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 - Funding Information:
Thomas B Campbell has served on advisory boards for Gilead Sciences, ViiV and Theratechnologies. Amita Gupta and Rupak Shivakoti has received grant funding from Gilead Foundation. All authors declare no conflicts of interest. This work was supported by the National Institutes of Health, National Institute of Allergy and Infectious Diseases [ UM1 AI069465 , R01 AI080417 ]. RS was supported by National Institute of Child Health and Human Development [grant numbers K99 HD089753 ] of the National Institutes of Health. The parent study was supported by NIAID grants UM1 AI068634 , UM1 AI068636 and UM1 AI106701 . The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The parent trial A5175 was also supported in part by Boehringer-Ingelheim, Bristol-Myers Squibb, Gilead Sciences, and GlaxoSmithKline. Funders had no role in study design, data collection, analysis, publication decision, or manuscript preparation.
Funding Information:
Thomas B Campbell has served on advisory boards for Gilead Sciences, ViiV and Theratechnologies. Amita Gupta and Rupak Shivakoti has received grant funding from Gilead Foundation. All authors declare no conflicts of interest. This work was supported by the National Institutes of Health, National Institute of Allergy and Infectious Diseases [UM1 AI069465, R01 AI080417]. RS was supported by National Institute of Child Health and Human Development [grant numbers K99 HD089753] of the National Institutes of Health. The parent study was supported by NIAID grants UM1 AI068634, UM1 AI068636 and UM1 AI106701. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The parent trial A5175 was also supported in part by Boehringer-Ingelheim, Bristol-Myers Squibb, Gilead Sciences, and GlaxoSmithKline. Funders had no role in study design, data collection, analysis, publication decision, or manuscript preparation. RS and ERE conducted the data analysis and wrote the primary version of the manuscript. NG conducted the data analysis and contributed to data interpretation. JG contributed to data interpretation and manuscript review. WY, CK, SWC, BS, KS, SB, JL, UL, FZ, JSP, CY, NK, JH, RP, BD, AB, and DA contributed to data collection and manuscript review. RDS contributed to study design, laboratory testing, and review of manuscript. TBC contributed to study design, data collection, oversight of study implementation, and manuscript review. AG obtained funding and contributed to study design, manuscript writing, and review. All authors meet criteria for authorship as recommended by the International Committee of Medical Journal Editors (ICMJE) and were fully responsible for all aspects of manuscript development.
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 -