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Genotypic Analysis of Cellular HIV V3 DNA to Predict Virologic Response to Maraviroc: Performance of Population-based and 454 Deep V3 Sequencing
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Reported by Jules Levin
CROI 2011 March 2 Boston
LC Swenson1, RA McGovern1, I James2 J Demarest3, D Chapman4, S Ellery5, J Heera5, H Valdez4, PR Harrigan1, AFY Poon1
1BC Centre for Excellence in HIV/AIDS, Vancouver, Canada; 2Pfizer Global Research and Development, Sandwich UK,
3ViiV Healthcare, Research Triangle Park, NC, USA; 4Pfizer, Inc. New York, NY; 5Pfizer Global Research and Development, New London, CT, USA
Background
· Tropism testing from cellular HIV DNA may be useful in patients when plasma HIV is unavailable (eg those with undetectable plasma viral loads).
· However, there is little data available for a DNA approach linked to virologic outcome!
· Here we assess genotypic testing of cellular HIV DNA from peripheral blood mononuclear cells (PBMC) to predict shortterm pVL change in treatment-experienced patients beginning maraviroc-containing regimens in the MOTIVATE and A4001029 studies
METHODS
· PBMC samples from 181 maraviroc recipients at study entry in MOTIVATE or A4001029 (51% R5 by original Trofile).!
· The V3 loop was amplified in triplicate from cellular HIV DNA (N=181)!
· HIV RNA was also amplified from matching available plasma samples (N=156)!
· Sequencing was performed using standard population-based ("PopSeq") methods and 454 deep sequencing ("DeepSeq"), with tropism assessment as defined previously.
· 5.75 cutoff by geno2pheno for population-based and 2% prevalence with 3.5 g2p cutoff for deep sequencing
· Performance was measured by prediction of week 8 virologic success
· defined as ≥2 log decrease in pVL from baseline or a pVL <50 copies/mL
· ESTA and Trofile-DNA results were not available for comparison in this population
Results
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