2517. Oral Fecal Microbiota Transplantation Increases Gut Microbiome Diversity and Alters the Microbiome Distribution in People with HIV

BACKGROUND: Reduced microbiota diversity (dysbiosis) in people with HIV (PWH) can damage the intestinal barrier and increase microbial translocation, resulting in inflammation, a driver of morbidity and mortality. We hypothesized that fecal microbiota transplants (FMT) would reverse dysbiosis in PWH. METHODS: We administered 6 weekly oral doses of a novel lyophilized fecal microbiota product from 2 healthy donors to 6 men who have sex with men with HIV on suppressive ART. Shotgun sequencing on stool before, after 6 weekly FMT, and 20 weeks after the last FMT (Weeks 0, 6 and 26), and from donors, was performed to determine bacterial community profiles. Biomarkers were measured by Luminex assays and ELISAs. All comparisons used Wilcoxon matched-pairs signed rank test. RESULTS: Median age at Week 0 was 41 years, CD4+ T-cell count 504 cells/mm(3), VL < 20 copies/mL. Mean α diversity by observed species index increased from Week 0 to 6 (61.2 to 70.2, P = 0.29; Figure 1) and decreased by Week 26 (70.2 to 52.2, P = 0.33) to be similar to the donors’ (63.5, P = 0.86). Microbiome distribution by principal component analysis shifted toward the donors’ distribution in most participants at Week 6 but shifted away by Week 26 (Figure 2). Biomarkers did not change significantly during the study. PID3, with HIV > 35 years, had chronic constipation that resolved with FMT with a large shift in distribution but recurred at Week 26. Fusobacterium gonidiaformans, Porphyromonas somerae, and Haemophilus parainfluenzae comprised 27% of his microbiome at Week 0 but 0.73% at Week 6; untyped Bacteroides comprised 35% at Week 6. I-FABP (6,899 to 2,736 pg/mL), sCD14 (1.67 to 1.31 μg/mL), IL-6 (1.51 to 1.13 pg/mL) and sTNFRII (11,659 to 8,300 pg/mL) levels decreased in PID3; Week 0 levels in PID3 were higher than in other recipients. No related serious adverse events occurred. CONCLUSION: Weekly FMT resulted in increased intestinal microbiome α diversity and a shift in microbiome distribution in most participants. These changes did not persist after stopping FMT. PWH with long-term HIV and/or greater inflammation or gut damage may be most likely to benefit from FMT. The effects of recurrent FMT were transient, suggesting longer duration of treatment or intermittent FMT boosting may be required to maintain its benefits. [Image: see text] [Image: see text] DISCLOSURES: All authors: No reported disclosures.