TY - JOUR
T1 - Improving the prediction of virological response to tipranavir: the development and validation of a tipranavir-weighted mutation score
AU - Schapiro, JM
AU - Scherer, J
AU - Boucher, Charles
AU - Baxter, JD
AU - Tilke, C
AU - Perno, CF
AU - Maggiolo, F
AU - Santoro, MM
AU - Hall, DB
PY - 2010
Y1 - 2010
N2 - Background: The purpose of this study was to develop a tipranavir-weighted mutation score that provides guidance to treating physicians on the relative effect of specific protease mutations on tipranavir activity. Methods: Weights were developed using data from RESIST tipranavir-treated patients based on regressions of virological response at weeks 8 and 24, accounting for baseline CD4(+) T-cell count and background regimen activity. The resulting weighted score and cutoffs were validated using a set of cohort patients external to the tipranavir development programme. Response rates were tabulated for the new weighted score and compared with other tipranavir mutation scores used in clinical practice. Results: The final weights were 74P, 82L/T, 83D and 47V (+4), 58E and 84V (+3), 36I, 43T and 54A/M/V (+2), 10V, 33F and 46L (+1), 24I and 76V (-2), 50L/V (-4), and 54L (-6). Tipranavir-weighted score susceptibility categories were susceptible <= 3, partially susceptible >3 but <= 10, and resistant Week 48 response rates for RESIST patients were 34.6%, 15.9% and 5.9%, respectively. Using the external cohort data (n=150), the weighted score was highly associated with week 8 viral load reduction (P=0.0027). Only one other score achieved statistical significance. Conclusions: The tipranavir-weighted score developed and externally validated here, in three datasets representing a broad population of treatment-experienced patients, can be used to make clinical decisions about whether to consider tipranavir in a treatment-experienced patient who has limited treatment options.
AB - Background: The purpose of this study was to develop a tipranavir-weighted mutation score that provides guidance to treating physicians on the relative effect of specific protease mutations on tipranavir activity. Methods: Weights were developed using data from RESIST tipranavir-treated patients based on regressions of virological response at weeks 8 and 24, accounting for baseline CD4(+) T-cell count and background regimen activity. The resulting weighted score and cutoffs were validated using a set of cohort patients external to the tipranavir development programme. Response rates were tabulated for the new weighted score and compared with other tipranavir mutation scores used in clinical practice. Results: The final weights were 74P, 82L/T, 83D and 47V (+4), 58E and 84V (+3), 36I, 43T and 54A/M/V (+2), 10V, 33F and 46L (+1), 24I and 76V (-2), 50L/V (-4), and 54L (-6). Tipranavir-weighted score susceptibility categories were susceptible <= 3, partially susceptible >3 but <= 10, and resistant Week 48 response rates for RESIST patients were 34.6%, 15.9% and 5.9%, respectively. Using the external cohort data (n=150), the weighted score was highly associated with week 8 viral load reduction (P=0.0027). Only one other score achieved statistical significance. Conclusions: The tipranavir-weighted score developed and externally validated here, in three datasets representing a broad population of treatment-experienced patients, can be used to make clinical decisions about whether to consider tipranavir in a treatment-experienced patient who has limited treatment options.
U2 - 10.3851/IMP1670
DO - 10.3851/IMP1670
M3 - Article
C2 - 21041916
SN - 1359-6535
VL - 15
SP - 1011
EP - 1019
JO - Antiviral Therapy
JF - Antiviral Therapy
IS - 7
ER -