HIV Reservoir Dynamics and Bacteriome Composition Along the Gut Axis

Area of Science:

• Microbiology
• Virology
• Immunology

Background:

• The gastrointestinal (GI) tract harbors a significant reservoir of HIV and a diverse microbiome.
• The influence of the gut bacteriome on local HIV persistence has not been previously investigated.

Purpose of the Study:

• To investigate the role of the gut bacteriome in modulating HIV persistence across different segments of the GI tract.

Main Methods:

• Utilized 113 rapid autopsy samples from 24 people with HIV (PWH).
• Performed 16S rRNA sequencing and quantified HIV DNA and RNA using ddPCR across five GI segments.
• Analyzed associations between bacterial taxa abundance and HIV reservoir characteristics using multivariable models.

Main Results:

• HIV DNA levels varied across GI segments, highest in the jejunum and lowest in the colon/rectum.
• Bacterial richness and composition differed significantly across segments.
• Gut bacteriome composition correlated with HIV transcriptional activity, with segment-specific effects observed for short-chain fatty acid producers, mucin degraders, and bile acid metabolizers.

Conclusions:

• The gut bacteriome significantly modulates HIV reservoir size and activity in a region-specific manner.
• These findings highlight the importance of GI tract regional specificity in developing bacteriome-based HIV cure strategies.