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Clin Nutr. 2019 Jun;38(3):1303-1309. doi: 10.1016/j.clnu.2018.05.014. Epub 2018 May 29.

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

Author information

1
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, USA. Electronic address: rshivak1@jhmi.edu.
2
Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA. Electronic address: erewald@gmail.com.
3
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, USA. Electronic address: nikhil_jhumit@yahoo.com.
4
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, USA. Electronic address: weiteng.yang@gmail.com.
5
UNC Lilongwe, Lilongwe, Malawi. Electronic address: ckanyama@unclilongwe.org.
6
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.
7
Hospital Nossa Senhora de Conceição, Porto Alegre, Brazil. Electronic address: breno@ghc.com.br.
8
Chiang Mai University, Chiang Mai, Thailand. Electronic address: khuanchai@rihes.org.
9
Department of Medicine, University of Witwatersrand, Johannesburg, South Africa. Electronic address: sfaesen@witshealth.co.za.
10
IMPACT PERU Clinical Trials Unit, Asociacion Civil Impacta Salud y Educacion, Lima, Peru. Electronic address: jrlama@impactaperu.org.
11
University of KwaZulu Natal, Nelson R Mandela School of Medicine, Durban, South Africa. Electronic address: umeshlalloo@gmail.com.
12
Malawi College of Medicine - Johns Hopkins Research Project, Kachere Rehabilitation Centre, Blantyre, Malawi. Electronic address: nez4@cdc.gov.
13
National AIDS Research Institute, Pune, India. Electronic address: jyotispawar.pawar@gmail.com.
14
Les Centres GHESKIO, Port-Au-Prince, Haiti. Electronic address: cynthiariviere@yahoo.com.
15
YR Gaitonde Center for AIDS Research and Education, Chennai, India. Electronic address: kumarasamy@yrgcare.org.
16
University of Zimbabwe, Harare, Zimbabwe. Electronic address: jhakim@mweb.co.zw.
17
Department of Medicine, University of California Davis, Sacramento, CA, USA. Electronic address: rbpollard@ucdavis.edu.
18
Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA. Electronic address: bdetrick@jhmi.edu.
19
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, USA. Electronic address: abalago1@jhmi.edu.
20
Department of Medicine, University of California Davis, Sacramento, CA, USA. Electronic address: dasmuth@ucdavis.edu.
21
Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, MD, USA. Electronic address: rdsemba@jhmi.edu.
22
Department of Medicine, Division of Infectious Diseases, University of Colorado School of Medicine, Aurora, CO, USA. Electronic address: Thomas.Campbell@ucdenver.edu.
23
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, USA. Electronic address: jgolub@jhmi.edu.
24
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, USA. Electronic address: agupta25@jhmi.edu.

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.

KEYWORDS:

CD4 reconstitution; CD4 recovery; HIV; Inflammation; Micronutrients; Nutrition

PMID:
29885777
PMCID:
PMC6265110
[Available on 2020-06-01]
DOI:
10.1016/j.clnu.2018.05.014

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