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Science 27 January 1995:
Vol. 267. no. 5197, pp. 483 - 489
DOI: 10.1126/science.7824947
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Articles

Science, Vol 267, Issue 5197, 483-489
Copyright © 1995 by American Association for the Advancement of Science

articles

HIV population dynamics in vivo: implications for genetic variation, pathogenesis, and therapy

JM Coffin

Department of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, MA 02111.

Several recent reports indicate that the long, clinically latent phase that characterizes human immunodeficiency virus (HIV) infection of humans is not a period of viral inactivity, but an active process in which cells are being infected and dying at a high rate and in large numbers. These results lead to a simple steady-state model in which infection, cell death, and cell replacement are in balance, and imply that the unique feature of HIV is the extraordinarily large number of replication cycles that occur during infection of a single individual. This turnover drives both the pathogenic process and (even more than mutation rate) the development of genetic variation. This variation includes the inevitable and, in principle, predictable accumulation of mutations such as those conferring resistance to antiviral drugs whose presence before therapy must be considered in the design of therapeutic strategies.


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Host Determinants in HIV Infection and Disease: Part 1: Cellular and Humoral Immune Responses.
C. M. Hogan and S. M. Hammer (2001)
Ann Intern Med 134, 761-776
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Clustered Mutations in HIV-1 Gag Are Consistently Required for Escape from Hla-B27-Restricted Cytotoxic T Lymphocyte Responses.
A. D. Kelleher, C. Long, E. C. Holmes, R. L. Allen, J. Wilson, C. Conlon, C. Workman, S. Shaunak, K. Olson, P. Goulder, et al. (2001)
J. Exp. Med. 193, 375-386
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Antiretroviral Therapy: Time To Think Strategically.
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Ann Intern Med 132, 320-322
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HIV-1 Genotypic Resistance Patterns Predict Response to saquinavir-ritonavir Therapy in Patients in Whom Previous Protease Inhibitor Therapy Had Failed.
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Ann Intern Med 131, 813-821
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Treat HIV-1 Infection Like Other Infections--Treat It.
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JAMA 280, 91-93
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Public Health Implications of Antiretroviral Therapy and HIV Drug Resistance.
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JAMA 279, 1977-1983
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Antiretroviral Therapy for HIV Infection in 1997: Updated Recommendations of the International AIDS Society--USA Panel.
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JAMA 277, 1962-1969
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J. Exp. Med. 185, 1153-1162
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JAMA 277, 145-153
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Science 274, 1010-1011
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Science 273, 415-416
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Inhibitors of HIV Nucleocapsid Protein Zinc Fingers as Candidates for the Treatment of AIDS.
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Science 270, 1194-1197
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