ABSTRACT Introduction Tuberculosis (TB) is the leading infectious cause of death globally. Despite WHO recommendations for Tuberculosis 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. Methods This is an observational cohort study with a nested case-control study. We enrolled consecutive patients initiated on TPT using the 3HP regimen. These are followed up bi-weekly 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 and CYP2E1 polymorphisms are done. Participants are followed up for 2 years to determine TPT outcomes. Analysis 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. Chi-square 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.

The authors have declared no competing interest.

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Ethical approval for this study was sought and approvals received from the Infectious Diseases Institute Research and Ethics Committee (IDI-REC), IREC Ref: 001/2021 and the Uganda National Council of Science and Technology (UNCST), UNCST Folio Number: HS1582ES. Written informed consent is obtained from all participants. Children between 8 and 17 years are requested for assent, in addition to consent from their parents or legally authorized representative. For children less than 8 years, consent is sought from their parents/ legally authorized representative. The study is conducted in accordance with good clinical practice and declaration of Helsinki.

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No datasets were generated or analysed during the current study. All relevant data from this study will be made available upon study completion.