Coreceptor tropism determined by genotypic assay in HIV-1 circulating in Thailand, where CRF01_AE predominates.
OBJECTIVE
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.
Department of Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
A
A
Phuphuakrat
S
S
Phawattanakul
E
E
Pasomsub
S
S
Kiertiburanakul
W
W
Chantratita
S
S
Sungkanuparph
D000328:Adult; D003430:Cross-Sectional Studies; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000453:epidemiology / Q000821:virology*; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D019713:Receptors, CCR5 / Q000502:physiology; D013785:Thailand / Q000453:epidemiology; D019562:Viral Load; D056189:Viral Tropism
D019713:Receptors, CCR5
CCR5; CXCR4; HIV-1; Thailand; coreceptor; genotypic testing; tropism