CROI 2016 Abstract eBook

Abstract Listing

Poster Abstracts

265 Effects of HAART Treatment on the Microbiome of HIV+ Patients Joshua Shorenstein 1 ; Netanya S. Utay 2 ; Basil Siewe 3 ; David Asmuth 4 ; Rob Knight 1 1 Univ of California San Diego, San Diego, CA, USA; 2 Univ of Texas Med Branch at Galveston, Galveston, TX, USA; 3 Rush Univ, Chicago, IL, USA; 4 Univ of California Davis Med Cntr, Sacramento, CA, USA Background: ​HIV depletes the mucosal immune system and leads to an imbalance of gut microbiota. Previous work demonstrates gut microbial dysbiosis in HIV patients.This study explores the effects of HAART treatments on the gut microbiome, and whether this treatment brings the community in line with HIV- individuals. Methods: 33 treatment naïve HIV patients were enrolled and randomly assigned to treatment by maraviroc, efavirenz, or MRV+RAL. Blood draws plus colonic and duodenal biopsies were performed before treatment and at the 9 month time point. CD4 and CD8 T-cell counts were taken from peripheral blood, colonic and duodenal biopsies. Measurements for viral load, zonulin, CD14, and lipoteichoic acid (lta) levels were also performed at both time points. 16S rRNA gene fragments were isolated from participant stool samples collected at both time points, and sequenced using Illumina’s MiSeq. Sequence data was processed using QIIME v1.9 pipeline, including demultiplexing (default parameters) and OTU-picking (SortMeRNA, closed-reference against Greengenes 13_8). Data was rarefied to 85,000 sequences/sample. Comparisons of alpha diversity (AD) use PD Whole Tree. Comparisons of beta diversity (BD) use unweighted UniFrac. Results: 24 patients completed the 9 month follow up and had amplifiable samples. Of these patients, maraviroc (n=9), efavirenz (n=8), and MRV+RAL (n=7). Preliminary analysis showed significant differences in microbial composition (using BD) between entry and 9 month samples (p=0.010), however segmenting by treatment regiment (p=0.14) and responders (defined as a CD4 increase of >100) (p=0.70) did not explain this change. Significant differences in BD were also found between HIV+ patients and HIV- controls (p=0.009), suggesting the recovery was not towards an HIV- state. AD was shown to weakly correlate with peripheral blood CD4% (r 2 =0.068, p=0.045) and lta readings (r 2 =0.086, p=0.037), while changes in alpha diversity over the 9 months were shown to correlate with changes in activated CD8 T-cell counts from peripheral blood (r 2 =0.74, p=0.00072). Conclusions: HAART treatment changes correlate to CD8 T-cell count, suggesting a tie between gut microbial diversity and CD8 T-cell expansion. These changes do not drive the gut towards an HIV- like state, suggesting long-term perturbations from HIV cause a different equilibrium than HIV- individuals. These observations suggest larger studies are warranted to assess what organisms are involved in the CD8 interaction and HIV+ recovery state. 266 Diet Effects on the Gut Microbiome of People LivingWith HIV-1 Javier Rivera Pinto 1 ; Marc Noguera-Julian 1 ; Carla Estany 2 ; Muntsa Rocafort 1 ;Yolanda Guillen 3 ; Mariona Parera 1 ; Pep Coll 1 ; Bonaventura Clotet 2 ; Roger Paredes 1 ; M. Luz Calle 4 1 IrsiCaixa Inst for AIDS Rsr, Badalona, Spain; 2 Lluita Contra la SIDA Fndn, Germans Trias i Pujol Univ Hosp, Barcelona, Spain; 3 IrsiCaixa Inst for AIDS Rsr, Barcelona, Spain; 4 Univ de Vic, Barcelona, Spain

Background: The human gut microbiome might be involved in HIV pathogenesis. In turn, long-term dietary patterns have been linked to human gut enterotypes. It is unknown how diet might affect the microbiome composition of people living with HIV Methods: Diet information was collected from HIV-1-infected and HIV-negative controls with MiSeq 16S rRNA gut microbiome information available in Barcelona, Catalonia, Spain, using two independent dietary questionnaires: (a) a standardized prospective daily registry of food/drink consumption during 3-to-5 day consecutive days including at least one weekend day, which was then converted to amounts of nutrients; and (b) a recall questionnaire on the average number of portions of food/drinks taken per week during the prior year. Nutritional data was standardized by energy intake and was evaluated by HIV-1 infection status, enterotype ( Prevotella vs. Bacteroides ) and sexual practice (MSM/non-MSM). A Dirichlet– Multinomial (DM) regression model was used to detect associations between bacterial genera and diet components from both questionnaires. Wilcoxon Mann-Whitney test plus Benjamin-Hochberg correction was used to evaluate dietary differences between groups. A LASSO logistic regression model was fitted to analyze the global predictive power of dietary data to classify subjects according to enterotype.

Poster Abstracts

Results: 127 (108 HIV-infected / 19 controls) and 116 subjects (99 HIV- infected / 17 controls) completed the prospective nutrient and the 1-year recall questionnaires, respectively. Energy intake was higher in MSM and in subjects in the Prevotella cluster. In the DM regression, the genus Prevotella was associated with decreased consumption of meat and dairy products, as well as decreased intake of saturated fat and digestible sugars and increased consumption of iron and dietary water; the exact opposite associations were found for the genus Bacteroides. Subjects in the Bacteroides cluster ate more meat and dairy products in line with reported associations. However, the Prevotella cluster had higher consumption of total protein which likely derived from the addition of different origins other than meat. However, none of the diet components, neither nutrients nor food portions, was selected by multivariate LASSO regression model as a consistent predictor of enterotype clustering and no associations were detected by HIV status. Conclusions: Diet exerts a moderate influence on enterotype clustering in people living with HIV.

267 Tryptophan Metabolites Are Associated to Gut Microbiota in HIV-1 Infected Patients Babilonia Barqasho 1 ; Ujjwal Neogi 1 ; Lilly Schwieler 1 ; Göran Engberg 1 ; MariusTroseid 2 ; Anders Sönnerborg 1 ; Piotr Nowak 1 1 Karolinska Inst, Stockholm, Sweden; 2 Oslo Univ Hosp, Ullevål Hosp, Oslo, Norway

Background: The catabolism of tryptophan (TRP) into kynurenine (kyn) by indoleamine 2,3-dioxygenase-1 (IDO-1) contributs to the immune dysfunction during chronic HIV infection. An increased IDO-1 activity has been associated with microbial translocation (MT), gut microbiota dysbiosis and HIV progression. We aimed to investigate the association between TRP catabolites and gut microbiota during chronic HIV-1 infection. Additionally we studied the effect of antiretroviral therapy (ART).

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