Pre-treatment Gut Microbiome Diversity and Function Linked to Cytotoxic and Natural Killer Cell Immune Responses after N-803 Treatment in People with HIV

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ID: 319670
2026
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Ranked #520 of 530 articles by views in Clinical infectious diseases : an official publication of the Infectious Diseases Society of America

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Abstract
Abstract Background 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. Methods 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. Results 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. Conclusions 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.
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Authors Ashma Chakrawarti, Ross Cromarty, Christopher M. Basting, J T Anderson, Ty Schroeder, Kevin Escandón-Vargas, Robin Shields‐Cutler, Robert Langat, E. R. Swanson, P Soon-Shiong, Jeffrey T. Safrit, Leonard S. Sender, Sandeep Reddy, Jeffrey S. Miller, Joshua Rhein, Timothy W. Schacker, Nichole R. Klatt
Journal Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
Year 2026
DOI
10.1093/cid/ciag369
URL
https://doi.org/10.1093/cid/ciag369
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