Oral Microbiota in Children Who Started Antiretroviral Therapy at Young Ages

ABSTRACT

Background: Infancy is an important developmental period when the human microbiome is shaped. Given links between young age at antiretroviral treatment (ART) initiation and smaller persisting viral reservoirs, we hypothesized that earlier ART initiation may leave distinct microbial signatures in the oral cavity detectable in children living with HIV (CLWH). Method(s) Oral swab samples were collected from 477 CLWH and 123 children without HIV at two sites in Johannesburg, South Africa. CLWH had started ART < 2 years of age with 60% starting < 6 months of age. Most were wellcontrolled on ART at a median of 10 years of age when the swab was collected. Controls were age-matched and recruited from the same communities. Sequencing of the V4 amplicon of the 16S rRNA gene was done using established protocols. DADA2, decontam, and phyloseq were used for sequence inference, contaminant removal, and subsequent analyses. All p-values were adjusted for multiple testing using Benjamini-Hochberg false discovery rate method. Statistical analyses were performed with R. Result(s) CLWH had lower alpha diversity than uninfected children (Shannon index p< 0.0001). Genus-level abundances of Granulicatella, Streptococcus and Gemella were greater and Neisseria and Haemophilus were less abundant among CLWH compared to uninfected children. Associations were strongest among boys. There was no evidence of attenuation of associations with earlier ART initiation. In fact, decreased bacterial diversity and differences in taxa abundances in CLWH versus controls were consistent regardless of whether ART was started before or after 6 months of age. Shifts in genus-level taxa abundances relative to uninfected controls were most marked in children on regimens containing lopinavir/ritonavir;with few shifts seen if on regimens containing efavirenz. Conclusion(s) A distinct profile of less diverse oral bacterial taxa was observed in school-age CLWH on ART versus uninfected age-matched children suggesting persisting interference of HIV and its treatments on microbiota in the mouth. Any effects of earlier ART initiation were not detectable at this age. Studies of treated adults with HIV have observed similar shifts in taxa abundances. Oral microbiota have been linked to salivary cytokine levels with associations between Granulicatella and IL-8 and Neisseria and IL-6. Declines in Neisseria abundances in oral samples have been associated with more severe outcomes in influenza and COVID-19.