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'.
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'.
Authors: Matthew Bidwell Goetz; Monique R Ferguson; Xueliang Han; Greg McMillan; Marty St Clair; Keith A Pappa; Daniel R McClernon; William A O'Brien Journal: J Acquir Immune Defic Syndr Date: 2006-12-15 Impact factor: 3.731