CROI 2017 Abstract e-Book

Abstract eBook

Poster and Themed Discussion Abstracts

249 B-CELL RESPONSES POST-ART INTERRUPTION IN PERSONS TREATED IN FIEBIG I Supranee Buranapraditkun 1 , Donn Colby 2 , Suwanna Pattamasavin 2 , Suteeraporn Pinyakorn 3 , Rapee Trichaviroj 4 , Nelson L. Michael 5 , Merlin L. Robb 3 , Jintanat Ananworanich 3 , Lydie Trautmann 3 , for the RV411 and RV254/SEARCH010 Study Groups 1 Henry M. Jackson Fndn for the Advancement of Military Med, Bethesda, MD, USA, 2 SEARCH, The Thai Red Cross AIDS Rsr Cntr, Bangkok, Thailand, 3 US Military HIV Rsr Prog, Bethesda, MD, USA, 4 Armed Forces Rsr Inst of Med Sci, Bangkok, Thailand, 5 Walter Reed Army Inst of Rsr, Silver Spring, MD, USA Background: Humoral immunity may be important for the control of HIV replication after antiretroviral therapy (ART) interruption but B cell responses are impaired in HIV infection. We previously showed that cTfh function and the B cell compartment were preserved in Fiebig I/II very early acute HIV infection (AHI). Whether this preserved B cell compartment plays a role in controlling viral rebound following treatment interruption (TI) is unknown. We investigated the B cell response after TI in participants who initiated ART during Fiebig I AHI. Methods: Eight HIV infected Thais who initiated ART during AHI Fiebig I (VL+, p24-, IgM-) were studied longitudinally from AHI to TI. At the time of TI, all were on ART ≥ 2 years, CD4 T cells ≥ 400 cells/mm3 and HIV-1 RNA < 50 copies/ml, all rebounded after ART cessation. B cells were characterized by flow cytometry at six time points: AHI pre-ART, 10 days after ART initiation, baseline TI, 2 weeks after TI, at viral rebound and 10 days after restart of ART. Results: The frequencies of resting memory (RM) B cells (CD21+CD27+IgG+CD20+) were decreased during AHI but restored on ART. During TI, the frequencies of RM B cells decreased at VL rebound (p=0.01) compared to baseline but were significantly higher than in AHI, suggesting the preservation of the memory B cell compartment during TI. Frequencies of plasmablasts (IgD-CD38hiCD20+) at the viremic time points in AHI and TI were significantly higher compared to the other time points (Fig.1a), suggesting that expansion of plasmablasts was triggered by exposure to HIV Ag. In pre-ART AHI, all were IgM- by 4thGEN immunoassay and showed increased frequencies of IgM+ B cells only 10 days after ART initiation (p= 0.01) (Fig.1b). Importantly, we observed an increase of IgM+ B cells during TI between baseline and 2 weeks after TI prior to detectable viremia (p=0.06) and 4 out of 6 donors seroconverted at viral rebound suggesting that B cell responses arise earlier after TI than in AHI. Conclusion: Treatment interruption in people treated in Fiebig I did not induce phenotypic perturbations in the mature B cell compartment observed in AHI but induced increased frequencies of plasmablasts associated with viremia. Increased frequencies of IgM+ B cells detected prior to viral rebound during TI and seropositivity at viral rebound suggest that B cell responses arise faster in TI than in AHI even though they are not sufficient to contain viral rebound.

Poster and Themed Discussion Abstracts

250 DC FUNCTIONALITY DISTINGUISHES HIV-1 CONTROLLERS WITH NEUTRALIZING ANTIBODY BREADTH Enrique Martin-Gayo 1 , Zhengyu Ouyang 1 , Dhohyung Kim 1 , Kellie E. Kolb 2 , Bruce D. Walker 1 , Alex K Shalek 2 , Xu G. Yu 1 1 Ragon Inst of MGH, MIT and Harvard, Cambridge, MA, USA, 2 MIT Inst for Med Engineering & Sci (IMES), Cambridge, MA, USA

Background: Understanding immune mechanisms driving the evolution of HIV-1 specific broadly neutralizing antibodies (bNAbs) is critical for the development of an effective vaccine against HIV-1. Typically, bNAbs develop in individuals with high-level viremia and increased immune activation, however, antibodies with high neutralizing breadth have also been detected in rare subgroups of HIV-1 controllers with low or undetectable viral loads in the absence of antiretroviral treatment. Recent data suggest that dendritic cells play an important role in development of T follicular helper cells (Tfh) and the evolution of bNAbs. Here, we studied transcriptional and functional features of primary conventional dendritic cells (cDCs) from the blood of HIV-1 controllers that develop neutralizing Ab breadth against HIV-1. Methods: Whole genome RNAseq transcriptional data were generated from sorted circulating cDC from HIV controllers with (n=44) or without (n=9) neutralizing antibody responses. In addition, functional in vitro experiments were performed to analyze the ability of primary cDCs from the different study groups to prime allogeneic naïve CD4 T cells into CXCR5+ PD-1+ Tfh in the presence of autologous B cells after 6 days of culture. Results: Transcriptional profiling analysis identified two different gene expression signatures in cDCs from HIV controller neutralizers, which we designate Nt1 and Nt2. While cDC signatures in Nt1 were non-distinguishable from a background cohort of non-neutralizer controllers (NC), Nt2 were defined by a distinct transcriptional cDC program characterized by a robust up-regulation of genes involved in inflammatory cytokine responses, activation of antigen presenting properties, and pathways involved in Tfh polarization. This specific gene expression profile corresponded to a higher functional ability of cDCs from Nt2 patients to prime Th1-biased PD-1+ Tfh-like cells in vitro, compared to cDCs from Nt1 (p=0.04) and NC (p=001). Moreover, Nt2 neutralizer controllers were characterized by higher residual viral loads (p=0.006) and lower frequency of protective HLA-B alleles than Nt1 (p=0.036) and NC patients (p=0.02). Conclusion: This study suggests that at least in a subgroup of HIV-1 controller neutralizers, cDC may provide a critical role in priming and maintaining Tfh-like cells and generating HIV-1-specific antibodies with increased levels of neutralizing breadth. 251 TELMISARTAN DOES NOT IMPROVE LYMPH NODE OR FAT FIBROSIS IN TREATED HIV INFECTION Netanya S. Utay 1 , Douglas Kitch 2 , Carl Fichtenbaum 3 , Michael M. Lederman 4 , Jacob D. Estes 5 , Clara Magyar 6 , Karin Klingman 7 , Judith S. Currier 6 , Jordan E. Lake 1 , for the A5317Team 1 Univ of Texas, Galveston, TX, USA, 2 Harvard Univ, Boston, MA, USA, 3 Univ of Cincinnati, Cincinnati, OH, USA, 4 Case Western Reserve Univ, Cleveland, OH, USA, 5 Frederick Natl Lab for Cancer Rsr, Frederick, MD, USA, 6 Univ of California Los Angeles, Los Angeles, CA, USA, 7 DAIDS, NIAID, Bethesda, MD, USA Background: Chronic HIV infection is characterized by persistent inflammation and immune activation that can lead to tissue injury and fibrosis. Lymph node (LN) fibrosis may limit CD4+ T-cell recovery; LN and adipose tissue (AT) fibrosis may contribute to systemic inflammation and comorbidities. Telmisartan is an angiotensin receptor blocker and

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