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Population and ultra-deep sequencing for tropism determination are correlated with Trofile ES: genotypic re-analysis of the A4001078 maraviroc study
© Portsmouth et al; licensee BioMed Central Ltd. 2010
Published: 8 November 2010
A4001078 is a study in therapy naive patients of Maraviroc (MVC) plus boosted atazanavir. The Trofile ES (ESTA) was used to determine tropism at Screening. Few re-analyses of genotypic tropism have examined all screened and non-reportable (NR) populations. We aimed to define correlations between methods at screening and evaluate the quantity of X4 using virus in discordant results using ultra-deep sequencing (UDS).
Population and UDS methods were employed on 178 of 220 screened subjects and 121 enrolled subjects. Correlation between methods was explored and the quantity of X4-using virus in both discordant and concordant samples was measured using UDS.
ESTA defined 123 (69%) as R5, 39 (22%) as Dual or Mixed tropism (D/M) and 16 (9%) as NR. Population sequencing (single amplification) defined 146 (82%) as R5, 26 as X4, and 6 tests were non reportable [Either failure to get a PCR product (no result for both, population sequencing and UDS) or non-evaluable Sanger traces]. Correlation between population and UDS for R5 use was 95%. Of the patients screened as R5 by population sequencing, UDS showed a median of 0% X4 with only 3 of 114 results being over 2% X4 use, suggesting this method is suitable for selecting individuals for CCR5 antagonist therapy. All Trofile NR results were reportable by population sequencing and showed tropism results consistent with the overall population.
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