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    Persistent HIV-1 replication maintains the tissue reservoir during therapy

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    Persistent HIV-1 replication ...
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    Genre
    Journal Article
    Date
    2016-02-04
    Author
    Lorenzo-Redondo, R
    Fryer, HR
    Bedford, T
    Kim, EY
    Archer, J
    Kosakovsky Pond, SL
    Chung, YS
    Penugonda, S
    Chipman, JG
    Fletcher, CV
    Schacker, TW
    Malim, MH
    Rambaut, A
    Haase, AT
    McLean, AR
    Wolinsky, SM
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    Subject
    Anti-HIV Agents
    Carrier State
    Drug Resistance, Viral
    HIV Infections
    HIV-1
    Haplotypes
    Humans
    Lymph Nodes
    Models, Biological
    Molecular Sequence Data
    Phylogeny
    Selection, Genetic
    Sequence Analysis, DNA
    Spatio-Temporal Analysis
    Time Factors
    Viral Load
    Virus Replication
    Show allShow less
    Permanent link to this record
    http://hdl.handle.net/20.500.12613/5740
    
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    DOI
    10.1038/nature16933
    Abstract
    © 2016 Macmillan Publishers Limited. All rights reserved. Lymphoid tissue is a key reservoir established by HIV-1 during acute infection. It is a site associated with viral production, storage of viral particles in immune complexes, and viral persistence. Although combinations of antiretroviral drugs usually suppress viral replication and reduce viral RNA to undetectable levels in blood, it is unclear whether treatment fully suppresses viral replication in lymphoid tissue reservoirs. Here we show that virus evolution and trafficking between tissue compartments continues in patients with undetectable levels of virus in their bloodstream. We present a spatial and dynamic model of persistent viral replication and spread that indicates why the development of drug resistance is not a foregone conclusion under conditions in which drug concentrations are insufficient to completely block virus replication. These data provide new insights into the evolutionary and infection dynamics of the virus population within the host, revealing that HIV-1 can continue to replicate and replenish the viral reservoir despite potent antiretroviral therapy.
    Citation to related work
    Springer Science and Business Media LLC
    Has part
    Nature
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    ae974a485f413a2113503eed53cd6c53
    http://dx.doi.org/10.34944/dspace/5722
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