Authors
Ashma Chakrawarti, Ross T Cromarty, Christopher M Basting, Jodi Anderson, Ty A Schroeder, Kevin Escandón, Robin Shields-Cutler, Robert Langat, Erik Swanson, Patrick Soon-Shiong, Jeffrey T Safrit, Leonard S Sender, Sandeep Reddy, Jeffrey S Miller, Joshua Rhein, Timothy W Schacker, Nichole R Klatt
Published in
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. Jul 06, 2026. Epub Jul 06, 2026.
Abstract
N-803, an IL-15 superagonist, is currently being studied in clinical trials as a treatment to reverse HIV latency. However, its effects on the gut microbiome are not well understood.
In this exploratory longitudinal metagenomic study, we analyzed fecal microbiomes from 10 ART-suppressed people with HIV at four different timepoints before, during, and after N-803 treatment.
Overall taxonomic and functional diversity did not change significantly, yet beneficial microbial taxa and pathways were nominally enriched after N-803. Specifically, the relative abundance of Faecalibacterium prausnitzii showed a nominal increase after N-803, whereas histidine degradation pathways, often associated with pro-inflammatory mucosal state, decreased. A higher baseline microbial diversity correlated with stronger CD8+ and natural killer (NK) cells activation and reduced frequency of rectal HIV RNA+ cells. MaAsLin2 analyses further identified potentially important associations between short-chain fatty acid (SCFA)-producing taxa and pathways with increased immune activation markers.
These findings in a limited Phase 1B clinical study suggest that gut microbiome diversity prior to immunotherapy may influence host response. These results provide a basis for further investigation into microbiome-based strategies to improve efforts to cure HIV.
PMID:
42402338
Bibliographic data and abstract were imported from PubMed on 06 Jul 2026.
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