CROI 2018 Abstract eBook

Abstract eBook

Poster Abstracts

taxa including Alphaproteobacteria (Proteobacteria), Paraprevotellaceae (Bacteroidetes) and several species of Firmicutes. Conclusion: The degree of glycosylation in the gut directly impacts the ability to maintain a functional mucus layer and healthy intestines. Our analyses identified a gut glycomic signature associated with lefitolimod treatment that may influence intestinal homeostasis by modulating alpha diversity of the gut microbiome. Our data highlight that host glycomics is an important tool for evaluating impact of novel HIV interventions, particularly within the context of HIV eradication. Muntsa Rocafort 1 , Marc Noguera-Julian 1 , Javier Rivera 1 , Lucia Pastor Palomo 2 , Yolanda Guillén 1 , Jost Langhorst 3 , Mariona Parera 1 , Inacio Mandomando 2 , Jorge Carrillo 1 , Bonaventura Clotet 1 , Julià Blanco 1 , Denise Naniche 2 , Roger Paredes 1 1 IrsiCaixa Institute for AIDS Research, Badalona, Spain, 2 Universitat de Barcelona, Barcelona, Spain, 3 University of Duisburg-Essen, Essen, Germany Background: The early events following acute HIV-1 infection might be critical to shape the long-term interaction between the human gut microbiome and the host. In previous studies in non-human primates, SIV infection was followed by expansion of the enteric virome but had a limited impact on the gut bacteriome. Human data are scarce. Methods: We prospectively evaluated 103 subjects who attended the outpatient clinic of the Manhiça District Hospital in Mozambique with fever, and were either diagnosed with primary HIV-1 infection (PHI, n=49) or were HIV- 1-negative (n=54) (baseline). Longitudinal fecal samples were collected over the first year starting at month 1, and were compared with single fecal samples from 98 chronically HIV-1-infected (CHI) subjects, 27 on ART and 71 ART-naïve. The fecal bacteriome was characterized with MiSeqTM 16S rDNA sequencing. Metagenomic Shotgun sequencing (MGS) was also performed in month 1, 4 and 9 samples in 13 subjects with PHI and 8 HIV-negative individuals. Presence of fecal Adenovirus (ADV), Cytomegalovirus (CMV), Enterovirus (ETV), and Human Herpes Viruses (HHV) 6A, 6B and 8 was evaluated by commercial real time PCR. Linear mixed models were used to assess longitudinal changes bacterial abundance and microbial richness. Results: At baseline, 49%, 14%, 14% and 23% PHI subjects were at Fiebig 3, 4, 5, and 6 stages, respectively. HIV-1 infection was associated with virus expansion: ADV were detected in >50% of PHI subjects, as well as in CHI individuals; CMV and ETV were mostly found in ART-naïve CHI subjects (Table). No HHVs were detected at all. Both PHI and HIV-neg groups showed reduced taxonomic (16S) and genetic (MGS) richness at month 1. Whereas both parameters recovered in HIV-neg, genetic richness remained low in PHI. Recovery in taxonomic richness in PHI was concomitant to increases in anti-inflammatory bacteria (Odoribacter, Rikenellaceae and Barnesiellaceae) alongside decreases in Proteobacteria. Conclusion: Primary HIV-1 infection is associated with virome expansion, transient loss of bacterial taxonomic richness and long-term reductions in microbial gene richness, all of which occur during hyperacute phases of HIV-1 infection.

that maintain low viral loads without ART. Fecal microbial composition was determined by 16S amplicon sequencing. Serum inflammatory markers were measured by immunological assay. These data were analyzed with cohort metadata and clinical data, including dietary micronutrients and macronutrients. Candidate bacteria of significance were selected for an in vitro transepithelial resistance (TER) co-culture assay with Caco-2 cells to determine the epithelial cell response to potential commensals and pathogens associated with HIV infection. Results: HIV infection was the predominant correlative factor, with significant differences between the bacterial communities of uninfected and HIV-infected individuals regardless of ART or immunologic control. HIV infection was associated with loss of alpha diversity, relative decrease in the phyla Firmicutes and families Bifidobacteriaceae and Bacteroidaceae, and expansion of the family Prevotellaceae. This shift correlated with serum levels of sCD163, an inflammatory marker, in HIV-infected patients. However, controllers uniquely had serum levels of sCD14, a bacterially mediated inflammatory marker, similar to healthy controls despite elevations in other HIV-infected subgroups. Diet, micronutrient, and clinical cohort data were not significant correlative factors. Initial Caco-2 TER assay demonstrated that bacteria significantly enriched by HIV infection have a mixed effect on epithelial integrity. Conclusion: Our findings demonstrate a complex model for how HIV may alter the gut microbiome and human host health. Our data suggests that bacterial communities, irrespective of means of HIV control, and inflammatory responses, with nuances, could be driven by HIV infection and baseline microbial community structure. However, this alone does not prove that the bacteria enriched in HIV infection elicit a pathogenic effect on the host and colonic epithelium as was previously presumed.

260 EVOLUTION OF THE GUT MICROBIOME FOLLOWING ACUTE HIV-1 INFECTION

Poster Abstracts

262 TIME BETWEEN HIV ACQUISITION AND ART INITIATION IMPACTS GI MICROBIOME Douglas Fadrosh 1 , Susan V. Lynch 1 , Javier R. Lama 2 , Ricardo Alfaro 3 , Delia Pinto-Santini 4 , Rachel A. Bender Ignacio 4 , Peter W. Hunt 1 , Jessica Rios 3 , Ann Duerr 4 1 University of California San Francisco, San Francisco, CA, USA, 2 University of Washington, Seattle, WA, USA, 3 Asociacion Civil Impacta Salud y Educacion, Lima, Peru, 4 Fred Hutchinson Cancer Research Center, Seattle, WA, USA Background: Recent data suggests that initiation of ART early in infection confers several benefits on HIV-related morbidity and clinical outcomes. Because initiation of ART during acute infection is not currently a viable public health strategy, it is important to investigate the relative long-term benefits of starting ART at different times during early infection. We evaluated how timing of ART initiation impacts the gastrointestinal microbiome during early infection in a subset of the Sabes study, a randomized clinical trial in Peru. Methods: HIV-infected MSM and transgender women who were diagnosed while sero-negative (acute HIV, A), or were sero-positive and 90 days or less from last negative RNA test (recent HIV, R) were randomized within strata to receive standard-of care ART immediately (I) or after 24 weeks deferral (D). Cryopreserved stool samples collected from enrollment to 24 wks, including 1, 2, 4,8 and 16 wks, were analyzed in 29 participants who started ART in acute infection (AI, N=8), recent infection (RI, N=12), or after 24 weeks deferral (AD, N=4; RD, N=5). The V4 hypervariable region of the 16S rRNA gene was

261 HIV-ASSOCIATED CHANGES OF THE GUT MICROBIOME IN ARV-TREATED, UNTREATED, & CONTROLLERS Jesus M. Luevano , David B. Gootenberg, Zoe Rogers, Jeff Paer, Douglas Kwon Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA Background: HIV infection is associated with gut microbiome alterations, enteropathy, and intestinal translocation of microbial products. It is unclear what HIV associated changes in the gut microbiome occur in HIV-infected individuals who control the disease immunologically without treatment, but they provide a unique model to investigate the effects of HIV infection. Methods: Our Boston cohort (n=183), the largest of its kind, includes HIV- uninfected controls and three HIV-infected sub-groups: anti-retroviral treated (ART), chronic untreated with high viral loads, and immunologic controllers

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CROI 2018