title: Persistent HIV-1 replication maintains the tissue reservoir during therapy.
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.
authors.affiliation: Division of Infectious Diseases, Northwestern University Feinberg School of Medicine, Chicago, IL 60011, USA.
authors.forename: Ramon
authors.initials: R
authors.lastname: Lorenzo-Redondo
authors.affiliation: Institute for Emerging Infections, Department of Zoology, University of Oxford, Oxford, OX1 3PS, UK.
authors.forename: Helen R
authors.initials: HR
authors.lastname: Fryer
authors.affiliation: Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
authors.forename: Trevor
authors.initials: T
authors.lastname: Bedford
authors.affiliation: Division of Infectious Diseases, Northwestern University Feinberg School of Medicine, Chicago, IL 60011, USA.
authors.forename: Eun-Young
authors.initials: EY
authors.lastname: Kim
authors.affiliation: Centro de Investigação em Biodiversidade e Recursos Genéticos Universidade do Porto, Vairão, Portugal.
authors.forename: John
authors.initials: J
authors.lastname: Archer
authors.affiliation: Department of Medicine, University of California, San Diego, CA 92093, USA.
authors.forename: Sergei L Kosakovsky
authors.initials: SLK
authors.lastname: Pond
authors.affiliation: Center for Infectious Disease Research, Korean National Institutes of Health, Osong, Korea.
authors.forename: Yoon-Seok
authors.initials: YS
authors.lastname: Chung
authors.affiliation: Division of Infectious Diseases, Northwestern University Feinberg School of Medicine, Chicago, IL 60011, USA.
authors.forename: Sudhir
authors.initials: S
authors.lastname: Penugonda
authors.affiliation: Department of Surgery, University of Minnesota, Minneapolis, MN, 55455 USA.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Chipman
authors.affiliation: Antiviral Pharmacology Laboratory, University of Nebraska Medical Center, College of Pharmacy, Omaha, NE 68198, USA.
authors.forename: Courtney V
authors.initials: CV
authors.lastname: Fletcher
authors.affiliation: Division of Infectious Diseases, University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: Timothy W
authors.initials: TW
authors.lastname: Schacker
authors.affiliation: Department of Infectious Diseases, King's College London, Guy's Hospital, London, UK.
authors.forename: Michael H
authors.initials: MH
authors.lastname: Malim
authors.affiliation: Centre for Immunology, Infection and Evolution, University of Edinburgh, Edinburgh, UK.
authors.forename: Andrew
authors.initials: A
authors.lastname: Rambaut
authors.affiliation: Department of Microbiology, University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: Ashley T
authors.initials: AT
authors.lastname: Haase
authors.affiliation: Institute for Emerging Infections, Department of Zoology, University of Oxford, Oxford, OX1 3PS, UK.
authors.forename: Angela R
authors.initials: AR
authors.lastname: McLean
authors.affiliation: Division of Infectious Diseases, Northwestern University Feinberg School of Medicine, Chicago, IL 60011, USA.
authors.forename: Steven M
authors.initials: SM
authors.lastname: Wolinsky
mesh_terms: D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D002353:Carrier State / Q000097:blood / Q000188:drug therapy* / Q000821:virology*; D024882:Drug Resistance, Viral / Q000187:drug effects; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy* / Q000821:virology*; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics / Q000254:growth & development* / Q000302:isolation & purification; D006239:Haplotypes / Q000187:drug effects; D006801:Humans; D008198:Lymph Nodes / Q000187:drug effects / Q000821:virology; D008954:Models, Biological; D008969:Molecular Sequence Data; D010802:Phylogeny; D012641:Selection, Genetic / Q000187:drug effects; D017422:Sequence Analysis, DNA; D062211:Spatio-Temporal Analysis; D013997:Time Factors; D019562:Viral Load / Q000187:drug effects; D014779:Virus Replication / Q000187:drug effects
chemical_list: D019380:Anti-HIV Agents
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