The impact of alcohol consumption on TB treatment outcomes

饮酒对结核病治疗结果的影响

• 批准号: 9103779
• 负责人: Karen R Jacobson
• 金额: $ 69.84万
• 依托单位: BOSTON MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-04-08 至 2021-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9103779
• 关键词: AIDS/HIV problem; Acute; Address; Adherence; Adverse drug effect; Affect; Aftercare; Alcohol abuse; Alcohol consumption; Alcoholism; Alcohols; Animal Model; Area; Area Under Curve; Behavior; Behavioral; Biological; Biological Markers; Biology; Blood specimen; Boston; Brazil; Car Phone; Cause of Death; Cessation of life; Chest; China; Chronic; Communicable Diseases; Communities; Community Workers; Complex; Country; Data; Deltastab; Disease; Dose; Drug Kinetics; Drug toxicity; Epidemic; Ethambutol; Farming environment; Female; HIV; Health; High Prevalence; Incidence; India; Individual; Infection; Ingestion; Intervention; Interviewer; Investigation; Lead; Length; Liver Dysfunction; Longitudinal Studies; Measures; Medical Research; Medical center; Metabolism; Monitor; Observational Study; Organ; Outcome; Outcome Measure; Pathway interactions; Patients; Pattern; Persons; Pharmaceutical Preparations; Pharmacodynamics; Population; Prevalence; Prospective Studies; Province; Pulmonary Tuberculosis; Pyrazinamide; Questionnaires; Recruitment Activity; Regimen; Relapse; Reporting; Research Personnel; Retrospective Studies; Rifampin; Risk; Rural; South Africa; South African; Sputum; Sterilization; System; Technology; Time; Toxic effect; Training; Treatment Failure; Treatment outcome; Tuberculosis; United States; Universities; Wine; absorption; alcohol misuse; attributable mortality; base; binge drinking; chronic alcohol ingestion; cohort; farm worker; improved; innovation; interdisciplinary approach; isoniazid; medical schools; medication compliance; mortality; novel; phosphatidylethanol; prospective; public health relevance; treatment adherence; treatment duration; treatment response; tuberculosis drugs; tuberculosis treatment

 DESCRIPTION (provided by applicant): After HIV/AIDS, tuberculosis (TB) remains the second leading cause of death due to an infectious disease globally. Retrospective studies from many countries, including South Africa, have consistently reported that in addition to having a higher burden of TB disease, patients with problem alcohol use have worse TB treatment outcomes, including delayed culture conversion and higher rates of treatment failure, relapse, and death, compared to patients who do not consume alcohol. An estimated 10% of TB deaths are attributable to problematic alcohol use globally. Although one causal pathway to worse TB outcomes is through poor treatment adherence, observational studies and animals models suggest that the relationship between alcohol use and TB treatment outcomes persists after adjustment for suboptimal adherence. One potential biological mechanism is through alcohol's impact on the pharmacokinetics (PK) and pharmacodynamics (PD) of TB drugs. Problem alcohol use may lead to poorer absorption and/or accelerated metabolism of TB drugs, thereby increasing the risk of suboptimal sterilization. There is an urgent need to identify modifiable factors that contribute to poor TB treatment response, and understanding drivers of poor treatment response, both at the individual and population level, is essential for TB control. Investigators at Boston Medical Center (BMC), Boston University School of Medicine (BUSM), the South African Medical Research Council (MRC), and the University of Cape Town (UCT) propose to conduct the first prospective study to attempt to clarify the causal mechanisms underlying the deleterious effects of problem alcohol use on TB treatment outcomes. We plan to recruit 438 culture positive, pulmonary TB patients in Worcester, South Africa, an area highly endemic for both TB and problem alcohol use. The specific aims of this study are: 1) examine the associations between problem alcohol use and TB treatment outcomes, and (ii) demonstrate that these associations persist independent of adherence to TB treatment, and 2) to evaluate the effect of problematic alcohol use on the PK/PD of TB drugs. Our multidisciplinary approach will provide the best evidence to date addressing the complex interactions between TB and alcoholism and inform management strategies for countries facing these two epidemics.