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Nature. 2016 Feb 4;530(7588):51-56. 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, IL 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, WA 98109, USA.
4
Centro de Investigação em Biodiversidade e Recursos Genéticos Universidade do Porto, Vairão, Portugal.
5
Department of Medicine, University of California, San Diego, CA 92093, USA.
6
Center for Infectious Disease Research, Korean National Institutes of Health, Osong, Korea.
7
Department of Surgery, University of Minnesota, Minneapolis, MN, 55455 USA.
8
Antiviral Pharmacology Laboratory, University of Nebraska Medical Center, College of Pharmacy, Omaha, NE 68198, USA.
9
Division of Infectious Diseases, University of Minnesota, Minneapolis, MN 55455, USA.
10
Department of Infectious Diseases, King's College London, Guy's Hospital, London, UK.
11
Centre for Immunology, Infection and Evolution, University of Edinburgh, Edinburgh, UK.
12
Department of Microbiology, University of Minnesota, Minneapolis, MN 55455, USA.
#
Contributed equally

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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