CROI 2017 Abstract e-Book

Abstract eBook

Poster and Themed Discussion Abstracts

Results: VI pts were similar for age, HIV/HCV duration of infection and viral load, type/length of cART and fibrosis. Compared to HC, VI pts showed a trend toward lower circulating CD8+MAIT (Table1), with significant increase of CD8+CD161-Va7.2+ (HIV, p=.004; HCV, p=.023; HIV/HCV, p=.0006 versus MAIT). In VI, residual CD8+MAIT tended to have higher proportion of activated CD39+, CD69+ (in HIV alone) cells (Table1), negatively correlating with CD8+MAIT frequency (r=-0.33 p=.04; r=-0.38 p=.02, respectively). VI featured higher perforin+CD8+MAIT, yet lacked intracellular cytokine production (Table1). Similarly, CD8+CD161-Va7.2+ of VI pts, particularly HIV/HCV, displayed an activated CD69+, exhausted PD-1+ phenotype with high proportion of perforin-producing cells (Table1), positively correlating with CD8+CD161-Va7.2+ frequency (r=0.29 p=0.03). Interestingly, despite no major differences in plasma 16s rDNA and faecal/plasma microbiota among VI patients, CD69+CD8+MAIT proportion positively correlated with 16s (r=.69 p=.019). Conclusion: In chronically HIV/HCV pts, irrespective of mono/dual infection, we describe reduced CD8+MAITs. Residual MAIT subset shows an activated/cytolytic phenotype, yet reduced ex vivo function, suggesting disrupted MAIT homeostasis. Excessively activated and yet functionally-impaired CD8+MAIT that positively correlate with circulating 16s, despite equivalent MT/microbiota, point to continuous MAIT engagement by microbial challenge, in turn exhausting functional competence.

Poster and Themed Discussion Abstracts

240 IMPACT OF MUCOSAL CMV AND EBV REPLICATION ON ENTERIC MICROBIOME DURING HIV INFECTION Antoine Chaillon 1 , Sara Gianella 2 , Ece A. Mutlu 3 , Phillip A. Engen 3 , Robin M. Voigt 3 , Ali Keshavarzian 3 , John Losurdo 3 , Steven Lada 2 , Masato Nakazawa 2 , Alan Landay 3 1 Univ of California San Diego, San Diego, CA, USA, 2 Univ of California San Diego, La Jolla, CA, 3 Rush Univ Med Cntr, Chicago, IL, USA Background: HIV-infection is associated with significant alterations in the enteric microbiome. The underlying mechanisms by which HIV perturbs intestinal homeostasis remains unclear, and the impact of other viral pathogens in the gut has not been investigated. Methods: A total of 80 mucosal biopsies from left and right colon (n=63) and terminal ileum (n=17) were collected from 18 HIV-infected and 20 uninfected healthy controls. Levels of CMV and EBV DNA were measured in each mucosal biopsy by droplet digital PCR. Microbiome analysis was performed using bacterial 16S ribosomal DNA pyrosequencing and sequences were processed with QIIME software. Bayesian hierarchical regression approach was used to model propensities to shed CMV and EBV and a negative binomial

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CROI 2017