Increased monocyte activation with age among HIV-infected long term non-progressor children

implications for early treatment initiation

R. R. D'Souza, B. P. Gopalan, N. Rajnala, C. Phetsouphanh, Anita Shet

Research output: Contribution to journalArticle

Abstract

Objectives: The key to newer therapeutic and eradication approaches often lies in understanding slow disease progression in HIV infection. The paediatric population has been poorly studied in this regard. We aimed to describe a cohort of perinatally infected long-term nonprogressor (LTNP) children living with HIV in India and to evaluate the immune biomarkers of disease progression. Methods: LTNPs (ART-naïve, with a CD4 count ≥ 500 cells/μL at age ≥ 7 years) among the cohort of HIV-infected children were identified and monitored longitudinally, and their CD4 T-cell counts and plasma viral loads were measured every 6 months. The plasma monocyte/macrophage activation markers, namely soluble CD14 (sCD14), soluble CD163 (sCD163) and interferon-inducible protein-10 (IP-10) were measured by enzyme-linked immunosorbent assay (ELISA) in LTNPs and progressors. The Mann–Whitney U-test was used to compare the two groups and P values < 0.05 were considered statistically significant. Spearman's rank or Pearson's correlation coefficient (r) was calculated to determine the associations between variables. Results: Among 378 children living with HIV-1 surveyed in our cohort, 40 (10.6%) were LTNPs. Longitudinal analysis of the LTNP data showed that both CD4 count and viral load declined significantly with age (P < 0.0001 for both). Plasma sCD14 levels were significantly (P < 0.005) higher in progressors and sCD163 levels were significantly (P < 0.0001) higher in LTNPs. Conclusions: The prevalence of LTNPs in our cohort of perinatally infected children living with HIV was 10.6%. We observed a trend for associations between the increasing sCD163 monocyte/macrophage activation marker levels, declining CD4 counts and the gradual loss of nonprogressor status with age in the LTNPs. These findings underscore the need for early antiretroviral therapy in those children with proven slow disease progression.

Original languageEnglish (US)
JournalHIV Medicine
DOIs
StatePublished - Jan 1 2019

Fingerprint

Monocytes
CD4 Lymphocyte Count
HIV
Disease Progression
Macrophage Activation
Viral Load
Chemokine CXCL10
Therapeutics
Immune System Diseases
Secondary Prevention
HIV Infections
HIV-1
India
Biomarkers
Enzyme-Linked Immunosorbent Assay
Pediatrics
T-Lymphocytes
Population

Keywords

  • children
  • HIV-1
  • immune biomarkers
  • long-term nonprogressors
  • monocyte activation

ASJC Scopus subject areas

  • Health Policy
  • Infectious Diseases
  • Pharmacology (medical)

Cite this

Increased monocyte activation with age among HIV-infected long term non-progressor children : implications for early treatment initiation. / D'Souza, R. R.; Gopalan, B. P.; Rajnala, N.; Phetsouphanh, C.; Shet, Anita.

In: HIV Medicine, 01.01.2019.

Research output: Contribution to journalArticle

@article{3c97e70761e34464a6a7ad6841b84a84,
title = "Increased monocyte activation with age among HIV-infected long term non-progressor children: implications for early treatment initiation",
abstract = "Objectives: The key to newer therapeutic and eradication approaches often lies in understanding slow disease progression in HIV infection. The paediatric population has been poorly studied in this regard. We aimed to describe a cohort of perinatally infected long-term nonprogressor (LTNP) children living with HIV in India and to evaluate the immune biomarkers of disease progression. Methods: LTNPs (ART-na{\"i}ve, with a CD4 count ≥ 500 cells/μL at age ≥ 7 years) among the cohort of HIV-infected children were identified and monitored longitudinally, and their CD4 T-cell counts and plasma viral loads were measured every 6 months. The plasma monocyte/macrophage activation markers, namely soluble CD14 (sCD14), soluble CD163 (sCD163) and interferon-inducible protein-10 (IP-10) were measured by enzyme-linked immunosorbent assay (ELISA) in LTNPs and progressors. The Mann–Whitney U-test was used to compare the two groups and P values < 0.05 were considered statistically significant. Spearman's rank or Pearson's correlation coefficient (r) was calculated to determine the associations between variables. Results: Among 378 children living with HIV-1 surveyed in our cohort, 40 (10.6{\%}) were LTNPs. Longitudinal analysis of the LTNP data showed that both CD4 count and viral load declined significantly with age (P < 0.0001 for both). Plasma sCD14 levels were significantly (P < 0.005) higher in progressors and sCD163 levels were significantly (P < 0.0001) higher in LTNPs. Conclusions: The prevalence of LTNPs in our cohort of perinatally infected children living with HIV was 10.6{\%}. We observed a trend for associations between the increasing sCD163 monocyte/macrophage activation marker levels, declining CD4 counts and the gradual loss of nonprogressor status with age in the LTNPs. These findings underscore the need for early antiretroviral therapy in those children with proven slow disease progression.",
keywords = "children, HIV-1, immune biomarkers, long-term nonprogressors, monocyte activation",
author = "D'Souza, {R. R.} and Gopalan, {B. P.} and N. Rajnala and C. Phetsouphanh and Anita Shet",
year = "2019",
month = "1",
day = "1",
doi = "10.1111/hiv.12751",
language = "English (US)",
journal = "HIV Medicine",
issn = "1464-2662",
publisher = "Wiley-Blackwell",

}

TY - JOUR

T1 - Increased monocyte activation with age among HIV-infected long term non-progressor children

T2 - implications for early treatment initiation

AU - D'Souza, R. R.

AU - Gopalan, B. P.

AU - Rajnala, N.

AU - Phetsouphanh, C.

AU - Shet, Anita

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Objectives: The key to newer therapeutic and eradication approaches often lies in understanding slow disease progression in HIV infection. The paediatric population has been poorly studied in this regard. We aimed to describe a cohort of perinatally infected long-term nonprogressor (LTNP) children living with HIV in India and to evaluate the immune biomarkers of disease progression. Methods: LTNPs (ART-naïve, with a CD4 count ≥ 500 cells/μL at age ≥ 7 years) among the cohort of HIV-infected children were identified and monitored longitudinally, and their CD4 T-cell counts and plasma viral loads were measured every 6 months. The plasma monocyte/macrophage activation markers, namely soluble CD14 (sCD14), soluble CD163 (sCD163) and interferon-inducible protein-10 (IP-10) were measured by enzyme-linked immunosorbent assay (ELISA) in LTNPs and progressors. The Mann–Whitney U-test was used to compare the two groups and P values < 0.05 were considered statistically significant. Spearman's rank or Pearson's correlation coefficient (r) was calculated to determine the associations between variables. Results: Among 378 children living with HIV-1 surveyed in our cohort, 40 (10.6%) were LTNPs. Longitudinal analysis of the LTNP data showed that both CD4 count and viral load declined significantly with age (P < 0.0001 for both). Plasma sCD14 levels were significantly (P < 0.005) higher in progressors and sCD163 levels were significantly (P < 0.0001) higher in LTNPs. Conclusions: The prevalence of LTNPs in our cohort of perinatally infected children living with HIV was 10.6%. We observed a trend for associations between the increasing sCD163 monocyte/macrophage activation marker levels, declining CD4 counts and the gradual loss of nonprogressor status with age in the LTNPs. These findings underscore the need for early antiretroviral therapy in those children with proven slow disease progression.

AB - Objectives: The key to newer therapeutic and eradication approaches often lies in understanding slow disease progression in HIV infection. The paediatric population has been poorly studied in this regard. We aimed to describe a cohort of perinatally infected long-term nonprogressor (LTNP) children living with HIV in India and to evaluate the immune biomarkers of disease progression. Methods: LTNPs (ART-naïve, with a CD4 count ≥ 500 cells/μL at age ≥ 7 years) among the cohort of HIV-infected children were identified and monitored longitudinally, and their CD4 T-cell counts and plasma viral loads were measured every 6 months. The plasma monocyte/macrophage activation markers, namely soluble CD14 (sCD14), soluble CD163 (sCD163) and interferon-inducible protein-10 (IP-10) were measured by enzyme-linked immunosorbent assay (ELISA) in LTNPs and progressors. The Mann–Whitney U-test was used to compare the two groups and P values < 0.05 were considered statistically significant. Spearman's rank or Pearson's correlation coefficient (r) was calculated to determine the associations between variables. Results: Among 378 children living with HIV-1 surveyed in our cohort, 40 (10.6%) were LTNPs. Longitudinal analysis of the LTNP data showed that both CD4 count and viral load declined significantly with age (P < 0.0001 for both). Plasma sCD14 levels were significantly (P < 0.005) higher in progressors and sCD163 levels were significantly (P < 0.0001) higher in LTNPs. Conclusions: The prevalence of LTNPs in our cohort of perinatally infected children living with HIV was 10.6%. We observed a trend for associations between the increasing sCD163 monocyte/macrophage activation marker levels, declining CD4 counts and the gradual loss of nonprogressor status with age in the LTNPs. These findings underscore the need for early antiretroviral therapy in those children with proven slow disease progression.

KW - children

KW - HIV-1

KW - immune biomarkers

KW - long-term nonprogressors

KW - monocyte activation

UR - http://www.scopus.com/inward/record.url?scp=85067638875&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85067638875&partnerID=8YFLogxK

U2 - 10.1111/hiv.12751

DO - 10.1111/hiv.12751

M3 - Article

JO - HIV Medicine

JF - HIV Medicine

SN - 1464-2662

ER -