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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

  • 1,
  • 2,
  • 3,
  • 4,
  • 2,
  • 5,
  • 5,
  • 4,
  • 5,
  • 6 and
  • 7
Journal of the International AIDS Society201013 (Suppl 4) :P128

https://doi.org/10.1186/1758-2652-13-S4-P128

  • Published:

Keywords

  • Public Health
  • Infectious Disease
  • Atazanavir
  • Discordant Result
  • Maraviroc

Background

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).

Methods

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.

Results

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.

Conclusions

Population sequencing appropriately identified patients with <2% CXCR4 using virus and who would be suitable for CCR5 antagonist therapy.
Figure 1
Figure 1

Correlation between methods and quantity of X4 use by UDS in concordant and discordant results and quantity of X4 using virus by UDS.

Authors’ Affiliations

(1)
Pfizer, Inc, 235 East 42nd Street, New York, USA
(2)
Pfizer Inc, New York, USA
(3)
Institute of Immunology and Genetics, SEQ.IT GmbH, Kaiserslautern, Germany
(4)
Max-Planck-Institute for Informatics, Saarbrücken, Germany
(5)
Pfizer Global Research, Sandwich, UK
(6)
ViiV Healthcare, Research Triangle Park, USA
(7)
Pfizer Global Research, New London, USA

Copyright

© Portsmouth et al; licensee BioMed Central Ltd. 2010

This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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