High sensitivity of specific genotypic tools for detection of X4 variants in antiretroviral-experienced patients suitable to be treated with CCR5 antagonists

Objectives Evaluation of the reliability of several V3-based genotypic predictors to infer viral tropism in patients infected with B and non-B strains of HIV-1. Methods Several genotypic tropism predictors were evaluated in plasma (RNA) samples from 198 HIV-1-infected patients, taking as gold standard the results of the phenotypic recombinant virus assay Phenoscript®. In addition, for 37 B subtype HIV-1 patients the phenotypic results from plasma samples were also compared with tropism predictions based on V3 amplification from paired peripheral blood mononuclear cells (PBMCs). Results A total of 150 paired genotypic/phenotypic results were obtained from plasma specimens. Concordance values ranged from 63% to 85%, depending on the genotypic algorithm used. The best predictors in terms of sensitivity/specificity to detect X4 variants were WebPSSMX4/R5 (77%/87%), Geno2phenoFPR = 5% (80%/77%) and an algorithm combining the ‘11/25’ and ‘Net charge’ rules, termed Garrido's rule (80%/79%). The performance of genotypic predictors was better testing B than non-B clades. The overall sensitivity ranged from 28% to 94%, reaching 100% in subtype B antiretroviral-experienced patients using WebPSSMSI/NSI, Geno2phenoFPR ≥ 5% and Garrido's rule. Conversely, the sensitivity when testing non-B subtypes was poorer, ranging from 17% to 67%. Interestingly, the correlation between genotypic and phenotypic results was better when testing PBMCs than plasma using all genotypic predictors. Conclusions Genotypic tools based on V3 sequences may provide reliable information on HIV-1 tropism when testing clade B viruses, especially in antiretroviral-experienced patients. The sensitivity to detect X4 variants using genotypic tools may improve by testing proviral DNA instead of plasma RNA.