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, Steven M. Wolinsky

Research output: Contribution to journalArticle

266 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)51-56
Number of pages6
JournalNature
Volume530
Issue number7588
DOIs
StatePublished - Feb 4 2016

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Lymphoid Tissue
HIV-1
Viruses
Viral RNA
Population Dynamics
Virus Diseases
Drug Combinations
Virus Replication
Antigen-Antibody Complex
Drug Resistance
Virion
Therapeutics
Infection
Pharmaceutical Preparations

ASJC Scopus subject areas

  • General

Cite this

Lorenzo-Redondo, R., Fryer, H. R., Bedford, T., Kim, E. Y., Archer, J., Kosakovsky Pond, S. L., ... Wolinsky, S. M. (2016). Persistent HIV-1 replication maintains the tissue reservoir during therapy. Nature, 530(7588), 51-56. https://doi.org/10.1038/nature16933

Persistent HIV-1 replication maintains the tissue reservoir during therapy. / Lorenzo-Redondo, Ramon; Fryer, Helen R.; Bedford, Trevor; Kim, Eun Young; Archer, John; Kosakovsky Pond, Sergei L.; Chung, Yoon Seok; Penugonda, Sudhir; Chipman, Jeffrey G.; Fletcher, Courtney V; Schacker, Timothy W.; Malim, Michael H.; Rambaut, Andrew; Haase, Ashley T.; McLean, Angela R.; Wolinsky, Steven M.

In: Nature, Vol. 530, No. 7588, 04.02.2016, p. 51-56.

Research output: Contribution to journalArticle

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 2016, 'Persistent HIV-1 replication maintains the tissue reservoir during therapy', Nature, vol. 530, no. 7588, pp. 51-56. https://doi.org/10.1038/nature16933
Lorenzo-Redondo R, Fryer HR, Bedford T, Kim EY, Archer J, Kosakovsky Pond SL et al. Persistent HIV-1 replication maintains the tissue reservoir during therapy. Nature. 2016 Feb 4;530(7588):51-56. https://doi.org/10.1038/nature16933
Lorenzo-Redondo, Ramon ; Fryer, Helen R. ; Bedford, Trevor ; Kim, Eun Young ; Archer, John ; Kosakovsky Pond, Sergei L. ; Chung, Yoon Seok ; Penugonda, Sudhir ; Chipman, Jeffrey G. ; Fletcher, Courtney V ; Schacker, Timothy W. ; Malim, Michael H. ; Rambaut, Andrew ; Haase, Ashley T. ; McLean, Angela R. ; Wolinsky, Steven M. / Persistent HIV-1 replication maintains the tissue reservoir during therapy. In: Nature. 2016 ; Vol. 530, No. 7588. pp. 51-56.
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