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‐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.

CD4+ T cell depletion does not affect the level of viremia in chronically SHIVSF162P3N-infected Chinese cynomolgus monkeys

“…Several studies showed that increased monocyte turnover better predicts the tempo of progression to AIDS in HIV-infected patients and SIV/SHIV-infected animals than declining level of CD4 + T cells alone [33,34]. Although CD4 + T cells are the major source of virus production in HIV-infected individuals, monocytes/macrophages contribute substantially to plasma viral load during late-stage of HIV disease when the levels of circulating CD4 + T cell are very low [35], even is associated with the gradual loss of nonprogressor status in the long-term nonprogressors (LTNPs) [36]. Our previous study showed that SHIV KU−1 -infected Chines RMs had the persistence of high virus loads (10 6 -10 8 viral RNA copies per ml) with a 1.5 years survival time, although their circulating CD4 + T cell levels were very low (10-250 cells/ul) over the course of infection.…”

CD4+ T Cell Depletion Does Not Affect the Level of Viremia in Chronically SHIVSF162P3N-Infected Chinese Cynomolgus Monkeys

“…Several studies showed that increased monocyte turnover better predicts the tempo of progression to AIDS in HIV-infected patients and SIV/SHIV-infected animals than declining level of CD4 + T cells alone [33,34]. Although CD4 + T cells are the major source of virus production in HIV-infected individuals, monocytes/macrophages contribute substantially to plasma viral load during late-stage of HIV disease when the levels of circulating CD4 + T cell are very low [35], even is associated with the gradual loss of nonprogressor status in the long-term nonprogressors (LTNPs) [36]. Our previous study showed that SHIV KU−1 -infected Chines RMs had the persistence of high virus loads (10 6 -10 8 viral RNA copies per ml) with a 1.5 years survival time, although their circulating CD4 + T cell levels were very low (10-250 cells/ul) over the course of infection.…”

Adults with Perinatally Acquired HIV; Emerging Clinical Outcomes and Data Gaps

“…In 2022, 82% (64–98%) of pregnant or breast feeding people living with HIV had access to antiretroviral therapy (ART), meaning 220,000 pregnant women could not access ART for themselves or to prevent transmission to their infants [ 2 , 3 ]. Without treatment, 50% of infants will die before their second birthday, although up to 10% will survive into adolescence, with minimal symptoms, reflecting the diverse disease progression of paediatric HIV [ 4 ]. AIDS-related deaths peaked in children in 2004 at 360,000 and whilst deaths fell by 64% from 2010 to 84,000 in 2022, this represented 13% of global AIDS-related deaths, yet children make up just 4% of people living with HIV [ 3 ].…”