%0 Journal Article
%T HIV-1 V3 envelope deep sequencing for clinical plasma specimens failing in phenotypic tropism assays
%A Ina Vandenbroucke
%A Herwig Van Marck
%A Wendy Mostmans
%A Veerle Van Eygen
%A Evelien Rondelez
%A Kim Thys
%A Kurt Van Baelen
%A Katrien Fransen
%A Dolores Vaira
%A Kabamba Kabeya
%A Stephane De Wit
%A Eric Florence
%A Michel Moutschen
%A Linos Vandekerckhove
%A Chris Verhofstede
%A Lieven J Stuyver
%J AIDS Research and Therapy
%D 2010
%I BioMed Central
%R 10.1186/1742-6405-7-4
%X A cut-off for sequence reads interpretation of 5 to10 times the sequencing error rate (0.2%) was implemented. On average, each sample contained 7 different V3 haplotypes. V3 haplotypes were submitted to tropism prediction algorithms, and 4/14 samples returned with presence of a dual/mixed (D/M) tropic virus, respectively at 3%, 10%, 11%, and 95% of the viral quasispecies. V3 tropism prediction was confirmed by gp120 phenotyping, except for two out of 4 D/M predicted viruses (with 3 and 95%) which were phenotypically R5-tropic. In the first case, the result was discordant due to the limit of detection for the phenotyping technology, while in the latter case the prediction algorithms were not computing the viral tropism correctly.Although only demonstrated on a limited set of samples, the potential of the combined use of "deep sequencing + prediction algorithms" in cases where routine gp160 phenotype testing cannot be employed was illustrated. While good concordance was observed between gp120 phenotyping and prediction of R5-tropic virus, the results suggest that accurate prediction of X4-tropic virus would require further algorithm development.The chemokine receptors CCR5 and CXCR4 are the main co-receptors for entry of HIV-1 into target cells [1,2]. Maraviroc (Selzentry/Celsentri, Pfizer, NY) is a chemokine co-receptor antagonist, designed to prevent HIV-1 infection of CD4+ T-cells by blocking the CCR5 co-receptor. Since the drug is only effective in individuals exclusively harboring CCR5-tropic (R5) virus, viral tropism has to be determined before the initiation of maraviroc treatment. Currently, the only clinically validated tropism test is the Trofile assay (Monogram Biosciences, CA). It has recently been replaced by the Enhanced Sensitivity Trofile Assay (ESTA), which detects minority CXCR4-using (X4) viruses with higher sensitivity in clinical specimens [3]. However, the use of this type of phenotypic assays has several limitations: (i) the need to perform thes
%U http://www.aidsrestherapy.com/content/7/1/4