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Science 15 March 1996:
Vol. 271. no. 5255, pp. 1582 - 1586
DOI: 10.1126/science.271.5255.1582
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Reports

HIV-1 Dynamics in Vivo: Virion Clearance Rate, Infected Cell Life-Span, and Viral Generation Time

Alan S. Perelson, Avidan U. Neumann, Martin Markowitz, John M. Leonard, David D. Ho *

A new mathematical model was used to analyze a detailed set of human immunodeficiency virus-type 1 (HIV-1) viral load data collected from five infected individuals after the administration of a potent inhibitor of HIV-1 protease. Productively infected cells were estimated to have, on average, a life-span of 2.2 days (half-life t1/2 = 1.6 days), and plasma virions were estimated to have a mean life-span of 0.3 days (t1/2 = 0.24 days). The estimated average total HIV-1 production was 10.3 × 109 virions per day, which is substantially greater than previous minimum estimates. The results also suggest that the minimum duration of the HIV-1 life cycle in vivo is 1.2 days on average, and that the average HIV-1 generation time--defined as the time from release of a virion until it infects another cell and causes the release of a new generation of viral particles--is 2.6 days. These findings on viral dynamics provide not only a kinetic picture of HIV-1 pathogenesis, but also theoretical principles to guide the development of treatment strategies.

A. S. Perelson and A. U. Neumann, Theoretical Division, Los Alamos National Laboratory, Los Alamos, NM 87545, USA.
M. Markowitz and D. D. Ho, Aaron Diamond AIDS Research Center, 455 First Avenue, New York, NY 10016, USA.
J. M. Leonard, Pharmaceutical Products Division, Abbott Laboratories, Abbott Park, IL 60064, USA.
* To whom correspondence should be addressed.


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N. M. Dixit and A. S. Perelson (2004)
J. Virol. 78, 8942-8945
   Abstract »    Full Text »    PDF »
Selection in Context: Patterns of Natural Selection in the Glycoprotein 120 Region of Human Immunodeficiency Virus 1 Within Infected Individuals.
A. R. Templeton, R. A. Reichert, A. E. Weisstein, X.-F. Yu, and R. B. Markham (2004)
Genetics 167, 1547-1561
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Detection of Human Immunodeficiency Virus Type 1 Antiretroviral Resistance Mutations by High-Density DNA Probe Arrays.
R. Gonzalez, B. Masquelier, H. Fleury, B. Lacroix, A. Troesch, G. Vernet, and J. N. Telles (2004)
J. Clin. Microbiol. 42, 2907-2912
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Roles of Target Cells and Virus-Specific Cellular Immunity in Primary Simian Immunodeficiency Virus Infection.
R. R. Regoes, R. Antia, D. A. Garber, G. Silvestri, M. B. Feinberg, and S. I. Staprans (2004)
J. Virol. 78, 4866-4875
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CSF quinolinic acid levels are determined by local HIV infection: cross-sectional analysis and modelling of dynamics following antiretroviral therapy.
M. Valle, R. W. Price, A. Nilsson, M. Heyes, and D. Verotta (2004)
Brain 127, 1047-1060
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Positive Selection Detection in 40,000 Human Immunodeficiency Virus (HIV) Type 1 Sequences Automatically Identifies Drug Resistance and Positive Fitness Mutations in HIV Protease and Reverse Transcriptase.
L. Chen, A. Perlina, and C. J. Lee (2004)
J. Virol. 78, 3722-3732
   Abstract »    Full Text »    PDF »
Benefits and limitations of testing for resistance to HIV drugs.
D. D. Richman (2004)
J. Antimicrob. Chemother. 53, 555-557
   Abstract »    Full Text »    PDF »
Unselected Mutations in the Human Immunodeficiency Virus Type 1 Genome Are Mostly Nonsynonymous and Often Deleterious.
F. Gao, Y. Chen, D. N. Levy, J. A. Conway, T. B. Kepler, and H. Hui (2004)
J. Virol. 78, 2426-2433
   Abstract »    Full Text »    PDF »
Influence of Random Genetic Drift on Human Immunodeficiency Virus Type 1 env Evolution During Chronic Infection.
D. Shriner, R. Shankarappa, M. A. Jensen, D. C. Nickle, J. E. Mittler, J. B. Margolick, and J. I. Mullins (2004)
Genetics 166, 1155-1164
   Abstract »    Full Text »    PDF »
Unifying the Epidemiological and Evolutionary Dynamics of Pathogens.
B. T. Grenfell, O. G. Pybus, J. R. Gog, J. L. N. Wood, J. M. Daly, J. A. Mumford, and E. C. Holmes (2004)
Science 303, 327-332
   Abstract »    Full Text »    PDF »
Predicting the therapeutic response in patients with chronic hepatitis C: the role of viral kinetic studies.
P. Ferenci (2004)
J. Antimicrob. Chemother. 53, 15-18
   Abstract »    Full Text »    PDF »
Bystander Killing during Avian Leukosis Virus Subgroup B Infection Requires TVBS3 Signaling.
F. Diaz-Griffero, S. A. Hoschander, and J. Brojatsch (2003)
J. Virol. 77, 12552-12561
   Abstract »    Full Text »    PDF »
Correspondence re: S. Maula et al., Intratumoral Lymphatics Are Essential for the Metastatic Spread and Prognosis in Squamous Cell Carcinoma of the Head and Neck. Cancer Res., 63: 1920-1926, 2003..
T. P. Padera, Y. Boucher, R. K. Jain, L. M. Wein, P. E. Holden, and D. H. Kirn (2003)
Cancer Res. 63, 8555-8557
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