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Two Tools for Sharpening Darunavir Response Predictions
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11th European AIDS Conference
October 24-27, 2007
Madrid
Mark Mascolini
Two resistance-predicting tools--HIV-GRADE and the French ANRS algorithm--did the best job forecasting response to darunavir/ritonavir in people with deep resistance to protease inhibitors (PIs), according to results of a 27-patient study by Berlin clinicians [1]. Both methods worked better than the REGA and Stanford HIVdb systems, and both outperformed a simple count of darunavir resistance mutations.
Martin Obermeier and Berlin colleagues prescribed darunavir/ritonavir plus other drugs picked after resistance testing for 27 heavily pretreated people with a median of nine PI mutations and seven reverse transcriptase mutations accumulated over a median 9.2 years of therapy. No one took another PI with darunavir/ritonavir, but 6 people took enfuvirtide and 1 took the investigational nonnucleoside etravirine (TMC125). Almost everyone took a fixed-dose combination, either Trizivir, Combivir, or Truvada.
After 12 weeks of darunavir-based salvage, 18 people (67%) had a viral load below 50 copies/mL. And among 20 people still taking darunavir after 48 weeks, 14 (70%) had an undetectable viral load.
Using a linear regression model to figure the correlation between each resistance predictor and the actual response, Obermeier and colleagues found the best correlation--that is, the highest R(2) value--with HIV-GRADE, followed by the ANRS algorithm (Table). Only those two correlations reached statistical significance.
The Berlin group urges other clinicians to use these resistance-prediction models when considering darunavir salvage therapy and not to rely solely on the number of darunavir-related mutations uncovered by genotyping. They caution that an "optimized backbone with enough residual activity is important for success"of darunavir salvage therapy.
Reference
1. Obermeier M, Baumgarten A, Carganico A, et al. Darunavir in heavily pretreated patients--excellent virological outcome at weeks 12 and 48 in patients harboring multi-drug-resistance. 11th European AIDS Conference. October 24-27, 2007. Madrid. Abstract P3.4/18.
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