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Education > Clinical Updates

Clinical Update #1 - News from 14^th Annual CROI Meeting

Bart Winters and colleagues from Virco presented a poster at the 14^th Conference on Retroviruses and Opportunistic Infections (CROI) which described the development of linear regression models (LM) used to predict fold change (FC) values for atazanavir (ATV) and fos-amprenavir (FPV) from genotypic sequences and the establishment of clinical cut-offs (CCO) for ritonavir-boosted atazanavir (ATV/r) and ritonavir-boosted fosamprenavir (FPV/r). This study was done in collaboration with GlaxoSmithKline (GSK), Bristol-Myers Squibb (BMS), and other external investigators.

Utilizing >16,000 clinical isolates for ATV and >43,000 for FPV, where both viral genotypic sequences and measured phenotypic FC values (by the Antivirogram^® assay) were available, LM were developed to identify individual mutations and mutations pairs that influenced phenotypic in vitro susceptibility to these two drugs. The LM also provided resistance weight factors (RWF) for these mutations which could be used to calculate the respective predicted phenotypic FC values from any nucleotide sequence of the protease gene. An examination of the relation between predicted and measured FC values for the same isolates showed a high degree of correlation (See Figure 1).

To establish CCOs for ATV/r and FPV/r, separate clinical trial and cohort data from patients whose regimens included either drug were used to model 8 week clinical response as measured by viral load reduction. The resulting response models were then used to establish two clinical cut-off values for each drug: CCO1, the lower clinical cut-off, is the point on the response model curve where the associated predicted FC value for a given virus corresponds with 20% loss of response compared to a wild type virus; CCO2, the upper clinical cut-off, is the predicted FC value associated with 80% loss of response compared to a wild type virus (See Figure 2).

The establishment of CCOs for ATV/r and FPV/r completes the definition of CCOs for all commercially available protease inhibitors, allowing for the interpretation of any viral genotype analyzed by virco^®TYPE HIV-1 in the context of how patients with similar predicted FC values responded to drugs in the clinical setting.

The new clinical cut-offs for ATV/r and FPV/r shown above will be included in all virco^®TYPE HIV-1 reports generated after March 5, 2007. To view the complete poster presented at CROI which includes these CCOs, please click here.

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