TY - JOUR
T1 - Vitamin A and D Deficiencies Associated with Incident Tuberculosis in HIV-Infected Patients Initiating Antiretroviral Therapy in Multinational Case-Cohort Study
AU - Tenforde, Mark W.
AU - Yadav, Ashish
AU - Dowdy, David W.
AU - Gupte, Nikhil
AU - Shivakoti, Rupak
AU - Yang, Wei Teng
AU - Mwelase, Noluthando
AU - Kanyama, Cecilia
AU - Pillay, Sandy
AU - Samaneka, Wadzanai
AU - Santos, Breno
AU - Poongulali, Selvamuthu
AU - Tripathy, Srikanth
AU - Riviere, Cynthia
AU - Berendes, Sima
AU - Lama, Javier R.
AU - Cardoso, Sandra W.
AU - Sugandhavesa, Patcharaphan
AU - Christian, Parul
AU - Semba, Richard D.
AU - Campbell, Thomas B.
AU - Gupta, Amita
N1 - Publisher Copyright:
Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.
PY - 2017/7/1
Y1 - 2017/7/1
N2 - Introduction: 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. Methods: 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. Results: Median pretreatment CD4 + T-cell count was 170 cells/mm 3; 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. Conclusions: 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.
AB - Introduction: 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. Methods: 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. Results: Median pretreatment CD4 + T-cell count was 170 cells/mm 3; 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. Conclusions: 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.
KW - HIV
KW - antiretroviral treatment
KW - case-cohort study
KW - micronutrients
KW - resource-limited settings
KW - tuberculosis
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U2 - 10.1097/QAI.0000000000001308
DO - 10.1097/QAI.0000000000001308
M3 - Article
C2 - 28169875
AN - SCOPUS:85011890563
SN - 1525-4135
VL - 75
SP - e71-e79
JO - Journal of Acquired Immune Deficiency Syndromes
JF - Journal of Acquired Immune Deficiency Syndromes
IS - 3
ER -