在泰国流行的以CRF01_AE为主的HIV-1中，通过基因检测确定的共受体嗜性。

Coreceptor tropism determined by genotypic assay in HIV-1 circulating in Thailand, where CRF01_AE predominates.

作者信息

Phuphuakrat A, Phawattanakul S, Pasomsub E, Kiertiburanakul S, Chantratita W, Sungkanuparph S

机构信息

Department of Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.

出版信息

HIV Med. 2014 May;15(5):269-75. doi: 10.1111/hiv.12108. Epub 2013 Nov 11.

DOI:10.1111/hiv.12108

PMID:24215399

Abstract

OBJECTIVES

Chemokine (C-C motif) receptor 5 (CCR5) inhibitors are a novel class of antiretroviral agents that are promising for treatment of patients who harbour the HIV-1 R5 strain. Data on coreceptor tropism in non-B HIV-1 subtypes are limited. We studied coreceptor tropism in HIV-1 circulating in Thailand, where CRF01_AE predominates, using a genotypic assay.

METHODS

We compiled V3 sequences of HIV-1 strains circulating in Thailand during 2010-2012. Coreceptor tropism was predicted based on V3 sequences using geno2pheno version 2.5 (http://coreceptor.bioinf.mpi-inf.mpg.de).

RESULTS

One hundred and fifty-five HIV-1-infected patients were enrolled in this study. Ninety-nine patients (63.9%) were antiretroviral-naïve, and the remainder had virological failure. The median (interquartile range) CD4 cell count and HIV-1 RNA were 220 (74-379) cells/μL and 75,374 (14,127-226,686) HIV-1 RNA copies/mL, respectively. Of the sequences obtained from these patients, 119 (76.8%) were CRF01_AE and 22 (14.2%) were subtype B. At a false positive rate of < 5%, 61 (39.4%) HIV-1-infected individuals were predicted to harbour the X4 phenotype. X4 viruses were detected more frequently in the treatment-failure group compared with the treatment-naïve group (30.3 vs. 55.4%, respectively; P = 0.002). Those with CRF01_AE had a higher proportion of X4 viruses compared with non-AE subtypes (47.9 vs. 11.1%, respectively; P < 0.001). By multivariate logistic regression, CRF01_AE and treatment failure were independently associated with predicted X4 phenotype [odds ratio (OR) 7.93; 95% confidence interval (CI) 2.57-24.50; P < 0.001, and OR 3.10; 95% CI 1.50-6.42; P = 0.002, respectively].

CONCLUSIONS

CRF01_AE and treatment failure are associated with the predicted X4 phenotype. In regions where CRF01_AE predominates, use of CCR5 inhibitors must be considered with caution. The phenotypic assay and its correlation with genotypes should be further investigated in CRF01_AE.

摘要

目的

趋化因子（C-C基序）受体5（CCR5）抑制剂是一类新型抗逆转录病毒药物，有望用于治疗携带HIV-1 R5毒株的患者。关于非B型HIV-1亚型共受体嗜性的数据有限。我们使用基因分型检测方法，研究了在泰国流行的HIV-1的共受体嗜性，该国以CRF01_AE亚型为主。

方法

我们汇总了2010 - 2012年期间在泰国流行的HIV-1毒株的V3序列。使用geno2pheno 2.5版本（http://coreceptor.bioinf.mpi-inf.mpg.de）基于V3序列预测共受体嗜性。

结果

本研究纳入了155例HIV-1感染患者。99例患者（63.9%）未接受过抗逆转录病毒治疗，其余患者存在病毒学失败情况。CD4细胞计数和HIV-1 RNA的中位数（四分位间距）分别为220（74 - 379）个细胞/μL和75,374（14,127 - 226,686）拷贝/mL。从这些患者获得的序列中，119例（76.8%）为CRF01_AE亚型，22例（14.2%）为B亚型。在假阳性率<5%的情况下，预计61例（39.4%）HIV-1感染个体携带X4表型。与未接受治疗组相比，治疗失败组中检测到X4病毒的频率更高（分别为30.3%和55.4%；P = 0.002）。与非AE亚型相比，CRF01_AE亚型的患者中X4病毒的比例更高（分别为47.9%和11.1%；P < 0.001）。通过多因素逻辑回归分析，CRF01_AE亚型和治疗失败与预测的X4表型独立相关[比值比（OR）7.93；95%置信区间（CI）2.57 - 24.50；P < 0.001，以及OR 3.10；95% CI 1.50 - 6.42；P = 0.002]。