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Biological and Clinical Cutoff Analyses for Etravirine in the PhenoSense HIV Assay
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Reported by Jules Levin
17th HIV Drug Resistance Workshop
June 10-14, 2008
Sitges, Spain
E Coakley1, C Chappey1, J Benhamida1, G Picchio2, L Tambuyzer3, J Vingerhoets3, and M-P de Bethune3
1 Monogram Biosciences Inc., South San Francisco CA USA; 2 Tibotec Inc, Yardley, PA, USA; 3 Tibotec, Mechelen, Belgium
AUTHOR CONCLUSIONS
The biologic cutoff for ETR is defined at 2.9 in the PhenoSense assay
Within the 199 samples from the DUET dataset and using models accounting for the activity of background therapy a LCCO for ETR was observed at FC 2.9.
- 76% had ETR FC < 2.9
- 60% with ETR FC <2.9 had HIV-1 RNA <50c/mL at Wk 24
The paucity of isolates with high ETR limited the ability to define an UCCO.
Further testing of additional samples is currently underway to define an ETR UCCO
In this highly treatment experienced population ETR HS was common, being observed in approximately one third of samples.
BACKGROUND
The DUET 1 and 2 trials demonstrated the efficacy of etravirine (ETR) in combination with darunavir/ritonavir (DRV/r) with NRTIs in treatment-experienced patients.
We explored the biologic and lower and upper clinical cut-offs (LCCO and UCCO) for ETR by evaluating week 2, 4, 8 and 24 HIV-1 RNA outcomes from the DUET studies in relation to baseline ETR fold-change (FC).
The 199 samples tested were from individuals whose on-study regimen did not include enfuvirtide.
Phenotyping and genotyping was performed on 199 baseline samples (PhenoSense HIV, Monogram Biosciences) from individuals whose optimized background therapy did not include enfuvirtide.
DEFINITIONS
The biologic CO was defined at the 99th percentile of ETR FC values in a population of viruses lacking known NNRTI-, NRTI-, or PI-selected mutations.
The LCCO was defined as the ETR fold-change (FC) above which HIV RNA response was first observed to decline relative to the reference wild type population, i.e., FC > biologic CO.
The UCO was defined as the FC above which the attributable week 4 HIV-1 RNA reduction from baseline was <0.3 log10copies/mL.
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