CROI 2018 Abstract eBook

Abstract eBook

Poster Abstracts

275 THE IMPACT OF SYNBIOTICS IN ADVANCED HIV DISEASE: A RANDOMIZED CLINICAL TRIAL Sergio Serrano-Villar 1 , Maria Lagarde 2 , Nadia Madrid 1 , Jose I. Bernardino 3 , Alejandro Vallejo 1 , Carolina Gutiérrez 1 , Alfonso Cabello 4 , Mariano Matarranz 2 , Judit Villar 5 , Alberto Díaz de Santiago 6 , Jose-Ramón Blanco 7 , Talía Sainz 3 , Federico Pulido 2 , Santiago Moreno 1 , Vicente Estrada 8 1 Hospital Ramón y Cajal, Madrid, Spain, 2 Hospital Universitario 12 de Octubre, Madrid, Spain, 3 Hospital La Paz Institute for Health Research, Madrid, Spain, 4 Fundacion Jimenez Diaz, Madrid, Spain, 5 Hospital del Mar, Barcelona, Spain, 6 Hospital Puerta de Hierro, Madrid, Spain, 7 Hospital San Pedro, La Rioja, Spain, 8 Hospital Universitario Clínico San Carlos, Madrid, Spain Background: Late diagnosis of HIV infection is associated with impaired immunological restoration during ART and poor prognosis. While nutritional interventions with prebiotics and probiotics seem to exert immunological effects, the clinical implications in this key population remain unclear. Methods: Pilot multicenter randomized placebo-controlled, double blind clinical trial in which 73 HIV-infected ART-naive subjects with <350 CD4 T cells/ mm3 or AIDS were randomized (1:1) to either daily nutritional supplementation with the synbiotic mixture PMT25341 or placebo for 48 weeks, each in combination with first-line ART. We performed an intention to treat analysis. Primary endpoints were change in CD4 T-cells and CD4/CD8 ratio levels from baseline to week 48 and safety. Secondary endpoints were changes in markers of inflammation, bacterial translocation and T cell activation and senescence (Clinicaltrials.gov: NCT00870363). Results: Fifty-nine patients completed the follow-up, mean (SD) age 37 (11 years), 92%men, 83%MSM, CD4 T cells 221 (108)/ul, CD4/CD8 ratio 0.27 (0.19), 10% diagnosed with an AIDS-defining condition. All patients initiated triple ART (61%with integrase inhibitors) and 94% had undetectable plasma HIV RNA at week 48. Baseline characteristics were balanced between arms. PMT25341 was well tolerated, and no grade 3-4 adverse effects attributable to the intervention were identified. Compared to placebo-treated subjects, PMT25341-treated subjects did not experience any significant change in the median change of CD4+ T cells (196 cells/ul vs. 206, P=0.974), CD8+ T cells (-28 cells/ul vs. 120, P=0.418), CD4/CD8 ratio (0.31 vs. 0.24, P =0.393), %HLADR+CD38+ CD4+ T cells (-5.5 vs. -5.4, P=0.356), %HLADR+CD38+ CD8+ T cells (-9.6 vs -7.3, P=0.522) or %CD28- CD8+ T cells (-6 vs. -8.3, P=0.299). Similarly, we did not detect differences between treatment arms in the median fold change of sCD14 (0.85 vs. 0.86, P=0.910), sCD163 (0.58 vs. 0.59, P=0.757), CRP (0.75 vs. 0.71, P=0.843) or LTA (0.51 vs. 0.52, P=0.847) plasma levels. Conclusion: After 48 weeks of dietary supplementation with a synbiotic mixture aimed at ameliorating the gut microbiota and mucosal immunity, we did not detect an impact on CD4 or CD8 T cell counts, inflammation, bacterial translocation or immune activation. Our data suggest that the clinical benefit of nutritional strategies targeting the gut is very limited in HIV-infected patients initiating ART at advanced disease.

decreased frequencies of Bacteroidales and Clostridia. Despite evidence for progressive and high levels of dysbiosis, no significant differences in viremia, immune activation, or systemic microbial translocation were noted between the experimental groups throughout SIV infection. Clinical indices of disease progression including survival curves did not reveal any evidence for enhanced disease progression in the dysbiotic animals. Conclusion: Our results demonstrate that microbial dysbiosis does not significantly influence host or viral dynamics during untreated SIV infection and may suggest that observed dysbioses in untreated HIV infection may be ancillary to disease progression. 274 EFFECTS OF PROBIOTIC VISBIOME ES ON COLONIC MUCOSAL CD4 CELLS: RESULTS FROM A5352S Rachel Presti 1 , Douglas W. Kitch 2 , Adriana Andrade 3 , Alan Landay 4 , Jeffrey Jacobson 5 , Cara Wilson 6 , Eunice Yeh 2 , Jacob D. Estes 7 , Claire Deleage 7 , Karin L. Klingman 8 , Netanya S. Utay 9 , Edgar T. Overton 10 , Jason Brenchley 8 , Brett Williams 4 1 Washington University St Louis, St Louis, MO, USA, 2 Harvard University, Cambridge, MA, USA, 3 Johns Hopkins University, Baltimore, MD, USA, 4 Rush University Medical Center, Chicago, IL, USA, 5 Drexel College of Medicine, Philadelphia, PA, USA, 6 University of Cologne, Cologne, Germany, 7 National Cancer Institute, Frederick, MD, USA, 8 NIAID, Bethesda, MD, USA, 9 University of Texas at Galveston, Galveston, TX, USA, 10 University of Alabama at Birmingham, Birmingham, AL, USA Background: HIV infection in the GI tract results in CD4 cell depletion, especially Th17 cells, and neutrophil (PMN) infiltration, characterized by myeloperoxidase (MPO) activity. This results in impaired mucosal barrier function and systemic inflammation. ART fails to fully restore GI mucosal CD4 cells. In non-human primate models, probiotics improve GI CD4 T cell recovery during ART. In A5352s, ART-suppressed HIV-infected individuals were randomized to probiotic Visbiome ES or placebo to determine whether probiotic administration reconstitutes mucosal CD4 cells & Th17 cells and decrease PMN activity. Here, we present results from immunohistochemistry (IHC) on colonic biopsies. Methods: At entry and after 24 weeks of intervention, participants underwent flexible sigmoidoscopy with 10 punch biopsies. Immunohistochemistry (IHC) staining was performed using antibodies to CD4, IL-17, and MPO. Stained slides were scanned using the ScanScope CS System (Aperio Technologies, Inc.); quantitative image analysis was performed to measure area of lamina propria occupied by CD4 cells, IL-17+ cells, or MPO. Changes from baseline to week 24 were calculated and arms were compared by exact Wilcoxon test. Results: Of 42 participants enrolled, 30 had paired biopsy specimens for analysis (15 in each arm). Mean age was 48 yrs (range 25,64); 27 males; median CD4 count 718 c/mm 3 (range 263,1839). At baseline, the median % positive staining for CD4 in the placebo armwas 2.1 and 2.0 in the Visbiome ES arm. Median % CD4 decreased to 1.65 in the placebo arm, but only to 1.74 in the Visbiome ES arm, with a median change of -0.21 for placebo, and change of -0.03 in Visbiome (p=0.089). IL-17 staining was highly variable, but demonstrated no median change over 24 weeks (p=0.65). MPO minimally decreased in placebo from 0.18 to 0.11, with a median change of -0.04, while it increased in Visbiome from 0.14 to 0.18 for a median change of 0.05 0.18 over 24 weeks(p=0.081). Conclusion: Although CD4 cells staining appeared to be more stable in the Visbiome armwhen compared to placebo, similar to non-human primate studies, we failed to detect significant differences in CD4, IL-17 or MPO alterations between arms. This may be due to no effect of Visbiome, small study size, diverse nature of HIV and ART history, or short course of probiotic administration. Future analyses will assess measures of systemic inflammation and GI permeability.

Poster Abstracts

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CROI 2018