Persistent HIV-1 replication maintains the tissue reservoir during therapy

Ramon Lorenzo-Redondo, Helen R. Fryer, Trevor Bedford, Eun-Young Kim, John Archer, Sergei L. Kosakovsky Pond, Yoon-Seok Chung, Sudhir Penugonda, Jeffrey G. Chipman, Courtney V. Fletcher, Timothy W. Schacker, Michael H. Malim, Andrew Rambaut, Ashley T. Haase, Angela R. McLean and Steven M. Wolinsky ()
Additional contact information
Ramon Lorenzo-Redondo: Northwestern University Feinberg School of Medicine
Helen R. Fryer: Institute for Emerging Infections, University of Oxford
Trevor Bedford: Fred Hutchinson Cancer Research Center
Eun-Young Kim: Northwestern University Feinberg School of Medicine
John Archer: Centro de Investigação em Biodiversidade e Recursos Genéticos Universidade do Porto
Sergei L. Kosakovsky Pond: University of California, San Diego
Yoon-Seok Chung: Center for Immunology and Pathology, Korea National Institutes of Health
Sudhir Penugonda: Northwestern University Feinberg School of Medicine
Jeffrey G. Chipman: University of Minnesota
Courtney V. Fletcher: Antiviral Pharmacology Laboratory, University of Nebraska Medical Center, College of Pharmacy
Timothy W. Schacker: University of Minnesota
Michael H. Malim: King’s College London, Guy’s Hospital
Andrew Rambaut: Centre for Immunology, Infection and Evolution, University of Edinburgh
Ashley T. Haase: University of Minnesota
Angela R. McLean: Institute for Emerging Infections, University of Oxford
Steven M. Wolinsky: Northwestern University Feinberg School of Medicine

Nature, 2016, vol. 530, issue 7588, 51-56

Abstract: 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.

Date: 2016
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DOI: 10.1038/nature16933

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