CROI 2025 Abstract eBook

Abstract eBook

Poster Abstracts

examined associations between RV, systemic immunologic effects, and reservoir composition and size. Methods: The 2000HIV study (NCT03994835), enrolling 1895 virally suppressed PWH in the Netherlands, divided into a discovery and validation cohort, was used to compare participants with RV and TND. We performed extensive immunophenotyping of circulating immune cells, measured cytokine production after ex-vivo stimulation in PBMCs and plasma proteome using Olink Explore panel (~3000 proteins). Differential expression analysis between RV and TND was performed, followed by gene set enrichment analysis (GSEA) using Hallmark library on proteins expressed in the same direction in both cohorts. Additionally proviral Cell Associated-HIV-DNA (CA-DNA) in circulating CD4 T cells were analyzed, along with intactness ratio using the Rainbow assay. Results: The discovery cohort included 474 PWH with RV and 1002 with TND, the validation cohort had 136 with RV and 190 with TND. No significant differences in immune cell populations, their activation markers and cytokine production capacity were found between RV and TND. There were no significant differentially expressed proteins, but GSEA identified 16 enriched pathways (Figure 1). PLHIV with RV had significantly higher total CA-DNA copies per 10 6 CD4-T cells in both the discovery (median [IQR]: RV 875 [387-1600] vs. TND 481 [191-1047], p<0.00) and validation cohort (RV 873 [331-1908] vs. TND 442 [200 1092], p<0.00). While the intactness ratio was similar, both intact and defective copies were higher in RV. Conclusions: RV is associated with higher total viral reservoir size, without differences in intactness ratio. Remarkably in this large study in PWH no signs of systemic inflammation or immune activation were found in RV. GSEA reveals upregulation of epithelial mesenchymal transition, that links with impaired mucosal barrier function and human papillomavirus malignancies, suggeting RV could potentially play a role in these conditions, warranting further investigation into its clinical significance and therapeutic options.

diversity in the bacterial microbiome than the undetected group, with more short-chain fatty acid (SCFA)-producing Lachnospiraceae and less E. coli . Cell free supernatant extracted from a laboratory strain of E. coli induced hyphal formation of C. albicans in vitro , while supernatants from Lactobacillus did not show such an effect. Purified BEV from E. coli induced the transactivation of hyphae-specific genes, such as Candida Als3 and Hwp1 , and yeast-to-hyphal transition of C. albicans in a few hours. Conclusions: Our results demonstrate the impact of BEVs secreted from specific commensal bacteria on Candida morphogenesis and clarify one of the mechanisms of Candida intestinal colonization. Normally, the host immune system, particularly soluble IgA, targets and eliminates Candida hyphae; however, under immunocompromised conditions, the hyphal invasion of Candida which has escaped the elimination process may promote systemic candidiasis. The effects of BEVs secreted by commensal bacteria are thought to be varied. Understanding the molecular basis of BEVs in hyphal formation of C. albicans in the intestinal tract may lead to new therapeutic strategies to prevent pathogenic overgrowth of C. albicans . The figure, table, or graphic for this abstract has been removed. The Mucosal Microbiome at Sites of HIV Acquisition Among Key Populations Vanessa Van Doren 1 , Cassie G. Ackerley 1 , Robert A. Arthur 2 , Henry Claussen 2 , Suparat Khemnark 5 , Phillip M. Murray 1 , S. Abigail Smith 1 , Vin Tangpricha 2 , Colleen Kelley 1 1 Emory Vaccine Center, Atlanta, GA, USA, 2 Emory University, Atlanta, GA, USA, 5 Bamrasnaradura Infectious Diseases Institute, Bangkok, Thailand Background: Microbiome effects on mucosal HIV acquisition risk have received significant attention. Yet, little is known about mucosal microbiome variation between key populations, including cisgender men who have sex with men (MSM) and transgender women (TW) using feminizing hormone therapy (FHT) or across geographic locations. Methods: We enrolled TW on FHT for ≥6 months [n=122; 25 in Atlanta, Georgia (ATL); 97 in Bangkok, Thailand (BK)] and MSM (n=83; 33 from ATL, 50 from BK) aged 18-59 years without HIV. We sequenced 16S rRNA in rectal secretions collected from all participants and neovaginal secretions from a subset of 13 TW in BK. We also collected rectal secretions from 21 TW before and median 4.7 months after FHT initiation. We used linear decomposition modeling (LDM) to compare the rectal microbiome between TW vs MSM, BK vs ATL, before/after FHT initiation, and to the neovagina. Results: In ATL, we found no difference in rectal α diversity between TW and MSM, but microbiome composition differed (global LDM p=0.006, 17 genera FDR (false discovery rate) <5%). In BK, rectal global composition differed between TW and MSM (global LDM p=0.01), but there was no difference in α diversity or individual genera. We found no difference in rectal α diversity or microbiome composition among TW before/after FHT initiation. At both sites, the Prevotellaceae family was enriched over Bacteroidaceae among MSM but not TW (p<0.0001, Fig1A ). Rectal α diversity did not differ in TW in BK vs ATL, but composition differed significantly (global LDM p=0.002, 24 genera FDR <5%). In MSM, rectal α diversity was higher in ATL than BK (p=0.008), and composition differed significantly (global LDM p=0.0004, 161 genera FDR <5%). Higher rectal α diversity and pronounced composition differences were seen in the neovagina vs rectum (global LDM p=0.0002, 125 genera FDR <5%: Fig1B ) with neovaginal enrichment for anaerobic taxa such as Finegoldia , Prevotella , and Peptoniphilus . Conclusions: Rectal microbiome differences were notable both between MSM and TW and by geography; however, we detected no effect of FHT initiation among TW. Lack of rectal enrichment for Prevotellaceae , as reported previously for MSM, and the distinct neovaginal microbiome typified by taxa previously associated with HIV acquisition in penile mucosa underscore the need to distinguish TW from MSM in HIV prevention research. Future studies examining microbiome impact on HIV acquisition should account for variations in composition among key populations.

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Relationship Between Gut Microbiome and Candida in PWH: Role of Bacterial Extracellular Vesicles Aya Ishizaka 1 , Michiko Koga 1 , Taketoshi Mizutani 2 , Tetsuro Matano 2 , Hiroshi Yotsuyanagi 1 1 University of Tokyo Institute of Medical Science, Tokyo, Japan, 2 National Institute of Infectious Diseases, Tokyo, Japan Background: Candida is an opportunistic pathogen that can cause a variety of infections, from superficial to systemic, where the immune system is weakened. It has been suggested that the intestinal tract is a source of Candida infection; however, the role of commensal bacteria and intestinal immunity in Candida colonization in the intestinal tract is unclear. This study aimed to understand the symbiotic relationship between gut bacteria and fungi in people with HIV (PWH). Methods: A total of 96 PWH with immunological recovery (median CD4 count: 637 cells/μl) were recruited and DNA was extracted from their stools. We identified bacterial and fungal flora by examining bacterial 16S rDNA V3-V4 and fungal ITS1 regions using the MiSeq next-generation sequencer and QIIME2 analysis pipeline. Bacterial extracellular vesicles (BEVs) were isolated from Escherichia coli culture supernatants using ultracentrifugation and size exclusion chromatography. Results: Candida were detected in 25% (24/96) of PWH. The undetected group was associated with a higher titer of anti- C. albicans -IgG antibodies in the plasma. The Candida -detected group had significantly higher alpha

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CROI 2025