Background
The gut virome is seeded at birth, rapidly develops in the first years of life, and is influenced by numerous behavioral and environmental factors including exposure to the maternal virome. Thus, maternal HIV infection could alter virome development and may contribute to the increased morbidity and mortality seen in children exposed to HIV. However, no study has characterized the gut virome of children who are HIV-exposed, uninfected (CHEU). To address this gap, we described and compared the gut virome of Kenyan CHEU and children who are HIV-unexposed, uninfected (CHUU) from birth-21 months.
Methods
We performed metagenomic sequencing of the DNA virome on stool samples collected between January 2019-December 2020 from a birth cohort of healthy infants in Nairobi, Kenya. Data from 37 CHUU and 32 CHEU whose mothers initiated ART prior to (n=29) or in early pregnancy (n=2) were included. To compare gut virome composition by HIV exposure and breastfeeding practices, we used generalized estimating equations models adjusted for maternal age, breastfeeding, and socioeconomic status for virome richness and Shannon (alpha) diversity, principal coordinates analysis and PERMANOVA for Bray-Curtis distances (beta diversity), and MaAsLin2 to identify discriminating viral taxa.
Results
Virome richness was lower among CHEU than CHUU (b= -130, 95% CI: -250 – -9.7, p=0.03), but there were no differences in Shannon diversity (beta= -0.3, 95% CI: -0.5–0.05, p=0.1) or Bray-Curtis distances (p=0.8) by HIV exposure. Relative abundances of 28 unique viral contigs were associated with CHEU status, of which 17 (61%) were of the family Anelloviridae. Consistent with previous studies of CHUU, older age (months; beta= 24.1, 95% CI: 4.2-43.9, p=0.02) and introduction of foods other than breast milk (beta= 343, 95% CI: 112-573, p=0.004) were also associated with higher virome richness among all infants.
Conclusions
Age, feeding practices, and HIV exposure altered gut virome richness, but not Shannon or beta diversity, suggesting the presence and/or absence of specific viruses within groups did not substantially shift overall community structure. Similarities between CHEU and CHUU suggest that HIV exposure is not a major determinant of the infant virome when mothers receive optimized ART before or in early pregnancy. Further research should assess whether lower abundance of Anelloviridae has a meaningful effect on health among CHEU.
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