title: Discrepant responses to triple combination antiretroviral therapy in advanced HIV disease.
abstract: OBJECTIVE
  To determine the clinical, virological and immunological outcome in a cohort of unselected patients receiving triple combination therapy for more than 1 year.
  
  
  METHODS
  Prospective follow-up of a cohort of 162 unselected, protease inhibitor-naive, antiretroviral-experienced patients with advanced HIV disease, treated with indinavir combined with two nucleoside analogues.
  
  
  RESULTS
  The mean CD4 cell count and plasma HIV RNA level in the study group at baseline were 69+/-5 x 10(6)/l and 4.75+/-0.07 log10 copies/ml, respectively. Five per cent of patients died prematurely or were lost to follow-up. Fifty-seven per cent of patients responded to therapy, as assessed by a sustained increase in CD4 cell counts above 50 x 10(6)/l and a decrease in plasma HIV RNA greater than 1 log10 copies/ml, throughout 12.1 months of follow-up. Seventeen per cent of patients were immunological and virological non-responders. Twenty-one per cent of patients exhibited discrepant virological and immunological responses to treatment, of whom one-half failed to exhibit significant increases in CD4 cells despite a virological response to therapy and one-half exhibited increased CD4 cell counts in the absence of significant decrease in plasma viral load. The incidence of AIDS-defining events in the latter group of patients was similar to that of responder patients, whereas their incidence was higher in patients who failed to exhibit a virological and immunological response and those who failed to increase CD4 cells despite a significant decrease in viral load.
  
  
  CONCLUSIONS
  Our observations of discrepant immunological and virological responses to treatment raise the issue of the significance of persistent elevated levels of plasma HIV RNA and of the relevance of measurements of plasma viral load for assessing the efficacy of antiretroviral therapy in patients whose CD4 cell counts increase despite the absence of significant decrease in plasma HIV viral load.
authors.affiliation: Department of Immunology, INSERM U430 and Université Pierre et Marie Curie, Hôpital Broussais, Paris, France.
authors.forename: C
authors.initials: C
authors.lastname: Piketty
authors.forename: P
authors.initials: P
authors.lastname: Castiel
authors.forename: L
authors.initials: L
authors.lastname: Belec
authors.forename: D
authors.initials: D
authors.lastname: Batisse
authors.forename: A
authors.initials: A
authors.lastname: Si Mohamed
authors.forename: J
authors.initials: J
authors.lastname: Gilquin
authors.forename: G
authors.initials: G
authors.lastname: Gonzalez-Canali
authors.forename: D
authors.initials: D
authors.lastname: Jayle
authors.forename: M
authors.initials: M
authors.lastname: Karmochkine
authors.forename: L
authors.initials: L
authors.lastname: Weiss
authors.forename: J P
authors.initials: JP
authors.lastname: Aboulker
authors.forename: M D
authors.initials: MD
authors.lastname: Kazatchkine
mesh_terms: D000328:Adult; D000368:Aged; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D015331:Cohort Studies; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology / Q000821:virology; D017320:HIV Protease Inhibitors / Q000627:therapeutic use*; D006801:Humans; D019469:Indinavir / Q000627:therapeutic use*; D019259:Lamivudine / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use*; D018119:Stavudine / Q000627:therapeutic use*; D016896:Treatment Outcome; D015215:Zidovudine / Q000627:therapeutic use*
chemical_list: D019380:Anti-HIV Agents; D017320:HIV Protease Inhibitors; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine; D015215:Zidovudine; D019469:Indinavir; D018119:Stavudine