{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T01:04:04Z","timestamp":1792803844358,"version":"4.5.0"},"reference-count":29,"publisher":"BMJ","issue":"12","license":[{"start":{"date-parts":[[2024,12,31]],"date-time":"2024-12-31T00:00:00Z","timestamp":1735603200000},"content-version":"unspecified","delay-in-days":30,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"The National Institute of Allergy And Infectious Diseases of the National Institutes of Health","award":["R01AI160434"],"award-info":[{"award-number":["R01AI160434"]}]},{"DOI":"10.13039\/100015691","name":"Division of Microbiology and Infectious Diseases","doi-asserted-by":"publisher","award":["NIAID K24AI150349"],"award-info":[{"award-number":["NIAID K24AI150349"]}],"id":[{"id":"10.13039\/100015691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2024,11,22]]},"published-print":{"date-parts":[[2024,12]]},"abstract":"<jats:sec>\n                  <jats:title>Introduction<\/jats:title>\n                  <jats:p>Tuberculosis (TB) is the leading infectious cause of death globally. Despite WHO recommendations for TB preventive therapy (TPT), challenges persist, including incompletion of treatment and adverse drug reactions (ADRs). There is limited data on the 3-month isoniazid and rifapentine (3HP) pharmacokinetics, pharmacogenomics and their relation with ADRs. Our study aims to describe the pharmacokinetic and pharmacogenomics of 3HP used for TPT, the ADRs and their association with completion rates, and TPT outcomes, providing vital insights for TB control strategies in resource-limited settings.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>This is an observational cohort study with a nested case\u2013control study. We enrolled consecutive patients who had been initiated on TPT using the 3HP regimen. These are followed up biweekly and then monthly during the active phase of treatment and 3 monthly for 2 years following completion of TPT. ADR evaluation includes clinical assessment and liver function tests. Cases are selected from those who experience ADRs and controls from those who do not. Serum isoniazid and rifapentine concentrations are measured and pharmacogenomic analysis for NAT2, AADAC and CYP2E1 polymorphisms are done. Participants are followed up for 2 years to determine TPT outcomes.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Analysis<\/jats:title>\n                  <jats:p>The safety profile of 3HP will be assessed using descriptive statistics, including proportions of patients experiencing ADRs and grade 3 or above events related to treatment. \u03c7<jats:sup>2<\/jats:sup> tests and regression models will determine predictors of ADRs and their impact on treatment completion. Pharmacokinetic-pharmacodynamic modelling will establish population parameters and factors influencing rifapentine and isoniazid concentrations.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Ethics and dissemination<\/jats:title>\n                  <jats:p>Ethical approval of this study inclusive of all the appropriate documents was obtained from the Infectious Diseases Institute Research and Ethics Committee and the Uganda National Council of Science and Technology. The study adheres to legal, ethical and Good Clinical Practice (GCP) guidelines. Deidentified genotype data from 300 patients will be shared after publication. The protocol and phenotype data will be publicly accessible. Abstracts will be submitted to conferences, and a manuscript will be published poststudy.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/bmjopen-2024-088389","type":"journal-article","created":{"date-parts":[[2024,12,31]],"date-time":"2024-12-31T11:30:12Z","timestamp":1735644612000},"page":"e088389","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":2,"title":["Clinical predictors of 3-month isoniazid rifapentine (3HP)-related adverse drug reactions (ADR) during tuberculosis preventive therapy (PAnDoRA-3HP study): an observational study protocol"],"prefix":"10.1136","volume":"14","author":[{"given":"Christine","family":"Sekaggya-Wiltshire","sequence":"first","affiliation":[{"name":"Infectious Diseases Institute, Makerere University College of Health Sciences, Kampala, Central, Uganda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-8353-9843","authenticated-orcid":false,"given":"Irene","family":"Mbabazi","sequence":"additional","affiliation":[{"name":"Infectious Diseases Institute, Makerere University College of Health Sciences, Kampala, Central, Uganda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruth Mirembe","family":"Nabisere","sequence":"additional","affiliation":[{"name":"Infectious Diseases Institute, Makerere University College of Health Sciences, Kampala, Central, Uganda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucy","family":"Alinaitwe","sequence":"additional","affiliation":[{"name":"Infectious Diseases Institute, Makerere University College of Health Sciences, Kampala, Central, Uganda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian","family":"Otaalo","sequence":"additional","affiliation":[{"name":"Infectious Diseases Institute, Makerere University College of Health Sciences, Kampala, Central, Uganda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florence","family":"Aber","sequence":"additional","affiliation":[{"name":"Infectious Diseases Institute, Makerere University College of Health Sciences, Kampala, Central, Uganda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juliet","family":"Nampala","sequence":"additional","affiliation":[{"name":"Infectious Diseases Institute, Makerere University College of Health Sciences, Kampala, Central, Uganda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rogers","family":"Owori","sequence":"additional","affiliation":[{"name":"Infectious Diseases Institute, Makerere University College of Health Sciences, Kampala, Central, Uganda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josephine","family":"Bayigga","sequence":"additional","affiliation":[{"name":"Infectious Diseases Institute, Makerere University College of Health Sciences, Kampala, Central, Uganda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Mayito","sequence":"additional","affiliation":[{"name":"Infectious Diseases Institute, Makerere University College of Health Sciences, Kampala, Central, Uganda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grace","family":"Banturaki","sequence":"additional","affiliation":[{"name":"Infectious Diseases Institute, Makerere University College of Health Sciences, Kampala, Central, Uganda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva Agnes Odongpiny","family":"Laker","sequence":"additional","affiliation":[{"name":"Infectious Diseases Institute, Makerere University College of Health Sciences, Kampala, Central, Uganda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7756-5032","authenticated-orcid":false,"given":"Barbara","family":"Castelnuovo","sequence":"additional","affiliation":[{"name":"Infectious Diseases Institute, Makerere University College of Health Sciences, Kampala, Central, Uganda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moorine Penninah","family":"Sekadde","sequence":"additional","affiliation":[{"name":"National TB and Leprosy Division, Republic of Uganda Ministry of Health, Kampala, Uganda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8984-8379","authenticated-orcid":false,"given":"Jotam","family":"Pasipanodya","sequence":"additional","affiliation":[{"name":"Vanderbilt University Medical Center, Nashville, Tennessee, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelly E","family":"Dooley","sequence":"additional","affiliation":[{"name":"Vanderbilt University Medical Center, Nashville, Tennessee, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Turyahabwe","family":"Stavia","sequence":"additional","affiliation":[{"name":"National Tuberculosis and Leprosy Program, Republic of Uganda Ministry of Health, Kampala, Uganda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8823-7082","authenticated-orcid":false,"given":"Stella","family":"Zawedde\u2010Muyanja","sequence":"additional","affiliation":[{"name":"Infectious Diseases Institute, Makerere University College of Health Sciences, Kampala, Central, Uganda"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2024,12,31]]},"reference":[{"key":"2025101812414001000_14.12.e088389.1","unstructured":"Organization WH . Global tuberculosis report 2023. Geneva, 2023."},{"key":"2025101812414001000_14.12.e088389.2","unstructured":"Organization WH . Global tuberculosis report 2013. World Health Organization; 2013."},{"key":"2025101812414001000_14.12.e088389.3","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pmed.1002152","article-title":"The Global Burden of Latent Tuberculosis Infection: A Re-estimation Using Mathematical Modelling","volume":"13","author":"Houben","year":"2016","journal-title":"PLoS Med"},{"key":"2025101812414001000_14.12.e088389.4","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.01245-2015"},{"key":"2025101812414001000_14.12.e088389.5","first-page":"1","article-title":"Recent studies in the epidemiology of tuberculosis, based on the risk of being infected with tubercle bacilli","volume":"19","author":"Sutherland","year":"1976","journal-title":"Adv Tuberc Res"},{"key":"2025101812414001000_14.12.e088389.6","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199709183371201"},{"key":"2025101812414001000_14.12.e088389.7","doi-asserted-by":"publisher","DOI":"10.1111\/ajt.15841"},{"key":"2025101812414001000_14.12.e088389.8","doi-asserted-by":"publisher","DOI":"10.7326\/M17-0609"},{"key":"2025101812414001000_14.12.e088389.9","unstructured":"Millington KA . Ending tuberculosis. 2018."},{"key":"2025101812414001000_14.12.e088389.10","unstructured":"Government of uganda ministry of health . Guidelines for programmatic management of latent tb infection in uganda 'Closing the tb tap' a health worker guide. 2021."},{"key":"2025101812414001000_14.12.e088389.11","doi-asserted-by":"crossref","first-page":"741","DOI":"10.5588\/ijtld.21.0676","article-title":"Implementing 3HP vs. IPT as TB preventive treatment in Pakistan","volume":"26","author":"Jaswal","year":"2022","journal-title":"Int Tuberc Lung Dis"},{"key":"2025101812414001000_14.12.e088389.12","doi-asserted-by":"publisher","DOI":"10.7326\/M17-1150"},{"key":"2025101812414001000_14.12.e088389.13","doi-asserted-by":"publisher","DOI":"10.1378\/chest.09-0394"},{"key":"2025101812414001000_14.12.e088389.14","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1001\/jamapediatrics.2014.3158","article-title":"Treatment for preventing tuberculosis in children and adolescents: a randomized clinical trial of a 3-month, 12-dose regimen of a combination of rifapentine and isoniazid","volume":"169","author":"Villarino","year":"2015","journal-title":"JAMA Pediatr"},{"key":"2025101812414001000_14.12.e088389.15","doi-asserted-by":"crossref","first-page":"1085","DOI":"10.1093\/cid\/cix505","article-title":"High Rate of Treatment Completion in Program Settings With 12-Dose Weekly Isoniazid and Rifapentine for Latent Mycobacterium tuberculosis Infection","volume":"65","author":"Sandul","year":"2017","journal-title":"Clin Infect Dis"},{"key":"2025101812414001000_14.12.e088389.16","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.tube.2018.05.013","article-title":"Twelve-dose weekly rifapentine plus isoniazid for latent tuberculosis infection: A multicentre randomised controlled trial in Taiwan","volume":"111","author":"Sun","year":"2018","journal-title":"Tuberculosis 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