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2004 Fiscal Year Final Research Report Summary

Evaluation of residual viral replication by proviral DNA level and T cell turnover for optimization of HAART.

Research Project

Project/Area Number 14570422
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field 内科学一般
Research InstitutionKumamoto University

Principal Investigator

YOSHIMURA Kazuhisa  Kumamoto University, Center for AIDS Research, Assistant Professor, エイズ学研究センター, 助手 (60315306)

Project Period (FY) 2002 – 2004
KeywordsHIV-1 / residual replication / Turnover / HAART / proviral DNA / CD4^+ T cell
Research Abstract

Using a highly sensitive assay to detect proviral DNA(pDNA) and the turnover of T lymphocytes, we are attempting to optimize HAART to minimize residual viruses in patients with undetectable plasma viremia. The pDNA levels in PBMCs from HIV-1 positive patients were measured in the LTR region using a novel hypersensitive nested PCR. Quantitative real-time PCR fluorogenic assay was performed to detect pDNA after conventional first PCR. We also investigated CD4^+ and CD8^+ T cell turnover by measuring the nuclear antigen Ki-67 with four-color flow cytometry analysis. We measured the HIV pDNA level in PBMCs of 340 samples from viremic or aviremic patients. Among the patients with undetectable plasma viremia by HAART, the CD4^+ T cell count and CD4/8 ratio were significantly higher in patients with undetectable pDNA than in patients with detectable pDNA(p<0.01). We also followed a patient who has an option to choose treatment optimization based on results of pDNA and T-cell turnover. Significant decline of the pDNA level was observed when the regimen of HAART was optimized to a more potent combination. Both normalization of accelerated turnover of CD4^+ subset and decline of pDNA were observed after 30 months from the addition of efavirenz(EFV). Our study suggests that the measurement of both pDNA and T-cell turnover is suitable for evaluating the residual replication of HIV-1 in patients. Long-term successful treatment is achievable by providing these results with an informed choice of a potent combination of antiretrovirals.

  • Research Products

    (10 results)

All 2005 2004 2003 2002

All Journal Article (10 results)

  • [Journal Article] Spontaneous recovery of hemoglobin and neutrophil levels in Japanese patients on a long-term Combivir【○!R】 containing regimen.2005

    • Author(s)
      Matsushita, S.
    • Journal Title

      J.Clin.Virol. 33

      Pages: 188-193

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Amino acid insertions near Gag cleavage sites restore the otherwise compromised replication of human immunodeficiency virus type 1 variants resistant to protease inhibitors.2004

    • Author(s)
      Tamiya, S
    • Journal Title

      J.Virol. 78

      Pages: 12030-12040

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Amino acid insertions near Gag cleavage sites restore the otherwise compromised replication of human immunodeficiency virus type 1 variants resistant to protease inhibitors.2004

    • Author(s)
      Tamiya, S
    • Journal Title

      J.Virol 28

      Pages: 12030-12040

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] The impact of highly active antiretroviral therapy by the oral route on the CD8 subset in monkeys infected chronically with SHIV89.6P.2003

    • Author(s)
      Yoshimura, K
    • Journal Title

      J.Virol.Methods. 112

      Pages: 121-128

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] A Potent Protease Inhibitor (PI) UIC-94003 Interacting with Main Chains of HIV Protease Active Site Amino Acids and the Development of a Novel Mutation A28S in the Protease of UIC-94003-Resistant HIV.2002

    • Author(s)
      Yoshimura, K
    • Journal Title

      J.Virol. 76

      Pages: 1349-1358

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Reconstitution of spontaneous neutralizing antibody response against autologous HIV-1 in chronically infected patients during highly active antiretroviral therapy.2002

    • Author(s)
      Kimura, T.
    • Journal Title

      J.Infectious Diseases 185

      Pages: 53-60

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Emergence of autologous neutralization-resistant variants from pre existing quasi species during viral-rebound of human immunodeficiency virus type-1 infected patients undertreatment of highly active anti retroviral therapy (HAART).2002

    • Author(s)
      Wang, F.X.
    • Journal Title

      J.Infectious Diseases 185

      Pages: 608-617

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] A potent protease inhibitor(PI) UIC-94003 interacting with main chains of HIV protease active site amino acids and the development of a novel mutation A28S in the protease of UIC-94003-resistant HIV.2002

    • Author(s)
      Yoshimura, K
    • Journal Title

      J.Virol. 78

      Pages: 12030-12040

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Reconstitution of spontaneous neutralizing antibody response against autologous HIV-1 in chronically infected patients during highly active antiretroviral therapy.2002

    • Author(s)
      Kimura, T
    • Journal Title

      J.Infectious Diseases 185

      Pages: 53-60

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Emergence of autologous neutralization-resistant variants from pre existing quasi species during viral-rebound of human immunodeficiency virus type-1 infected patients undertreatment of highly active anti retroviral therapy(HAART).2002

    • Author(s)
      Wang, F.X.
    • Journal Title

      J.Infectious Diseases 185

      Pages: 608-617

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2006-07-11  

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