Vitamin A and D Deficiencies Associated With Incident Tuberculosis in HIV-Infected Patients Initiating Antiretroviral Therapy in Multinational Case-Cohort Study.

TitleVitamin A and D Deficiencies Associated With Incident Tuberculosis in HIV-Infected Patients Initiating Antiretroviral Therapy in Multinational Case-Cohort Study.
Publication TypeJournal Article
Year of Publication2017
AuthorsTenforde MW, Yadav A, Dowdy DW, Gupte N, Shivakoti R, Yang W-T, Mwelase N, Kanyama C, Pillay S, Samaneka W, Santos B, Poongulali S, Tripathy S, Riviere C, Berendes S, Lama JR, Cardoso SW, Sugandhavesa P, Christian P, Semba RD, Campbell TB, Gupta A
Corporate AuthorsNWCS319 and ACTG 5175 study team
JournalJ Acquir Immune Defic Syndr
Volume75
Issue3
Paginatione71-e79
Date Published2017 07 01
ISSN1944-7884
KeywordsAdult, Anti-Retroviral Agents, Antiretroviral Therapy, Highly Active, CD4-Positive T-Lymphocytes, Coinfection, Female, HIV Infections, Humans, Male, Malnutrition, Micronutrients, Prevalence, Prospective Studies, Tuberculosis, Vitamin A Deficiency, Vitamin D Deficiency
Abstract

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; 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.

DOI10.1097/QAI.0000000000001308
Alternate JournalJ. Acquir. Immune Defic. Syndr.
PubMed ID28169875
PubMed Central IDPMC5472489
Grant ListU01 AI069497 / AI / NIAID NIH HHS / United States
UM1 AI069423 / AI / NIAID NIH HHS / United States
UM1 AI069476 / AI / NIAID NIH HHS / United States
UM1 AI069424 / AI / NIAID NIH HHS / United States
UM1 AI069432 / AI / NIAID NIH HHS / United States
T32 AI007044 / AI / NIAID NIH HHS / United States
R01 AI080417 / AI / NIAID NIH HHS / United States
U01 AI068636 / AI / NIAID NIH HHS / United States
UM1 AI069463 / AI / NIAID NIH HHS / United States
UM1 AI069465 / AI / NIAID NIH HHS / United States
UM1 AI069497 / AI / NIAID NIH HHS / United States
UM1 AI069436 / AI / NIAID NIH HHS / United States
UM1 AI068636 / AI / NIAID NIH HHS / United States