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

Abstract

Background: Human 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.

Methods: In 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.

Results: Human 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.

Conclusions: Human immunodeficiency virus-infected children have altered gut microbiota. Prolonged ART may restore the richness of the microbiota closer to that of HIV-uninfected children.

Keywords: Africa; HIV infection; antiretroviral therapy; children; gut microbiota.

Figure 1.

Alpha diversity indices in human immunodeficiency virus (HIV)-infected and there was found a significantly lower richness in HIV infected participants compared to HIV uninfected by (a) Observed OTUs and (b) Chao1 index. Mid line showing median and error bars showing the interquartile range. OTUs, operational taxonomic units.

Figure 2.

Beta-diversity comparison between study groups. Principal cooridnate (PC) analysis plot showing beta-diversity by Bray-Curtis dissimilarity comparing (a) human immunodeficiency virus (HIV)-infected (red) and HIV-uninfected (blue) participants (P < .01) and (b) HIV-infected with chronic lung disease (red), HIV-infected without chronic lung disease (green), and HIV-uninfected (blue) participants. P value obtained using Wilcoxon rank-sum test.

Figure 3.

Linear discriminant analysis effect size plot. This plot shows enriched taxa that are significantly different between human immunodeficiency virus (HIV)-infected (blue) and HIV-uninfected (red) participants. Only taxa meeting a significant level of 0.05 and effect size threshold of 1.0 are included. P values shown are only those significant after adjustment for false discovery rate.