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Preparation and Use of HIV-1 Infected Primary CD4+ T-Cells as Target Cells in Natural Killer Cell Cytotoxic Assays
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Preparation and Use of HIV-1 Infected Primary CD4+ T-Cells as Target Cells in Natural Killer Cell Cytotoxic Assays

Published on: March 14, 2011

Protease inhibitor-resistant HIV-1 from patients with preserved CD4 cell counts is cytopathic in activated CD4 T

T J Liegler1, M S Hayden, K H Lee

  • 1Gladstone Institute of Virology and Immunology, San Francisco, California 94141-9100, USA.

AIDS (London, England)
|February 24, 2001
PubMed
Abstract

Insights

Protease inhibitor-resistant HIV isolates from patients with stable CD4 counts are as cytopathic as sensitive strains. Virus cytopathicity is mainly determined by coreceptor preference, not drug resistance.

Area of Science:

  • Virology
  • Immunology
  • HIV Research

Background:

  • Long-term virologic failure in HIV patients on protease inhibitor (PI) therapy can lead to PI-resistant viral strains.
  • Some patients maintain stable or increasing CD4 T-cell counts despite virologic failure, suggesting compensatory mechanisms.
  • The cytopathicity of PI-resistant HIV isolates and its impact on CD4 T-cell counts require further investigation.

Purpose of the Study:

  • To evaluate the CD4 T-cell cytopathicity of protease inhibitor (PI)-resistant HIV isolates from patients with preserved CD4 cell counts after long-term virologic failure.
  • To compare the cytopathicity of PI-resistant isolates with PI-sensitive isolates.
  • To determine factors influencing the cytopathicity of PI-resistant HIV.

Main Methods:

  • Primary HIV-1 isolates from 14 patients with virologic failure on PI therapy were analyzed.
  • Replication and cytopathicity were assessed in peripheral blood mononuclear cell cultures.
  • Coreceptor use, syncytia-inducing (SI) phenotype, and protease sequences were determined.

Main Results:

  • PI-resistant isolates from patients on therapy showed decreased PI susceptibility.
  • PI-resistant syncytia-inducing (SI) isolates were highly to moderately cytopathic; non-SI isolates were less cytopathic.
  • The cytopathicity of PI-resistant isolates was similar to PI-sensitive isolates and not altered by PI presence.

Conclusions:

  • Primary PI-resistant HIV isolates from patients with virologic rebound but stable CD4 counts are as cytopathic as PI-sensitive isolates.
  • Coreceptor preference, not PI resistance, primarily determines HIV cytopathicity.
  • Sustained immune responses after PI regimen failure are not due to less cytopathic PI-resistant strains.

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