title: Baseline HIV drug resistance profile predicts response to ritonavir-saquinavir protease inhibitor therapy in a community setting.
abstract: OBJECTIVE
  To determine whether baseline drug resistance assays could help to predict treatment failure with the protease inhibitor combination ritonavir-saquinavir.
  
  
  METHODS
  Baseline HIV-1 drug resistance was determined for 76 consecutive patients who started treatment with the dual protease inhibitor combination ritonavir-saquinavir between September 1996 and June 1997 either alone or in combination with other antiviral agents. Resistance to 10 different antiviral agents was assessed by both phenotype (Virco Antivirogram) and genotype (Vircogen).
  
  
  RESULTS
  Resistance inferred from viral genotype was similar to measured phenotypic resistance for both ritonavir and saquinavir (P<0.01). Baseline drug resistance phenotype was predictive of poor virological response to this dual protease inhibitor combination, despite the confounding effects of other antivirals. Patients were at least four times less likely to achieve a 0.5 log10 decrease in plasma HIV RNA viral load if their viral isolates were resistant to ritonavir or saquinavir. Patients classified as resistant to either drug using either method had median decreases in plasma viral load of 0.05 log10 HIV RNA copies/ml or less, compared to >0.8 log10 for those with sensitive virus. Patients resistant to both drugs never achieved plasma viral loads <100000 copies/ml. As little as fourfold increases in baseline resistance appeared to be sufficient to compromise even dual protease inhibitor therapy.
  
  
  CONCLUSIONS
  Baseline resistance to ritonavir or saquinavir or both was associated with a poor antiviral response. Our data suggest that the measurement of drug resistance may assist in optimizing antiretroviral therapy in the clinic.
authors.affiliation: British Columbia Centre for Excellence in HIV/AIDS, Vancouver, Canada.
authors.forename: P R
authors.initials: PR
authors.lastname: Harrigan
authors.forename: K
authors.initials: K
authors.lastname: Hertogs
authors.forename: W
authors.initials: W
authors.lastname: Verbiest
authors.forename: R
authors.initials: R
authors.lastname: Pauwels
authors.forename: B
authors.initials: B
authors.lastname: Larder
authors.forename: S
authors.initials: S
authors.lastname: Kemp
authors.forename: S
authors.initials: S
authors.lastname: Bloor
authors.forename: B
authors.initials: B
authors.lastname: Yip
authors.forename: R
authors.initials: R
authors.lastname: Hogg
authors.forename: C
authors.initials: C
authors.lastname: Alexander
authors.forename: J S
authors.initials: JS
authors.lastname: Montaner
mesh_terms: D019380:Anti-HIV Agents / Q000627:therapeutic use*; D004352:Drug Resistance, Microbial; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D015658:HIV Infections / Q000188:drug therapy*; D017320:HIV Protease Inhibitors / Q000627:therapeutic use*; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development; D006801:Humans; D008297:Male; D011237:Predictive Value of Tests; D012111:Residence Characteristics; D019438:Ritonavir / Q000627:therapeutic use*; D019258:Saquinavir / Q000627:therapeutic use*; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents; D017320:HIV Protease Inhibitors; D019258:Saquinavir; D019438:Ritonavir