Tenforde Mark W, Yadav Ashish, Dowdy David W, Gupte Nikhil, Shivakoti Rupak, Yang Wei-Teng, Mwelase Noluthando, Kanyama Cecilia, Pillay Sandy, Samaneka Wadzanai, Santos Breno, Poongulali Selvamuthu, Tripathy Srikanth, Riviere Cynthia, Berendes Sima, Lama Javier R, Cardoso Sandra W, Sugandhavesa Patcharaphan, Christian Parul, Semba Richard D, Campbell Thomas B, Gupta Amita
*Division of Allergy and Infectious Diseases, Department of Medicine, University of Washington School of Medicine, Seattle, WA; Departments of †International Health; ‡Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD; §Division of Infectious Diseases, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD; ‖Department of Medicine, Bridgeport Hospital, Yale New Haven Health, Bridgeport, CT; ¶Department of Medicine, University of Witwatersrand, Johannesburg, South Africa; #UNC Lilongwe, Lilongwe, Malawi; **Durban International Clinical Research Site, Durban University of Technology, Durban, South Africa; ††University of Zimbabwe Clinical Research Centre, Harare, Zimbabwe; ‡‡Hospital Nossa Senhora de Conceição, Porto Alegre, Brazil; §§YR Gaitonde Centre for AIDS Research and Education, Chennai, India; ‖‖National AIDS Research Institute, Pune, India; ¶¶Les Centres GHESKIO, Port-Au-Prince, Haiti; ##Malawi College of Medicine, Johns Hopkins University Research Project, Blantyre, Malawi; ***Liverpool School of Tropical Medicine, Liverpool, United Kingdom; †††Asociacion Civil Impacta Salud y Educacion, Lima, Peru; ‡‡‡STD/AIDS Clinical Research Laboratory, Instituto de Pesquisa Clinica Evandro Chagas, Fundacao Oswaldo Cruz, Rio de Janeiro, Brazil; §§§Research Institute for Health Sciences, Chiang Mai, Thailand; ‖‖‖Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, MD; and ¶¶¶Division of Infectious Diseases, Department of Medicine, University of Colorado School of Medicine, Aurora, CO.
J Acquir Immune Defic Syndr. 2017 Jul 1;75(3):e71-e79. doi: 10.1097/QAI.0000000000001308.
Numerous micronutrients have immunomodulatory roles that may influence risk of tuberculosis (TB), but the association between baseline micronutrient deficiencies and incident TB after antiretroviral therapy (ART) initiation in HIV-infected individuals is not well characterized.
We conducted a case-cohort study (n = 332) within a randomized trial comparing 3 ART regimens in 1571 HIV treatment-naive adults from 9 countries. A subcohort of 30 patients was randomly selected from each country (n = 270). Cases (n = 77; main cohort = 62, random subcohort = 15) included patients diagnosed with TB by 96 weeks post-ART initiation. We determined pretreatment concentrations of vitamin A, carotenoids, vitamin B6, vitamin B12, vitamin D, vitamin E, and selenium. We measured associations between pretreatment micronutrient deficiencies and incident TB using Breslow-weighted Cox regression models.
Median pretreatment CD4 T-cell count was 170 cells/mm; 47.3% were women; and 53.6% Black. In multivariable models after adjusting for age, sex, country, treatment arm, previous TB, baseline CD4 count, HIV viral load, body mass index, and C-reactive protein, pretreatment deficiency in vitamin A (adjusted hazard ratio, aHR 5.33, 95% confidence interval, CI: 1.54 to 18.43) and vitamin D (aHR 3.66, 95% CI: 1.16 to 11.51) were associated with TB post-ART.
In a diverse cohort of HIV-infected adults from predominantly low- and middle-income countries, deficiencies in vitamin A and vitamin D at ART initiation were independently associated with increased risk of incident TB in the ensuing 96 weeks. Vitamin A and D may be important modifiable risk factors for TB in high-risk HIV-infected patients starting ART in resource-limited highly-TB-endemic settings.
多种微量营养素具有免疫调节作用，可能会影响结核病（TB）风险，但在HIV感染者中，基线微量营养素缺乏与开始抗逆转录病毒治疗（ART）后发生结核病之间的关联尚未得到充分描述。
我们在一项随机试验中开展了一项病例队列研究（n = 332），该试验比较了来自9个国家的1571名未接受过HIV治疗的成年患者的3种ART方案。从每个国家随机选取30名患者组成一个亚队列（n = 270）。病例组（n = 77；主要队列 = 62，随机亚队列 = 15）包括在开始ART后96周内被诊断为结核病的患者。我们测定了维生素A、类胡萝卜素、维生素B6、维生素B12、维生素D、维生素E和硒的治疗前浓度。我们使用Breslow加权Cox回归模型测量了治疗前微量营养素缺乏与结核病发病之间的关联。
治疗前CD4 T细胞计数中位数为170个细胞/mm³；47.3%为女性；53.6%为黑人。在调整了年龄、性别、国家、治疗组、既往结核病、基线CD4计数、HIV病毒载量、体重指数和C反应蛋白的多变量模型中，维生素A（调整后风险比，aHR 5.33，95%置信区间，CI：1.54至18.43）和维生素D（aHR 3.66，95% CI：1.16至11.51）的治疗前缺乏与ART后发生结核病相关。
在一个主要来自低收入和中等收入国家的多样化HIV感染成年人群体中，开始ART时维生素A和维生素D缺乏与随后96周内发生结核病的风险增加独立相关。在资源有限且结核病高发的环境中，开始ART的高危HIV感染患者中，维生素A和D可能是结核病重要的可改变风险因素。
