RESUMO
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 modeling will establish population parameters and factors influencing rifapentine and isoniazid concentrations.
RESUMO
Background: Completion of tuberculosis (TB) treatment presents several challenges to patients, including long treatment duration, medication adverse-effects and heavy pill burden. WHO emphasize the need for patient-centered TB care, but such approaches require understanding of patient experiences and perceptions. Methods: In 2020, we nested a qualitative study within a clinical trial that recruited 128 HIV-TB co-infected adults in Kampala receiving rifampicin-based TB treatment, alongside anti-retroviral therapy. A purposively selected sub-sample of 46 trial participants contributed to nine gender segregated focus group discussions. Of these, 12 also participated in in-depth interviews. Sessions were recorded, transcribed verbatim and translated from local languages into English. Thematic analysis focused on drug adverse-effects, use of self-prescribed medications and barriers to treatment adherence. Results: Patients seemed more concerned about adverse effects that clinicians sometimes overlook such as change in urine color. Those who remembered pre-treatment counselling advice were disinclined to manage adverse-effects by self-prescription. Difficulty in accessing a medical practitioner was reported as a reason for self-medication. Obstacles to adherence included stigma (especially from visible adverse-effects like "red urine"), difficulties with pill size and number, discomfort with formulation and medication adverse effects. Conclusion: Tailored pre-treatment counselling, improved access to clinical services, and simpler drug administration will deliver more patient-centered care.
