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

Authors : D'Souza RR, Gopalan BP, Rajnala N, Phetsouphanh C, Shet A

Publication Year : 2019

Abstract :

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.

LTNPs (ART-naïve, with a CD4 count greater than or equal to 500 cells/µL at age greater than or equal to 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 less than 0.05 were considered statistically significant. Spearman's rank or Pearson's correlation coefficient (r) was calculated to determine the associations between variables.

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 less than 0.0001 for both). Plasma sCD14 levels were significantly (P less than 0.005) higher in progressors and sCD163 levels were significantly (P less than 0.0001) higher in LTNPs.

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.