Abstract
BackgroundAn estimated 10% of tuberculosis (TB) deaths are attributable to problematic alcohol use globally, however the causal pathways through which problem alcohol use has an impact on TB treatment outcome is not clear. This study aims to improve understanding of these mechanisms. Specifically, we aim to 1) assess whether poor TB treatment outcomes, measured as delayed time-to-culture conversion, are associated with problem alcohol use after controlling for non-adherence to TB pharmacotherapy; and 2) to determine whether pharmacokinetic (PK) changes in those with problem alcohol use are associated with delayed culture conversion, higher treatment failure/relapse rates or with increased toxicity.MethodsOur longitudinal, repeated measures, prospective cohort study aims to examine the associations between problem alcohol use and TB treatment outcomes and to evaluate the effect of alcohol on the PK and pharmacodynamics (PD) of TB drugs. We will recruit 438 microbiologically confirmed, pulmonary TB patients with evidence of rifampicin susceptibility in Worcester, South Africa with 200 HIV uninfected patients co-enrolled in the PK aim. Participants are followed for the six months of TB treatment and an additional 12 months thereafter, with sputum collected weekly for the first 12 weeks of treatment, alcohol consumption measures repeated monthly in concert with an alcohol biomarker (phosphatidylethanol) measurement at baseline, and in person directly observed therapy (DOT) using real-time mobile phone-based adherence monitoring. The primary outcome is based on time to culture conversion with the second objective to compare PK of first line TB therapy in those with and without problem alcohol use.DiscussionGlobally, an urgent need exists to identify modifiable drivers of poor TB treatment outcomes. There is a critical need for more effective TB treatment strategies for patients with a history of problem alcohol use. However, it is not known whether poor treatment outcomes in alcohol using patients are solely attributable to noncompliance. This study will attempt to answer this question and provide guidance for future TB intervention trials.Trial registrationClinicaltrials.gov Registration Number: NCT02840877. Registered on 19 July 2016.
Highlights
An estimated 10% of tuberculosis (TB) deaths are attributable to problematic alcohol use globally, the causal pathways through which problem alcohol use has an impact on TB treatment outcome is not clear
Evaluation of adherence In order to capture comprehensive data on adherence in those with problem alcohol use, Treatment and Alcohol Use Study (TRUST) has developed a system for patient engagement including active tracking of participants with daily documentation of their pill-taking by a team of study-employed directly observed therapy (DOT) workers, coupled with frequent reminders and graded subject reimbursements based on adherence
In addition to reimbursement for regular study visits, TRUST employs graded reimbursement in the form of grocery vouchers based on percent of DOT visits and weekly sputa captured successfully during the first three months of treatment
Summary
An estimated 10% of tuberculosis (TB) deaths are attributable to problematic alcohol use globally, the causal pathways through which problem alcohol use has an impact on TB treatment outcome is not clear. We aim to 1) assess whether poor TB treatment outcomes, measured as delayed time-to-culture conversion, are associated with problem alcohol use after controlling for non-adherence to TB pharmacotherapy; and 2) to determine whether pharmacokinetic (PK) changes in those with problem alcohol use are associated with delayed culture conversion, higher treatment failure/relapse rates or with increased toxicity. The causal pathways by which problem alcohol use affect TB treatment response, are poorly understood. This is due largely to difficulties in studying patients with alcohol-related problems and a lack of detailed data on their TB medication adherence. One potential mechanism for worse TB outcomes is poor treatment adherence and loss to follow up [2], yet observational and animal studies suggest biological mechanisms are contributing to the association between alcohol use and poor TB clinical outcomes
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