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

Abstract

Background 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. Methods 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. Results 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. 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 long-standing HIV infection with delayed cART initiation.

A scoping review of lung function in children and adolescents living with HIV in the era of antiretroviral treatment

“…The BREATHE trial was a multicountry trial conducted in Zimbabwe and Malawi, and the findings were reported in two manuscripts 14,15 . Six papers reported two cohorts in Zimbabwe: ZENITH cohort of ART‐naïve HIV‐positive children and INHALE cohort of ART‐established children 17–22 . Three cohorts were in South Africa, including two earlier cohorts in 2012 and 2015, 27,28 and the more recent Cape Town Adolescent Antiretroviral Cohort (CTAAC), which was summarised in four papers 6,23–25 .…”

“…Twelve papers enrolled participants established on ART 6,10,14,15,18–25 and six papers enrolled participants regardless of their ART status with the percentage on ART ranging from 69% to 97% 5,11–13,26,28 . Three papers did not report ART prevalence 16,17,27 .…”

“…Comparison or control groups were present in nine studies as follows: eight studies included HIV-uninfected children or adolescents (range 95-224 participants) and one study included 375 HIV-infected adult participants as comparison group. 11 Twelve papers enrolled participants established on ART 6,10,14,15,[18][19][20][21][22][23][24][25] and six papers enrolled participants regardless of their ART status with the percentage on ART ranging from 69% to 97%. 5,[11][12][13]26,28 Three papers did not report ART prevalence.…”

“…The prevalence of reduced FVC was reported in 10 studies and ranged from 10% to 42% prebronchodilator. 10,11,[16][17][18][21][22][23][24]26 Table 3 compares the prevalence of lung function abnormality reported from 11 studies where both children and adolescents living with HIV were included, 6,[17][18][19][21][22][23][24][25][26]28 to five studies where only adolescents living with HIV were included, 5,[10][11][12]16 and seven studies of HIV negative children and adolescents. 16,18,[21][22][23][24][25] It appears that lung function impairment was more severe and prevalent in the adolescents living with HIV-only group.…”

“…16,17,27 The median age of ART initiation ranged from 4.2 to 8.4 years, 6,12,13,15,18,[23][24][25] and the median duration of ART ranged from 9.8 months to 7.9 years on the time of enrollment among all the papers. 5,6,11,[13][14][15][18][19][20][22][23][24][25][26][27][28]…”