CROI 2024 Abstract eBook

Abstract eBook

Poster Abstracts

BMI was significantly associated with IL-16 and CXCL13, both of which are involved in intestinal inflammation and bacterial migration. A low abundance of Parabacteroides which lead to the disturbances of secondary bile acid metabolism, was associated with a BMI of 25 and over, low α diversity, low abundance of SCFA-producing bacteria, as well as weight gain for 4 years. Conclusion: HIV-specific dysbiosis progressed despite effective ART. This dysbiosis correlated with weight gain and was characterized by Intestinal permeability that also persisted and was associated with systemic inflammation. This suggests that the intestinal environment in PLWH may potentially affect metabolic imbalance and inflammation.

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CX3CR1+ Vδ1 T-Cells Are Clonally Expanded and Driven by CMV, Microbiota, and HIV- 1 in the Gut on ART Nived Collercandy 1 , Camille Vellas 1 , Manon Nayrac 2 , Mary Requena 1 , Thomas Richarme 2 , Justine Latour 1 , Karl Barange 1 , Laurent Alric 1 , Nicolas Carrere 1 , Guillaume Martin-Blondel 1 , Matteo Serino 2 , Jacques Izopet 1 , Pierre Delobel 1 1 Toulouse University Hospital, Toulouse, France, 2 Institut National de la Santé et de la Recherche Médicale, Toulouse, France Background: The Vδ1 subset of γδ T cells resides mainly in tissues, where it participates in innate and adaptive immunosurveillance, notably in the gut, a major site for HIV-1 persistence. Vδ1 cells normally represent a minor part of blood γδ T cells, but they expand during HIV-1 infection, with an inversion of the Vδ1/Vδ2 ratio, the causes of which are not yet clear. Methods: Duodenal biopsies and blood samples from 15 virologically suppressed people living with HIV-1 (PLWH) and 15 uninfected controls recruited in the ANRS EP61 GALT study were used to assess the frequency, phenotype and function of Vδ1 T cells by FACS. Samples from 5 PLWH and 5 controls were used to sequence the TRDV1 chain repertoire. Single-cell RNAseq was performed on sorted circulating Vδ1 T cells from 6 PLWH and 6 controls. Total and intact HIV-1 DNA and residual HIV-1 RNA were quantified, and 16S-RNA PCR was used to amplify and sequence bacterial DNA in gut and blood samples. All selected subjects were CMV seropositive. Results: PLWH had increased circulating CX3CR1+ Vδ1 effector cells compared with uninfected controls (median 17.2/μL, [4.5-26.3] vs. 3.3/μL [1.2-7.3] respectively; P=0.03). The phenotype of expanded CX3CR1+ Vδ1 cells globally clustered with terminal differentiation markers (TEMRA: CD27-CD45RA+), and into subpopulations expressing the activating receptor NKG2C and the exhaustion marker TIM-3. CX3CR1+ Vδ1 TEMRA cells were highly cytotoxic, with high levels of granzyme B and perforin, but low production of IFNγ and TNFα. Gut intra-epithelial lymphocytes (IEL) were more cytotoxic (perforin+) and activated (NKG2C+) in PLWH, the latter correlating with the Vδ1/Vδ2 ratio in blood. Repertoire analysis revealed clonal expansions in PLWH blood, compared with matched duodenal IELs and uninfected controls. The expansion, phenotype, and cytotoxicity of blood Vδ1 cells in PLWH were notably associated with the CMV IgG index, the abundance of various bacterial species in the duodenal and blood microbiome, and HIV-1 RNA and DNA in blood and gut (Figure). Conclusion: Highly cytotoxic CX3CR1+ Vδ1 effector cells are clonally expanded in the blood and associated with Vδ1 IEL activation in the gut of PLWH on ART. They may be triggered by the interplay between residual CMV replication, gut and blood microbiome, and the gut HIV-1 reservoir. CX3CR1+ Vδ1 effector cells may contribute to the control of HIV-1 persistence on ART, but might also be involved in chronic vascular inflammation in PLWH due to their endothelial tropism.

Poster Abstracts

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Comparisons of Oral and Gut Bacteria Highlight Role of Veillonella in Systemic Inflammation in HIV Grace Cho, Julie Elliott, Katharine Newman, Fan Li, Nicole H. Tobin, Steven Shoptaw, Pamina Gorbach, Grace M. Aldrovandi, Jennifer A Fulcher University of California Los Angeles, Los Angeles, CA, USA Background: Chronic inflammation contributes to multiple comorbidities in people living with HIV. Translocation of gut bacteria and resultant immune activation may in part drive this inflammation; however, the role of the oral microbiome in this phenomenon is unknown. We investigated the effects of HIV on the oral microbiome and the relative contribution of oral and gut bacteria to systemic inflammation. Methods: Oral and gut microbiome composition was determined by 16S rRNA gene sequencing of saliva samples and rectal swabs from 98 men who have sex with men (MSM) with HIV and 99 MSM without HIV. Biomarkers were quantified in serum using multiplex Luminex assays. Relative contributions of oral versus gut bacteria to biomarker variation was analyzed using PERMANOVA and significant relationships identified using mixOmics. Anti-bacteria IgG ELISAs were developed to assess oral bacteria translocation and quantified by serum endpoint IgG titers. Relationships between immune biomarkers and endpoint IgG titers were examined using correlation analysis. Results: The oral microbiome composition in MSM differed by HIV status with increased Veillonella , Capnocytophaga , and Megasphaera seen with HIV. Known inflammatory biomarkers also increased with HIV (fatty acid binding protein 2 (FABP2) p<0.001; sCD27 p=0.006; sCD163 p=0.01; CXCL10 p<0.001; IL-6 p=0.03; TNF-alpha p=0.007). The oral microbiome was an important contributor to inflammatory biomarker variance showing greater influence than the gut for several biomarkers (sCD27, LPS-binding protein (LBP), CRP, CXCL10, TNF-alpha, IL-6) (Figure). Anti-bacteria ( Veillonella parvula, Fusobacterium nucleatum, Porphromonas gingivalis ) endpoint IgG titers did not differ by HIV status. However, there was a significant correlation between both LBP (r s =0.34, p=0.02) and sCD14 (r s =0.3, p=0.04) with Veillonella parvula IgG in MSM with HIV. mixOmics analysis also identified key correlations between oral Veillonellla with IL-6 and FABP2. In vitro studies showed heightened inflammatory potential of Veillonella parvula with peripheral immune cells. Conclusion: The oral microbiome differs in MSM with HIV and is an important contributor to altered inflammatory biomarkers. Correlations between key oral bacteria and inflammatory biomarkers suggest that systemic circulation of oral bacteria, including Veillonella parvula , could be another important mechanism driving chronic inflammation in HIV.

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CROI 2024