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

被引:16
作者
Phuphuakrat, A. [1 ]
Phawattanakul, S. [1 ]
Pasomsub, E. [2 ]
Kiertiburanakul, S. [1 ]
Chantratita, W. [2 ]
Sungkanuparph, S. [1 ]
机构
[1] Mahidol Univ, Ramathibodi Hosp, Fac Med, Dept Med, Bangkok 10400, Thailand
[2] Mahidol Univ, Ramathibodi Hosp, Fac Med, Dept Pathol, Bangkok 10400, Thailand
关键词
coreceptor; HIV-1; CCR5; Thailand; genotypic testing; CXCR4; tropism; IMMUNODEFICIENCY-VIRUS TYPE-1; CXCR4-USING HIV-1; CCR5; INHIBITOR; AIDS; POPULATION; R5; EPIDEMIOLOGY; PREDICTION; GUIDELINES; MARAVIROC;
D O I
10.1111/hiv.12108
中图分类号
R51 [传染病];
学科分类号
100401 ;
摘要
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 (). Results One hundred and fifty-five HIV-1-infected patients were enrolled in this study. Ninety-nine patients (63.9%) were antiretroviral-naive, and the remainder had virological failure. The median (interquartile range) CD4 cell count and HIV-1 RNA were 220 (74-379) cells/mu L 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-naive 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.
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收藏
页码:269 / 275
页数:7
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