Composition of Gut Microbiota of Children and Adolescents With Perinatal Human Immunodeficiency Virus Infection Taking Antiretroviral Therapy in Zimbabwe.

Trym T Flygel,Mark P Nicol,Jon Ø Odland,Trond Flægstad,Kilaza S Mwaikono,Breathe Study Team ,Grace Mchugh,Evgeniya Sovershaeva,Jorunn P Cavanagh,Tore J Gutteberg,Shantelle Classen-Weitz,Erik Hjerde,Rashida A Ferrand

doi:10.1093/infdis/jiz473

Abstract

BackgroundHuman immunodeficiency virus (HIV) infection causes impairment of the gastrointestinal barrier, with substantial depletion of CD4+ T cells in the gut. Antiretroviral therapy (ART) restores CD4+ counts and may have beneficial effects on gut microbiota in adults. Little is known about effect of long-term ART on gut microbiome in HIV-infected children. We investigated composition of gut microbiota in HIV-infected and -uninfected children and assessed associations between gut microbiota and patient characteristics.MethodsIn a cross-sectional study, rectal swabs were collected from 177 HIV-infected and 103 HIV-uninfected controls. Gut microbial composition was explored using 16S ribosomal ribonucleic acid sequencing.ResultsHuman immunodeficiency virus-infected children had significantly lower alpha-diversity and higher beta-diversity compared to HIV-uninfected. No association was observed between microbiome diversity and CD4+ T-cell count, HIV viral load, or HIV-associated chronic lung disease. We found enriched levels of Corynebacterium (P < .01), Finegoldia (P < .01), and Anaerococcus (P < .01) in HIV-infected participants and enrichment of Enterobacteriaceae (P = .02) in participants with low CD4+ counts (<400 cells/mm3). Prolonged ART-treatment (≥10 years) was significantly associated with a richer gut microbiota by alpha diversity.ConclusionsHuman immunodeficiency virus-infected children have altered gut microbiota. Prolonged ART may restore the richness of the microbiota closer to that of HIV-uninfected children.

Highlights

The gastrointestinal (GI) tract plays an important role in the pathogenesis of human immunodeficiency virus (HIV) infection, with the majority of CD4+ T-cells residing in the GI-tract and associated lymphatic tissue [1]
The study group characteristics are presented in sc Table 1. nu HIV infected participants were older compared to the HIV uninfected participants ((15.6 a years (IQR 12.8-17.7) vs 9.9 (IQR 7.4-12.7), p
When comparing HIV infected c participants based on these subgroups, we found that participants who had been on us Antiretroviral therapy (ART) 10 years had an alpha diversity similar to the HIV uninfected study group (Table n 2)

Summary

Introduction

The gastrointestinal (GI) tract plays an important role in the pathogenesis of human immunodeficiency virus (HIV) infection, with the majority of CD4+ T-cells residing in the GI-tract and associated lymphatic tissue [1]. HIV-induced depletion of CD4+ T-cells causes structural impairment of the GI epithelial barrier, systemic microbial t translocation and alteration of the gut microbial community composition [2]. Studies suggest ART may only partially restore the gut microbiota ce towards levels observed in HIV uninfected populations, and patients continue to suffer Ac from dysbiosis even when HIV infection is controlled [1, 11, 12]. Gut dysbiosis, and associated microbial translocation may drive systemic chronic inflammation which increases the risk of chronic non-infectious HIV complications, such as cardiovascular disease and lung complications [13, 14] 15, 16]. We found enriched levels of Corynebacterium (p

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