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Evaluation of the genotypic tipranavir resistance interpretation algorithm
following the Spanish drug resistance guidelines
L. Anta, J. Morello, S. Rodríguez-Novoa, V. Soriano, C. de Mendoza
Hospital Carlos III, Infectious Diseases, Madrid, Spain
Background: The tipranavir weighted score (TWS) has recently been improved using clinical data. The Spanish Guidelines for the Interpretation of Drug Resistance Mutations have proposed and alternative interpretation (STWS) based on clinical outcomes. Herein we compare both scores and evaluate their performance in a separate cohort of multiexperienced patients rescued with TPV/r.
Methods: The STWS included the following mutations with different weights: M36I, K43T, M46I/L/V, I54A/V, V82A/C/M/F/S and I84V (+1); I47V, Q58E, T74P and N83D (+2); V82L/T (+3); L24I, I50L/V, I54L and L76V (-1); 10IF/R/V/Y and L33F (+1 only when the score is 4). Interpretation was Susceptible (S) ≤2, Intermediate Resistance (IR) =3-4 and Resistance (R) ≥5. Baseline drug resistance genotypes, VL reductions at week 12 and TPV plasma through concentrations were recorded along the number of concomitant active drugs.
Results: A total of 51 patients on regular follow-up at one reference HIV outclinic in Madrid, were examined. Using the STWS, patients were classified as S, IR and R in 58.8%, 25.5% and 15.7%, respectively. The median number of active drugs in the combination was 1 (IQR, 1-3). Enfuvirtide was included in 23 (45.1%). Median TPV plasma levels were 24.7 µg/mL (IQR, 11-46).A correlation of 80.4% was obtained comparing the STWS with TWS. Mean VL reductions at week 12 was -1.84 (S), -1.45 (IR) and -0.97 (R) using STWS showing a significant association (B=0.4; p=0.034). By contrast, for TWS it was -1.7, -1.6 and -0.008 (B=0.071; p=0.095). In addition, baseline VL was significantly associated (B=0.7; p=0.001) whereas the number of active drugs, co-administration of enfuvirtide or TPV plasma concentrations did not shown relationship.
Conclusions: The STWS seems predict better VL reductions in HIV patients rescued with TPV than the latest improved TWS. However, using either algorithm the specificity for prediction non-responders is low. Additional studies are required to improve their performance
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