CROI 2015 Program and Abstracts

Abstract Listing

Poster Abstracts

(RA) of Bacteroidetes was significantly reduced in individuals receiving EFV- as compared to those receiving PI-based regimen (p=0.0054) and to non-HIV-infected controls (p=0.0175). At the genus level, the RA of Prevotella was significantly reduced (p=0.0415) and the RA of Bacteroides was significantly enriched (p=0.0328) in individuals receiving EFV- compared to PI-based regimen. Conclusions: Individuals on EFV-based regimen showed an alteration along the Prevotella/Bacteroides gradient, compared to those on a PI-based regimen. Further analyses are required to account for confounding factors. Deciphering the effects of different ARV regimens on gut microbiota composition is of great interest to develop therapies aimed at restoring the latter to a healthy state. 266 Targeting Gut Dysbiosis With Prebiotics and Glutamine in HIV-Infected Subjects Sergio Serrano-Villar 1 ; JorgeVázquez-Castellanos 2 ; AlejandroVallejo 1 ; Sara Ferrando-Martínez 4 ;Talía Sainz 3 ; MarVera 5 ; Santiago Moreno 1 ; Andrés Moya 2 ; María José Gosalbes 2 ;Vicente Estrada 6 1 University Hospital Ramón y Cajal, Madrid, Spain; 2 FISABIO-Salud Pública, Valencia, Spain; 3 University Hospital La Paz, Madrid, Spain; 4 University Hospital Virgen del Rocío, Sevilla, Spain; 5 Centro Sandoval, Madrid, Spain; 6 University Hospital Clínico San Carlos, Madrid, Spain Background: Altered interplay between gut mucosa and dysbiotic microbes during treated HIV infection has been linked to chronic immune dysfunction. Studies evaluating the effects of therapies aimed at shaping gut microbiota in HIV-infected subjects are needed. Methods: In this study, 45 subjects including 12 HIV+ viremic untreated (VU), 24 ART-treated virally suppressed (AT) and 9 HIV- controls (HIV - ) were blindly randomized to receive either prebiotics (scGOS/lcFOS) and glutamine or placebo (34/11), during 6 weeks. We performed a comprehensive assessment of changes in fecal microbiota composition using 16S rRNA deep sequencing and measured a number of immunological markers in plasma and PBMC. Results: VU showed significantly higher bacterial richness (Chao1 and ACE estimators). In contrast, AT displayed the highest compositional heterogeneity (Shanon index). Unifrac distances showed that VU was the group with greatest bacterial dysbiosis, while AT represented an intermediate state between VU and HIV - (Adonis; all P<0.05). Using linear discriminant analylis effect size (LefSe) the most enriched bacteria in VU and AT patients was Prevotella , while Bacteroides and butyrate-producers bacteria were depleted. Patients in the active arm experienced a compositional shift that was not appreciated in the placebo arm (Figure 1). Clustering analyses revealed that among VU and, to a lesser extent, among AT, the intervention shaped bacterial communities towards the HIV-uninfected group. LefSe indicated that in VU and AT Prevotella abundance decreased during the intervention. To identify potential microbial targets for interventions, we assessed in the active arm correlations between changes in dysbiotic bacteria and markers of disease progression. After adjusting for multiple comparisons, variations in Butyrivibrio , Desulfovibrio and Blautia strongly correlated with significant improvements of thymic output (sj/ β TREC ratio), while changes in Catenibacterium and Eubacterium strongly correlated with significant declines of activated (%HLA-DR+CD38+) T cells in both VU and AT (all, P<0.05).

Poster Abstracts

Conclusions: A short dietary supplementation with prebiotics and glutamine ameliorated HIV-associated dysbiosis in ART naïve and treated patients, although gut microbiota of treated patients was found more resilient. We identified several bacteria correlated with improvements of markers of immune reconstitution and T cell activation, and hence, potential targets for interventions.

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CROI 2015