CROI 2018 Abstract eBook

Abstract eBook

Poster Abstracts

sequenced on the Illumina Nextseq and the resulting microbiota profiles were analyzed. Differences in bacterial community composition were assessed both longitudinally and cross-sectionally using weighted UniFrac; statistical significance was determined using Linear Mixed Effects Models (LME) and permutational multivariate ANOVA (PERMANOVA), respectively. Results: Using repeated measure analyses, significant differences in the bacterial community composition (beta diversity scores) were observed in the AD group compared to either of recent infection groups (LME, p=0.009 and 0.007 for the RI and RD groups, respectively). Significant differences in bacterial community composition based on a 4-way comparison (groups AI, AD, RI, RD) were also observed at the 1 (p=0.035), 2 (p=0.007) and 24 (p=0.025) week collections with trends toward significant differences at enrollment (p=0.142) and the 4 (p=0.133) week collection. Conclusion: Our pilot data indicate that time of ART initiation after HIV acquisition is associated with significant differences in gut microbiota composition of HIV-infected patients. Microbiome analysis of samples from HIV uninfected and chronically infected controls, as well as analysis of the microbiome, latent HIV reservoir, and immunologic function in this cohort during long-term follow-up (up to 4.5 years after diagnosis) is ongoing in the MERLIN study.

individuals revealed several taxa associated with decreased immune activation as well as increased viral load. Conclusion: This study provides an in-depth characterization of microbiome differences that occur in a US population infected with HIV and the degree to which these differences may be driven by lifestyle factors, ART, and HIV infection itself. This understanding will help to guide efforts to investigate the functional implications of these differences to ultimately target the microbiome to improve the health of this population. 264 ELEVATED FECAL INFLAMMATORY BIOMARKERS IN HIV-/+ MSM ASSOCIATE TO GUT MICROBIOTA Jennifer M. Schneider , Sam Li, Charles P. Neff, Nichole Nusbacher, Nancy Moreno-Huizar, Catherine Lozupone, Brent E. Palmer University of Colorado Anschutz Medical Campus, Aurora, CO, USA Background: HIV replication and bacterial translocation associate with inflammatory biomarkers in the blood, however less is known about the gut. To more directly assess the effect of HIV and gut microbiota on GI inflammation and barrier integrity we measured inflammatory biomarkers in feces. Recent studies have shown pronounced differences in gut microbiome composition between HIV- men who have sex with women (MSW) and HIV- men who have sex with men (MSM), but the effects of this altered gut microbiome in MSM on gut inflammation are not understood. Using MSM as a control allows for investigation of contributions of HIV and/or the HIV-associated gut microbiome to gut inflammation by eliminating differences driven by sexual behavior. Methods: Fecal samples were collected from 73 subjects from: HIV- low risk (HIV-LR), high risk (HR) MSM, HIV+ ART treated (HIV+ART+) and HIV+ ART naïve (HIV+ART-) subjects. 30 biomarkers of inflammation, innate cell activation and intestinal barrier integrity were measured by ELISA either from the feces itself or water extracted from 2 grams of stool. Results: There were no significant differences between any of the biomarkers measured in HR-MSM and HIV+ subjects. However, 12 biomarkers, primarily inflammatory cytokines (e.g. IL-1b (p=0006), IL-12/p23p40 (p<0.0001)) and calprotectin (p=0.009), were elevated in HIV+ART- compared to HIV-LR subjects. Except for ICAM-1 (p=0.03), there were no significant differences between HIV+ subjects on or off ART. Seven biomarkers were elevated in HR-MSM such as IL-12/23p40 (p=0.001), ICAM-1 (p=0.0003) and sCD14 (p=0.008) compared to HIV-LR subjects. Fecal IL-12/23p40 (p=0.001) and ICAM-1 (p=0.0005) were elevated in HR-MSM and further increased in HIV+ART- subjects (p<0.0001, p<0.0001) which correlated to viral load (IL- 12/23p40, r=0.42, p=0.015) and CD8+/HLA-DR+/CD38+ T-cells (ICAM, r=0.48, p=0.003) in peripheral blood. We found fecal IL-12/23p40 in HIV- subjects correlated with Peptococcus, while in HIV+ subjects associated with Prevotella from the Paraprevotellacaea family. Conclusion: These data show that gut inflammation is elevated in MSM, and by some measurements exacerbated with HIV infection. Similar to gut microbiome phenotypes, these inflammatory phenotypes are primarily associated with HR-MSM, suggesting that gut inflammation is more impacted by sexual behavior and associated gut microbiome differences than by HIV infection itself. These data highlight the importance of including HIV- MSM controls in GI inflammation studies. 265 EFFECTS OF SUBSTANCE USE AND SEXUAL BEHAVIOR ON THE INTESTINAL MICROBIOME IN HIV Jennifer A. Fulcher 1 , Ryan Cook 1 , Fan Li 1 , Shehnaz K. Hussain 2 , Nicole Tobin 1 , Amy Ragsdale 1 , Steven Shoptaw 1 , Pamina Gorbach 1 , Grace M. Aldrovandi 1 1 University of California Los Angeles, Los Angeles, CA, USA, 2 Cedars–Sinai Medical Center, Los Angeles, CA, USA Background: HIV-1 infection alters the human intestinal microbiome; however, the factors driving these changes remain poorly defined. In this study, we examine the effects of substance use and sexual behavior on the intestinal microbiome during chronic HIV-1 infection in men who have sex with men (MSM). Methods: Samples were obtained from an ongoing cohort (The mSTUDY) examining the effects of substance use on HIV-1 transmission and pathogenesis in young MSM. Rectal swabs, urine drug testing, and substance use and sexual behavior questionnaires were obtained from HIV-positive participants at baseline and 6-month follow-up visits (n=37). Microbiome profiling was performed using 16S rRNA gene sequencing and data processed using QIIME v1.9.1. Associations between substance use and sexual behavior variables and

Poster Abstracts

263 COMPLEXITIES OF GUT MICROBIOME DYSBIOSIS IN HIV INFECTED AND HIGH RISK POPULATIONS Abigail Armstrong , Michael Shaffer, Nichole Nusbacher, Thomas Campbell, Brent E. Palmer, Catherine Lozupone University of Colorado Anschutz Medical Campus, Aurora, CO, USA Background: Gut microbiome composition in HIV-infected populations has been shown by our lab and others to be significantly different from that of HIV negative individuals, even with effective Antiretrovoral Therapy (ART). However, understanding compositional changes associated specifically with HIV infection and immune dysfunction is hindered by several confounding factors including factors unrelated to HIV disease itself such as gender, geography, diet, and sexual behavior. These confounding factors in addition to the complexity of HIV disease itself such as degree of immune suppression and ART usage highlight the need for large cohorts in order to performwell controlled analysis. Methods: In this study, 16S rRNA targeted sequencing was performed to characterize the fecal microbiome of the largest concurrently analyzed cohort to date for understanding compositional changes that occur in HIV-infected populations, including samples from 217 individuals from Colorado, USA. The analyses controlled for sexual behavior and diet to further characterize gut microbiome attributes that are associated with HIV infection and ART, and show unique HIV-associated changes in men versus women. Results: We confirmed previous reports that Prevotella-rich microbiomes with increased alpha diversity characterize men who have sex with men (MSM) regardless of their HIV infection status. However, stratified analysis in women and in MSM show significant alterations in microbiome taxa in treated and untreated HIV infection. Furthermore, several taxa changes may be associated specifically with ART usage in both our cross-sectional and longitudinal samples. Lastly, analyses of immune activation in ART-naïve HIV-infected

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CROI 2018