title: Efficacy and safety of ritonavir dose reduction based on the tipranavir inhibitory quotient in HIV-infected patients on salvage antiretroviral therapy with tipranavir/ritonavir.
abstract: Ritonavir-related adverse events have been reported in patients taking tipranavir/ritonavir at the licensed dosage of 500/200 mg twice daily (bid). The aim of this open-label, prospective, single-arm pilot study was to evaluate the efficacy and safety of a ritonavir dose reduction to 100 mg bid guided by the tipranavir virtual inhibitory quotient (vIQ) in HIV-infected patients receiving tipranavir/ritonavir 500/200 mg bid whose viral load was <50 copies/ml and whose tipranavir vIQ was >60. Viral load, blood chemistry, and tipranavir and ritonavir trough concentrations (C(trough)) in plasma were determined at baseline and up to 48 weeks. If the tipranavir vIQ fell to <40, the ritonavir dose was increased to 200 mg bid. The primary endpoint was the percentage of treatment failure after 48 weeks. Eleven patients were enrolled. At baseline, the median (IQR) CD4+ T-cell count and vIQ were 380 (231-520) cells/mm(3) and 233.4 (73.8-584.8), respectively. Ten patients (90.9%) maintained a viral load <50 copies/ml at week 48. Geometric mean (95% confidence interval) tipranavir C(trough) decreased from 24.7 (12.9-47.5) mg/l at baseline to 13.6 (7.1-26.2) mg/l at week 48 (p = 0.194), but the ritonavir dose had to be raised in only one patient. Median triglycerides and ALT concentrations decreased from 177.2 (132.9-292.4) mg/dl and 59 (23-128) IU/l at baseline to 158.0 (131.0-186.0) mg/dl and 28 (20-71) IU/l at week 48 (p = 0.047, p = 0.041), respectively. As a conclusion, ritonavir-dose reduction to 100 mg bid as a treatment-simplification strategy guided by the tipranavir vIQ in patients receiving salvage therapy with tipranavir/ritonavir 500/200 mg bid seems to be safe enough to be tested in adequately powered clinical trials.
authors.affiliation: Lluita contra la Sida Foundation, HIV Unit, Hospital Universitari Germans Trias i Pujol, Badalona, Spain. jmolto@flsida.org
authors.forename: José
authors.initials: J
authors.lastname: Moltó
authors.forename: Marta
authors.initials: M
authors.lastname: Valle
authors.forename: José Ramón
authors.initials: JR
authors.lastname: Santos
authors.forename: Cristina
authors.initials: C
authors.lastname: Miranda
authors.forename: Samandhy
authors.initials: S
authors.lastname: Cedeño
authors.forename: Eugenia
authors.initials: E
authors.lastname: Negredo
authors.forename: Mercedes
authors.initials: M
authors.lastname: Yritia
authors.forename: Sebastián
authors.initials: S
authors.lastname: Videla
authors.forename: Bonaventura
authors.initials: B
authors.lastname: Clotet
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000009:adverse effects* / Q000493:pharmacokinetics; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods; D001774:Blood Chemical Analysis; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D008297:Male; D008875:Middle Aged; D010949:Plasma / Q000737:chemistry; D011446:Prospective Studies; D011725:Pyridines / Q000008:administration & dosage* / Q000009:adverse effects* / Q000493:pharmacokinetics; D011753:Pyrones / Q000008:administration & dosage* / Q000009:adverse effects* / Q000493:pharmacokinetics; D019438:Ritonavir / Q000008:administration & dosage* / Q000009:adverse effects* / Q000493:pharmacokinetics; D016879:Salvage Therapy / Q000379:methods; D013449:Sulfonamides; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents; D011725:Pyridines; D011753:Pyrones; D013449:Sulfonamides; D019438:Ritonavir; C107201:tipranavir