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

Post Date: 
2018-05-29
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Countries: 
Publication: 
Clinical Nutrition
Summary: 

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.

Citation: 
Shivakoti R, Ewald ER, Gupte N, Yang WT, Kanyama C, Cardoso SW, Santos B, Supparatpinyo K, Badal-Faesen S, Lama JR, Lalloo U, Zulu F, Pawar JS, Riviere C, Kumarasamy N, Hakim J, Pollard R, Detrick B, Balagopal A, Asmuth DM, Semba RD, Campbell TB, Golub J, Gupta A; NWCS 319 and ACTG PEARLS Study Team. Effect of baseline micronutrient and inflammation status on CD4 recovery post-cART initiation in the multinational PEARLS trial. Clin Nutr. 2018 May 29. pii: S0261-5614(18)30199-7. doi: 10.1016/j.clnu.2018.05.014. PMID: 29885777.
Collaborators: 
  • Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, USA. Electronic address: rshivak1@jhmi.edu.
  • Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA. Electronic address: erewald@gmail.com.
  • Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, USA. Electronic address: nikhil_jhumit@yahoo.com.
  • Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, USA. Electronic address: weiteng.yang@gmail.com.
  • UNC Lilongwe, Lilongwe, Malawi. Electronic address: ckanyama@unclilongwe.org.
  • STD/AIDS Clinical Research Laboratory, Instituto de Pesquisa Clinica Evandro Chagas, Fundacao Oswaldo Cruz, Rio de Janeiro, Brazil. Electronic address: sandra.wagner@ipec.fiocruz.br.
  • Hospital Nossa Senhora de Conceição, Porto Alegre, Brazil. Electronic address: breno@ghc.com.br.
  • Chiang Mai University, Chiang Mai, Thailand. Electronic address: khuanchai@rihes.org.
  • Department of Medicine, University of Witwatersrand, Johannesburg, South Africa. Electronic address: sfaesen@witshealth.co.za.
  • IMPACT PERU Clinical Trials Unit, Asociacion Civil Impacta Salud y Educacion, Lima, Peru. Electronic address: jrlama@impactaperu.org.
  • University of KwaZulu Natal, Nelson R Mandela School of Medicine, Durban, South Africa. Electronic address: umeshlalloo@gmail.com.
  • Malawi College of Medicine - Johns Hopkins Research Project, Kachere Rehabilitation Centre, Blantyre, Malawi. Electronic address: nez4@cdc.gov.
  • National AIDS Research Institute, Pune, India. Electronic address: jyotispawar.pawar@gmail.com.
  • Les Centres GHESKIO, Port-Au-Prince, Haiti. Electronic address: cynthiariviere@yahoo.com.
  • YR Gaitonde Center for AIDS Research and Education, Chennai, India. Electronic address: kumarasamy@yrgcare.org.
  • University of Zimbabwe, Harare, Zimbabwe. Electronic address: jhakim@mweb.co.zw.
  • Department of Medicine, University of California Davis, Sacramento, CA, USA. Electronic address: rbpollard@ucdavis.edu.
  • Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA. Electronic address: bdetrick@jhmi.edu.
  • Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, USA. Electronic address: abalago1@jhmi.edu.
  • Department of Medicine, University of California Davis, Sacramento, CA, USA. Electronic address: dasmuth@ucdavis.edu.
  • Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, MD, USA. Electronic address: rdsemba@jhmi.edu.
  • Department of Medicine, Division of Infectious Diseases, University of Colorado School of Medicine, Aurora, CO, USA. Electronic address: Thomas.Campbell@ucdenver.edu.
  • Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, USA. Electronic address: jgolub@jhmi.edu.
  • Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, USA. Electronic address: agupta25@jhmi.edu.