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Genotyping for Coreceptor Use Concordant With Trofile in PBMCs and Plasma: from Jules- genotyping this falls short
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7th European HIV Drug Resistance Workshop, March 25-27, 2009, Stockholm
Mark Mascolini
Three genotyping systems to predict viral coreceptor use proved 70% or more concordant with the Trofile phenotyping assay in plasma and peripheral blood mononuclear cells (PBMCs), according to results of a 73-person French study [1]. Prevalence of maraviroc-related resistance mutations was equivalent in plasma and PBMCs.
The multicenter study involved 73 antiretroviral-experienced people who began using the CCR5 antagonist maraviroc in France's expanded access program for that drug. Laurence Morand-Joubert and colleagues used the Trofile phenotypic assay and three genotype-based tools (PSSMsinsi and geno2pheno with a specificity setting of 5% or 10%) to determine coreceptor use in both plasma and PBMCs. The investigators amplified V3 env sequences from plasma HIV-1 RNA and from PBMC HIV-1 DNA. They considered virus that could use either CCR5 or CXCR4 as X4 virus.
The study group had a median CD4 count of 307 and a median viral load just below 10,000 copies. Morand-Joubert successfully performed the Trofile phenotypic assay in 80% of samples, while the genotypic approaches worked for 88% to 90%. (Trofile requires a sample with a viral load of at least 1000 copies.) The investigators had paired plasma and PBMC samples for 89% of study participants.
Prevalence of X4 virus in plasma was 20% by phenotype, 16% by PSSM, 19% by geno2pheno at 5% specificity, and 31% by geno2pheno at 10% specificity. X4 prevalence in PBMCs was higher than in plasma by PSSM (18%) and geno2pheno at 5% specificity (23%), but not by geno2pheno at 10% specificity (30%).
Concordance of the genotype-based calls with Trofile phenotype-based coreceptor assignment always exceeded 69%:
• PSSM in plasma: 80%
• geno2pheno at 5% specificity in plasma: 84%
• geno2pheno at 10% specificity in plasma: 70%
• PSSM in PBMCs: 80%
• geno2pheno at 5% specificity in PBMCs: 81%
• geno2pheno at 10% specificity in PBMCs: 78%
PSSM and both geno2pheno approaches rated virus X4 more often in plasma or PBMC samples from people with a CD4 count below the median of 307 than in those with a CD4 count above the median. The frequency of mutations associated with resistance to maraviroc was similar in plasma and PBMC samples.
Morand-Joubert and coworkers suggested that determining viral coreceptor use in cellular compartments by a genotypic tool may prove important when deciding on maraviroc use in people with an undetectable viral load in plasma. They noted, though, that the clinical utility of this approach must be validated in a study that determines clinical outcomes.
Reference
1. Morand-Joubert L, Flandre P, Soulie C, et al. Higher detection of CXCR4 tropic virus by genotypic coreceptor analysis in peripheral blood mononuclear cells (PBMC) than in plasma. 7th European HIV Drug Resistance Workshop, March 25-27, 2009, Stockholm. Abstract 51.
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