Shorter Granulocyte Telomeres Among Children and Adolescents With Perinatally Acquired Human Immunodeficiency Virus Infection and Chronic Lung Disease in Zimbabwe

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Abstract
Chronic lung disease (CLD) has been reported among African children with perinatally-acquired HIV infection (C-PHIV), despite combination antiretroviral therapy (cART). In adults, shorter telomere length (TL) has been reported in association with both CLD and HIV. As little is known in children, our objective was to compare TL in HIV+ (cART-naïve or treated) and HIV-negative children with and without CLD. Participants included Zimbabwean C-PHIV, aged 6-16, who were either newly diagnosed and cART-naïve, or on cART for >6 months, and HIV-negative controls of similar age and sex. Packed blood cell (granulocyte) TL from 621 children were compared cross-sectionally between groups. For a subset of newly diagnosed C-PHIV, changes in TL following cART initiation was evaluated. C-PHIV had shorter granulocyte TL compared to uninfected peers, regardless of cART. Among 255 C-PHIV without CLD, TL was shorter in cART-naïve participants. In multivariable analyses adjusted for age, sex, CLD, and HIV/cART status, shorter TL was independently associated with older age, being HIV+, and having reduced forced vital capacity (FVC). Lastly, cART initiation increased TL. In this cohort, C-PHIV and those with reduced FVC have shorter granulocyte TL, possibly the result of increased immune activation and cellular turnover due to long-standing HIV infection with delayed cART initiation.
Funding Information
  • Canadian Institutes of Health Research (TCO-125269)
  • International AIDS Society Collaborative Initiative for Paediatric Human Immunodeficiency Virus Education and Research Programme (2016/345-YIN)
  • Royal Society of Tropical Medicine and Hygiene (095878/Z/11/Z)