Format

Send to:

Choose Destination
See comment in PubMed Commons below
Antimicrob Agents Chemother. 2014 Jul;58(7):3927-33. doi: 10.1128/AAC.02522-14. Epub 2014 Apr 28.

Enhanced antiretroviral therapy in rhesus macaques improves RT-SHIV viral decay kinetics.

Author information

  • 1Center for AIDS Research, Emory University School of Medicine, Atlanta, Georgia, USA Atlanta Veterans Affairs Medical Center, Decatur, Georgia, USA University of California Davis, Davis, California, USA.
  • 2Center for AIDS Research, Emory University School of Medicine, Atlanta, Georgia, USA.
  • 3Center for AIDS Research, Emory University School of Medicine, Atlanta, Georgia, USA Atlanta Veterans Affairs Medical Center, Decatur, Georgia, USA.
  • 4University of California Davis, Davis, California, USA.
  • 5Center for AIDS Research, Emory University School of Medicine, Atlanta, Georgia, USA Atlanta Veterans Affairs Medical Center, Decatur, Georgia, USA rschina@emory.edu.

Abstract

Using an established nonhuman primate model, rhesus macaques were infected intravenously with a chimeric simian immunodeficiency virus (SIV) consisting of SIVmac239 with the human immunodeficiency virus type 1 (HIV-1) reverse transcriptase from clone HXBc2 (RT-SHIV). The impacts of two enhanced (four- and five-drug) highly active antiretroviral therapies (HAART) on early viral decay and rebound were determined. The four-drug combination consisted of an integrase inhibitor, L-870-812 (L-812), together with a three-drug regimen comprising emtricitabine [(-)-FTC], tenofovir (TFV), and efavirenz (EFV). The five-drug combination consisted of one analog for each of the four DNA precursors {using TFV, (-)-FTC, (-)-β-D-(2R,4R)-1,3-dioxolane-2,6-diaminopurine (amdoxovir [DAPD]), and zidovudine (AZT)}, together with EFV. A cohort treated with a three-drug combination of (-)-FTC, TFV, and EFV served as treated controls. Daily administration of a three-, four-, or five-drug combination of antiretroviral agents was initiated at week 6 or 8 after inoculation and continued up to week 50, followed by a rebound period. Plasma samples were collected routinely, and drug levels were monitored using liquid chromatography-tandem mass spectrometry (LC-MS-MS). Viral loads were monitored with a standard TaqMan quantitative reverse transcriptase PCR (qRT-PCR) assay. Comprehensive analyses of replication dynamics were performed. RT-SHIV infection in rhesus macaques produced typical viral infection kinetics, with untreated controls establishing persistent viral loads of >10(4) copies of RNA/ml. RT-SHIV loads at the start of treatment (V0) were similar in all treated cohorts (P > 0.5). All antiretroviral drug levels were measureable in plasma. The four-drug and five-drug combination regimens (enhanced HAART) improved suppression of the viral load (within 1 week; P < 0.01) and had overall greater potency (P < 0.02) than the three-drug regimen (HAART). Moreover, rebound viremia occurred rapidly following cessation of any treatment. The enhanced HAART (four- or five-drug combination) showed significant improvement in viral suppression compared to the three-drug combination, but no combination was sufficient to eliminate viral reservoirs.

Copyright © 2014, American Society for Microbiology. All Rights Reserved.

PMID:
24777106
[PubMed - in process]
PMCID:
PMC4068512
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Write to the Help Desk