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

Author:

Ajaykumar Abhinav12,Wong Glenn C3,Yindom Louis-Marie3,McHugh Grace4,Dauya Ethel4,Majonga Edith45,Mujuru Hilda6,Ferrand Rashida A45,Rowland-Jones Sarah L3,Côté Hélène C F12

Affiliation:

1. Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada

2. Centre for Blood Research, University of British Columbia, Vancouver, British Columbia, Canada

3. Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom

4. Biomedical Research and Training Institute, Harare, Zimbabwe

5. Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom

6. University of Zimbabwe, Harare, Zimbabwe

Abstract

Abstract Background Chronic lung disease (CLD) has been reported among African children with perinatally acquired human immunodeficiency virus (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-positive (cART-naive or -treated) and HIV-negative children with and without CLD. Methods Participants included Zimbabwean C-PHIV, aged 6–16, who were either newly diagnosed and cART-naive, or on cART for >6 months, and HIV-negative controls of similar age and sex. Packed blood cell (granulocyte) TLs from 621 children were compared cross-sectionally between groups. For a subset of newly diagnosed C-PHIV, changes in TL following cART initiation were evaluated. Results C-PHIV had shorter granulocyte TL compared with uninfected peers, regardless of cART. Among 255 C-PHIV without CLD, TL was shorter in cART-naive participants. In multivariable analyses adjusted for age, sex, CLD, and HIV/cART status, shorter TL was independently associated with older age, being HIV positive, and having reduced forced vital capacity (FVC). Last, cART initiation increased TL. Conclusions 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 longstanding HIV infection with delayed cART initiation.

Funder

Canadian Institutes of Health Research

International AIDS Society Collaborative Initiative for Paediatric Human Immunodeficiency Virus Education and Research Programme

Royal Society of Tropical Medicine and Hygiene

Publisher

Oxford University Press (OUP)

Subject

Infectious Diseases,Microbiology (medical)

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