title: Switching to darunavir/ritonavir 800/100 mg once-daily containing regimen maintains virological control in fully suppressed pre-treated patients infected with HIV-1.
abstract: The objective of this study was to evaluate the switch to once-daily darunavir/ritonavir 800/100 mg in treatment-experienced patients with suppressed HIV-1 replication on a twice-daily ritonavir-boosted protease-inhibitor (bid PI/r) containing regimen, that is in a setting where genotypic resistance test cannot be performed. In this open label, non-comparative, multicenter study, patients on a bid PI/r-containing triple combination, with suppressed viral replication, were switched to once-daily darunavir/r 800/100 mg containing triple combination. The primary endpoint was the proportion of patients with plasma HIV-RNA < 50 copies/ml 24 weeks after the switch. Intensive darunavir pharmacokinetic evaluation was performed at Week 4 (W4) in 11 patients. Eighty-five patients were enrolled. All had HIV-RNA < 50 copies/ml at screening with a pre-exposure to a median of 2 PI/r (1-5). By intent-to-treat analysis (missing = failure), 78/85 patients (92%, 95% CI [83;96]) maintained an HIV-RNA < 50 copies/ml at W24. Seven patients experienced protocol-defined treatment failure between baseline and W24: Two had confirmed low-level viral rebound, one discontinued study treatment for adverse event, three withdrew their consent, and one was lost to follow-up. By on-treatment analysis, 78/80 patients (97%, 95% CI [91;99]) maintained an HIV-RNA < 50 copies/ml at W24. Results were similar at Week 48. The median area under the darunavir plasma concentration-time curve measured in 11 patients was 61,380 ng hr/ml; darunavir median trough concentration 1,340 ng/ml and darunavir half-life was 12.2 hr. Tolerability of once-daily darunavir/r 800/100 mg was excellent. Optimally suppressed, treatment-experienced patients can switch safely from a twice-daily PI/r regimen to a once-daily darunavir/r 800/100 mg containing regimen.
authors.affiliation: APHP, Department of Internal Medicine, Bicetre University Hospital, Le Kremlin Bicetre, France. jade.ghosn@bct.aphp.fr
authors.forename: Jade
authors.initials: J
authors.lastname: Ghosn
authors.forename: Laurence
authors.initials: L
authors.lastname: Slama
authors.forename: Aziza
authors.initials: A
authors.lastname: Chermak
authors.forename: Allal
authors.initials: A
authors.lastname: Houssaini
authors.forename: Sidonie
authors.initials: S
authors.lastname: Lambert-Niclot
authors.forename: Luminita
authors.initials: L
authors.lastname: Schneider
authors.forename: Erwan
authors.initials: E
authors.lastname: Fourn
authors.forename: Claudine
authors.initials: C
authors.lastname: Duvivier
authors.forename: Anne
authors.initials: A
authors.lastname: Simon
authors.forename: Eve
authors.initials: E
authors.lastname: Courbon
authors.forename: Robert
authors.initials: R
authors.lastname: Murphy
authors.forename: Philippe
authors.initials: P
authors.lastname: Flandre
authors.forename: Gilles
authors.initials: G
authors.lastname: Peytavin
authors.forename: Christine
authors.initials: C
authors.lastname: Katlama
mesh_terms: D000328:Adult; D000368:Aged; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods*; D000069454:Darunavir; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology*; D015497:HIV-1 / Q000302:isolation & purification*; D006801:Humans; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000097:blood; D019438:Ritonavir / Q000008:administration & dosage*; D013449:Sulfonamides / Q000008:administration & dosage* / Q000493:pharmacokinetics; D016896:Treatment Outcome; D019562:Viral Load; D055815:Young Adult
chemical_list: D019380:Anti-HIV Agents; D012367:RNA, Viral; D013449:Sulfonamides; D019438:Ritonavir; D000069454:Darunavir