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Published on: January 31, 2020
Increased monocyte activation with age among HIV-infected long term non-progressor children: implications for early
R R D'Souza1,2, B P Gopalan2,3, N Rajnala2
1Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, UK.
Insights
Understanding slow disease progression in children with HIV is key. Long-term nonprogressor (LTNP) children showed declining CD4 counts and viral loads with age, highlighting the need for early antiretroviral therapy.
Area of Science:
- Pediatric Infectious Diseases
- Immunology
- HIV/AIDS Research
Background:
- Understanding slow disease progression in HIV infection is crucial for developing new therapies.
- The pediatric population with HIV has been understudied regarding disease progression.
- Long-term nonprogressor (LTNP) status in children living with HIV requires further investigation.
Purpose of the Study:
- To describe a cohort of perinatally infected children living with HIV in India who are long-term nonprogressors (LTNPs).
- To evaluate immune biomarkers associated with disease progression in pediatric HIV.
- To assess the longitudinal changes in CD4 counts and viral loads in LTNP children.
Main Methods:
- Identified and longitudinally monitored ART-naïve LTNP children (CD4 count ≥ 500 cells/μL at age ≥ 7 years).
- Measured CD4 T-cell counts and plasma viral loads every 6 months.
- Quantified plasma monocyte/macrophage activation markers (sCD14, sCD163, IP-10) using ELISA and compared LTNPs with progressors.
Main Results:
- 10.6% of the 378 children with HIV in the cohort were identified as LTNPs.
- Both CD4 count and viral load significantly declined with age in LTNP children (P < 0.0001).
- Progressors had significantly higher plasma sCD14 levels (P < 0.005), while LTNPs had significantly higher sCD163 levels (P < 0.0001).
Conclusions:
- The prevalence of LTNPs in this cohort of perinatally infected children was 10.6%.
- Increasing sCD163 levels correlated with declining CD4 counts and loss of nonprogressor status in LTNP children.
- Early antiretroviral therapy is recommended for children with HIV exhibiting slow disease progression.
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.
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