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Is HIV eradication a realistic aim? Joep M.A. Lange Center for Poverty-related Communicable Diseases Academic Medical Center / University of Amsterdam & Amsterdam Institute for Global Health and Development
Siliciano JD, et al. Nat Med 2003;9:727-8 Figure 1 Extremely slow decay of the latent reservoir in patients on HAART. (a) Frequency of latently infected cells in 62 HIV-1 infected adults who maintained suppression of viremia on combination therapy without failure.Results are expressed in terms of IUPM resting CD4 + T cells. Colored lines, repeat measurements in individual patients; closed symbols, successful detection of resting CD4 + T cells harboring replication-competent HIV-1 at the indicated frequencies; open symbols, unsuccessful virus isolation (in this instance, the upper bound on the infected-cell frequency, estimated based on the number of input cells, is plotted.).
Siliciano JD, et al. Nat Med 2003;9:727-8 Figure 1 Extremely slow decay of the latent reservoir in patients on HAART. (b) Decay of the latent reservoir in the subset of 18 patients who maintained suppression of viremia on HAART for 3-7 years without blips (colored lines and symbols). a and b : Heavy black line, mean decay rate; ligth black lines, 95% confidence interval around the mean decay rate.
Half-life of the latent reservoir estimated to be 4.6 months (range 1.9-8.7 months). Projected time for complete elimination of HIV in this compartment 7.7 years. Chun TW, et al. J Infect Dis 2007;195:1762-4
Effect of treatment, during primary infection on establishment and clearance of cellular reservoirs of HIV-1 Strain MC, et al. J Infect Dis 2005;191:1410-8
Total cell-associated infectivity (CAI) after 1 year of treatment undetectable in:
9/9 patients initiating treatment during primary infection
6/8 initiating treatment < 6 months after seroconversion
In contrast, all 17 control patients who initiated HAART during chronic infection retained detectable CAI after 3-6 years of treatment
Strain MC, et al. J Infect Dis 2005;191:1410-8
Palmer S, et al. Proc Natl Acad Sci USA 2008;105:3879-84
Using the SCA, 77% of samples had quantifiable viremia; all patients had at least one sample with quantifiable viremia Palmer S, et al. Proc Natl Acad Sci USA 2008;105:3879-84
What does residual viral expression in patients who receive ART reflect?
Incomplete suppression of ongoing viral replication?
Intermittent production from stable reservoirs of chronically infected cells?
Viral expression from self-limited reactivation of latently infected cells?
Yukl & Wong. J Infect Dis 2008;197:640-2.
Persistence of HIV in Gut-Associated Lymphoid Tissue despite Long-Term Antiretroviral Therapy
Tae-Wook Chun, 1.a David C. Nickle, 6.a Jesse S. Justement, 1 Jennifer H. Meyers, 1 Gregg Roby, 1 Claire W. Hallahan, 2 Shyam Kottlilil, 1 Susan Moir, JoAnn M. Mican, 4 James I. Mullins, 6 Douglas J. Ward, 7 Joseph A. Kovacs, 5 Peter J. Mannon, 3 and Anthony S. Fauci 1
1 Laboratory of Immunoregulation, 2 Biostatistical Research Branch, 3 Laboratory of Host Defense, 4 Division of Clinical Research, National Institute of Allergy and Infectious Diseases, 5 Critical Care Medicine Department, Clinical Center, National Institutes of Health, Bethesda, Maryland; 6 Department of Microbiology, University of Washington, Seattle; 7 Dupont Circle Physicians Group, Washington, DC
Immuno-activation with anti-CD3 and recombinant human IL-2 in HIV-1-infected patients on potent antiretroviral therapy
Jan M. Prins a* , Suzanne Jurriaans c* , Rieneke M.E. van Praag a , Hetty Blaak e , Ronald van Rij e ,
Peter Th.A. Schellekens b , Ineke J.M. ten Berge b , Si-La Yong b , Cecil H. Fox f , Marijke T.L. Roos e ,
Frank de Wolf c , Jaap Goudsmit c , Hanneke Schuitemaker e and Joep M.A. Lange ad
From the a Department of Internal Medicine, Division of Infectious Diseases, Tropical Medicine and AIDS, and b Division of Clinical Immunology and Rheumatology, c Department of Human Retrovirology, d National AIDS Therapy Evaluation Centre (NATEC), Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands; e Department of Clinical Viro-Immunology, Central Laboratory of the Netherlands Red Cross Blood Transfusion Service, Amsterdam , the Netherlands; and f Molecular Histology Labs Inc., Gaithersburg, MD, USA. *The first two authors contributed equally to this study.
OKT3 and IL-2 Treatment for Purging of the Latent HIV-1 Reservoir in Vivo Results in Selective Long-Lasting CD4+ T Cell Depletion
R.M.E. van Praag 1 , J.M. Prins 1 , M.T.L. Roos 2 , P.Th. Schellekens 3 , I.J.M. ten Berge 3 , S-L. Yong 3 , H. Schuitemaker 2 , A.J.M. Eerenberg 2 , S. Jurriaans 4 , F. de Wolf 4 , C.H. Fox 5 , J. Goudsmit 4 , F. Miedema 2 , J.M.A. Lange 1
1 National Aids Therapy Evaluation Center (NATEC), Department of Internal Medicine, Division of Infectious Diseases, Tropical Medicine and AIDS, Academic Medical Center, Amsterdam, The Netherlands. 2 Department of Clinical Viro-Immunology, CLB, and Laboratory for Experimental and Clinical Immunology, Academic Medical Center, Amsterdam, The Netherlands. 3 Division of Clinical Immunology and Reumatology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. 4 Department of Human Retrovirology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. 5 Molecular Histology Lab Inc., Gaithersburg, Maryland.
Van Praag R, et al. J Clin Immunol 2001;21:218-26
IL-7 is a potent and proviral strain–specific inducer of latent HIV-1 cellular reservoirs of infected individuals on virally suppressive HAART
Feng-Xiang Wang, 1 Yan Xu, 1 Julie Sullivan, 1 Emily Souder, 1 Elias G. Argyris, 1
Edward A. Acheampong, 1 Jaime Fisher, 1 Maria Sierra, 2 Michael M. Thomson, 2
Rafael Najera, 2 Ian Frank, 3 Joseph Kulkosky, 1 Roger J. Pomerantz, 1 and Giuseppe Nunnari 1
1 Center for Human Virology and Biodefense, Division of Infectious Diseases and Environmental Medicine, Department of Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania, USA. 2 Area de Patogenia Viral, Centro Nacional de Microbiologia, Instituto de Salud Carlos III, Madrid, Spain. 3 University of Pennsylvania, Division of Infectious Diseases, Philadelphia, Pennsylvania, USA.
Wang FX, et al. J Clin Invest 2005;115:128-37
Depletion of latent HIV-1 infection in vivo: a proof-of-concept study
Ginger Lehrman, Ian B Hogue, Sarah Palmer, Cheryl Jennings, Celsa A Spina, Ann Wiegand,
Alan L Landay, Robert W Coombs, Douglas D Richman, John W Mellors, John M Coffin,
Ronald J Bosch, David M Margolis
Intensifying HAART with an HDAC inhibitor (valproic acid) and enfuvirtide for 3 months led to a decline in the frequency of resting cell infection (in 4 volunteers).
Long-Term Control of HIV by CCR5 Delta32/Delta32 Stem-Cell Transplantation Gero Hütter, M.D., Daniel Nowak, M.D., Maximilian Mossner, B.S., Susanne Ganepola, M.D., Arne Müßig, M.D., Kristina Allers, Ph.D., Thomas Schneider, M.D., Ph.D., Jörg Hofmann, Ph.D., Claudia Kücherer, M.D., Olga Blau, M.D., Igor W. Blau, M.D., Wolf K. Hofmann, M.D., and Eckhard Thiel, M.D. N Engl J Med 2009;360:692-8. Long-Term Control of HIV by CCR5 Delta32/Delta32 Stem-Cell Transplantation Gero Hütter, M.D., Daniel Nowak, M.D., Maximilian Mossner, B.S., Susanne Ganepola, M.D., Arne Müßig, M.D., Kristina Allers, Ph.D., Thomas Schneider, M.D., Ph.D., Jörg Hofmann, Ph.D., Claudia Kücherer, M.D., Olga Blau, M.D., Igor W. Blau, M.D., Wolf K. Hofmann, M.D., and Eckhard Thiel, M.D. SUMMARY Infection with the human immunodeficiency virus type 1 (HIV-1) requires the presence of a CD4 receptor and a chemokine receptor, principally chemokine receptor 5 (CCR5). Homozygosity for a 32-bp deletion in the CCR5 allele provides resistance against HIV-1 acquisition. We transplanted stem cells from a donor who was homozygous for CCR5 delta32 in a patient with acute myeloid leukemia and HIV-1 infection. The patient remained without viral rebound 20 months after transplantation and discontinuation of antiretroviral therapy. This outcome demonstrates the critical role CCR5 plays in maintaining HIV-1 infection. PowerPoint Slide Set PDA Full Text PDF Summary Editorial E-mail When Letters Appear E-mail When Cited Notify a Friend Add to Citation Manager Add to Personal Archive PubMed Citation by Levy, J. A.
Is HIV eradication at the individual level a worthy goal?
Although the eradication of HIV is a daunting task,
the goal of long-term containment of viral replication
and prevention of immune dysfunction
is eminently achievable.
Stebbing J, et al. N Engl J Med 2004;350:1872-80
Is HIV eradication at the individual level a worthy goal?