Four Weeks of Treatment With Rifaximin Fails to Significantly Alter Microbial Diversity in Rectal Samples of HIV-Infected Immune Non-Responders (ACTG A5286) Which May be Attributed to Rectal Swab Use

Brett B. Williams, Stefan J. Green, Ronald J. Bosch, Ellen S. Chan, Jeffrey M. Jacobson, David M. Margolis, Phillip Engen, Alan L. Landay, Cara C. Wilson

Abstract


Introduction: HIV-infected individuals have evidence of intestinal microbial translocation which is associated with immune activation and unfavorable clinical outcomes. Rifaximin, a non-absorbable antibiotic which reduces microbial translocation in other disease states, was shown to have a marginal beneficial effect on microbial translocation, T-cell activation, and inflammation in a multisite randomized trial (ACTG A5286; NCT01466595) of HIV-infected persons with poor immunologic recovery receiving ART. Here, we report analysis of the rectal microbiome changes associated with that trial.

Methods: HIV-1-infected individuals receiving ART with CD4-T cell count <350cells/mm3 and viral suppression were randomized 2:1 to rifaximin or no therapy for 4 weeks. Rectal swabs were collected at baseline (pre-treatment) and at week 4 of rifaximin therapy. Genomic DNA extracted from rectal swab samples was analyzed using high throughput sequencing and quantitative PCR of bacterial 16S ribosomal RNA (rRNA) genes.

Results: Forty-eight HIV-infected participants (31 received rifaximin, 17 no treatment) were included. There was broad variability in the recovery of bacterial rRNA from the specimens at baseline. No major significant (FDR P<0.05) effects of rifaximin treatment on alpha- or beta- diversity or individual taxa were observed between or within the treatment arms, with analyses conducted at taxonomic levels from phylum to genus.

Conclusions: Rifaximin did not meaningfully alter the diversity or composition of the rectal microbiome of HIV-infected individuals after 4 weeks of therapy, although rectal swab specimens varied widely in their microbial load.


Keywords


HIV; microbiome; immune activation; microbial translocation; rifaximin

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Copyright (c) 2019 Brett B. Williams, Stefan J. Green, Ronald J. Bosch, Ellen S. Chan, Jeffrey M. Jacobson, David M. Margolis, Phillip Engen, Alan L. Landay, Cara C. Wilson, A5286 protocol team

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