Towards an HIV Cure Workshop: HIV Reservoirs and Strategies to Control Them
16 & 17 July 2010| Vienna, Austria

Background

In 2010, the International AIDS Society (IAS), with the support of the National Institutes of Health (NIH), the French Agence Nationale de Rechereche sur le SIDA et les hépatitis virales (ANRS), the Austrian Federal Ministry of Science and Reserach, Sidaction and the Treatment Action Group (TAG), organized a workshop on HIV Reservoirs in conjunction with the XVIII International AIDS Conference (AIDS 2010) in Vienna, Austria. The workshop, chaired by 2008 Nobel Laureate for Medicine and IAS President Françoise Barré-Sinoussi, was designed to increase the focus of basice science at the AIDS 2010 conference.

The workshop focused on the topic of HIV reservoirs and strategies to control them and was followed by translational sessions at AIDS 2010 that reported back on the discussions held at the workshop.

Scientific research has led to remarkable discoveries in the quarter century since HIV was first discovered. Today, individuals living with HIV can expect to live a relatively normal lifespan if they are diagnosed and treated early enough and are able to access and adhere to potent antiretroviral drug regimens. A deadly disease has been transformed into a chronic manageable condition, largely due to the efforts of basic scientists.

The strategies currently being investigated to control HIV reservoirs may hold the key to a cure for HIV disease in the future. It is widely known that current antiretroviral drugs cannot completely eradicate the virus from the body because HIV remains in some cells in a non-replicating stage called latent infection. The persistence of latent HIV reservoirs in different compartments of the body is one of the main barriers to the eradication of HIV infection.

Objectives

  • To promote state-of-the-art research on HIV transmission, pathogenesis and disease progression.
     
  • To attract the world’s leading basic scientists including senior, mid-career and junior scientists; a small number of clinical researchers and selected editors of scientific journals to come together at a global experts’ meeting, and discuss the advances and direction of basic HIV research – focusing on HIV reservoirs and strategies to control them.
     
  • To explore the road ‘towards a cure’, highlight implications and potential for translation of cutting edge research on HIV reservoirs for clinical research, drug development, public health and other applications – and contribute to defining research priorities in HIV prevention, treatment and care.
     
  • To increase interactions between basic scientists and other stakeholders in the HIV response by creating incentives for basic scientists to participate in the International AIDS Conference and creating incentives for the wider HIV/AIDS community to engage in basic science.

Themes of the workshop; presentations & abstracts

The workshop was articulated around an opening keynote, 5 thematic sessions that included invited and abstract presentations, a closing keynote and a poster exhibition. The themes of the workshop sessions were (click on the theme to see presentations and abstracts):

Day 1

  • The clinical implications of HIV persistence during therapy
  • Where and what are viral reservoirs? HIV-1 Reservoirs and Sanctuary Sites
  • What are the mechanisms of HIV persistence?

Day 2

  • What is the role of the immune system in HIV persistence?
  • What host factors are at play in HIV persistence?
  • What are potential therapeutic interventions and how to evaluate them?
  • Eradication versus remission: is eradication possible?

Links to AIDS 2010

 The workshop was closely linked to the AIDS 2010 conference. Selected Track A and B (basic and clinical sciences) abstracts submitted to the International AIDS Conference and related to the topic of viral reservoirs and strategies to control them were also presented and discussed at the closed workshop (oral presentations and posters), and results from the workshop were shared with the participants attending AIDS 2010. The IAS/ANRS Young Investigator Award on HIV Reservoirs was awarded to a young investigator whose abstract demonstrates innovation, originality, rationale and quality in the field of HIV and AIDS research.


    Workshop International Steering Committee

    Workshop Programme Committee

     

    Symposium material

    • Related documents
    • Day 1
    • Day 2
    • Poster exhibition
    • Multimedia

    Opening Session

    Keynote Address: The clinical implications of HIV persistence during therapy
    Steven G. Deeks, University of California, San Francisco, USA

    Presentation | Video

    Session 1: Where and what are viral reservoirs?

    Overview Presentation - HIV-1 Reservoirs and Sanctuary Sites
    Satya Dandekar, University of California, Davis, USA

    Presentation | Video

    Abstract Presentation S1.1. - CD4+ T-cell reconstitution, T-cell activation, and memory T-cell subset composition in blood and gut of HIV- and ART-suppressed HIV+ patients: implications for HIV persistence in the gut
    Joseph Wong, University of California, San Francisco/San Francisco VA Medical Center, USA

    Presentation | Video

    Abstract Presentation S1.2. - Residual HIV replication in the gut of aviremic treated individuals correlates with persistent immune activation and increased plasma levels of LPS
    Gabriella D’Ettorre, University of Rome Sapienza, Italy

    Video

    Abstract Presentation S1.3. - Most HIV DNA in PBMC is present in non-gut homing, resting memory CD4 T-cell with a ß7-CD38-CD127 high phenotype
    John Zaunders, University of New South Wales / NCHECR, Australia

    Presentation | Video

    Abstract Presentation S1.4. - Astrocytes are a significant CNS reservoir of proviral HIV-1 DNA and contribute to the pathogenesis of HIV-associated dementia
    Melissa Churchill, Burnet Institute / Monash University, Australia

    Abstract Presentation S1.5. - Where Are Macrophage-Tropic Viruses
    Ronald Swanstrom, University of North Caroline Center for AIDS Research, USA

    Presentation | Video

    Session 2: What are the mechanisms of persistence?

    Overview Presentation - Mechanisms of HIV Latency in CD4 T cells
    Eric Verdin, University of California, San Francisco, USA

    Presentation | Video

    Abstract Presentation S2.1. - Novel pathways of transcriptional and post-transcriptional regulation of post-integrative HIV-1 latency
    Alessandro Marcello, International Centre for Genetic Engineering and Biotechnology, Italy

    Presentation | Video

    Abstract Presentation S2.2. - The cellular cofactor CTIP2 is a key regulator of HIV-1 latency
    Olivier Rohr, Inserm Unit 748/University of Strasbourg, France

    Abstract Presentation S2.3. - HIV-1 Tat complexes reveal subunit composition of active P-TEFb and stable association with 7SKsnRNP
    Bijan Sobhian, Institut de Génétique Humaine, CNRS, France

    Presentation | Video

    Invited Presentation - Mechanisms of HIV Persistence in Infected Individuals Receiving Antiretroviral Therapy
    Tae-Wook Chun, Laboratory of Immunoregulation, NIAID, NIH, USA

    Presentation

    Debate - A 3 years follow-up of long term control of HIV-1 after allogeneic CCR5-delta32 stem cell transplantation
    Presenter: Gero Hütter
    Facilitators: Monsef Benkirane & Mark Wainberg
    Participants: Eric Verdin, Tae-Wook Chun

    IAS-ANRS Young Investigator Prize on HIV Reservoirs - Abstract: Peripheral blood CCR4+ CCR6+ and CXCR3+ CCR6+ CD4+ T-cells are highly permissive to HIV-1 infection
    Awardee: Patricia Monteiro, University of Montreal, Canada

    Presentation

    Session 3: What is the Role of the Immune System in HIV Persistence?

    Overview Presentation - Can the Immune System Control HIV Reservoirs?
    Brigette Autran, Pitié – Salpêtrière Institute of Research on Immunity – Cancer and Infection, Paris, France

    Abstract Presentation S3.1 - Homeostatic proliferation of memory T – cells and expansion of the HIV – 1 latent reservoir
    Vincente Planelles, University of Utah, Pathology, Salt Lake City, USA

    Presentation | Video

    Abstract Presentation S3.2 - Systemic immune activation and duodenal CD4+ T - cell depletion are associated with increased proportions of gut Enterobacteriales and Bacteroidales by 16S rDNA sequence analysis in HIV infected subjects
    David. M. Asmuth, University of California Davis Medical Center, Internal Medicine, Sacaramento, USA

    Abstract Presentation S3.3 - Myeloid dendritic cells induce HIV-1 latency in non – proliferating CD4+ T – cells
    Vanessa. A. Evans, Monash University, Medicine, Victoria, Australia

    Presentation | Video

    Abstract Presentation S3.4 - Protective HLA alleles limit HIV reservoirs in long – term non – progressors central memory CD4+ T - cells
    Benjamin Descours, UPMC, Paris VI, umrs945, Paris, France

    Abstract Presentation S3.5 - HIV – 1 elite controllers resist HIV – 1 infection via p21 (cip -1/waf-1)
    Mathias Lichterfeld, Massachusetts General Hospital, Infectious Disease Division, Boston, USA

    Session 4: What Host Factors are at Play?

    Overview speaker - What host factors are at play?
    Paul de Bakker, Harvard Medical School, Division of Genetics, Boston, USA

    Presentation | Video

    Abstract Presentation S4.1 - Tetherin restricts direct cell – cell viral transfer and transmission of HIV – 1
    Bjorn Kuhl, McGill University, AIDS Center, Montreal, Canada

    Presentation | Video

    Abstract Presentation S4.2 - The role of the ubiquitin – proteasome pathway in rh TRIM5 restriction of HIV-1
    Cindy Danielson, Northwestern University, Cell and Molecular Biologz, Chicago, USA

    Presentation | Video

    Abstract Presentation S4.3 - LEDG\p75 is critical but not essential for multiple round HIV – 1 replication
    Rik Luc Guy Schrijvers, KU Leuven, Molecular Virology and Gene Therapy, Leuven, Belgium

    Presentation | Video

    Abstract Presentation S4.4 - Changes in CD4+ cells miRNA expression following exposure to HIV – 1
    Claudio Casoli, Università degli Studi di Milano, Dipartimento di Scienye Cliniche, Milano, Italy

    Presentation | Video

    Session 5: What are Potential Therapeutic Interventions and How to Evaluate Them?

    Overview speaker - Targeting ‘Residual HIV’ In Its Reservoirs: Where We Are And Where Do We Go?
    Frank Maldarelli, National Cancer Institute, HIV Drug Resistance Program, Bethesda, USA

    Presentation | Video

    Abstract Presentation S5.1 - Impact of raltegravir on immune reconstitution and thymopoiesis in HIV – 1 – infected patients with undetectable ciremia on HAART
    Carolina Garrido, Hospital Ramón y Cajal, Madrid, Spain

    Presentation | Video

    Abstract Presentation S5.2 - Effect of 24 – weeks intensification with A CCR5 – antagonist on the decay of the HIV – 1 latent reservoir
    Carolina Gutierrez, Hospital Ramón y Cajal, Madrid, Spain

    Presentation | Video

    Abstract Presentation S5.3 - Epigenetic drug Gar1041 in combination with antiretroviral therapy (ART) transiently reduces the proviral DNA reservoir in SIVmac251-infected macaques
    Andrea Savarino, Istituto Superiore di Sanita, Department of Infectious, Parasitic and Immune Diseases, Rome, Italy

    Presentation | Video

    Abstract Presentation S5.4 - Purging the HIV – 1 reservoir through the disruption of the PD-1 pathway
    Sandrina Da Fonesca, Vaccine and Gene Therapy Institute, Part St Lucie, USA

    Presentation | Video

    Abstract Presentation S5.5 - Measurements of total and integrated HIV DNA demonstrate sporadic blips of unintegrated HIV DNA in HIV+ patients on HAART
    Una O’Doherty, University of Pennsylvania, Pathology and Laboratory Medicine, Philadelphia, USA

    Presentation

    Closing Session: Is Eradication Possible?

    Closing presentation - HIV Reservoirs at AIDS 2010
    Sharon Lewin, Monash University, Medicine, Melbourne, Australia

    Keynote presentation - Eradication versus Remission: Is Eradication possible?
    Daria Hazuda, Antiviral and Infectious Disease Basic Research, Merck Research Labs, New Jersey, USA

    Presentation | Video

    Theme 1: Where and what are viral reservoirs?

    Assessment of residual HIV-1 viremia and persistent viral replication in highly suppressed patients: comparison of direct and indirect methods
    B. Hernandez-Novoa, N. Madrid, A. Vallejo, C. Gutierrez, L. Diaz, M. Abad, E. Dominguez, V. Dahl, R. Rubio, E. Navas, J. Zamora, H. Valdez, S. Palmer, M.A. Muñoz-Fernandez, S. Moreno

    Impact of short term HAART on SIV infection of the male genital tract
    M. Moreau, A. Le Tortorec, H. Denis, C. Deleage, A.-P. Satie, O. Bourry, P. Roques, B. Jégou, R. Le Grand, N. Dejucq-Rainsford

    Effect of a CCR5 antagonist in immune activation in highly suppressed HIV-1 infected patients
    A. Vallejo, L. Diaz, M. Abad, C. Gutiérrez, B. Hernández, E. Domínguez, N. Madrid, F. Dronda, J.L. Casado, R. Rubio, E. Muñoz, M.Á. Muñoz-Fernández, S. Moreno

    Role of the viral reservoir on adaptive HIV-1 evolution throughout viral recombination under ART and immune pressures
    M.J. Buzon, T. Wrin, F.M. Codoñer, J. Dalmau, A. Bonjoch, E. Coakley, B. Clotet, J. Martinez-Picado

    Rapid infectious viral assay (RIVA) of monocytes in patients with VL< 50 copies/ml of blood
    O.A. Ducoudret, N.S. Baichoo, M.R. Ruff, C.B. Pert, L. Agrawal

    The prevalence of CXCR4-using HIV-1 subtype C variants during progressive infection is comparable to subtype B infection, but is not associated with accelerated CD4+ T-cell decline
    M.R. Jakobsen, A. Ellett, C. Erikstrup, L. Gray, H. Hoare, N. Saksena, B. Wang, D. Purcell, H. Ullum, P. Kallestrup, R. Zinyama-Gutsire, E. Gomo, L. Østergaard, M. Churchill, P. Gorry

    Naïve CD4+ T cells are latently infected in vitro and in vivo
    A. Mexas, L. Agosto, M. Liszewski, M. Pace, S. Migueles, J. Brenchley, M. Connors, U. O'Doherty

    The chemokine receptors CCR4 and CXCR3 are biomarkers for central memory CD4+ T-cell subsets with increased permissiveness to HIV-1 integration in infected individuals
    A. Gosselin, P. Monteiro, N. Chomont, M. El-Far, M.-R. Boulassel, J.-P. Routy, R.-P. Sekaly, P. Ancuta

    Theme 2: What are the mechanisms of persistence?

    Promoter-targeted siRNA colocalizes with Argonaute 1 and 2 during RNA-induced transcriptional gene silencing of simian immunodeficiency virus infection
    C.L. Hood, H.G. Lim, K. Suzuki, D.A. Cooper, A.D. Kelleher 

    Human microRNA and the regulation of HIV-1 expression/replication
    L. Houzet, K.T. Jeang

    Rrp6 represses transcription from the HIV-1 promoter
    X. Contreras, E. Rousset, R. Kiernan

    SJ23B, a jatrophane diterpene, induces HIV Receptors down-regulation and HIV transcription through activation of PKCs and Ras-MEK pathway
    L.M. Bedoya, N. Marquez, N. Martinez, S. Gutiérrez-Eisman, A. Alvarez, M.A. Calzado, J.M. Rojas, G. Appendino, E. Muñoz, J. Alcami

    Post-transcriptional blocks limit HIV-1 expression in a novel in vitro model of HIV latency in primary T-cells
    S. Saleh, P. Cameron, V. Evans, G. Sallmann, A. Solomon, F. Wightman, E. Haddad, R.-P. Sekaly, S. Lewin

    HIV uses cellular miRNA to overcome cell restriction factors and to better replicate
    C. Chable-Bessia, O. Meziane, S. Emiliani, O. Schwartz, O. Lambotte, Y. Lévy, B. Autran, J. Reynes, Y. Bennasser, M. Benkirane

    A three years follow-up of long term control of HIV-1 after allogeneic CCR5-delta32 stem cell transplantation
    K. Allers, T. Schneider, C. Loddenkemper, J. Hofmann, K. Rieger, E. Thiel, G. Hütter

    Influence of chromatin at the integration site on the establishment of HIV latency: a role for co-transcriptional chromatin reassembly factors
    E. Gallastegui, A. Jordan

    HIV eradication and the development of drug resistance in humanized mice
    P. Denton, S. Choudhary, D. Margolis, J.V. Garcia

    Identification of Tat-responsive pre-initiation complexes (PICHs) at the HIV-1 core promoter
    E. Wilhelm, M.-C. Doyle, N. Dumais, B. Bell

    The interplay between RNA splicing, chromatin, Tat and transcription from the HIV LTR: implications for HIV-1 post-integration latency
    M.R. Alexander, A.K. Wheatley, R.J. Center, K. Suzuki, S. Saleh, S.R. Lewin, A. Kelleher, D.F.J. Purcell

    Theme 3: What is the role of the immune system in HIV persistence?

    Unique functional properties of dendritic cells in HIV-1 elite controllers
    J. Huang, P. Burke, F. Peyrera, B. Walker, L. Borges, M. Lichterfeld, X.G. Yu

    Rebound with original virus after sustained HIV suppression on antiretroviral therapy (ART) and daily ultra-low dose interleukin-2 (IL-2) suggests IL-2 enhancement of anti-HIV immunity
    J. Margolick, M. James, L. Apuzzo, S. Langan, J. Gallant, S. Eshleman

    Increased thymic production of naive regulatory T-cells distinguish patients with HAART-mediated control from those with spontaneous control of HIV
    N.I. Rallón, C. Restrepo, M. Salgado, C. de Mendoza, S. Lozano, M. López, A. Peris, V. Soriano, J.M. Benito

    Role of NFAT in reactivation of HIV-1 latency in primary memory CD4+ T cells
    A. Bosque, V. Planelles

    Peripheral blood CCR4+ CCR6+ and CXCR3+ CCR6+ CD4+ T cells are highly permissive to HIV-1 infection
    P. Monteiro, A. Gosselin, N. Chomont, F. Diaz-Griffero, E.A. Said, S. Fonseca, V. Wacleche, M. El-Far, M.-R. Boulassel, J.-P. Routy, R.-P. Sekaly, P. Ancuta

    Low levels of immune activation in viremic non-progressors HIV-infected individuals
    J. Taaffe, B. Julg, B. Rodriguez, S. Gordon, I. Frank, D. Ripamonti, A. Gori, M. Lederman, B. Walker, C. Torti, G. Silvestri

    Impact of antigen persistence on CD4+ T cell activation in chronic HIV infection
    M.Z.D. Smith, U. Karrer, S. Bastidas, A. Oxenius

    Theme 4: What host factors are at play?

    APOBEC3G genetic variants do not influence CD4 T cell counts, HIV viral load and are not associated with protection against HIV-1 infection
    J.A. Vázquez Perez, G. Cerezo, C.E. Ormsby, R. Hernandez-Juan, K.J. Torres, G. Reyes-Teran

    IL-10 promoter genetic variants affect IL-10 plasma levels, breadth of cytotoxic T-cell lymphocte response and the rate of CD4 T-cell loss during chronic HIV-1 infection
    D.D. Naicker, B. Wang, E. Losina, J. Zupkosky, T. Hongo, S. Reddy, K. Bishop, F. Chonco, P.J.R. Goulder, B.D. Walker, D.E. Kaufmann, T. Ndung'u

    Detection of HIV-1 proviral hypermutation and evaluation of its association with disease outcomes
    V. Correa Vieira, A. de Oliveira Afonso, J. Silveira, E. Stankiewicz Machado, M. Alves Soares, A.M. Barral de Martinez

    Polymorphisms in the lens epithelium derived growth factor/p75 gene (PSIP1) influence susceptibility to HIV-1 infection and disease progression
    P. Madlala, A. Hombrouck, R. Gijsbers, F. Christ, L. Werner, E. Kormuth, K. Mlisana, S.A. Karim, C. Winkler, Z. Debyser, T. Ndung'u, the CAPRISA Acute Infection Study Team

    Single nucleotide polymorphisms (SNPs) in cytokine-coding genes in HIV-infected patients from Brazil
    A.R.O. Léda, A.N. Barbosa, R.A.M.B. Almeida, L.R. Souza, D.A. Meira, D. Elgui de Oliveira

    Emetine blocks RNA processing bodies and impacts on HIV replication
    A.L.C. Valadão, B.M. Peterlin, A. Tanuri, R.S. Aguiar

    HIV-1 Vpu and TASK proteins inhibit HIV-1 transciption
    N. Emeagwali

    Theme 5: What are potential therapeutic interventions and how to evaluate them?

    Persistent low-level viremia despite clinically successful antiretroviral therapy appears to be correlated with more frequent resting CD4+ T cell infection
    N. Archin, J. Anderson, K. Keedy, K. Barton, M. Cheema, R. Sackmann, A. Wiegand, J. Kuruc, J. Eron, M. Cohen, J. Coffin, R. Swanstrom, D. Margolis

    Level of HIV-1 unspliced RNA in peripheral blood mononuclear cells: a longitudinal marker of infection progression in untreated individuals and a predictive marker of virological rebound in patients on antiretroviral therapy with undetectable plasma viremia
    A. Pasternak, S. Jurriaans, M. Bakker, J. Prins, B. Berkhout, V. Lukashov

    Susceptibility of human seminal vesicles to HIV-1 infection
    C. Deléage, H. Denis, N. Rioux-Leclercq, A. Ruffault, B. Jégou, N. Dejucq-Rainsford

    Association between genital tract inflammation during acute HIV-1 infection and HIV disease progression
    L. Roberts, J.-A. Passmore, C. Williamson, F. Little, L. Bebell, K. Mlisana, F. van Loggerenberg, G. Walzl, Q. Abdool Karim, S. Abdool Karim

    The cell-associated HIV-1 DNA level after 15 years of perinatal infection is strongly correlated with lifetime viral replication - The ANRS-EP38-IMMIP Study
    V. Avettand-Fenoel, S. Blanche, J. Lechenadec, C. Dollfus, D. Scott-Algara, J.-P. Viard, N. Bouallag, Y. Benmebarek, Y. Rivière, J. Warszawski, C. Rouzioux, F. Buseyne

    Immunotoxin complementation of HAART to deplete persisting HIV infected cell reservoirs
    E. Berger, I. Pastan

    Synergistic activation of HIV-1 expression by deacetylase inhibitors and prostratin: implications for treatment of latent infection
    S. Reuse, L. Colin, M. Calao, K. Kabeya, J.-S. Gatot, S. Bouchat, A. Guiguen, V. Quivy, C. Vanhulle, C. Cardona, A. Lamine, D. Vaira, D. Demonte, V. Martinelli, E. Veithen, T. Cherrier, V. Avettand, S. Poutrel, J. Piette, Y. de Launoit, M. Moutschen, A. Burny, C. Rouzioux, S. De Wit, G. Herbein, O. Rohr, Y. Collette, O. Lambotte, N. Clumeck, C. Van Lint

    amfAR research consortium on HIV eradication
    R. Johnston

    Webcast