Vitamin A and D Deficiencies Associated With Incident Tuberculosis in HIV-Infected Patients Initiating Antiretroviral Therapy in Multinational Case-Cohort Study.
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.
*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.
Mark W
MW
Tenforde
Ashish
A
Yadav
David W
DW
Dowdy
Nikhil
N
Gupte
Rupak
R
Shivakoti
Wei-Teng
WT
Yang
Noluthando
N
Mwelase
Cecilia
C
Kanyama
Sandy
S
Pillay
Wadzanai
W
Samaneka
Breno
B
Santos
Selvamuthu
S
Poongulali
Srikanth
S
Tripathy
Cynthia
C
Riviere
Sima
S
Berendes
Javier R
JR
Lama
Sandra W
SW
Cardoso
Patcharaphan
P
Sugandhavesa
Parul
P
Christian
Richard D
RD
Semba
Thomas B
TB
Campbell
Amita
A
Gupta
D000328:Adult; D044966:Anti-Retroviral Agents / Q000008:administration & dosage / Q000009:adverse effects*; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects; D015496:CD4-Positive T-Lymphocytes; D060085:Coinfection; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy / Q000276:immunology*; D006801:Humans; D008297:Male; D044342:Malnutrition / Q000097:blood* / Q000150:complications; D018977:Micronutrients / Q000097:blood / Q000172:deficiency*; D015995:Prevalence; D011446:Prospective Studies; D014376:Tuberculosis / Q000188:drug therapy / Q000276:immunology*; D014802:Vitamin A Deficiency / Q000097:blood* / Q000150:complications / Q000276:immunology; D014808:Vitamin D Deficiency / Q000097:blood* / Q000150:complications / Q000276:immunology
D044966:Anti-Retroviral Agents; D018977:Micronutrients