CROI 2019 Abstract eBook

Abstract eBook

Poster Abstracts

228 MODULATION OF GUT MICROBIOTA IMPROVES MUCOSAL PERMEABILITY IN HIV+ PATIENTS Claudia Pinacchio 1 , Luca Laghi 2 , Giacomo Rossi 3 , Eugenio Nelson Cavallari 1 , Letizia Santinelli 1 , Giuseppe P. Innocenti 1 , Paolo Vassalini 1 , Giancarlo Ceccarelli 1 , Carolina Scagnolari 1 , Gabriella d’Ettorre 1 , Vincenzo Vullo 1 1 Sapienza University of Rome, Rome, Italy, 2 University of Bologna, Bologna, Italy, 3 University of Camerino, Camerino, Italy Background: Intestinal dysbiosis and the disruption of enterocytes tight junctions play a major role in the pathogenesis of HIV infection. Recent findings support the role of probiotics in restoring intestinal microbiota in HIV+ patients. Methods: 15 Caucasian HIV-1 positive patients on long-term suppressive combined antiretroviral therapy (cART) and 30 healthy control individuals matched by age and gender were recruited at the Department of Public Health and Infectious Diseases, “Sapienza” University of Rome (Italy). HIV+ participants received two sachets of Vivomixx®, containing 450 × 109 billion bacteria each, twice a day for a period of six month. All patients underwent pancolonoscopy and fecal sample collection before (T0) and after 6 months of probiotic supplementation (T6). Mucosal biopsies taken from distal ileum and different colonic tracts of intestine were evaluated before and after the probiotics treatment. Occludin, Zonulin, E-cadherin and Claudin-2 expression was detected in biopsies at T0 and T6. Metabolomics investigation were performed by 1H-NMR (X). Results: Occludin and Zonulin were significantly lower in the T0 samples compared to the T6 biopses (T0 vs T6 p<0.0001). No significant differences were observed for E-cadherin and Claudin-2 expression before and after the treatment, while, in the large intestine, Claudin-2 was significantly higher amongst the pre-treated HIV infected patients compared to the same patients after probiotic therapy (T0 vs T6 P<0.0001).Ultrastructural examination of biopsies revealed the morphological conformation of the tight junctions: open, for the structures near the basolateral pole of enterocytes, or for those detected at the intercellular contact sites, near the apical surface of the colonic cells, before the treatment (T0). By contrast, the junctional complex exhibited a closed conformation after 6 months of supplementation (T6). Although no difference was observed at baseline in fecal concentration of phenylalanine and tryptophan between HIV+ subjects and controls, metabolomics investigation resulted in lower levels of tyrosine and a higher phe/tyr in HIV+ participants at baseline. At T6, HIV+ individuals showed a significant decrease of fecal tryptophan concentration and a lower phe/tyr. Conclusion: Our data show evidence that supplementation with oral probiotics drives a beneficial functional modulation of intestinal microbiota with the recovery of mucosal integrity. 229 RECTAL MICROBIOME ALTERATIONS ASSOCIATED WITH TDF/FTC FOR PREEXPOSURE PROPHYLAXIS Jennifer A. Fulcher 1 , Fan Li 1 , Ryan Cook 1 , Sarah Zabih 1 , Cora Woodward 1 , Alexander Louie 2 , Hideaki Okochi 2 , Nicole Tobin 1 , Monica Gandhi 2 , Steven Shoptaw 1 , Pamina Gorbach 1 , Grace M. Aldrovandi 1 1 University of California Los Angeles, Los Angeles, CA, USA, 2 University of California San Francisco, San Francisco, CA, USA Background: Oral daily tenofovir (TFV) disoproxil fumarate/emtricitabine (TDF/FTC) for HIV pre-exposure prophylaxis (PrEP) is highly effective at preventing HIV infection, yet long-term adverse effects are not fully understood. We investigated the effects of PrEP on the rectal microbiome in a cohort of men who have sex with men (MSM). Methods: Rectal swabs were obtained from an ongoing cohort (The mSTUDY) examining the effects of substance use on HIV-1 transmission and pathogenesis in young MSM. This cross-sectional analysis included HIV-negative participants currently on PrEP based on clinician review and confirmed by self-report (n=37). HIV-negative control participants not on PrEP (n=37) were selected using 1:1 matching on a propensity score which was calculated using multiple clinical and behavioral confounding factors (including sexual activity). Hair specimens were used to quantify TFV and FTC exposure over the past 6 weeks on a subset of participants. Microbiome composition was analyzed using targeted sequencing of the V4 region of the 16S rRNA gene followed by exact sequence inference using DADA2. Associations between PrEP use and microbiota abundance were examined using zero-inflated negative binomial regression (ZINB) and binomial least absolute shrinkage and selection operator (LASSO) regression analyses. Results: The median duration of oral TDF/FTC use in the PrEP group was 7 months (IQR 2 -13), and self-reported adherence was good to excellent among

86% of participants. Hair analyses on a subset (n=15) of PrEP participants showed median tenofovir concentrations of 0.027 ng/mg hair (IQR 0.022- 0.031); consistent with adherence of 4 or more doses per week. No significant differences in rectal microbiome diversity were seen between PrEP and control participants, but changes in microbiome composition were seen. PrEP use was associated with significant increase in abundance of Streptococcus (adjusted p=0.015) using ZINB models. Similar associations were selected using LASSO regression, confirming the increase in Streptococcus abundance and also showing increased Mitsuokella , Fusobacterium , and decreased Escherichia/ Shigella . Conclusion: Oral TDF/FTC for PrEP use is associated with changes in the rectal microbiome compared to well-matched controls not taking PrEP, specifically increased Streptococcus abundance. This study highlights the need for future investigation of the role of microbiome changes on HIV susceptibility and effectiveness of PrEP. 230 JOINT EFFECTS OF HIV AND OBESITY ON THE MICROBIOME OF YOUNG MEN WHO HAVE SEX WITH MEN Ryan Cook 1 , Jennifer A. Fulcher 1 , Nicole Tobin 1 , Fan Li 1 , David Lee 1 , Marjan Javanbakht 1 , Ron Brookmeyer 1 , Steven Shoptaw 1 , Robert Bolan 2 , Cora Woodward 1 , Sarah Zabih 1 , Grace M. Aldrovandi 1 , Pamina Gorbach 1 1 University of California Los Angeles, Los Angeles, CA, USA, 2 Los Angeles LGBT Center, Los Angeles, CA, USA Background: The prevalence of obesity among people living with HIV continues to rise rapidly. Both obesity and chronic HIV infection are pro- inflammatory conditions which can alter the composition and function of the gastrointestinal microbiome. However, the combined effects of HIV and obesity on the microbiome have not been examined. Methods: Participants (N=381) with archived rectal swabs collected between 2014 and 2017 were selected from an ongoing cohort of diverse young men who have sex with men (The mSTUDY). Both HIV+ (n=182) and HIV- (n=199) participants were included. Obesity was defined as BMI > 30 or waist circumference > 40 inches. Microbiome composition was assessed by targeted sequencing of the V4 region of the 16S rRNA gene followed by exact sequence inference with DADA2. For analysis, specimens were compared between HIV+ and obese (H+O+) participants and HIV+/non-obese, HIV-/obese, and HIV-/non-obese controls. Analyses included permutational multivariate ANOVA (PERMANOVA) with Bray-Curtis distance to test for differences in overall composition and zero-inflated negative binomial (ZINB) models to test for differential abundance of specific genera. All analyses utilized inverse probability of treatment weighting to control for a large set of clinical and behavioral factors including demographics, ART use, sexual behavior, positive rectal STI test by PCR, smoking, and self-reports of methamphetamine, marijuana, and alcohol use. Results: PERMANOVA analyses showed that HIV and obesity combined explained a significant amount of between-subject variation in the microbiome over and above each factor alone (R 2 for the marginal contribution of the H+O+ group = .007, p = .002). H+O+ participants had the highest average ratio of Prevotella to Bacteroides, a pro-inflammatory enterotype that has been described in HIV and obesity separately. Using ZINB models, a number of differences in bacterial genera between H+O+ and other participants were also observed. Namely, the double positive H+O+ participants had higher levels of Bifidobacterium and Collinsella and lower levels of Bacteroides, Brachyspira, and Veillonella than all other groups. Conclusion: Our findings indicate that microbial composition is altered by the combination of HIV and obesity over and above the contributions of each condition alone. Synergistic effects of HIV and obesity on bacterial communities may help explain the increased risk of inflammation-associated comorbidities among those living with HIV and obesity.

Poster Abstracts


CROI 2019

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