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J Acquir Immune Defic Syndr. 2014 Jul 1;66(3):239-44. doi: 10.1097/QAI.0000000000000127.

Association between HIV-1 tropism and CCR5 human haplotype E in a Caucasian population.

Author information

1
*Department of Microbiology, Faculty of Medicine, University of Tartu, Tartu, Estonia; †West-Tallinn Hospital Laboratories, Tallinn, Estonia; ‡Department of Bioinformatics, Institute of Molecular and Cell Biology, University of Tartu and Estonian Biocentre, Tartu, Estonia; §Tartu Prison Hospital, Tartu, Estonia; ‖National Institute for Health Development, Tallinn, Estonia; ¶Department of Public Health, Faculty of Medicine, University of Tartu, Tartu, Estonia; #Department of Medicine, University of Texas Health Science Center, San Antonio, TX; and **Veterans Administration Research Center for AIDS and HIV-1 Infection, and ††Center for Personalized Medicine, South Texas Veterans Health Care System, San Antonio, TX.

Abstract

BACKGROUND:

The influence of the diversity of CCR5 on HIV susceptibility and disease progression has been clearly demonstrated but how the variability of this gene influences the HIV tropism is poorly understood. We investigated whether CCR5 haplotypes are associated with HIV tropism in a Caucasian population.

METHODS:

We evaluated 161 HIV-positive subjects in a cross-sectional study. CCR5 haplotypes were derived after genotyping 9 CCR2-CCR5 polymorphisms. The HIV subtype was determined by phylogenetic analysis using the maximum likelihood method and viral tropism by the genotypic tropism assay (geno2pheno). Associations between CCR5 haplotypes and viral tropism were determined using logistic regression analyses. Samples from 500 blood donors were used to evaluate the representativeness of HIV-positives in terms of CCR5 haplotype distribution.

RESULTS:

The distribution of CCR5 haplotypes was similar in HIV-positive subjects and blood donors. The majority of viruses (93.8%) belonged to HIV-1 CRF06_cpx; 7.5% were X4, and the remaining were R5 tropic. X4 tropic viruses were over represented among people with CCR5 human haplotype E (HHE) compared with those without this haplotype (13.0% vs 1.4%; P = 0.006). People possessing CCR5 HHE had 11 times increased odds (odds ratio = 11.00; 95% confidence interval: 1.38 to 87.38) of having X4 tropic viruses than those with non-HHE. After adjusting for antiretroviral (ARV) therapy, neither the presence of HHE nor the use of ARV was associated with X4 tropic viruses.

CONCLUSIONS:

Our results suggest that CCR5 HHE and ARV treatment might be associated with the presence of HIV-1 X4 tropic viruses.

PMID:
24508837
PMCID:
PMC4146654
DOI:
10.1097/QAI.0000000000000127
[Indexed for MEDLINE]
Free PMC Article
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