Improving outcomes in children with HIV: what does telomere length dynamics tell us?
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Author(s)
Type
Journal Article
Abstract
Background: Understanding telomere length (TL) dynamics may shed light on mechanisms influencing immunological health and inform treatment strategies for children with perinatally-acquired HIV.
Methods: TL was assessed through PCR using DNA extracted from peripheral blood mononuclear cells from South African children without HIV recruited from an observational study, and participants from the randomised Children with HIV Early antiRetroviral (CHER) trial, where infants aged < 12 weeks with HIV were randomised to early limited versus deferred continuous antiretroviral therapy (ART). TL determinants were evaluated alongside clinical and immunological data using Spearman’s using multi-linear regression models.
Findings: TL was measured in 160 children without HIV (median age = 1.95 [0.98-3.56] years), and 106 children with HIV (n = 79 samples at 2 years, n = 50 at 5 years). At 2 years, the shorter TL negatively correlated with higher thymic output (correlation coefficient = -0.554 (95% CI: -0.824/-0.081), p = 0.026) in children with HIV, who also had shorter TL than age-matched controls (p< 0.0001), but not at 5 years. Early and longer ART duration correlated with longer TL. At 5 years, all children in CHER had TL similar to those without HIV. No relationship between TL and cytomegalovirus or Epstein-Barr virus co-infection, HIV-serostatus or HIV proviral DNA reservoir was identified.
Interpretation: Our findings illustrate the dynamic activity of the thymus in early childhood years, suggesting a positive feedback mechanism in response to immunological stress, as reflected by TL shortening. However, TL is preserved after early HIV diagnosis and ART initiation as recommended in current guidance.
Methods: TL was assessed through PCR using DNA extracted from peripheral blood mononuclear cells from South African children without HIV recruited from an observational study, and participants from the randomised Children with HIV Early antiRetroviral (CHER) trial, where infants aged < 12 weeks with HIV were randomised to early limited versus deferred continuous antiretroviral therapy (ART). TL determinants were evaluated alongside clinical and immunological data using Spearman’s using multi-linear regression models.
Findings: TL was measured in 160 children without HIV (median age = 1.95 [0.98-3.56] years), and 106 children with HIV (n = 79 samples at 2 years, n = 50 at 5 years). At 2 years, the shorter TL negatively correlated with higher thymic output (correlation coefficient = -0.554 (95% CI: -0.824/-0.081), p = 0.026) in children with HIV, who also had shorter TL than age-matched controls (p< 0.0001), but not at 5 years. Early and longer ART duration correlated with longer TL. At 5 years, all children in CHER had TL similar to those without HIV. No relationship between TL and cytomegalovirus or Epstein-Barr virus co-infection, HIV-serostatus or HIV proviral DNA reservoir was identified.
Interpretation: Our findings illustrate the dynamic activity of the thymus in early childhood years, suggesting a positive feedback mechanism in response to immunological stress, as reflected by TL shortening. However, TL is preserved after early HIV diagnosis and ART initiation as recommended in current guidance.
Date Issued
2024-09-17
Date Acceptance
2024-09-03
Citation
Journal of HIV/AIDS and Infectious Diseases, 2024, 11 (1)
ISSN
2332-483X
Publisher
JScholar
Journal / Book Title
Journal of HIV/AIDS and Infectious Diseases
Volume
11
Issue
1
Copyright Statement
©2024 The Authors. Published by the JScholar under the terms of the Crea-tive Commons Attribution License http://creativecommons.org/licenses/by/3.0/, which permits unrestricted use, provided the original author and source are credited.
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Publication Status
Published
Date Publish Online
2024-09-20