title: Efficacy and tolerability of a double boosted protease inhibitor (lopinavir + saquinavir/ritonavir) regimen in HIV-infected patients who failed treatment with nonnucleoside reverse transcriptase inhibitors.
abstract: OBJECTIVE
  Long-term nonnucleoside reverse transcriptase inhibitor (NNRTI)-based antiretroviral treatment failure in most developing countries has led to broad cross-resistance within NNRTI and nucleoside reverse transcriptase inhibitor (NRTI) classes. In this study, we investigated the efficacy and tolerability of a double boosted protease inhibitor (PI) regimen in this setting.
  
  
  METHODS
  A total of 64 HIV-infected patients who had failed NNRTI-based regimens were randomized to receive either lopinavir/saquinavir/ritonavir [LPV/SQV/r; 400/1000/100 mg twice a day (bid)] alone or indinavir/ritonavir (IDV/r; 800/100 mg bid) plus two NRTIs optimized with genotypic drug resistance guidance. Patients who had no available optimized NRTI backbone were allocated to the LPV/SQV/r arm.
  
  
  RESULTS
  At 48 weeks, the percentages of patients with plasma viral load<50 HIV-1 RNA copies/mL were 60% (31 of 52 patients) in the LPV/SQV/r arm vs 50% (six of 12) in the IDV/r/2NRTIs arm in the intent-to-treat (ITT) analysis, and 61% (31 of 51) vs 71% (five of seven), respectively, in the as-treated analysis. The median (interquartile range) increases in absolute CD4 cell count from baseline were 177 (91-269) and 100 (52-225) cells/microL in the LPV/SQV/r and IDV/r/2NRTIs groups, respectively (P=0.32). Four of 12 patients (33%) in the IDV/r/2NRTIs group experienced severe nausea and vomiting and four patients (8%) in the LPV/SQV/r group had significant hepatitis.
  
  
  CONCLUSIONS
  LPV/SQV/r and high-dose boosted IDV were not well tolerated and led to <65% ITT virological efficacy outcomes. A randomized larger scale study with new formulations and/or more tolerable boosted PIs in NNRTI-based failure is warranted.
authors.affiliation: Srinagarind Hospital, Khon Kaen University, Khon Kaen, Thailand. ploencha@kku.ac.th
authors.forename: P
authors.initials: P
authors.lastname: Chetchotisakd
authors.forename: S
authors.initials: S
authors.lastname: Anunnatsiri
authors.forename: P
authors.initials: P
authors.lastname: Mootsikapun
authors.forename: S
authors.initials: S
authors.lastname: Kiertiburanakul
authors.forename: T
authors.initials: T
authors.lastname: Anekthananon
authors.forename: C
authors.initials: C
authors.lastname: Bowonwatanuwong
authors.forename: B
authors.initials: B
authors.lastname: Kowadisaiburana
authors.forename: K
authors.initials: K
authors.lastname: Supparatpinyo
authors.forename: K
authors.initials: K
authors.lastname: Ruxrungtham
mesh_terms: D000328:Adult; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D017320:HIV Protease Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D012367:RNA, Viral; D019438:Ritonavir / Q000494:pharmacology / Q000627:therapeutic use*; D016879:Salvage Therapy / Q000379:methods; D019258:Saquinavir / Q000494:pharmacology / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D017320:HIV Protease Inhibitors; D012367:RNA, Viral; D019258:Saquinavir; D019438:Ritonavir