Viral sanctuaries during highly active antiretroviral therapy in a nonhuman primate model for AIDS

Thomas W. North, Joanne Higgins, Jesse D. Deere, Timothy L. Hayes, Andradi Villalobos, Lourdes Adamson, Barbara Shacklett, Raymond F. Schinazi, Paul A Luciw

Research output: Contribution to journalArticle

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Abstract

Highly active antiretroviral therapy (HAART) enables long-term suppression of plasma HIV-1 loads in infected persons, but low-level virus persists and rebounds following cessation of therapy. During HAART, this virus resides in latently infected cells, such as resting CD4+ T cells, and in other cell types that may support residual virus replication. Therapeutic eradication will require elimination of virus from all reservoirs. We report here a comprehensive analysis of these reservoirs in fluids, cells, and tissues in a rhesus macaque model that mimics HAART in HIV-infected humans. This nonhuman primate model uses RT-SHIV, a chimera of simian immunodeficiency virus containing the HIV-1 reverse transcriptase (RT). Methods were developed for extraction, preamplification, and real-time PCR analyses of viral DNA (vDNA) and viral RNA (vRNA) in tissues from RT-SHIV-infected macaques. These methods were used to identify viral reservoirs in RT-SHIV-infected macaques treated with a potent HAART regimen consisting of efavirenz, emtricitabine, and tenofovir. Plasma virus loads at necropsy ranged from 11 to 28 copies of vRNA per ml. Viral RNA and DNA were detected during HAART, in tissues from numerous anatomical locations. Additional analysis provided evidence for full-length viral RNA in tissues of animals with virus suppressed by HAART. The highest levels of vDNA and vRNA in HAART-treated macaques were in lymphoid tissues, particularly the spleen, lymph nodes, and gastrointestinal tract tissues. This study is the first comprehensive analysis of the tissue and organ distribution of a primate AIDS virus during HAART. These data demonstrate widespread persistence of residual virus in tissues during HAART.

Original languageEnglish (US)
Pages (from-to)2913-2922
Number of pages10
JournalJournal of Virology
Volume84
Issue number6
DOIs
StatePublished - Mar 2010

Fingerprint

Highly Active Antiretroviral Therapy
Primates
Acquired Immunodeficiency Syndrome
animal models
therapeutics
Viral RNA
Viruses
RNA-directed DNA polymerase
RNA-Directed DNA Polymerase
Viral DNA
Macaca
viruses
RNA
Tenofovir
efavirenz
Human immunodeficiency virus 1
HIV
DNA
Simian Immunodeficiency Virus
Simian immunodeficiency virus

ASJC Scopus subject areas

  • Immunology
  • Virology

Cite this

Viral sanctuaries during highly active antiretroviral therapy in a nonhuman primate model for AIDS. / North, Thomas W.; Higgins, Joanne; Deere, Jesse D.; Hayes, Timothy L.; Villalobos, Andradi; Adamson, Lourdes; Shacklett, Barbara; Schinazi, Raymond F.; Luciw, Paul A.

In: Journal of Virology, Vol. 84, No. 6, 03.2010, p. 2913-2922.

Research output: Contribution to journalArticle

North, TW, Higgins, J, Deere, JD, Hayes, TL, Villalobos, A, Adamson, L, Shacklett, B, Schinazi, RF & Luciw, PA 2010, 'Viral sanctuaries during highly active antiretroviral therapy in a nonhuman primate model for AIDS', Journal of Virology, vol. 84, no. 6, pp. 2913-2922. https://doi.org/10.1128/JVI.02356-09
North TW, Higgins J, Deere JD, Hayes TL, Villalobos A, Adamson L et al. Viral sanctuaries during highly active antiretroviral therapy in a nonhuman primate model for AIDS. Journal of Virology. 2010 Mar;84(6):2913-2922. https://doi.org/10.1128/JVI.02356-09
North, Thomas W. ; Higgins, Joanne ; Deere, Jesse D. ; Hayes, Timothy L. ; Villalobos, Andradi ; Adamson, Lourdes ; Shacklett, Barbara ; Schinazi, Raymond F. ; Luciw, Paul A. / Viral sanctuaries during highly active antiretroviral therapy in a nonhuman primate model for AIDS. In: Journal of Virology. 2010 ; Vol. 84, No. 6. pp. 2913-2922.
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