TY - JOUR
T1 - Effect of baseline micronutrient and inflammation status on CD4 recovery post-cART initiation in the multinational PEARLS trial
AU - for the NWCS 319 and ACTG PEARLS Study Team
AU - Shivakoti, Rupak
AU - Ewald, Erin R.
AU - Gupte, Nikhil
AU - Yang, Wei Teng
AU - Kanyama, Cecilia
AU - Cardoso, Sandra W.
AU - Santos, Breno
AU - Supparatpinyo, Khuanchai
AU - Badal-Faesen, Sharlaa
AU - Lama, Javier R.
AU - Lalloo, Umesh
AU - Zulu, Fatima
AU - Pawar, Jyoti S.
AU - Riviere, Cynthia
AU - Kumarasamy, Nagalingeswaran
AU - Hakim, James
AU - Pollard, Richard
AU - Detrick, Barbara
AU - Balagopal, Ashwin
AU - Asmuth, David M.
AU - Semba, Richard D.
AU - Campbell, Thomas B.
AU - Golub, Jonathan
AU - Gupta, Amita
N1 - Publisher Copyright:
© 2018 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism
PY - 2019/6
Y1 - 2019/6
N2 - Background & aims: Nutritional deficiency and inflammation may impact CD4+ T cell recovery during combination antiretroviral therapy (cART), particularly in resource-limited settings where malnutrition is prevalent. The aim of this study was to investigate the relationship of micronutrient and inflammation biomarkers to CD4 recovery after cART initiation. Methods: We conducted a secondary analysis of a random sub-cohort sample (n = 270) from a multinational randomized trial of cART regimen efficacy among 1571 cART-naïve adults. We measured pre-cART serum levels of micronutrients (Vitamin A, B 6 , B 12 , D, total carotenoids, selenium, and iron) and inflammation (C-reactive protein, soluble CD14 (sCD14), IFNγ, TNFα, Interleukin-6, and C-X-C motif chemokine 10 (CXCL10/IP10), EndoCab (IgM)) biomarkers. Biomarker status (i.e. micronutrient deficiency vs. sufficiency and elevated vs. low inflammation) was defined using established cutoffs or quartiles. Mixed-effects linear regression models were used to determine the association of baseline (pre-cART) concentrations of individual biomarkers with CD4 recovery through 96 weeks post-cART initiation. Results: In models adjusting for time-dependent viral load and baseline CD4 count, age, sex, body mass index, country, treatment regimen, anemia and hypoalbuminemia status, pre-cART vitamin D deficiency was associated with lower CD4 recovery (−14.9 cells/mm 3 , 95% CI: −27.9, −1.8) compared to sufficiency. In contrast, baseline selenium deficiency (20.8 cells/mm 3 , 95% CI: 3.3, 38.3), vitamin A deficiency (35.9 cells/mm 3 , 95% CI: 17.6, 54.3) and high sCD14 (23.4 cells/mm 3 , 95% CI: 8.9, 37.8) were associated with higher CD4 recovery compared to sufficient/low inflammation status. Conclusions: In summary, baseline vitamin D deficiency was associated with diminished CD4 recovery after cART initiation; impaired CD4 recovery may contribute to the poor clinical outcomes recently observed in individuals with vitamin D deficiency. Vitamin A, selenium and sCD14 were associated with CD4 recovery but future studies are needed to further explore these relationships.
AB - Background & aims: Nutritional deficiency and inflammation may impact CD4+ T cell recovery during combination antiretroviral therapy (cART), particularly in resource-limited settings where malnutrition is prevalent. The aim of this study was to investigate the relationship of micronutrient and inflammation biomarkers to CD4 recovery after cART initiation. Methods: We conducted a secondary analysis of a random sub-cohort sample (n = 270) from a multinational randomized trial of cART regimen efficacy among 1571 cART-naïve adults. We measured pre-cART serum levels of micronutrients (Vitamin A, B 6 , B 12 , D, total carotenoids, selenium, and iron) and inflammation (C-reactive protein, soluble CD14 (sCD14), IFNγ, TNFα, Interleukin-6, and C-X-C motif chemokine 10 (CXCL10/IP10), EndoCab (IgM)) biomarkers. Biomarker status (i.e. micronutrient deficiency vs. sufficiency and elevated vs. low inflammation) was defined using established cutoffs or quartiles. Mixed-effects linear regression models were used to determine the association of baseline (pre-cART) concentrations of individual biomarkers with CD4 recovery through 96 weeks post-cART initiation. Results: In models adjusting for time-dependent viral load and baseline CD4 count, age, sex, body mass index, country, treatment regimen, anemia and hypoalbuminemia status, pre-cART vitamin D deficiency was associated with lower CD4 recovery (−14.9 cells/mm 3 , 95% CI: −27.9, −1.8) compared to sufficiency. In contrast, baseline selenium deficiency (20.8 cells/mm 3 , 95% CI: 3.3, 38.3), vitamin A deficiency (35.9 cells/mm 3 , 95% CI: 17.6, 54.3) and high sCD14 (23.4 cells/mm 3 , 95% CI: 8.9, 37.8) were associated with higher CD4 recovery compared to sufficient/low inflammation status. Conclusions: In summary, baseline vitamin D deficiency was associated with diminished CD4 recovery after cART initiation; impaired CD4 recovery may contribute to the poor clinical outcomes recently observed in individuals with vitamin D deficiency. Vitamin A, selenium and sCD14 were associated with CD4 recovery but future studies are needed to further explore these relationships.
KW - CD4 reconstitution
KW - CD4 recovery
KW - HIV
KW - Inflammation
KW - Micronutrients
KW - Nutrition
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U2 - 10.1016/j.clnu.2018.05.014
DO - 10.1016/j.clnu.2018.05.014
M3 - Article
C2 - 29885777
AN - SCOPUS:85048713253
SN - 0261-5614
VL - 38
SP - 1303
EP - 1309
JO - Clinical Nutrition
JF - Clinical Nutrition
IS - 3
ER -