title: Once-daily dosing of saquinavir soft-gel capsules and ritonavir combination in HIV-1-infected patients (IMEA015 study).
abstract: This was a prospective pilot study evaluating a saquinavir (SQV) soft-gel capsules (SGC)/ritonavir (RTV)-containing once-daily regimen over a follow-up of 3 months. The primary end-point was to determine the number of patients both remaining on treatment at month 3 and with trough SQV plasma concentration 24 h after the last intake (C24h) exceeding the inhibition of 95% of viral replication in vitro (IC95). The secondary end-points were to investigate the immuno-virological efficacy and safety of SQV-SGC/RTV once daily, and to explore SQV concentrations in peripheral blood mononuclear cells (PBMCs). Twenty-three antiretroviral-naive and 17 protease inhibitors (PIs) experienced HIV-1-infected patients with plasma HIV-1 RNA level below 200 copies/ml were enrolled. They were assigned to SQV-SGC/RTV (1600/100 mg once daily) combined with nucleoside and/or non-nucleoside reverse transcriptase inhibitors. In a subgroup of 13 patients, both plasma and intracellular SQV concentrations were determined. By intent to treat analysis the percentage of success at month 3 was 87.5% (confidence interval: 73.2-95.8%) with 78.3% in naive and 100% in PI-experienced patients. SQV C24h and intracellular concentrations [median (range, n)] were 241 ng/ml (40-1209, 35) and 323 ng/ml (168-475, 12), respectively. Intracellular concentrations showed an accumulation of SQV in PBMCs persisting during 24 h. Neither immunological nor virological failure was observed. Clinical and biological tolerance was acceptable in all patients but three with adverse effects leading to discontinuation. These data confirmed the short-term efficacy of SQV-SGC/RTV once-daily regimen based on SQV therapeutic drug monitoring.
authors.affiliation: Service de Pharmacie Clinique et des Biomatériaux Groupe Hospitalier Bichat-Cl. Bernard, Paris, France.
authors.forename: Claire
authors.initials: C
authors.lastname: Lamotte
authors.forename: Roland
authors.initials: R
authors.lastname: Landman
authors.forename: Gilles
authors.initials: G
authors.lastname: Peytavin
authors.forename: France
authors.initials: F
authors.lastname: Mentre
authors.forename: Juliette
authors.initials: J
authors.lastname: Gerbe
authors.forename: Françoise
authors.initials: F
authors.lastname: Brun-Vezinet
authors.forename: François
authors.initials: F
authors.lastname: Boue
authors.forename: Gabriella
authors.initials: G
authors.lastname: Spiridon
authors.forename: Marc-Antoine
authors.initials: MA
authors.lastname: Valantin
authors.forename: Christian
authors.initials: C
authors.lastname: Michelet
authors.forename: Robert
authors.initials: R
authors.lastname: Farinotti
authors.forename: Patrick
authors.initials: P
authors.lastname: Yeni
mesh_terms: D000328:Adult; D000368:Aged; D018791:CD4 Lymphocyte Count; D002214:Capsules; D004359:Drug Therapy, Combination; D005260:Female; D005782:Gels; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology / Q000821:virology; D017320:HIV Protease Inhibitors / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D015497:HIV-1 / Q000187:drug effects / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011446:Prospective Studies; D012367:RNA, Viral / Q000097:blood; D019438:Ritonavir / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D019258:Saquinavir / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D002214:Capsules; D005782:Gels; D017320:HIV Protease Inhibitors; D012367:RNA, Viral; D019258:Saquinavir; D019438:Ritonavir