HIV, ART May Influence Subdominant Gut Bacteria in Children With HIV

Research published in PLoS ONE shows that HIV infection and antiretroviral therapy (ART) may influence subdominant gut bacteria in association with immune status in children living with HIV.

The study showed that several subdominant gut bacteria—including Streptococcus, Enterococcus, and Enterobacteriaceae—were positively associated with age in children without HIV, but not in children with HIV. The authors noted that this is consistent with past findings.

The investigators also looked at the impact of specific drug regimens, such as those including nucleoside reverse transcriptase inhibitors (NRTIs).

“Our study is consistent with the previous study that ART, especially NRTI-including regimens, had more suppressive impacts on the composition and the variability of the gut microbiota,” they said. “Further study is needed to investigate whether NRTIs influence the gut microbiota, directly or indirectly, through the restoration of immune status in children with HIV who are on ART.”

This nonrandomized, cross-sectional study was conducted at the Vietnam National Children’s Hospital in Hanoi, Vietnam, in 2012. The study included children with HIV who did not start ART, children with HIV who have started ART, and children without HIV. Participants ranged from 2 to 8.8 years of age.

For children with HIV, the Clostridium coccoides group was positively associated with the CD4+ cell count and its subsets.

In children with HIV receiving ART, Staphylococcus and Clostridium perfringens—a potentially harmful bacterium—were positively correlated with CD4+ cells and their subsets but negatively correlated with activated CD8+ cells. The C coccoides group and the Bacteroides fragilis group were linked to regulatory T-cell counts.

Staphylococcus was negatively correlated with age in children vertically infected with HIV. ART duration had an independent positive association with C perfringens and Th17 count with Staphylococcus in children with HIV receiving ART.

In children without HIV, the numbers of dominant gut bacteria—C coccoides group, Clostridium leptum subgroup, Bifidobacterium, and Atopobium cluster—did not correlate with age.

“This finding is consistent with previous findings that the gut microbiota of healthy children stabilizes and becomes similar to that of adults at around 2 or 3 years of age,” the authors said.

Fifteen of the 30 participating children with HIV not receiving ART and 9 of the 29 children receiving ART also received cotrimoxazole. Cotrimoxazole treatment did not significantly affect the gut microbiota profile in the former group; however, in those receiving ART, the median (interquartile range) number of C perfringens was significantly lower among children treated with cotrimoxazole (3.4 [2.2−5.4]) compared with those not treated with cotrimoxazole (6.2 [4.8−7.5]; P = .01).

Additionally, ART duration was independently associated with C perfringens, but the use of cotrimoxazole was not.

The authors also mentioned that all children with HIV receiving ART in the study were treated with NRTIs as “backbone drugs” and only 4 also received a protease inhibitor (PI). This means the positive correlation between the number of C perfringens and ART duration could be due to the use of NRTIs, but not PIs, which are known to lower the diversity of the gut microbiota.

“These findings require confirmation in longitudinal studies that compare the gut microbiome between age-matched children with and without HIV, 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,” the authors said.

Reference

Nguyen QT, Ishizaki A, Bi X, et al. Alterations in children’s subdominant gut microbiota by HIV infection and antiretroviral therapy. PLoS ONE. Published online October 11, 2021. doi:10.1371/journal.pone.0258226