|
18th International HIV Drug Resistance WorkshopBasic Principles & Clinical ImplicationsJune 9–13 2009, Fort Myers, Florida, USA |
PHENOTYPIC PROTEASE INHIBITOR RESISTANCE IN THE CLINIC FROM 2006 TO 2008: AVAILABLE TREATMENT OPTIONS
Antivir Ther 2009; 14 Suppl 1:A54 (abstract no. 50)
D Hall1, J Scherer2, M Witvrouw3, A Paquet4, E Coakley4 and R Bethell3
1Boehringer Ingelheim, CT, USA; 2Boehringer Ingelheim, Ingelheim, Germany; 3Boehringer Ingelheim (Canada) Ltd., Laval, Québec, Canada; 4Monogram Biosciences, CA, USA
OBJECTIVES: Current guidelines recommend that resistance testing should be performed when considering a change to the treatment regimens of protease-experienced patients. To explore their available options, the database of matched genotypic and phenotypic test results from HIV clinical isolates at Monogram Biosciences was queried for the years 2006–2008. Phenotypic results were analysed to see how many patients could consider the second-generation protease inhibitors (PIs), darunavir (DRV) and tipranavir (TPV), based on phenotypic results.
METHODS: The analysis set included 7,775 results for the Monogram Biosciences PhenoSense GT. Results were categorized according to their upper and lower clinical cutoffs as resistant (R), partially susceptible (PS) or susceptible (S) to ritonavir-boosted DRV, lopinavir, saquinavir, atazanavir and fosamprenavir. Selection criteria were specimens collected 2006–2008 and at least one of these five PIs not S. For TPV, the susceptible range was further divided to consider hypersusceptibility, defined as those with an IC50 fold change (FC) <0.5.
RESULTS: There were 4.9% (378) of results that were R for all six PIs and 31.0% (2,407) that were not R to any of the PIs. TPV was an available option for 98% of those with no R for the other PIs, 92.5% of those R to one PI, 85.3% R to two PIs, 74.0% to three PIs, 49.6% to four PIs and 32.5% to all five PIs. When considering those R to the other four PIs, the percentage R for DRV increased from 21.2% in 2006, to 33.0% in 2007 and to 41.9% in 2008. R for TPV was constant, range 53.9–57.3%. Among the 40.9% of results that were S for at least 3 of the other PIs, 9.5% had TPV FC <0.5.
CONCLUSIONS: Based on phenotypic testing 95% of patients had at least one PI option available. The second generation profile for TPV is supported by susceptibility observed in 32.5% of those resistant to all four first- generation PIs and DRV. When multiple PIs are available, differences in position in the PS range will be important.
ACKNOWLEDGEMENTS: Supported by Boehringer Ingelheim Pharmaceuticals.
2009-06-09
50
Copyright © 2009 - International Medical Press Ltd.. Reproduction of this abstract (other than one copy for personal reference) must be cleared through the International Medical Press Ltd. 2-4 Idol Lane, London EC3R 5DD UK.