title: Lamivudine and indinavir/ritonavir maintenance therapy in highly pretreated HIV-infected patients (Vista ANRS 109).
abstract: OBJECTIVE
  In patients with extensive HIV resistance, one option is to delay salvage therapy until new drugs become available. We hypothesized that this delay period could be based on a simplified treatment, which would reduce drug toxicity, stabilize resistance, and prevent resurgence of wild-type virus.
  
  
  METHODS
  A prospective 24-week treatment simplification study in HIV-1-infected patients having failed several lines of antiretroviral therapy, with CD4+ T-cell counts > or = 100 cells/ml, plasma HIV RNA (viral load [VL]) > or = 4 log10 copies/ml and a resistance genotype predicting less than two active drugs. Treatment associated ritonavir-boosted low-dose indinavir (200 mg twice daily) and lamivudine (150 mg twice daily). The primary endpoint was a decrease in CD4+ T-cell counts > or = 25% or increase in VL > or = 0.7 log copies/ml relative to baseline.
  
  
  RESULTS
  Twenty-six patients were included. Baseline median VL was 4.5 log10 copies/ml and median CD4+ T-cell count was 290 cells/ml. During the study, 10/26 patients (38%, 95% confidence interval = 20.2-59.4) reached the primary endpoint. No patient had an AIDS-defining event. At week 24, the median change in plasma VL was +0.2 log10 copies/ml (interquartile range (IQR): 0-0.5; P = 0.003). The median change in CD4+ T-cell counts was -49 cells/ml (IQR: -14 to -93, P < 0.001), with a median decline slope of 10 cells/ml/month, which was not different from that measured under full highly active antiretroviral therapy during the 6 months preceding inclusion. There were no significant changes in HIV-1 protease and reverse transcriptase genotypes during the study.
  
  
  CONCLUSIONS
  In patients with advanced resistance, treatment simplification prevented resurgence of wild-type HIV, reduced drug burden, but failed to stabilize progression of the immune deficiency.
authors.affiliation: Faculté de Médecine, Université Paris-Descartes, Service de Medecine Interne, Hopital Cochin, AP-HP, Paris, France.
authors.forename: Odile
authors.initials: O
authors.lastname: Launay
authors.forename: Xavier
authors.initials: X
authors.lastname: Duval
authors.forename: Cécile
authors.initials: C
authors.lastname: Dalban
authors.forename: Diane
authors.initials: D
authors.lastname: Descamps
authors.forename: Gilles
authors.initials: G
authors.lastname: Peytavin
authors.forename: Agnès
authors.initials: A
authors.lastname: Certain
authors.forename: Saïd
authors.initials: S
authors.lastname: Mouajjah
authors.forename: Pascal
authors.initials: P
authors.lastname: Ralaimazava
authors.forename: Renaud
authors.initials: R
authors.lastname: Verdon
authors.forename: Dominique
authors.initials: D
authors.lastname: Costagliola
authors.forename: François
authors.initials: F
authors.lastname: Clavel
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage*; D018791:CD4 Lymphocyte Count; D004334:Drug Administration Schedule; D024882:Drug Resistance, Viral; D023381:Endpoint Determination; D005260:Female; D005602:France; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D016333:HIV Protease / Q000235:genetics; D017320:HIV Protease Inhibitors / Q000008:administration & dosage; D054303:HIV Reverse Transcriptase / Q000235:genetics; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D019469:Indinavir / Q000008:administration & dosage / Q000627:therapeutic use*; D019259:Lamivudine / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D019438:Ritonavir / Q000008:administration & dosage*; D013045:Species Specificity; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents; D017320:HIV Protease Inhibitors; D019259:Lamivudine; D019469:Indinavir; D054303:HIV Reverse Transcriptase; D016333:HIV Protease; D019438:Ritonavir