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Concordance between HIV‐1 genotypic coreceptor tropism predictions based on plasma RNA and proviral DNA
Author(s) -
Verhofstede C,
Brudney D,
Reynaerts J,
Vaira D,
Fransen K,
De Bel A,
SeguinDevaux C,
De Wit S,
Vandekerckhove L,
Geretti AM
Publication year - 2011
Publication title -
hiv medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.53
H-Index - 79
eISSN - 1468-1293
pISSN - 1464-2662
DOI - 10.1111/j.1468-1293.2011.00922.x
Subject(s) - concordance , rna , dna , tropism , biology , genotype , microbiology and biotechnology , virology , genetics , gene , virus
Objective The aim of the study was to evaluate the use of proviral DNA as a source of viral genetic material for genotypic coreceptor tropism testing (GTT). Methods GTT consisted of bulk V3 sequencing followed by geno2pheno interpretation with the interpretative cut‐off [false positive rate (FPR)] set at 5 and 10%. GTT was performed for 165 patients with a viral load of >500 HIV‐1 RNA copies/mL on simultaneously collected plasma RNA and proviral DNA, and for 126 patients with a viral load of <500 copies/mL on current proviral DNA and pretreatment plasma RNA. Phenotypic tropism testing (PTT) results were available for 142 samples. Results In the simultaneous RNA/DNA comparison, concordance in prediction was 95.2% (at FPR 10%) and 96.4% (at FPR 5%). Six RNA‐R5/DNA‐X4 and two RNA‐X4/DNA‐R5 discordances were observed at an FPR of 10%, and six RNA‐R5/DNA‐X4 discordances were observed at an FPR of 5%. In the longitudinal RNA/DNA comparison, concordance was 88.1% (at FPR 10%) and 90.5% (at FPR 5%). Eight RNA‐X4/DNA‐R5 and seven RNA‐R5/DNA‐X4 discordances were seen at an FPR of 10%, and 10 RNA‐R5/DNA‐X4 and two RNA‐X4/DNA‐R5 discordances at an FPR of 5%. The overall concordance of RNA GTT with PTT was 82% (at FPR 10%) and 83% (at FPR 5%). The overall concordance of DNA GTT with PTT was 85% (at both 10 and 5% FPRs). Conclusions GTT produced highly concordant tropism predictions for proviral DNA and plasma RNA. GTT on proviral DNA offers a promising approach for tropism prediction in clinical practice, particularly for the assessment of treated patients with low or suppressed viraemia.