CROI 2017 Abstract e-Book

Abstract eBook

Poster and Themed Discussion Abstracts

family model was applied to estimate how CMV and EBV replication affects the microbiome composition among HIV-infected and uninfected controls in the colon and terminal ileum. Results: Overall, CMV and EBV were detected in at least one gut sample in 61% and 79% of all participants. HIV-infected individuals were less likely to shed CMV (median Odd Ratio(OR)=0.2 [95% CI= 0.1~0.7], p=0.04) and CMV was more frequently detected in ileum than colon (OR=2.8 [CI=1.0~9.2], p=0.04). EBV shedding was more frequent among HIV-infected individuals (OR = 3.5 [CI=1.1~14.6], p=0.05) without differences by intestinal site. The relative abundance of the main phyla in the colon and ileumwas assessed in relation to HIV-status and presence of CMV or EBV replication. After quality–filtering, 455,452 microbial sequences were analyzed (mean 3,733 reads/sample). While HIV-infection was associated with significantly lower beta-diversity, the number of operational taxonomic unit did not differ according to CMV or EBV detection status. Network approach based on Bray-Curtis distance confirmed clustering of samples by HIV-status but not by CMV/EBV (Fig.1). Among HIV-infected participants, higher levels of CMV were associated with greater relative abundance of Actinobacteria (b=2.1+/-0.9, p=0.02) and Beta-Proteobacteria (b=1.9+/-0.6, p=0.01) in the colon. CMV was not associated with any significant shift in the microbiome of healthy controls. There was no significant association between EBV replication and microbiome composition for either group or site. Conclusion: These results illustrate a complex interplay between HIV and CMV replication in the gut mucosa and highlight a possible modulatory effect of CMV replication on the microbial homeostasis during HIV-infection.

Poster and Themed Discussion Abstracts

241 EFFECT OF HIV STATUS, CMV, AND EBV REPLICATION ON MUCOSAL GENE EXPRESSION IN THE GUT Sara Gianella 1 , Antoine Chaillon 2 , Ece A. Mutlu 3 , Phillip A. Engen 3 , Robin M. Voigt 3 , Ali Keshavarzian 3 , John Losurdo 3 , Steven Lada 1 , Masato Nakazawa 1 , Alan Landay 3 1 Univ of California San Diego, La Jolla, CA, USA, 2 Univ of California San Diego, San Diego, CA, USA, 3 Rush Univ, Chicago, IL, USA Background: HIV-infection is associated with pro-inflammatory changes in the intestinal mucosa, which might contribute to barrier dysfunction and dysbiosis. Cytomegalovirus (CMV) and Epstein Barr Virus (EBV) can replicate in the gut and contribute to systemic inflammation during HIV-infection. The effect of viral co-infections on intestinal mucosal gene expression has not been investigated. Methods: Gut mucosal biopsies from left and right colon (n=57) and terminal ileum (n=36) were collected from 16 HIV-infected and 20 healthy control subjects. Levels of CMV and EBV DNA were measured in each sample by droplet digital PCR. Mucosal gene expression of 40 cytokines was measured via a QuantiGene multiplex assay and normalized by expression of housekeeping gene GAPDH. To summarize the high-dimensional dataset, factor analysis for mixed data was used to compute dimensions that together explained >60% of the total variance. A set of 3 cytokines that contributed most was identified (CCL2, IL-8, IFN-β1). Since CMV can induce IL-6, IFN-γ and IL-1β, those cytokines were selected a priori to be part of the analysis. We applied a linear mixed-effects regression model to examine how presence of CMV or EBV, HIV status, and intestinal site interacted to influence cytokine activities. Results: CMV and EBV DNA were detected in at least one gut biopsy in 38% and 81% of HIV-infected and 77% and 77% of healthy controls, respectively. Gene expression of all 6 selected cytokines was significantly upregulated in HIV-infected subjects compared to controls (P<0.01). Additionally, we identified a significant interaction between HIV status, intestinal site, cytokine type and presence of CMV (P<0.001). Specifically among the healthy controls, the presence of detectable CMV was associated with significantly upregulated expression of all 6 cytokines in the ileum (all P<0.01) and higher expression of IL-8 and IFN-β1 in the colon (P<0.04) Figure 1. When CMV was detectable, gene expression levels in the ileum of healthy controls were similar to those of HIV-infected subjects. Presence of CMV was not associated with any difference in mucosal gene expression among HIV-infected people. There was no significant effect of EBV replication on any gut mucosal biopsy site in both groups. Conclusion: Our data highlight a possible immune-modulatory role of CMV replication in the gut of HIV-uninfected subjects. Both HIV and CMV are associated with similar pro- inflammatory changes in the intestinal mucosa, but no additive effect was observed.

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CROI 2017