u003cp\u003eIn Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003e, the darker the area, the higher the rate of loss to follow-up. We observed that over the study period, loss to follow-up was decreasing. Most (7/15) of the regions started at a rate of more than 40 per 1,000 TPT patients, and 3 years later, only one region was still at a greater than 40 per 1,000 rates. Kampala subregion experienced the highest decline in loss to follow-up, decreasing from as high as 98 per 1,000 in January 2020 to 0 per 1,000 in June 2023, whereas the Lango subregion experienced the least decline in loss to follow-up, going from 65 per 1,000 in January 2020 to 22 per 1,000 in June 2023. This denotes an improving trend in the reduction of loss to follow-up of ART patients initiated on TPT.\u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eOur assessment revealed approximately 80% of all PLHIV on ART eligible for TPT successfully passed through all stages of the TPT cascade and finished their treatment. The uptake (initiation) of TPT among all eligible patients on ART was 87%, with a completion rate of 92% among those who began the treatment. Both uptake and completion rates showed significant improvement from 2020 to 2023, nearing the targeted 90% mark for both indicators. Among those who did not complete the treatment, over one-third were lost to follow-up, with the Mideastern region (Tooro) experiencing the highest rate of loss to follow-up during the study period.\u003c/p\u003e \u003cp\u003eThe TPT care cascade results are similar to findings from other studies, which found that over 70% of all PLHIV on ART eligible for TPT progressed through all steps of the care cascade and completed the treatment [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. The loss registered at initiation can be attributed to inadequate counseling techniques used to educate clients who did not have TB to otherwise accept TPT [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. Another study found that the lockdown during the COVID-19 outbreak in Uganda greatly affected access and utilization of healthcare services; this may have had a major impact on the number of clients who initiated TPT in that year [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. The higher uptake rates in our study could be explained by the fact that guidelines on the initiation of TPT are clear and integrated within the HIV prevention and treatment guidelines. In another study done in Thailand and Vietnam, two settings where integration had not yet been implemented, TPT uptake rates were low (75%), and this was attributed to delays in initiating TPT [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. Although TPT uptake improved during the same period, this fell short of the national and global target of 90%. Studies have suggested that challenges with uptake may be related to clinicians\u0026rsquo; fears, beliefs, and lack of sufficient information on TPT [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]. Additional studies may be needed to understand the causes of low TPT uptake in poorly performing regions.\u003c/p\u003e \u003cp\u003eThe TPT completion surpassed the national and global target of 90% with regional variations ranging from 68\u0026ndash;94%. This was consistent with a 2022 study done in Uganda on TPT, which showed a national TPT completion of 94% [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. This achievement could be attributed to the enhanced integration of HIV and TB management among PLHIV by the Ministry of Health. In a systematic review and meta-analysis of studies from multiple country programs serving similar populations, an overall completion rate of 59.8% was registered, attributed to the integration of TB and HIV care [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. Commodity availability and implementing partners' support for TPT demand creation among the beneficiaries made this possible [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eDespite the regional level reduction in loss to follow-up, we did not find significant differences in the proportion of patients lost to follow-up over the three and half years of the study. A 2022 study on factors contributing to pulmonary TB treatment lost to follow-up in Low-Middle income countries demonstrated that treatment illiteracy and insufficient pre-treatment counseling were the most important factors associated with LTFU [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]. This same study suggested that enhancing pre-screening and pre-treatment counseling could help reduce LTFU. The regional loss to follow-up varied, influenced not only by cultural differences and healthcare perceptions but also by a range of other factors such as socioeconomic status, access to healthcare services, and levels of education. For instance, a study conducted in Kenya highlighted that healthcare perceptions can significantly hinder the uptake of TPT, contributing to increased loss to follow-up [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]. However, it is essential to consider that these perceptions may interact with other barriers, creating a complex landscape that affects patient engagement and retention in care.\u003c/p\u003e \u003cp\u003eIn our study, we observed many clients who did not complete treatment because of TPT side effects, a finding similar to a 2023 study in Uganda on treatment outcomes for drug-resistant TB patients, where a high frequency of adverse events led to persisting discontinuation of treatment [\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e]. To address the persistent issue of anti-TB drug side effects, several measures have been proposed elsewhere and one such is nanomedicine, which is an emerging research area that offers the potential of effective drug delivery using nanoparticles and a reduction in drug doses. A study done in 2023 explored the progress of this research and found that this technology offers a slow, sustained, and controlled release of anti-TB drugs and provides the advantages of low doses, reduced side effects, and improved patient compliance [\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eOur findings have implications for TB prevention and control programs in Uganda and other similar settings. First, the study demonstrates that initiation and completion of TPT can improve over time, implying that 100% coverage of TPT is feasible. Secondly, addressing the issues that lead to high loss to follow-up of PLHIV on TPT could help the programs achieve 100% completion rates.\u003c/p\u003e\n\u003ch3\u003eStudy limitations\u003c/h3\u003e\n\u003cp\u003eThe study has some limitations to consider when interpreting the results. First, we used secondary data from the DHIS2, which may have issues of completeness and accuracy since the reporting rates were at 93%. The unreported 7% could introduce bias or inaccuracies, affecting the overall reliability of the findings. Secondly, it was not possible to do age and sex disaggregation because this was aggregated data. This prevented us from studying the differences within the population.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eDespite marked improvements in TPT uptake and completion among PLHIV over three years, a proportion of patients discontinued treatment prematurely, which may impact the long-term efficacy of TPT and delay progress toward End TB strategy goals. Understanding the reasons for non-return to clinics can significantly enhance interventions. These insights enrich the evidence base on TPT implementation among PLHIV in Uganda and similar settings, supporting efforts to accelerate TB elimination through prevention. We recommend a similar study on specific factors associated with high TPT uptake in our setting to inform program implementation.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eART\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eAntiretroviral Therapy\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eDHIS2\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eDistrict Health Information System version 2\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eHC\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eHealth Center\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eLTFU\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eLoss to follow-up\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eHIV\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eHuman Immunodeficiency Virus\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eMoH\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eMinistry of Health\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eTB\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eTuberculosis\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eTPT\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eTB preventive therapy\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eUS CDC\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eUnited States Centers for Disease Control and Prevention\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eWHO\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eWorld Health Organization\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e \u003ch2\u003eEthical considerations\u003c/h2\u003e \u003cp\u003eWe used TPT surveillance data from the DHIS2 that are routinely collected and reported by health facilities as part of the national health information system. Ministry of Health Uganda gave the administrative clearance to use the TPT data. The data are aggregated and anonymized and do not contain any personal identifiers of the patients or health workers as such it was determined to be non-research. The office of the Center for Global Health, US Center for Disease Control and Prevention determined that this activity was not human subject research, with its primary intent being for public health practice or disease control. In agreement with the International Guidelines for Ethical Review of Epidemiological Studies by the Council for International Organizations of Medical Sciences (1991). This activity was reviewed by the U.S. CDC and was conducted in a manner consistent with applicable federal law and CDC policy. \u0026sect;\u0026sect;See, e.g., 45 C.F.R. part 46, 21 C.F.R. part 56; 42 U.S.C. \u0026sect;\u0026nbsp;241(d); 5 U.S.C. \u0026sect;\u0026nbsp;552a; 44 U.S.C. \u0026sect;\u0026nbsp;3501 et seq.\u003c/p\u003e \u003c/p\u003e\u003cp\u003e \u003ch2\u003eConsent for publication\u003c/h2\u003e \u003cp\u003eNot applicable\u003c/p\u003e \u003c/p\u003e\u003cp\u003e \u003ch2\u003eCompeting interests:\u003c/h2\u003e \u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e \u003c/p\u003e\u003cp\u003e\u003cstrong\u003eFunding and disclaimer:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis publication has been supported by the President\u0026apos;s Emergency Plan for AIDS Relief (PEPFAR) through the U.S. Centers for Disease Control and Prevention (CDC) under the terms of GH001353-01 through Makerere University School of Public Health to the Uganda Public Health Fellowship Program, Ministry of Health. The findings and conclusions in this report are those of the author(s) and do not necessarily represent the official position of the funding agencies.\u0026nbsp;\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eIS: participated in the conception, design, analysis, and interpretation of the study and wrote the draft manuscript; MN, SW, BK, and DL supported the concept development. CN, LB, and DL reviewed the report, reviewed the drafts of the manuscript for intellectual content, and made multiple edits and recommendations to the drafts; ARA and DL reviewed the final manuscript to ensure intellectual content and scientific integrity. All authors read and approved the final manuscript.\u003c/p\u003e\u003ch2\u003eAcknowledgments\u003c/h2\u003e \u003cp\u003eThe authors would like to thank the Ministry of Health and the AIDS Control Program for their permission and support in accessing the data utilized in this project. We would also like to thank the US Centers for Disease Control and Prevention (CDC) for their technical support.\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eThe datasets upon which our findings are based belong to the Ugandan Public Health Fellowship Program and Ministry of Health Uganda. For confidentiality reasons, the datasets are not publicly available. However, the data sets can be made available upon reasonable request from the corresponding author (Innocent Ssemanda, Email: [email protected]) and with permission from the Uganda Public Health Fellowship Program and Ministry of Health Uganda.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003e(WHO), W.H.O. \u003cem\u003eTuberculosis profile Report: WHO Western Pacific Region \u003c/em\u003e2022 [cited 2024 24-April-2024]; Available from: https://worldhealthorg.shinyapps.io/tb_profiles/?_inputs_\u0026amp;group_code=%22WPR%22\u0026amp;entity_type=%22group%22\u0026amp;lan=%22EN%22.\u003c/li\u003e\n\u003cli\u003eKomrower, D. and M. Thillai, \u003cem\u003eTuberculosis and HIV co-infection.\u003c/em\u003e Clin Tuberc A Pract Handb, 2015: p. 157-70.\u003c/li\u003e\n\u003cli\u003eKomrower, D. and M. 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Available from: https://www.usaid.gov/sites/default/files/2022-05/Uganda_TBRM21_TB_DIAH_Version_Final.pdf.\u003c/li\u003e\n\u003cli\u003eLukoye, D., et al., \u003cem\u003eTuberculosis Preventive Therapy among Persons Living with HIV, Uganda, 2016\u0026ndash;2022.\u003c/em\u003e Emerging Infectious Diseases, 2023. \u003cstrong\u003e29\u003c/strong\u003e(3): p. 609.\u003c/li\u003e\n\u003cli\u003eWHO. \u003cem\u003eThe TB infection cascade of care - operations Handbook\u003c/em\u003e. 2023 [cited 2024 June 11th]; Available from: https://tbksp.org/en/node/2399.\u003c/li\u003e\n\u003cli\u003eSubbaraman, R., et al., \u003cem\u003eConstructing care cascades for active tuberculosis: a strategy for program monitoring and identifying gaps in quality of care.\u003c/em\u003e PLoS medicine, 2019. \u003cstrong\u003e16\u003c/strong\u003e(2): p. e1002754.\u003c/li\u003e\n\u003cli\u003eministry of Health, U.a.C.P.H.L. \u003cem\u003eDHIS2 User Manual, Uganda\u003c/em\u003e. 2022.\u003c/li\u003e\n\u003cli\u003eMinsitry of Health, U. \u003cem\u003eHealth Facility inventory\u003c/em\u003e. 2018; Available from: https://health.go.ug/sites/default/files/Signed%20n%20final%20mfl.pdf.\u003c/li\u003e\n\u003cli\u003eMinistry of Health, U. \u003cem\u003eConsolidated HIV and AIDS gudilines 2023\u003c/em\u003e. 2022; Available from: https://dsduganda.com/wp-content/uploads/2023/05/Consolidated-HIV-and-AIDS-Guidelines-20230516.pdf.\u003c/li\u003e\n\u003cli\u003eBastos, M.L., et al., \u003cem\u003eThe latent tuberculosis cascade-of-care among people living with HIV: A systematic review and meta-analysis.\u003c/em\u003e PLoS Medicine, 2021. \u003cstrong\u003e18\u003c/strong\u003e(9): p. e1003703.\u003c/li\u003e\n\u003cli\u003eSajjad, S.S., et al., \u003cem\u003eThe impact of structured counselling on patient knowledge at a private TB program in Karachi.\u003c/em\u003e Pakistan Journal of Medical Sciences, 2020. \u003cstrong\u003e36\u003c/strong\u003e(1): p. S49.\u003c/li\u003e\n\u003cli\u003eKurnia, A.D., et al., \u003cem\u003eEffect of Counselling on Medication Adherence in Tb Patients with the DOTS Strategy: A Scoping Review.\u003c/em\u003e Jurnal Aisyah: Jurnal Ilmu Kesehatan, 2021. \u003cstrong\u003e6\u003c/strong\u003e(4): p. 773\u0026ndash;780.\u003c/li\u003e\n\u003cli\u003eTumwesigye, N.M., et al., \u003cem\u003eEffects of the COVID-19 pandemic on health services and mitigation measures in Uganda.\u003c/em\u003e 2021.\u003c/li\u003e\n\u003cli\u003eCowger, T.L., et al., \u003cem\u003eProgrammatic evaluation of an algorithm for intensified tuberculosis case finding and isoniazid preventive therapy for people living with HIV in Thailand and Vietnam.\u003c/em\u003e JAIDS Journal of Acquired Immune Deficiency Syndromes, 2017. \u003cstrong\u003e76\u003c/strong\u003e(5): p. 512-521.\u003c/li\u003e\n\u003cli\u003eMusaazi, J., et al., \u003cem\u003eIncreased uptake of tuberculosis preventive therapy (TPT) among people living with HIV following the 100-days accelerated campaign: A retrospective review of routinely collected data at six urban public health facilities in Uganda.\u003c/em\u003e PloS one, 2023. \u003cstrong\u003e18\u003c/strong\u003e(2): p. e0268935.\u003c/li\u003e\n\u003cli\u003eUganda, M.o.H. \u003cem\u003eUganda National Guidelines for Tuberculosis \u003cem\u003eInfection Control in Health Care Facilities, \u003cem\u003eCongregate Settings and Households\u003c/em\u003e. 2020 [cited 2023 January 21st ]; Available from: https://www.health.go.ug/cause/100-day-accelerated-isoniazid-preventive-therapy-scale-up-plan/.\u003c/em\u003e\u003c/em\u003e\u003c/li\u003e\n\u003cli\u003eBaluku, J.B., et al., \u003cem\u003eOne dollar incentive improves tuberculosis treatment outcomes in programmatic settings in rural Uganda.\u003c/em\u003e Scientific Reports, 2021. \u003cstrong\u003e11\u003c/strong\u003e(1): p. 19346.\u003c/li\u003e\n\u003cli\u003eOpperman, M. and I. Du Preez, \u003cem\u003eFactors contributing to pulmonary TB treatment lost to follow-up in developing countries: an overview.\u003c/em\u003e African Journal of Infectious Diseases, 2023. \u003cstrong\u003e17\u003c/strong\u003e(1): p. 60-73.\u003c/li\u003e\n\u003cli\u003eNgugi, S.K., et al., \u003cem\u003eFactors affecting uptake and completion of isoniazid preventive therapy among HIV-infected children at a national referral hospital, Kenya: a mixed quantitative and qualitative study.\u003c/em\u003e BMC infectious diseases, 2020. \u003cstrong\u003e20\u003c/strong\u003e: p. 1-11.\u003c/li\u003e\n\u003cli\u003eKintu, T., et al., \u003cem\u003eUnfavorable treatment outcomes among patients with drug-resistant TB in Uganda.\u003c/em\u003e The International Journal of Tuberculosis and Lung Disease, 2023. \u003cstrong\u003e27\u003c/strong\u003e(4): p. 291-297.\u003c/li\u003e\n\u003cli\u003eBorah Slater, K., et al., \u003cem\u003eA Current Perspective on the Potential of Nanomedicine for Anti-Tuberculosis Therapy.\u003c/em\u003e Tropical Medicine and Infectious Disease, 2023. \u003cstrong\u003e8\u003c/strong\u003e(2): p. 100.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Tuberculosis, People Living with HIV, TB Preventive Therapy, Uganda","lastPublishedDoi":"10.21203/rs.3.rs-5314078/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5314078/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eIntroduction\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIn 2015, Uganda adopted the World Health Organization (WHO) guidelines for Tuberculosis Preventive Therapy (TPT) among people living with HIV (PLHIV). The country has implemented several initiatives to scale up TPT including the integration of TPT into HIV care services. The WHO target for both initiation and completion of TPT among PLHIV in care is 90% by 2035. We described trends and spatial distribution of TPT uptake and completion, and reasons for non-completion among PLHIV in Uganda to track progress towards meeting the targets.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe extracted and analyzed national and subnational aggregated data on TPT among PLHIV on Antiretroviral Therapy (ART) as reported through the District Health Information System Version 2 (DHIS2) from January 2020 to December 2023. TPT eligibility, initiation, and completion rates were calculated. Reasons for failure to complete TPT were categorized as loss to follow-up, TB diagnosis, stopping due to side effects, and death while on TPT. We analyzed trends using the Mann-Kendall test and described spatial distribution by region over time. P-values of \u0026lt; 0.05 were considered statistically significant.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eBy June 2023, 1,330,693 PLHIV on ART were eligible for TPT, of which 87% (1,157,703) had been initiated and 92% (1,065,086) of the initiated had completed TPT treatment. Between January 2020 and December 2023, uptake of TPT increased from 21% of eligible PLHIV to 89% and completion increased from 91–96%. Of the 92,617 (8%) ART clients who did not complete their TPT regimen, 29,435 (37%) were lost to follow-up, 2,356 (3%) died, and 1,589 (2%) were diagnosed with TB.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eUganda is close to achieving the WHO TPT initiation target and has already met the target for TPT completion among PLHIV. It is important for the Ministry of Health to maintain the high initiation rates of TPT among PLHIV who are newly enrolled in care.\u003c/p\u003e","manuscriptTitle":"Uptake and completion of Tuberculosis Preventive Therapy among people living with HIV on Antiretroviral Therapy in Uganda, 2020–2023","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-11-06 12:58:28","doi":"10.21203/rs.3.rs-5314078/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"191f6f98-0d4c-4a19-b324-009fa616c8d4","owner":[],"postedDate":"November 6th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-02-04T06:08:52+00:00","versionOfRecord":[],"versionCreatedAt":"2024-11-06 12:58:28","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-5314078","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5314078","identity":"rs-5314078","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}