Development and performance of a new recombinant virus phenotypic entry assay to determine HIV-1 coreceptor usage

被引:62
作者
Raymond, Stephanie [1 ,2 ,3 ]
Delobel, Pierre [2 ,3 ,4 ]
Mavigner, Maud [2 ]
Cazabat, Michelle [1 ,2 ]
Souyris, Corinne [1 ,2 ]
Encinas, Stephanie [1 ,2 ]
Bruel, Patrick [1 ,2 ]
Sandres-Saune, Karine [1 ,2 ,3 ]
Marchou, Bruno [3 ,4 ]
Massip, Patrice [3 ,4 ]
Izopet, Jacques [1 ,2 ,3 ]
机构
[1] CHU Toulouse, Hop Purpan, Virol Lab, F-31300 Toulouse, France
[2] INSERM, U563, F-31300 Toulouse, France
[3] Univ Toulouse 3, Ctr Physiopathol Toulouse Purpan, F-31300 Toulouse, France
[4] CHU Toulouse, Hop Purpan, Serv Malad Infect & Trop, F-31300 Toulouse, France
关键词
HIV-1; Phenotypic entry assay; Coreceptor; CCR5; CCR5; ANTAGONIST; SMALL-MOLECULE; RECEPTOR; TYPE-1; MARAVIROC; COFACTOR; TROPISM; POTENT;
D O I
10.1016/j.jcv.2009.11.018
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Background: Clinical trials of CCR5 antagonists have relied on the phenotypic determination of HIV-1 coreceptor usage. Few phenotypic assays are available, with few data on their concordance, and none has been designed to determine tropism from cell-associated HIV-1 DNA. Objectives: To assess the performance of the new Toulouse Tropism Test (TTT) phenotypic assay to characterize HIV-1 tropism using blood plasma and peripheral blood mononuclear cells (PBMC). Study design: 434 plasma and 168 PBMC samples were tested with the TTT assay. We determined the correlation between our assay results on plasma samples and those of the commercial Trofile (TM) assay. Results: The TTT assay determined the tropism of 97% of samples after successful amplification of the env gene. It performed well on both cell samples and plasma samples with various HIV-1 loads and subtypes. It detected 0.5% of minor CXCR4-using variants in the virus population. The TTT and the Trofile (TM) assays were >90% concordant for predicting HIV-1 tropism. Conclusion: We have validated a new recombinant virus phenotypic assay for determining HIV-1 tropism using both plasma and cell samples from patients who are candidates for treatment with CCR5 antagonists. (C) 2009 Elsevier B. V. All rights reserved.
引用
收藏
页码:126 / 130
页数:5
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