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Science 14 November 1997:
Vol. 278. no. 5341, pp. 1291 - 1295
DOI: 10.1126/science.278.5341.1291
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Reports

Recovery of Replication-Competent HIV Despite Prolonged Suppression of Plasma Viremia

Joseph K. Wong, * Marjan Hezareh, Huldrych F. Günthard, Diane V. Havlir, Caroline C. Ignacio, Celsa A. Spina, Douglas D. Richman

In evaluating current combination drug regimens for treatment of human immunodeficiency virus (HIV) disease, it is important to determine the existence of viral reservoirs. After depletion of CD8 cells from the peripheral blood mononuclear cells (PBMCs) of both patients and normal donors, activation of patient CD4 lymphocytes with immobilized antibodies to CD3 and CD28 enabled the isolation of virus from PBMCs of six patients despite the suppression of their plasma HIV RNA to fewer than 50 copies per milliliter for up to 2 years. Partial sequencing of HIV pol revealed no new drug resistance mutations or discernible evolution, providing evidence for viral latency rather than drug failure.

J. K. Wong, M. Hezareh, H. F. Günthard, C. C. Ignacio, C. A. Spina, Departments of Medicine and Pathology, University of California, San Diego, School of Medicine, 9500 Gilman Drive, La Jolla, CA 92093, USA.
D. V. Havlir, Departments of Medicine and Pathology, University of California, San Diego, School of Medicine, 9500 GIlman Drive, La Jolla, CA 92093, USA, and Treatment Center, University of California, San Diego, 2760 Fifth Avenue, Suite 300, San Diego, CA 92103, USA.
D. D. Richman, Departments of Medicine and Pathology, University of California, San Diego, School of Medicine, 9500 Gilman Drive, La Jolla, CA 92093, USA, and Veterans Affairs San Diego Healthcare System, San Diego, CA 92063, USA.
*   To whom correspondence should be addressed.

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M. Pion, A. Jordan, A. Biancotto, F. Dequiedt, F. Gondois-Rey, S. Rondeau, R. Vigne, J. Hejnar, E. Verdin, and I. Hirsch (2003)
J. Virol. 77, 4025-4032
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New Anti-Human Immunodeficiency Virus Type 1 6-Aminoquinolones: Mechanism of Action.
C. Parolin, B. Gatto, C. Del Vecchio, T. Pecere, E. Tramontano, V. Cecchetti, A. Fravolini, S. Masiero, M. Palumbo, and G. Palu (2003)
Antimicrob. Agents Chemother. 47, 889-896
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Genetic Characterization of Rebounding Human Immunodeficiency Virus Type 1 in Plasma during Multiple Interruptions of Highly Active Antiretroviral Therapy.
M. Dybul, M. Daucher, M. A. Jensen, C. W. Hallahan, T.-W. Chun, M. Belson, B. Hidalgo, D. C. Nickle, C. Yoder, J. A. Metcalf, et al. (2003)
J. Virol. 77, 3229-3237
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HIV Envelope Induces Virus Expression from Resting CD4+ T Cells Isolated from HIV-Infected Individuals in the Absence of Markers of Cellular Activation or Apoptosis.
A. L. Kinter, C. A. Umscheid, J. Arthos, C. Cicala, Y. Lin, R. Jackson, E. Donoghue, L. Ehler, J. Adelsberger, R. L. Rabin, et al. (2003)
J. Immunol. 170, 2449-2455
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Gene expression and viral prodution in latently infected, resting CD4+ T cells in viremic versus aviremic HIV-infected individuals.
T.-W. Chun, J. S. Justement, R. A. Lempicki, J. Yang, G. Dennis Jr., C. W. Hallahan, C. Sanford, P. Pandya, S. Liu, M. McLaughlin, et al. (2003)
PNAS 100, 1908-1913
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Latency in Human Immunodeficiency Virus Type 1 Infection: No Easy Answers.
D. Persaud, Y. Zhou, J. M. Siliciano, and R. F. Siliciano (2003)
J. Virol. 77, 1659-1665
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In a Subset of Subjects on Highly Active Antiretroviral Therapy, Human Immunodeficiency Virus Type 1 RNA in Plasma Decays from 50 to <5 Copies per Milliliter, with a Half-Life of 6 Months.
M. Di Mascio, G. Dornadula, H. Zhang, J. Sullivan, Y. Xu, J. Kulkosky, R. J. Pomerantz, and A. S. Perelson (2003)
J. Virol. 77, 2271-2275
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HIV viral suppression in the era of antiretroviral therapy.
H K Thaker and M H Snow (2003)
Postgrad. Med. J. 79, 36-42
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Vaccination of Macaques with Long-Standing SIVmac251 Infection Lowers the Viral Set Point After Cessation of Antiretroviral Therapy.
E. Tryniszewska, J. Nacsa, M. G. Lewis, P. Silvera, D. Montefiori, D. Venzon, Z. Hel, R. W. Parks, M. Moniuszko, J. Tartaglia, et al. (2002)
J. Immunol. 169, 5347-5357
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Targeted Derepression of the Human Immunodeficiency Virus Type 1 Long Terminal Repeat by Pyrrole-Imidazole Polyamides.
J. J. Coull, G. He, C. Melander, V. C. Rucker, P. B. Dervan, and D. M. Margolis (2002)
J. Virol. 76, 12349-12354
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Stimulation of HIV-specific cellular immunity by structured treatment interruption fails to enhance viral control in chronic HIV infection.
A. Oxenius, D. A. Price, H. F. Gunthard, S. J. Dawson, C. Fagard, L. Perrin, M. Fischer, R. Weber, M. Plana, F. Garcia, et al. (2002)
PNAS 99, 13747-13752
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Synergistic Activation of Human Immunodeficiency Virus Type 1 Promoter Activity by NF-{kappa}B and Inhibitors of Deacetylases: Potential Perspectives for the Development of Therapeutic Strategies.
V. Quivy, E. Adam, Y. Collette, D. Demonte, A. Chariot, C. Vanhulle, B. Berkhout, R. Castellano, Y. de Launoit, A. Burny, et al. (2002)
J. Virol. 76, 11091-11103
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Quantitation of Human Immunodeficiency Virus Type 1 DNA Forms with the Second Template Switch in Peripheral Blood Cells Predicts Disease Progression Independently of Plasma RNA Load.
L. G. Kostrikis, G. Touloumi, R. Karanicolas, N. Pantazis, C. Anastassopoulou, A. Karafoulidou, J. J. Goedert, and A. Hatzakis (2002)
J. Virol. 76, 10099-10108
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