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Nature. 2016 Feb 4;530(7588):51-6. doi: 10.1038/nature16933. Epub 2016 Jan 27.

Persistent HIV-1 replication maintains the tissue reservoir during therapy.

Author information

1
Division of Infectious Diseases, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60011, USA.
2
Institute for Emerging Infections, Department of Zoology, University of Oxford, Oxford, OX1 3PS, UK.
3
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA.
4
Centro de Investigação em Biodiversidade e Recursos Genéticos Universidade do Porto, 4485-661 Vairão, Portugal.
5
Department of Medicine, University of California, San Diego, California 92093, USA.
6
Division of AIDS, Center for Immunology and Pathology, Korea National Institutes of Health, Chungju-si, Chungcheongbuk-do, 28159, South Korea.
7
Department of Surgery, University of Minnesota, Minneapolis, Minnesota 55455, USA.
8
Antiviral Pharmacology Laboratory, University of Nebraska Medical Center, College of Pharmacy, Omaha, Nebraska 68198, USA.
9
Division of Infectious Diseases, University of Minnesota, Minneapolis, Minnesota 55455, USA.
10
Department of Infectious Diseases, King's College London, Guy's Hospital, London SE21 7DN, UK.
11
Centre for Immunology, Infection and Evolution, University of Edinburgh, Edinburgh EH9 3FL, UK.
12
Department of Microbiology, University of Minnesota, Minneapolis, Minnesota 55455, USA.

Abstract

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.

Comment in

PMID:
26814962
PMCID:
PMC4865637
DOI:
10.1038/nature16933
[Indexed for MEDLINE]
Free PMC Article

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