期刊
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
卷 187, 期 4, 页码 439-445出版社
AMER THORACIC SOC
DOI: 10.1164/rccm.201208-1352OC
关键词
latent tuberculosis infection; isoniazid; IFN-gamma release assays; clinical trial; ELISPOT reversion
资金
- Medical Research Council (UK)
- European and Developing Countries Clinical Trials Partnership Career Development Fellowship [CG_ta_2005_40203_001]
- MRC [MC_U190081968, MC_U190071468, MC_UP_A900_1122] Funding Source: UKRI
- Medical Research Council [MC_U190071468, MC_UP_A900_1122, MC_U190081968] Funding Source: researchfish
Rationale: Biomarkers that can be used to evaluate new interventions against latent tuberculosis infection (LTBI) and predict reactivation TB disease are urgently required. Objectives: To evaluate ESAT-6 and CFP-10 (EC) IFN-gamma ELISPOT as a biomarker for treatment efficacy in LTBI. Methods: This was a randomized, blinded, and placebo-controlled trial of INH in EC ELISPOT and Mantoux test positive participants. Measurements and Main Results: Participants received a 6-month course of 900 mg INH twice weekly or a matching placebo. INH acetylator genotypes were determined and urine tested for INH metabolites to confirm adherence. The proportion of positive responders for CFP-10 and ESAT-6 between treatment arms was compared using mixed effects logistic regression models. A Tweedie (compound Poisson) model was fitted to allow for zero inflation and overdispersion of quantitative response. The proportions of EC ELISPOT-positive subjects reduced over time (P < 0.001) but did not differ by study arm (P = 0.36). Median spot-forming units for ESAT-6 and CFP-10 also declined significantly with time (P < 0.001) but did not differ by study arm (P = 0.74 and 0.71, respectively). There was no evidence of an interaction between acetylator status and INH treatment with respect to ELISPOT results over time. Conclusions: In contacts with LTBI, INH therapy plays no role in observed decreases in Mycobacterium tuberculosis antigen specific T-cell responses over time. IFN-gamma ELISPOT is probably not a useful biomarker of treatment efficacy in LTBI. Clinical trial registered with www.clinicaltrials.gov (NCT 00130325).
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