title: Tipranavir (TPV) genotypic inhibitory quotient predicts virological response at 48 weeks to TPV-based salvage regimens.
abstract: The virological response (VR) to a tipranavir-ritonavir (TPV-RTV)-based regimen had been shown to be associated with a number of mutations in the protease gene, the use of enfuvirtide (T20), and the TPV phenotypic inhibitory quotient (IQ). The role of the TPV genotypic IQ (gIQ) has not yet been fully investigated. The aim of our study was to evaluate the relationship between the TPV gIQ and the VR at 48 weeks to TPV-based salvage regimens. Patients placed on regimens containing two nucleoside reverse transcriptase inhibitors plus TPV-RTV 500/200 mg twice a day with or without T20 were prospectively studied. Regular follow-up was performed over the study period. VR, considered a viral load (VL) decrease of >or=1 log unit and/or the achievement of <50 copies/ml with no VL rebound of >0.5 log unit compared to the maximal VL decrease at week 48, was assessed. Thirty-eight patients who had received multiple drugs were included. At week 48 the VL decrease was -1.48 (interquartile range [IQR], -2.88 to -0.48), 15 patients (39.5%) had VLs of <50 copies/ml, and the CD4+ cell count increase was 37 cells/mm3 (IQR, -30 to +175). Twenty subjects (52.6%) achieved VRs. The TPV gIQ and optimized background score (OBS) were independently associated with higher VL decreases. The TPV gIQ and OBS were also independent predictors of a VR at week 48. TPV gIQ and OBS cutoff values of 14,500 and 2, respectively, were associated with a higher rate of VR. The TPV gIQ was shown to be able to predict the VR at 48 weeks to TPV-containing salvage regimens better than the TPV trough concentration or TPV-associated mutations alone. A possible TPV gIQ cutoff value of 14,500 for reaching a VR at week 48 was suggested. Further studies are needed in order to evaluate the calculation of TPV gIQ as a new tool for the optimization of TPV-based salvage therapy.
authors.affiliation: Department of Infectious Diseases, University of Turin, Turin, Italy. danifarre@hotmail.com
authors.forename: Daniel Gonzalez
authors.initials: DG
authors.lastname: de Requena
authors.forename: Stefano
authors.initials: S
authors.lastname: Bonora
authors.forename: Andrea
authors.initials: A
authors.lastname: Calcagno
authors.forename: Antonio
authors.initials: A
authors.lastname: D'Avolio
authors.forename: Marco
authors.initials: M
authors.lastname: Siccardi
authors.forename: Silvia
authors.initials: S
authors.lastname: Fontana
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Milia
authors.forename: Mauro
authors.initials: M
authors.lastname: Sciandra
authors.forename: Silvia
authors.initials: S
authors.lastname: Garazzino
authors.forename: Antonio
authors.initials: A
authors.lastname: Di Garbo
authors.forename: Lorena
authors.initials: L
authors.lastname: Baietto
authors.forename: Laura
authors.initials: L
authors.lastname: Trentini
authors.forename: Giovanni
authors.initials: G
authors.lastname: Di Perri
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D024882:Drug Resistance, Viral / Q000235:genetics; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology*; D016333:HIV Protease / Q000235:genetics*; D017320:HIV Protease Inhibitors / Q000493:pharmacokinetics* / Q000494:pharmacology / Q000627:therapeutic use; D015497:HIV-1 / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D011237:Predictive Value of Tests; D011725:Pyridines / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D011753:Pyrones / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use; D019438:Ritonavir / Q000494:pharmacology / Q000627:therapeutic use; D016879:Salvage Therapy; D013449:Sulfonamides; D016896:Treatment Outcome
chemical_list: D019380:Anti-HIV Agents; D017320:HIV Protease Inhibitors; D011725:Pyridines; D011753:Pyrones; D018894:Reverse Transcriptase Inhibitors; D013449:Sulfonamides; D016333:HIV Protease; D019438:Ritonavir; C107201:tipranavir