Duration and predictors of CD4 T-cell gains in patients who continue combination therapy despite detectable plasma viremia

AIDS. 2002 Jan 25;16(2):201-7. doi: 10.1097/00002030-200201250-00009.

Abstract

Background: Sustained elevations in CD4 cell counts commonly occur despite incomplete viral suppression with protease inhibitor-based antiretroviral therapy.

Objectives: To determine the incidence and risk factors associated with return of CD4 cell count to pre-therapy levels in patients experiencing virologic failure of protease inhibitor therapy.

Design: This is a clinic-based cohort study of HIV-infected adults who failed to maintain durable viral suppression on a protease inhibitor-based regimen.

Main outcome measures: Virologic failure was defined as persistent plasma HIV RNA level > 500 copies/ml. Immunologic failure was defined as return of CD4 cell count to pre-therapy levels.

Results: A total of 291 patients experienced virologic failure on a protease inhibitor-based regimen and had a treatment-mediated CD4 cell increase above pre-therapy levels at the time of virologic failure. If patient data were censored at the time a successful salvage regimen was initiated, then the median time to immunologic failure after the onset of virologic failure was 3 years. If patient data were also censored at the time therapy was discontinued, then 36.8% of the cohort experienced immunologic failure after 3 years of continuous virologic failure. The change in viral load from a pre-treatment baseline, and not the absolute level of viremia achieved, was a strong and independent predictor of immunologic failure. Discontinuing therapy was associated with immunologic failure independent of viral load changes.

Conclusion: Reduction in T CD4+ cell numbers may eventually occur during prolonged virologic failure of a protease inhibitor-based regimen and is predicted by the degree of virologic suppression below a pre-therapy 'set-point'.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Antiretroviral Therapy, Highly Active
  • CD4 Lymphocyte Count
  • CD4-Positive T-Lymphocytes / cytology
  • CD4-Positive T-Lymphocytes / drug effects*
  • Disease Progression
  • HIV Infections / blood
  • HIV Infections / drug therapy*
  • HIV Infections / immunology
  • HIV Infections / virology
  • HIV Protease Inhibitors / therapeutic use*
  • HIV-1 / drug effects*
  • HIV-1 / genetics
  • Humans
  • Indinavir / therapeutic use
  • Nelfinavir / therapeutic use
  • RNA, Viral / blood
  • Ritonavir / therapeutic use
  • Saquinavir / therapeutic use
  • Time Factors
  • Treatment Failure
  • Viremia / blood
  • Viremia / drug therapy*
  • Viremia / immunology
  • Viremia / virology

Substances

  • HIV Protease Inhibitors
  • RNA, Viral
  • Indinavir
  • Nelfinavir
  • Saquinavir
  • Ritonavir