Increased monocyte activation with age among HIV‐infected long term non‐progressor children: implications for early treatment initiation

• Published in: HIV medicine Vol. 20; no. 8; pp. 513 - 522
• Main Authors: D'Souza, RR, Gopalan, BP, Rajnala, N, Phetsouphanh, C, Shet, A
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01.09.2019
• Subjects: Adolescent; Age; Aging - immunology; Antigens, CD - blood; Antigens, Differentiation, Myelomonocytic - blood; Antiretroviral agents; Antiretroviral drugs; Antiretroviral therapy; Biomarkers; Biomarkers - blood; CD14 antigen; CD163 antigen; CD4 antigen; CD4 Lymphocyte Count; Cell activation; Chemokine CXCL10 - blood; Child; Children; Correlation coefficient; Correlation coefficients; Cross-Sectional Studies; Disease Progression; Enzyme-linked immunosorbent assay; Female; HIV; HIV Infections - epidemiology; HIV Infections - immunology; HIV Infections - transmission; HIV Long-Term Survivors; HIV-1 - physiology; HIV‐1; Human immunodeficiency virus; Humans; immune biomarkers; India - epidemiology; Infectious Disease Transmission, Vertical - statistics & numerical data; Interferon; Longitudinal Studies; long‐term nonprogressors; Macrophages; Male; Mathematical analysis; monocyte activation; Monocytes; Monocytes - immunology; Population studies; Prevalence; Receptors, Cell Surface - blood; Statistical analysis; Viral Load; India; HIV-1; long-term nonprogressors; monocyte activation; children; immune biomarkers
• ISSN: 1464-2662; 1468-1293
• DOI: 10.1111/hiv.12751

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.