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Clinically Relevant Virco Phenotypic Resistance and Cross Resistance to Tipranavir Among Recent Routine Clinical Isolates
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Download the poster this article is based on in PDF format
Reported by Jules Levin
L Bacheler1, H Vermeiren2, B Winters2, K Van Der Borght2 and D Mayers3
1VircoLab, Inc, Durham, NC, USA - 2Virco BVBA, Mechelen, BE - 3Boehringer Ingelheim, Ridgefield, Conn, USA
Presented at the 4th Euopean HIV Drug Resistance Workshop, Monte Carlo, Monaco, March 29 to 31, 2006
Author Conclusions
virco TYPE HIV-1 resistance analysis based on linear regression modeling integrates complex interactions among multiple protease gene mutations to provide a quantitative prediction of TPV drug susceptibility
virco TYPE HIV-1 clinical cut-offs for ritonavir boosted tipranavir of 1.2 FC and 5.4 FC have been defined and validated on unseen data
-- Since the highly treatment experienced population used to define these CCO was specifically selected, it is unknown whether these values are applicable across the entire spectrum of antiretroviral treatment experience
Most clinical isolates with clinically relevant resistance to older PIs retain at least partial susceptibility to TPVÚr with 16% to 46% < CCO1 for TPVÚr.
BACKGROUND
Tipranavir (TPV), a non-peptidic inhibitor of HIV-1 protease, has recently been approved for use in combination therapy for highly treatment-experienced patients or those resistant to multiple protease inhibitors.
Evaluation of the clinical impact of viral resistance in such populations is a complex and evolving process.
METHODS
Based on >6,000 clinical isolates with both drug susceptibility phenotypes (Antivirogram ) and viral genotypes, a multiple linear regression model
(VirtualPhenotype-LM, VPT-LM ) was developed to predict TPV fold change in IC50 (FC) from the viral genotype (virco TYPE HIV-1 4.0.00).
Using data from RESIST 1 and 2, a separate linear regression model was developed to predict 8-week change in viral load on regimens containing ritonavir-boosted TPV (TPVÚr). 495 and 250 TPVÚr containing regimens were used to define and validate two clinical cut-offs (CCO) corresponding to predicted TPV FC values associated with a 20% or 80% loss of the TPVÚr response predicted for subjects infected with wild type strains.
Predicted protease inhibitor FC values for >50,000 clinical isolates submitted for routine resistance analysis in 2004-5 were used to assess current resistance and cross-resistance to TPV.
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