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Nat Commun. 2018 Nov 16;9(1):4811. doi: 10.1038/s41467-018-06843-5.

A majority of HIV persistence during antiretroviral therapy is due to infected cell proliferation.

Author information

1
Vaccine and Infectious Diseases Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave., Seattle, WA, 98122, USA.
2
Department of Medicine, University of Washington, 1959 NE Pacific St., Seattle, WA, 98195, USA.
3
Department of Pediatrics, University of Washington, 1959 NE Pacific St., Seattle, WA, 98195, USA.
4
Center for Global Infectious Disease Research, Seattle Children's Research Institute, 1900 9th Ave., Seattle, WA, 98101, USA.
5
Centre for Virus Research, The Westmead Institute for Medical Research, University of Sydney, 176 Hawkesbury Rd., Sydney, NSW, 2145, Australia.
6
Department of Medicine, University of Utah, 30N 1900 E, Salt Lake City, UT, 84132, USA.
7
Vaccine and Infectious Diseases Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave., Seattle, WA, 98122, USA. jschiffe@fhcrc.org.
8
Department of Medicine, University of Washington, 1959 NE Pacific St., Seattle, WA, 98195, USA. jschiffe@fhcrc.org.
9
Clinical Research Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave., Seattle, WA, 98122, USA. jschiffe@fhcrc.org.

Abstract

Antiretroviral therapy (ART) suppresses viral replication in people living with HIV. Yet, infected cells persist for decades on ART and viremia returns if ART is stopped. Persistence has been attributed to viral replication in an ART sanctuary and long-lived and/or proliferating latently infected cells. Using ecological methods and existing data, we infer that >99% of infected cells are members of clonal populations after one year of ART. We reconcile our results with observations from the first months of ART, demonstrating mathematically how a fossil record of historic HIV replication permits observed viral evolution even while most new infected cells arise from proliferation. Together, our results imply cellular proliferation generates a majority of infected cells during ART. Therefore, reducing proliferation could decrease the size of the HIV reservoir and help achieve a functional cure.

PMID:
30446650
PMCID:
PMC6240116
DOI:
10.1038/s41467-018-06843-5
[Indexed for MEDLINE]
Free PMC Article

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