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

Abhinav Ajaykumar,Edith Majonga,Ethel Dauya,Hilda Mujuru,Grace Mchugh,Hélène C F Côté,Louis-Marie Yindom,Glenn C Wong,Rashida A Ferrand,Sarah L Rowland-Jones

doi:10.1093/cid/ciaa1134

Abstract

BackgroundChronic 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.MethodsParticipants 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.ResultsC-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.ConclusionsIn 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.

Highlights

Despite the success of combination antiretroviral therapy to prevent perinatal HIV transmission, the most recent estimates from UNAIDS suggest that 1.7M children under the age of 15 years are living with HIV-1 infection, 90% in sub-Saharan Africa (SSA) [1]
We report shorter granulocyte telomere length (TL) among children with perinatally-acquired HIV infection (C-PHIV), t regardless of combination antiretroviral therapy (cART) status, as well as among children presenting with Chronic lung disease (CLD) defined by reduced rip forced vital capacity (FVC)
TL was shortest in cART-naïve C-PHIV with CLD, and appeared to improve following c cART initiation in a subset of children. us Our findings are in contrast with the only other study of leukocyte TL and lung function in n children which reported no association between TL and any spirometry index of lung function a among 11-year old children [24]

Summary

Introduction

Despite the success of combination antiretroviral therapy (cART) to prevent perinatal HIV transmission, the most recent estimates from UNAIDS suggest that 1.7M children under the age of 15 years are living with HIV-1 infection, 90% in sub-Saharan Africa (SSA) [1]. S pediatric HIV programs are seeing substantial and increasing numbers of older children and u adolescents with HIV-1 infection. These young people often experience significant comorbidities an [3,4], affecting multiple systems, which may not improve especially if cART is initiated later in childhood [5]. Chronic lung disease (CLD) has been reported among African children with perinatally-acquired HIV infection (C-PHIV), despite combination antiretroviral therapy (cART). Ip Methods: Participants included Zimbabwean C-PHIV, aged 6-16, who were either newly cr diagnosed and cART-naïve, or on cART for >6 months, and HIV-negative controls of similar s age and sex. P cART initiation increased TL. ce Conclusions: In this cohort, C-PHIV and those with reduced FVC have shorter granulocyte TL, Ac possibly the result of increased immune activation and cellular turnover due to long-standing

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Conclusion