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The intrinsic rate of viral replication in HIV-infected patients treated with antiretroviral combination therapy is estimated by using a mathematical model of viral dynamics. This intrinsic replication is found to be episodic, varying considerably in quantity between patients (even among those achieving long-term undetectable levels of viremia) and is always reduced by increasing the potency of the antiviral drug regimen. The analysis reveals that even in conditions of perfect patient adherence and drug penetration a substantial level of residual viral replication is expected. The rate of evolution in the viral quasispecies, and thus also the probability of new drug-resistant viral strains being created, is proportional to the total amount of residual viral replication. Under most circumstances, the viral population continues to turn over rapidly during therapy, albeit at a much reduced level.

Original publication

DOI

10.1073/pnas.261283598

Type

Journal article

Journal

Proceedings of the National Academy of Sciences of the United States of America

Publication Date

11/12/2001

Volume

98

Pages

15167 - 15172

Addresses

Department of Infectious Disease Epidemiology, Faculty of Medicine, Imperial College of Science, Technology and Medicine, St Mary's Campus, Norfolk Place, Paddington, London W2 1PG, United Kingdom. c.fraser@ic.ac.uk

Keywords

Humans, HIV-1, HIV Infections, Anti-HIV Agents, Models, Statistical, Virus Replication