title: Absence of resistance mutations in antiretroviral-naive patients treated with ritonavir-boosted saquinavir.
abstract: BACKGROUND
  There are few data on the selection of resistance by ritonavir-boosted saquinavir (SQV/r), particularly in antiretroviral (ARV)-naive patients.
  
  
  OBJECTIVE
  To assess the incidence of virological failure and evolution of resistance in ARV-naive individuals receiving SQV/r in the induction phase of the Staccato trial.
  
  
  METHODS
  ARV-naive subjects (n = 272) received SQV/r 1,600/100 mg once daily with two nucleoside reverse transcriptase inhibitors (NRTIs) for at least 24 weeks. Patients were defined as having virological failure (VF) when there were two consecutive HIV-1 RNA measurements > 500 copies/ml after week 12. Viral genotypes (reverse transcriptase [RT] and protease [PRO]) were determined at baseline in all patients and as close as possible to the time of initial failure in patients experiencing VF.
  
  
  RESULTS
  VF was observed in 9/272 patients receiving SQV/r 1,600/100 mg once daily with two NRTIs (3.3%) and occurred 19-48 weeks after treatment initiation. Eight of these patients were evaluable at failure. No major PRO mutations were detected, but 2/8 displayed single new minor PRO substitutions (M36I, L10I) at VF that were known or suspected not to have been present at baseline; both these substitutions exist as natural polymorphisms. A third patient displayed a single new RT mutation (M184I).
  
  
  CONCLUSIONS
  SQV/r plus two NRTIs (1,600/100 mg once daily) is an effective initial treatment option for ARV-naive patients, resulting in a low rate of viral rebound (3.3%). Furthermore, no major protease mutations were detected following VF, suggesting that future treatment options are preserved.
authors.affiliation: The HIV Netherlands Australia Thailand Research Collaboration (HIV-NAT), Bangkok, Thailand. jintanat.a@hivnat.org
authors.forename: Jintanat
authors.initials: J
authors.lastname: Ananworanich
authors.forename: Bernard
authors.initials: B
authors.lastname: Hirschel
authors.forename: Sunee
authors.initials: S
authors.lastname: Sirivichayakul
authors.forename: Sasiwimol
authors.initials: S
authors.lastname: Ubolyam
authors.forename: Thidarat
authors.initials: T
authors.lastname: Jupimai
authors.forename: Wisit
authors.initials: W
authors.lastname: Prasithsirikul
authors.forename: Ploenchan
authors.initials: P
authors.lastname: Chetchotisakd
authors.forename: Sasisopin
authors.initials: S
authors.lastname: Kiertiburanakul
authors.forename: Warangkana
authors.initials: W
authors.lastname: Munsakul
authors.forename: Phitsanu
authors.initials: P
authors.lastname: Raksakulkarn
authors.forename: Somboon
authors.initials: S
authors.lastname: Tansuphasawadikul
authors.forename: Malte
authors.initials: M
authors.lastname: Schutz
authors.forename: Wendy
authors.initials: W
authors.lastname: Snowden
authors.forename: Kiat
authors.initials: K
authors.lastname: Ruxrungtham
mesh_terms: D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D024882:Drug Resistance, Viral / Q000235:genetics*; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000201:enzymology / Q000821:virology; D016333:HIV Protease / Q000235:genetics* / Q000378:metabolism; D017320:HIV Protease Inhibitors / Q000627:therapeutic use*; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D015497:HIV-1 / Q000201:enzymology / Q000235:genetics*; D006801:Humans; D008297:Male; D009154:Mutation; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use; D019438:Ritonavir / Q000627:therapeutic use*; D019258:Saquinavir / Q000627:therapeutic use*; D013785:Thailand; D017211:Treatment Failure; D019562:Viral Load
chemical_list: D017320:HIV Protease Inhibitors; D018894:Reverse Transcriptase Inhibitors; D054303:HIV Reverse Transcriptase; D016333:HIV Protease; D019258:Saquinavir; D019438:Ritonavir