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8Th IAS Conference on HIV Pathogenesis, Treatment & ONLINE ONLINE OPEN PEER-REVIEWD PEER-REVIEWD ONLINE A PEER-REVIEWD OPEN ACCESS OPEN HIV/AIDS JOURNAL HIV/AIDS JOURNAL CCESS ONLINEONLINE CCESS A OPEN OPEN PEER-REVIEWD ONLINE HIV/AIDS JOURNAL HIV/AIDS HIV/AIDS JOURNAL PEER-REVIEWD PEER-REVIEWD OPEN ACCESSONLINEPEER-REVIEWD A ONLINEPEER-REVIEWD CCESS HIV/AIDS JOURNALPEER-REVIEWD OPEN ACCESS CCESS A OPEN ONLINE ONLINE HIV/AIDS JOURNAL ONLINE PEER-REVIEWDHIV/AIDS JOURNALONLINEONLINE PEER-REVIEWDOPEN ACCESS PEER-REVIEWD ONLINE ONLINE OPEN ACCESSONLINE OPEN HIV/AIDS JOURNAL CCESS OPEN ACCESS HIV/AIDS JOURNAL PEER-REVIEWD PEER-REVIEWD PEER-REVIEWD HIV/AIDS JOURNAL PEER-REVIEWD A HIV/AIDS JOURNAL OPEN ACCESS PEER-REVIEWD PEER-REVIEWD PEER-REVIEWDONLINE HIV/AIDS JOURNAL HIV/AIDS JOURNAL OPEN ACCESS ONLINE ONLINEONLINE HIV/AIDS JOURNAL HIV/AIDS PEER-REVIEWD A PEER-REVIEWD ONLINE ONLINE HIV/AIDS JOURNAL CCESS HIV/AIDS JOURNALOPEN ONLINE PEER-REVIEWDONLINE PEER-REVIEWD HIV/AIDS JOURNAL OPEN PEER-REVIEWDJOURNAL HIV/AIDS HIV/AIDS JOURNAL HIV/AIDS JOURNAL CCESS ONLINE A A ONLINE OPEN ACCESS HIV/AIDS JOURNAL ONLINE HIV/AIDS JOURNAL CCESS PEER-REVIEWD OPEN ACCESS HIV/AIDS JOURNAL OPEN ACCESS ONLINE HIV/AIDS JOURNAL HIV/AIDS ONLINE OPEN OPEN ACCESS HIV/AIDS JOURNAL PEER-REVIEWD OPEN HIV/AIDS JOURNALPEER-REVIEWD PEER-REVIEWD OPEN ACCESS PEER-REVIEWD CCESS A OPEN PEER-REVIEWDONLINE PEER-REVIEWD PEER-REVIEWD HIV/AIDS JOURNALAbstractHIV/AIDS JOURNAL SupplementHIV/AIDS JOURNAL PEER-REVIEWD OPEN ACCESS CCESS PEER-REVIEWD A PEER-REVIEWD A 8th IAS Conference on HIV Pathogenesis, Treatment & Prevention CCESS OPEN ACCESS 19–22 July 2015, Vancouver, Canada OPEN HIV/AIDS JOURNAL Volume 18, Supplement 4 Scan this QR code with your mobile device to view July 2015 the special issue online 8th IAS Conference on HIV Pathogenesis, Treatment and Prevention (IAS 2015) Journal of the International AIDS Society 2015, 18 (Suppl 4) http://www.jiasociety.org/index.php/jias/article/view/20479 ORAL ABSTRACTS Cg-PrkdcscidIl2rgtm1Wjl/SzJ (NSG) mice resulted in viral amplification MO Á MONDAY in the mouse. Successful xenograft of mice was confirmed by flow cytometry. Human CD8 T cells were depleted in humanized mice with depleting antibody, and CD4 T cells were activated in a subset MOAA0101 of mice with activating anti-CD3. Plasma viral loads in xenografted A murine viral outgrowth assay to detect HIV in patients mice were quantified using qRT-PCR, and compared to plasma viral with undetectable viral loads load and QVOA results from the human or macaque donor. Kelly Metcalf Pate1; Chris Pohlmeyer2; Victoria Walker-Sperling2; Results: With this murine viral outgrowth assay (MVOA), we amplified Jeremy Foote1; Kevin Najarro1; Catherine Cryer1,3; Maria Salgado2,4; HIV-1 from all 10 HIV subjects with undetectable plasma viral load, Lucio Gama1; Elizabeth Engle1; Erin Shirk1; Suzanne Queen1; including an ES from whom we were unable to recover virus by QVOA. Stanley Chioma2; Meghan Vermillion1; Brandon Bullock1; Ming Li1; We detected HIV in mice an average of 20 days after xenograft with Claire Lyons1,5; Robert Adams1; Chris Zink1; Janice Clements1; PBMCs from patients on suppressive ART, and an average of 28 days Joseph Mankowski1 and Joel Blankson2 after xenograft with PBMCs or resting CD4 T cells from ES. For two 1Department of Molecular and Comparative Pathobiology, Johns of the mice xenografted with CD4 T cells from ES, we detected HIV Hopkins University School of Medicine, Baltimore, United States. only after activation with anti-CD3. We similarly detected SIV in 2Department of Medicine, Johns Hopkins University School of macaquized mice by seven days post-xenograft. Medicine, Baltimore, United States. 3School of Veterinary Medicine, Conclusions: The MVOA has the potential to serve as a powerful tool University of Pennsylvania, Philadelphia, United States. 4Institue to identify residual HIV-1 in patients with undetectable viral loads, IrsiCaixa, Universitat Auto`noma de Barcelona, Badalona, Spain. such as those who have undergone promising cure therapies. 5 Cummings School of Veterinary Medicine, Tufts University, http://dx.doi.org/10.7448/IAS.18.5.20320 North Grafton, United States. Presenting author email: [email protected] MOAA0102 Introduction: Sensitive assays are needed for detection of residual Virologic and immunologic correlates of viral control post- HIV in patients with undetectable plasma viral loads to determine if ART interruption in SIV-infected rhesus macaques eradication strategies are effective. The gold standard quantitative Luca Micci1; Emily Ryan1;Re´mi Fromentin2; Clarisse Benne3; viral outgrowth assay (QVOA) underestimates the magnitude of the Nicolas Chomont2; Jeffrey Lifson4 and Mirko Paiardini1 viral reservoir, while sensitive PCR-based assays lack the ability to 1YNPRC, Emory University, Atlanta, United States. 2De´partement de distinguish replication competent from defective virus. We sought microbiologie, infectiologie et immunologie, Universite´ de Montre´al, to determine whether xenograft of leukocytes from HIV-1 infected Montreal, Canada. 3Case Western Reserve University, Cleveland, patients with undetectable plasma viral loads into severely immuno- United States. 4NCI/NIH, Frederick, United States. compromised mice would result in viral amplification and measurable Presenting author email: [email protected] viral loads within the aberrant murine host. Methods: We evaluated whether xenograft of 1) peripheral blood Introduction: Antiretroviral therapy (ART) does not eradicate HIV mononuclear cells (PBMCs) from five HIV-1 patients on suppressive and the virus rebounds upon treatment interruption. Recently, a antiretroviral therapy (ART), 2) PBMCs or purified resting CD4 sustained control of HIV replication in the absence of ART has been T cells from 5 HIV-1 elite suppressors (ES), or 3) PBMCs from a achieved in a subset of patients starting ART early after infection, Simian Immunodeficiency Virus (SIV) pigtailed macaque on sup- defined as post-ART treatment controllers (PTC). Unfortunately, the pressive ART, all with undetectable plasma viral loads, into NOD. virologic and immunologic determinants of post-ART control of HIV Abstract MOAA0101ÁFigure 1. MVOA for detection of residual virus. 1 8th IAS Conference on HIV Pathogenesis, Treatment and Prevention (IAS 2015) Journal of the International AIDS Society 2015, 18 (Suppl 4) Oral Abstracts replication are still unclear, particularly in tissues. Here, we used the 1Department of Medicine, University of California San Francisco, well-established model of SIV-infection in rhesus macaques (RMs) to San Francisco, United States. 2Department of Immunology, University investigate the existence of PTC in this model and the features of Montreal, Montreal, Canada. 3Department of Medicine, Johns associated with post-ART SIV control. Hopkins University, Baltimore, United States. 4Department of Methods: Fifteen RMs (B*08- and B*17) were infected (i.v.) with Medicine, University of California San Diego, La Jolla, United States. 5 SIVmac239. All 15 animals initiated a five-drug ART regimen 60 days after Department of Pathology and Laboratory Medicine, University of infection, which was maintained for seven months. ART was then inter- Pennsylvania, Philadelphia, United States. 6Department of Medicine, rupted and RMs monitored for eight additional months. Blood (PB), University of Sydney, Sydney, Australia. 7National Institute of Dental lymph node (LN) and colorectal (RB) biopsies were collected throughout and Craniofacial Research, Clinical Dental Research Core, Bethesda, the study. Quantitative assessment of total SIV-DNA and RNA was per- United States. formed on purified blood CD4 T cells and mucosal tissues by quantitative Presenting author email: [email protected] PCR; immunological parameters were determined by flow cytometry. Introduction: A major challenge to HIV eradication strategies is Results: ART suppressed SIV-RNA to 60 copies/mL in all RMs. After B accurate measurement of the latent HIV reservoir. We assessed ART interruption, six RMs controlled SIV viremia at 103 copies/mL B whether the host response to residual virus may be a sensitive up to eight months off-ART (PTC), while nine RMs rebounded to pre- measure of reservoir size by comparing anti-HIV antibody profiles in ART levels (non-controllers, NC). At pre-ART, PTC had significantly relation to several HIV reservoir assays. lower plasma viremia and SIV-DNA content, as well as higher CD4 Tcell Methods: Using a luciferase immunoprecipitation systems (LIPS) assay, counts as compared to NC. Levels of intestinal CD4 Tcells were similar, but PTC had higher frequencies of Th17 cells than NC. On-ART, PTC had we quantitatively analyzed seven anti-HIV antibody profiles from significantly lower levels of residual plasma viremia (3 copies/mL, limit 61 patients who initiated long-term (]3 years) antiretroviral therapy of detection) and SIV-DNA content (both in blood and colorectum). (ART) during chronic HIV infection. HIV antibody levels were evaluated in relation to 12 HIV reservoir measures: total, integrated and 2-LTR After ART interruption, SIV-DNA content rapidly increased in NC while it progressively decreased in PTC. Finally, in PTC control of SIV rebound DNA (rtPCR, n 48); unspliced RNA (rtPCR, n 44), total and 2-LTR associated with higher CD4 T cell levels and reduced immune DNA (droplet digital PCR, n 27); integrated DNA (aluPCR, n 16); viral outgrowth assay (VOA, n 27) and plasma HIV RNA (single copy activation in PB and RB during the entire off-ART period. Conclusions: Lower
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