title: The pharmacokinetics, safety, and initial virologic response of a triple-protease inhibitor salvage regimen containing amprenavir, saquinavir, and ritonavir.
abstract: The aim of this study was to quantify the change in saquinavir and amprenavir exposure when combined and used with low-dose ritonavir; to evaluate 24-week safety and immunologic and virologic response. It was a randomized, nonblinded, prospective study. There were 11 HIV-1-infected, antiretroviral-experienced, male and female subjects > or = 18 years old, median HIV-1 RNA and CD4(+) T-cell count of 4.86 log copies/mL and 10(6) cells/mm(3), respectively. Subjects were randomly assigned to receive saquinavir 1000 mg/ritonavir 100 mg every 12 hours or amprenavir 600 mg/ritonavir 100 mg every 12 hours for 7 days. After 12-hour pharmacokinetic sampling, the third protease inhibitor (PI) was added, and pharmacokinetics sampling was repeated 14 days later. Subsequent PI dosage adjustments were based on real-time pharmacokinetic assessment. Saquinavir did not affect amprenavir or ritonavir pharmacokinetics. Amprenavir decreased area under the concentration-time curve (AUC(0-12h)) and C(12h) for saquinavir 82 and 61%, and 74 and 75% for ritonavir. An adjusted PI regimen of amprenavir 600 mg/saquinavir 1400 mg/ritonavir 200 mg every 12 hours returned saquinavir exposure to baseline. At 24 weeks, HIV RNA declined a median of 1.55 log copies/mL and CD4(+) T-cell counts increased a median of 52 cells/mm(3). Gastrointestinal events predominated and were mild to moderate. These data suggest that amprenavir/saquinavir/ritonavir may be a viable salvage regimen in heavily PI-experienced individuals. New formulations of amprenavir and saquinavir may simplify this regimen.
authors.affiliation: Schools of Pharmacy and Medicine, University of North Carolina Center for AIDS Research, University of North Carolina at Chapel Hill, 27599, USA.
authors.forename: Amanda H
authors.initials: AH
authors.lastname: Corbett
authors.forename: Joseph J
authors.initials: JJ
authors.lastname: Eron
authors.forename: Susan A
authors.initials: SA
authors.lastname: Fiscus
authors.forename: Naser L
authors.initials: NL
authors.lastname: Rezk
authors.forename: Angela D M
authors.initials: AD
authors.lastname: Kashuba
mesh_terms: D000328:Adult; D018791:CD4 Lymphocyte Count; D002219:Carbamates; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D005663:Furans; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D017320:HIV Protease Inhibitors / Q000493:pharmacokinetics / Q000627:therapeutic use*; D015497:HIV-1; D006801:Humans; D008297:Male; D008875:Middle Aged; D019438:Ritonavir / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016879:Salvage Therapy; D019258:Saquinavir / Q000493:pharmacokinetics / Q000627:therapeutic use*; D013449:Sulfonamides / Q000493:pharmacokinetics / Q000627:therapeutic use*; D019562:Viral Load
chemical_list: D002219:Carbamates; D005663:Furans; D017320:HIV Protease Inhibitors; D013449:Sulfonamides; C095108:amprenavir; D019258:Saquinavir; D019438:Ritonavir