Vitamin A and D deficiencies associated with incident tuberculosis in HIV-infected patients initiating antiretroviral therapy in multinational case-cohort study

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Journal of Acquired Immune Deficiency Syndromes

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 (ART) initiation in HIV-infected individuals is not well characterized.


Methods: We conducted a case-cohort study (n=332) within a randomized trial comparing three ART regimens in 1571 HIV treatment-naïve adults from nine 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 pre-treatment concentrations of vitamin A, carotenoids, vitamin B6, vitamin B12, vitamin D, vitamin E, and selenium. We measured associations between pre-treatment micronutrient deficiencies and incident TB using Breslow-weighted Cox regression models.


Results: Median pre-treatment CD4+ T-cell count was 170 cells/mm; 47.3% were female; and 53.6% Black. In multivariable models after adjusting for age, sex, country, treatment arm, prior TB, baseline CD4 count, HIV viral load, body mass index, and C-reactive protein, pre-treatment deficiency in vitamin A (adjusted hazard ratio, aHR 5.33, 95% confidence interval, CI 1.54-18.43) and vitamin D (aHR 3.66, 95%CI 1.16-11.51) were associated with TB post-ART.


Conclusion: 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.

Tenforde MW, Yadav A, Dowdy DW, Gupte N, Shivakoti R, Yang WT, 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; NWCS319 and ACTG 5175 study team. Vitamin A and D deficiencies associated with incident tuberculosis in HIV-infected patients initiating antiretroviral therapy in multinational case-cohort study. J Acquir Immune Defic Syndr. 2017 Feb 6. doi: 10.1097/QAI.0000000000001308. PMID: 28169875 [Epub ahead of print]
  • University of Washington School of Medicine, Seattle, WA 
  • Johns Hopkins Bloomberg School of Public Health, Baltimore, MD
  • Bridgeport Hospital Yale New Haven Health, Bridgeport, CT
  • Department of Medicine, University of Witwatersrand, Johannesburg, South Africa
  • 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, UK
  • 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
  • University of Colorado School of Medicine, Aurora, CO