Effect of Antiretroviral Therapy on Gut Microbiota in Children With HIV Infection

In children with HIV infection, treatment with antiretroviral therapy (ART), in association with immune status, may directly or indirectly alter the subdominant gut microbiota, according to findings from a small Vietnamese study published in PLoS One.

In this nonrandomized, cross-sectional study, researchers aimed to investigate the effect of ART on the gut microbiota in children with HIV infection who were enrolled at the Vietnam National Children’s Hospital in Hanoi in 2012. Fecal samples were collected from 29 children treated with ART, 30 with HIV infection who were not taking ART, and 20 without HIV infection. Quantification of bacteria in fecal samples was performed using reverse-transcription quantitative polymerase chain reaction assays. Immunologic analysis was performed with blood sample specimens.

Among a total of 29 children with HIV infection in the ART group, the median age was 6.1 (range, 3.6-8.6) years and the median duration of ART was 3.5 (range, 0.8-5.8) years. Of children with HIV infection who were not treated with ART, the median age was 5.9 (range, 2.0-8.8) years. The researchers noted that children in the HIV-negative group were 2 years younger than those in the other 2 groups (median, 4.1 years). All children in the ART group were treated with nucleoside reverse transcriptase inhibitors as backbone drugs, and only 4 received a protease inhibitor.

Although gut microbiota structures were similar between children in the HIV-positive and HIV-negative groups, several subdominant gut bacteria were positively associated with age among those without HIV infection but not among those with HIV infection: Streptococcus (ρ = 0.59; P =.006), Enterococcus (ρ = 0.61; P =.005), and Enterobacteriaceae (ρ = 0.57; P =.008). Of note, the number of Staphylococcus spp was negatively correlated with age among children in the HIV-positive group (ρ = -0.47; P =.009).

When analyzing the association between gut microbiota and immune status, the number of Atopobium cluster was inversely correlated with CD4+ cell and T helper 17 (Th17) counts among children in the HIV-negative group. Among children in the HIV-positive group, the number of Clostridium coccoides spp was positively correlated with CD4+ cell count and its subsets. In Children with HIV infection who received ART, the number of Staphylococcus and C perfringens spp were positively correlated with CD4+ cell counts and their subsets, as well as ART duration, and were negatively correlated with the percentage of activated CD8+ cells. In addition, “the C coccoides group and Bacteroides fragilis group were positively associated with regulatory T-cell count,” the researchers noted.

The researchers found that treatment with cotrimoxazole did not affect the gut microbiota of children with HIV infection. However, in children with HIV infection treated with ART, the number of C perfringens spp was decreased among those who received cotrimoxazole vs those who did not receive cotrimoxazole (3.4 vs 6.2, respectively; P =.01).

In multiple linear regression analyses including age, ART duration, immune status, and use of cotrimoxazole, ART duration was found to be independently associated with the number of C perfringens spp(P <.001), and Th17 count was independently associated with the number of Staphylococcus spp (P =.02).

Limitations of this study included its small sample size, the age differences between the treatment groups, and the lack of a controlled diet among the study population. In addition, researchers were unable to assess HIV-exposure history among children in the HIV-negative group who were born to mothers with HIV infection.

“Findings require confirmation in longitudinal studies that compare the gut microbiome between age-matched children with and without HIV [infection], with and without HIV-exposure history, and/or before and after initiating ART to assess the effect of ART on the composition of the gut microbiota in children with HIV infection,” the researchers concluded.

Reference

Nguyen QT, Ishizaki A, Bi X, et al. Alterations in children’s sub-dominant gut microbiota by HIV infection and anti-retroviral therapy. PLoS One. 2021;16(10): e0258226. doi:10.1371/journal.pone.0258226