title: Determination of the high prevalence of Dual/Mixed- or X4-tropism among HIV type 1 CRF01_AE in Hong Kong by genotyping and phenotyping methods.
abstract: In Hong Kong, the CCR5 antagonist has recently been introduced into salvage therapy for multiclass drug-resistant HIV-1-infected patients. Coreceptor usage must be determined prior to the usage of the CCR5 antagonist, which does not inhibit X4-tropic viruses. This study aimed to determine the tropism prevalence for HIV-1 subtypes B and CRF01_AE in Hong Kong. In addition, a modified promoter-PCR phenotypic assay was used to validate the genotypic tropism prediction on CRF01_AE. One hundred and five subtype B and 98 CRF01_AE antiretroviral-naive patients were recruited for this study. The viral env V3 region isolated from the patients was sequenced and analyzed by Geno2pheno (FPR=5.75% or 10%, Clonal or Clinical), position-specific scoring matrix (WebPSSM, x4r5 subtype B matrix), and the combination of 11/25 and net charge rules. Fifteen concordant and 22 discordant tropism genotyped CRF01_AE samples were further phenotyped by either enhanced sensitivity Trofile assay or an optimized promoter-PCR phenotypic assay. The prevalence of Dual/Mixed- or X4-tropic virus in antiretroviral-naive subtype CRF01_AE was 39.1%, which was significantly higher than subtype B (p<0.05), regardless of the choices of genotypic algorithms. Our phenotypic data proposed that a better genotypic tropism prediction for HIV-1 CRF01_AE would be using both Geno2pheno (FPR=10%, Clonal) and WebPSSM (x4r5 subtype B matrix) algorithms in combination. The sensitivity and specificity for this combination were 88.9% and 89.3%, respectively. The comparatively high prevalence of Dual/Mixed- or X4-tropic virus in CRF01_AE demonstrated the need for special attention to future treatment strategies.
authors: Department of Microbiology, Queen Mary Hospital, the University of Hong Kong, Hong Kong Special Administrative Region, China.
authors: Sabrina Wai-Chi
authors: SW
authors: To
authors: Jonathan Hon-Kwan
authors: JH
authors: Chen
authors: Ka-Hing
authors: KH
authors: Wong
authors: Kenny Chi-Wai
authors: KC
authors: Chan
authors: Zhiwei
authors: Z
authors: Chen
authors: Wing-Cheong
authors: WC
authors: Yam
mesh_terms: D005838:Genotype; D015699:HIV Envelope Protein gp120 / Q000235:genetics*; D015658:HIV Infections / Q000453:epidemiology / Q000821:virology*; D015497:HIV-1 / Q000502:physiology*; D006723:Hong Kong / Q000453:epidemiology; D006801:Humans; D010641:Phenotype; D016133:Polymerase Chain Reaction; D056510:Position-Specific Scoring Matrices; D015995:Prevalence; D056189:Viral Tropism
chemical_list: D015699:HIV Envelope Protein gp120
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