Effect of baseline micronutrient and inflammation status on CD4 recovery post-cART initiation in the multinational PEARLS trial

for the NWCS 319 and ACTG PEARLS Study Team

Research output: Contribution to journalArticle

Abstract

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, B6, B12, 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/mm3, 95% CI: −27.9, −1.8) compared to sufficiency. In contrast, baseline selenium deficiency (20.8 cells/mm3, 95% CI: 3.3, 38.3), vitamin A deficiency (35.9 cells/mm3, 95% CI: 17.6, 54.3) and high sCD14 (23.4 cells/mm3, 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.

Original languageEnglish (US)
JournalClinical Nutrition
DOIs
StateAccepted/In press - Jan 1 2018

Fingerprint

Micronutrients
Inflammation
Vitamin D Deficiency
Selenium
Biomarkers
Therapeutics
Vitamin A
Malnutrition
Linear Models
Chemokine CXCL10
CXC Chemokines
Vitamin A Deficiency
Hypoalbuminemia
Vitamin B 6
Carotenoids
CD4 Lymphocyte Count
Viral Load
C-Reactive Protein
Immunoglobulin M
Anemia

Keywords

  • CD4 reconstitution
  • CD4 recovery
  • HIV
  • Inflammation
  • Micronutrients
  • Nutrition

ASJC Scopus subject areas

  • Nutrition and Dietetics
  • Critical Care and Intensive Care Medicine

Cite this

Effect of baseline micronutrient and inflammation status on CD4 recovery post-cART initiation in the multinational PEARLS trial. / for the NWCS 319 and ACTG PEARLS Study Team.

In: Clinical Nutrition, 01.01.2018.

Research output: Contribution to journalArticle

@article{264838a9db344079869da8ba09418dcd,
title = "Effect of baseline micronutrient and inflammation status on CD4 recovery post-cART initiation in the multinational PEARLS trial",
abstract = "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-na{\"i}ve adults. We measured pre-cART serum levels of micronutrients (Vitamin A, B6, B12, 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/mm3, 95{\%} CI: −27.9, −1.8) compared to sufficiency. In contrast, baseline selenium deficiency (20.8 cells/mm3, 95{\%} CI: 3.3, 38.3), vitamin A deficiency (35.9 cells/mm3, 95{\%} CI: 17.6, 54.3) and high sCD14 (23.4 cells/mm3, 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.",
keywords = "CD4 reconstitution, CD4 recovery, HIV, Inflammation, Micronutrients, Nutrition",
author = "{for the NWCS 319 and ACTG PEARLS Study Team} and Rupak Shivakoti and Ewald, {Erin R.} and Nikhil Gupte and Yang, {Wei Teng} and Cecilia Kanyama and Cardoso, {Sandra W.} and Breno Santos and Khuanchai Supparatpinyo and Sharlaa Badal-Faesen and Lama, {Javier R.} and Umesh Lalloo and Fatima Zulu and Pawar, {Jyoti S.} and Cynthia Riviere and Nagalingeswaran Kumarasamy and James Hakim and Pollard, {Richard B} and Barbara Detrick and Ashwin Balagopal and David Asmuth and Semba, {Richard D.} and Campbell, {Thomas B.} and Jonathan Golub and Amita Gupta",
year = "2018",
month = "1",
day = "1",
doi = "10.1016/j.clnu.2018.05.014",
language = "English (US)",
journal = "Clinical Nutrition",
issn = "0261-5614",
publisher = "Churchill Livingstone",

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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 B

AU - Detrick, Barbara

AU - Balagopal, Ashwin

AU - Asmuth, David

AU - Semba, Richard D.

AU - Campbell, Thomas B.

AU - Golub, Jonathan

AU - Gupta, Amita

PY - 2018/1/1

Y1 - 2018/1/1

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, B6, B12, 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/mm3, 95% CI: −27.9, −1.8) compared to sufficiency. In contrast, baseline selenium deficiency (20.8 cells/mm3, 95% CI: 3.3, 38.3), vitamin A deficiency (35.9 cells/mm3, 95% CI: 17.6, 54.3) and high sCD14 (23.4 cells/mm3, 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, B6, B12, 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/mm3, 95% CI: −27.9, −1.8) compared to sufficiency. In contrast, baseline selenium deficiency (20.8 cells/mm3, 95% CI: 3.3, 38.3), vitamin A deficiency (35.9 cells/mm3, 95% CI: 17.6, 54.3) and high sCD14 (23.4 cells/mm3, 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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UR - http://www.scopus.com/inward/citedby.url?scp=85048713253&partnerID=8YFLogxK

U2 - 10.1016/j.clnu.2018.05.014

DO - 10.1016/j.clnu.2018.05.014

M3 - Article

JO - Clinical Nutrition

JF - Clinical Nutrition

SN - 0261-5614

ER -