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

• Published in: PloS one 2010-07, Vol.5 (7), p.e11640-e11640
• Main Authors: Deere, Jesse D, Higgins, Joanne, Cannavo, Elda, Villalobos, Andradi, Adamson, Lourdes, Fromentin, Emilie, Schinazi, Raymond F, Luciw, Paul A, North, Thomas W
• Format: Article
• Language: English
• Subjects: Acquired immune deficiency syndrome; AIDS; AIDS (Disease); Analysis; Animals; Antiretroviral agents; Antiretroviral drugs; Antiretroviral Therapy, Highly Active - methods; Benzoxazines - therapeutic use; Chromatography, High Pressure Liquid; Cloning; Decay; DNA polymerases; Drug therapy; Half-life; Highly active antiretroviral therapy; HIV; HIV Reverse Transcriptase - genetics; HIV-1 - genetics; Human immunodeficiency virus; Human immunodeficiency virus 1; Hypotheses; Infections; Kinetics; Laboratories; Leukemia; Macaca; Macaca mulatta; Medicine; Pediatrics; Polymerase chain reaction; Reverse engineering; Reverse Transcriptase Inhibitors - therapeutic use; Reverse Transcriptase Polymerase Chain Reaction; Ribonucleic acid; RNA; RNA-directed DNA polymerase; Simian Acquired Immunodeficiency Syndrome - drug therapy; Simian Acquired Immunodeficiency Syndrome - virology; Simian immunodeficiency virus; Simian Immunodeficiency Virus - genetics; Simian Immunodeficiency Virus - physiology; Therapy; Ultracentrifugation; Vaccines; Viremia; Viremia - pathology; Virology/Animal Models of Infection; Virology/Antivirals, including Modes of Action and Resistance; Virology/Immunodeficiency Viruses; Virology/Persistence and Latency; Viruses
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0011640

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.