XIX International AIDS Conference

THAA01 HIV Reservoirs: Where and How is the Virus Hiding?
  Oral Abstract Session : Track A
Venue: Session Room 9
Time: 26.07.2012, 14:30 - 16:00
Co-Chairs: Nicolas Chomont, United States
Lachlan Gray, Australia

Long-term reduction in peripheral blood HIV-1 reservoirs following reduced-intensity conditioning allogeneic stem cell transplantation in two HIV-positive individuals
T.J. Henrich1,2, G. Sciaranghella3, J.Z. Li1,2, S. Gallien4, V. Ho2,5, A.S. LaCasce2,5, D.R. Kuritzkes1,2
1Brigham and Women's Hospital, Boston, United States, 2Harvard Medical School, Boston, United States, 3Ragon Institute of MGH, MIT and Harvard, Boston, United States, 4Hopital Saint-Louis, Paris, France, 5Dana-Farber Cancer Institute, Boston, United States
T. Henrich, United States

Viral tissue reservoirs are determined early and little viral RNA is detected during suppression by three or four drug regimens in the macaque model
C. Kline1, J. Ndjomou1, T. Franks1, R. Kiser2, V. Coalter2, M. Piatak, Jr.2, J. Estes2, J. Mellors1, J. Lifson2, Z. Ambrose1
1University of Pittsburgh School of Medicine, Medicine, Pittsburgh, United States, 2SAIC-Frederick, Inc., NCI Frederick, AIDS and Cancer Virus Program, Frederick, United States
Z. Ambrose, United States

Distribution of the HIV reservoir in patients spontaneously controlling HIV infection after treatment interruption
C. Bacchus1, L. Hocqueloux2, V. Avettand-Fenoël3, A. Saez-Cirion4, A. Mélard3, B. Descours5, A. Samri1, C. Blanc6, B. Autran1, C. Rouzioux3, VISCONTI and ALT ANRS study groups
1Cellular and Tissular Immunology Laboratory, Pierre and Marie Curie University, INSERM UMR-S 945, Pitié-Salpêtrière Hospital, Paris, France, 2Infectious and Tropical Diseases Department, Regional Hospital, Orléans, France, 3Virology Laboratory, René Descartes University, Necker Hospital, Paris, France, 4Institut Pasteur, Unité de Régulation des Infections Rétrovirales, Paris, France, 5Human Genetic Institute, Molecular Virology Laboratory, CNRS UPR1142, Montpellier, France, 6Flow Cytometry Platform CyPS, Pierre and Marie Curie University, Pitié-Salpêtrière Hospital, Paris, France
C. Bacchus, France

SIVagm infection of rhesus macaques: a model of functional cure with persistent reservoirs of replication-competent virus
D. Ma1, A. Cillo2, C.L. Xu1, J. Kristoff1, J. Fang1, G. Haret-Richter1, J. Mellors2, I. Pandrea1, C. Apetrei1
1University of Pittsburgh, Center for Vaccine Research, Pittsburgh, United States, 2University of Pittsburgh, Division of Infectious Diseases, Department of Medicine, Pittsburgh, United States
C. Apetrei, United States

Characterization of persistent HIV-1 in a broad spectrum of CD4+ T cells isolated from peripheral blood and gut associated lymphoid tissue from patients on long-term suppressive therapy
L. Josefsson1,2, S. Eriksson2, E. Sinclair3, T. Ho3, M. Killian3, L. Epling3, A. Tan3, P. Lemey4, N.R. Faria4, W. Shao5, P. Hunt3, M. Somsouk3, D. Douek6, P. Bacchetti7, L. Loeb3, J. Custer3, L. Poole3, S. Deeks3, F.M. Hecht3, S. Palmer1,2
1Karolinska Institutet, Department of Microbiology, Tumor and Cellbiology, Solna, Sweden, 2The Swedish Institute for Communicable Disease Control, Department of Diagnostics and Vaccinology, Solna, Sweden, 3University of California - San Francisco, Department of Medicine, San Francisco, United States, 4KU Leuven, Rega Institute, Leuven, Belgium, 5National Institiute of Cancer, Advanced Biomedical Computing Center, SAIC, Frederick, United States, 6National Institute of Allergy and Infectious Diseases, National Institutes of Health, Immunology Laboratory, Vaccine Research Center, Bethesda, United States, 7University of California - San Francisco, Department of Epidemiology and Biostatistics, San Francisco, United States
L. Josefsson, Sweden

Concluding Slides

L. Gray, Australia

Powerpoints presentations
Long-term reduction in peripheral blood HIV-1 reservoirs following reduced-intensity conditioning allogeneic stem cell transplantation in two HIV-positive individuals - Timothy J. Henrich

Viral tissue reservoirs are determined early and little viral RNA is detected during suppression by three or four drug regimens in the macaque model - Zandrea Ambrose

Concluding Slides - Lachlan Gray

Rapporteur report

Track A report by Galit Alter

The HIV viral reservoirs session was an exciting session highlighting 5 novel studies aimed at defining the kinetics of reservoir establishment, the activity of the reservoir under suppressive therapy, as well as novel strategies that could potentially functionally cure patients. The session began with a talk by Dr. Henrichs, who presented the first data demonstrating persistent viral suppression in 2 HIV+ patients undergoing hematopoetic stem cell transplantation on continued antiviral therapy. The 2 patients exhibited undetectable viremia and decaying anti-HIV antibody responses following complete reconstitution of CD4+ T cells by the graft. Dr. Ambrose then presented data on the kinetics and properties of the viral reservoir in SIV infection using the rhesus macaque model. Interestingly, while proviral DNA was identified in all tissues sampled in untreated and treated macaques, proviral RNA was only detected in untreated macaques. Tissue viral loads were strongly associated early viral replication, suggesting that the viral reservoir is seeded extremely early in infection. The third presentation in the session, by Dr. Bacchus, highlighted data from the VISCONTI trial aimed at understanding the mechanism by which viral control induced by early scheduled treatment interruption may alter the viral reservoir, allowing for durable control of viremia. Interestingly, post-treatment control (PTC) was associated with a unique viral reservoir profile, with a majority of  transitional memory cells (>50%) and only a minor amount of naive and central memory CD4+ T (the later cells are typical of the reservoir in natural elite controllers). The reservoir in PTC patients was fully inducible, suggesting that treatment induced control is marked by a low reservoir size, in unique CD4+ T cell subsets, likely due to early treatment. The fourth talk, presented by Dr. Apetrei, highlighted an exciting non-human model in which eradication may be investigated in the setting of an active immune system. African green monkeys (AGM) represent a unique model in which viral control is established soon after infection. CD8+ T cell depletion results in a rapid viral rebound that Dr. Apetrei's team was now able to show is composed of infectious virus. These data highlight that AGM may represent a unique opportunity to examine immune mechanisms by which a functional cure may be achieved in vivo. Finally, the last presentation in the session, by Ms. Josefsson, described a comprehensive investigation of the viral dynamics of the viral reservoir in long-term treated patients either treated in acute (<6months) or chronic (>1.5years) viral infection. The data clearly demonstrated little viral evolution in blood and tissues (gut associated lymphoid tissue, bone marrow, or lymph nodes) on therapy, irrespective of length of untreated infection, despite greater viral diversification in patients treated later in infection, highlighting the stability of the viral reservoir on therapy.


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