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Association Between HIV-1 Tropism and CCR5 Human Haplotype E in a Caucasian Population

Huik, Kristi PhD*; Avi, Radko PhD*; Uibopuu, Helen MSc; Pauskar, Merit MScHS*; Margus, Tõnu PhD; Karki, Tõnis MD, PhD*; Krispin, Tõnu MD, PhD*; Kool, Piret MD§; Rüütel, Kristi MD, PhD; Talu, Ave MSc; Abel-Ollo, Katri MScPH; Uusküla, Anneli MD, PhD; Carrillo, Andrew BS#,**,††; He, Weijing MD#,**,††; Ahuja, Sunil K. MD#,**,††; Lutsar, Irja MD, PhD*

JAIDS Journal of Acquired Immune Deficiency Syndromes: July 1st, 2014 - Volume 66 - Issue 3 - p 239–244
doi: 10.1097/QAI.0000000000000127
Basic and Translational Science

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.

*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.

Correspondence to: Kristi Huik, PhD, Department of Microbiology, University of Tartu, Ravila 19, Tartu 50411, Estonia (e-mail:

Supported by European Union through the European Regional Development Fund, Estonian Science Foundation (Grants 8415 and 8856), Basic Financing and the Target Financing of Estonian Ministry of Education and Research (SF0180004s12 and SF0180026s09), European Commission funded project Expanding Network for Comprehensive and Coordinated Action on HIV/AIDS prevention among IDUs and Bridging Population Nr. 2005305 (ENCAP), Global Fund to Fight HIV, Tuberculosis and Malaria Program “Scaling up the response to HIV in Estonia” for 2003–2007, National HIV/AIDS Strategy for 2006–2015, US Civilian Research Development Foundation (Grant ESX0-2722-TA-06), US National Institutes of Health, National Institute on Drug Abuse (Grant R01DA03574), the Archimedes Foundation and Norwegian Financial Mechanism/EEA(Grant EE0016), the Veterans Affairs (VA) Center for AIDS and HIV Infection and VA Center for Personalized Medicine of the South Texas Veterans Health Care System, a National Institutes of Health MERIT Grant (R37AI046326), and the Doris Duke Distinguished Clinical Scientist Award to S.K.A. S.K.A. is also supported by a VA MERIT award, the Elizabeth Glaser Pediatric AIDS Foundation, the Burroughs Welcome Clinical Scientist Award in Translational Research, and the Senior Scholar Award from the Max and Minnie Tomerlin Voelcker Fund.

Presented in part in an oral presentation at the 10th European Meeting on HIV & Hepatitis—Treatment Strategies & Antiviral Drug Resistance, March 28–30, 2010, Barcelona, Spain.

The authors have no conflicts of interest to disclose.

Received January 22, 2014

Accepted January 22, 2014

© 2014 by Lippincott Williams & Wilkins