Viral decay kinetics in the highly active antiretroviral therapy-treated rhesus macaque model of AIDS

Jesse D. Deere, Joanne Higgins, Elda Cannavo, Andradi Villalobos, Lourdes Adamson, Emilie Fromentin, Raymond F. Schinazi, Paul A Luciw, Thomas W. North

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

To prevent progression to AIDS, persons infected with human immunodeficiency virus type 1 (HIV-1) must remain on highly active antiretroviral therapy (HAART) indefinitely since this modality does not eradicate the virus. The mechanisms involved in viral persistence during HAART are poorly understood, but an animal model of HAART could help elucidate these mechanisms and enable studies of HIV-1 eradication strategies. Due to the specificity of non-nucleoside reverse transcriptase (RT) inhibitors (NNRTIs) for HIV-1, we have used RT-SHIV, a chimeric virus of simian immunodeficiency virus with RT from HIV-1. This virus is susceptible to NNRTIs and causes an AIDS-like disease in rhesus macaques. In this study, two groups of HAART-treated, RT-SHIV-infected macaques were analyzed to determine viral decay kinetics. In the first group, viral loads were monitored with a standard TaqMan RT-PCR assay with a limit of detection of 50 viral RNA copies per mL. Upon initiation of HAART, viremia decayed in a bi-phasic manner with half-lives of 1.7 and 8.5 days, respectively. A third phase was observed with little further decay. In the second group, the macaques were followed longitudinally with a more sensitive assay utilizing ultracentrifugation to concentrate virus from plasma. Bi-phasic decay of viral RNA was also observed in these animals with half-lives of 1.8 and 5.8 days. Viral loads in these animals during a third phase ranged from 2-58 RNA copies/mL, with little decay over time. The viral decay kinetics observed in these macaques are similar to those reported for HIV-1 infected humans. These results demonstrate that low-level viremia persists in RT-SHIV-infected macaques despite a HAART regimen commonly used in humans.

Original languageEnglish (US)
Article numbere11640
JournalPLoS One
Volume5
Issue number7
DOIs
StatePublished - 2010

Fingerprint

RNA-directed DNA polymerase
Highly Active Antiretroviral Therapy
Macaca mulatta
Viruses
Human immunodeficiency virus 1
Acquired Immunodeficiency Syndrome
deterioration
HIV-1
Macaca
kinetics
RNA-Directed DNA Polymerase
therapeutics
Kinetics
viruses
Reverse Transcriptase Inhibitors
Viremia
viremia
Viral RNA
RNA
viral load

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Deere, J. D., Higgins, J., Cannavo, E., Villalobos, A., Adamson, L., Fromentin, E., ... North, T. W. (2010). Viral decay kinetics in the highly active antiretroviral therapy-treated rhesus macaque model of AIDS. PLoS One, 5(7), [e11640]. https://doi.org/10.1371/journal.pone.0011640

Viral decay kinetics in the highly active antiretroviral therapy-treated rhesus macaque model of AIDS. / Deere, Jesse D.; Higgins, Joanne; Cannavo, Elda; Villalobos, Andradi; Adamson, Lourdes; Fromentin, Emilie; Schinazi, Raymond F.; Luciw, Paul A; North, Thomas W.

In: PLoS One, Vol. 5, No. 7, e11640, 2010.

Research output: Contribution to journalArticle

Deere, JD, Higgins, J, Cannavo, E, Villalobos, A, Adamson, L, Fromentin, E, Schinazi, RF, Luciw, PA & North, TW 2010, 'Viral decay kinetics in the highly active antiretroviral therapy-treated rhesus macaque model of AIDS', PLoS One, vol. 5, no. 7, e11640. https://doi.org/10.1371/journal.pone.0011640
Deere, Jesse D. ; Higgins, Joanne ; Cannavo, Elda ; Villalobos, Andradi ; Adamson, Lourdes ; Fromentin, Emilie ; Schinazi, Raymond F. ; Luciw, Paul A ; North, Thomas W. / Viral decay kinetics in the highly active antiretroviral therapy-treated rhesus macaque model of AIDS. In: PLoS One. 2010 ; Vol. 5, No. 7.
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