Vitamin A and D deficiencies associated with incident tuberculosis in HIV-infected patients initiating antiretroviral therapy in multinational case-cohort study
Citation: 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 Jul 1;75(3):e71-e79. doi: 10.1097/QAI.0000000000001308. PMID: 28169875. PMCID: PMC5472489.
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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.
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.
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.
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.
J Acquir Immune Defic Syndr. 2017 Feb 6. doi: 10.1097/QAI.0000000000001308. [Epub ahead of print]