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Open Access Research article

High prevalence of CXCR4 usage among treatment-naive CRF01_AE and CRF51_01B-infected HIV-1 subjects in Singapore

Kah Ying Ng1, Kuan Kiat Chew1, Palvinder Kaur1, Joe Yap Kwan1, Wei Xin Khong1, Li Lin2, Arlene Chua1, Mei Ting Tan1, Thomas C Quinn34, Oliver Laeyendecker34, Yee Sin Leo1 and Oon Tek Ng1*

Author Affiliations

1 Institute of Infectious Disease and Epidemiology, Communicable Disease Centre, Tan Tock Seng Hospital, Singapore 308433, Singapore

2 Department of Infectious Disease, Jurong General Hospital, Singapore, 159964, Singapore

3 Johns Hopkins School of Medicine, Baltimore, MD, USA

4 Laboratory of Immunoregulation, Division of Intramural Research, National Institute of Allergy and Infectious Disease, National Institutes of Health, Baltimore, MD, USA

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BMC Infectious Diseases 2013, 13:90  doi:10.1186/1471-2334-13-90

Published: 19 February 2013

Abstract

Background

Recent studies suggest HIV-1 inter-subtype differences in co-receptor usage. We examined the correlation between HIV-1 subtype and co-receptor usage among treatment-naïve HIV-1 subjects in Singapore. Additionally, we investigated whether the subtype co-receptor association was influenced by stage of infection.

Methods

V3 sequences of HIV-1 envelope protein gp120 were obtained from 110 HIV treatment-naïve patients and genotypic co-receptor tropism determination was performed using Geno2pheno. Two false-positive rate (FPR) cut-offs, 10% and 5.75% were selected for tropism testing.

Results

Subtype assignment of viral strains from 110 HIV-infected individuals based on partial sequencing of HIV-1 pol, gp120 and gp41 were as follows: 27 subtype B, 64 CRF01_AE, 10 CRF51_01B, and 9 other subtypes. At FPR=10%, 10 (100%) CRF51_01B-infected subjects and 26 (40.6%) CRF01_AE-infected subjects had CXCR4-using virus, compared to 7 (25.9%) subtype B subjects and 1 (11.1%) CRF33_01B-infected subject (P < 0.001). At FPR=5.75%, 10 (100%) CRF51_01B-infected subjects and 20 (31.3%) CRF01_AE-infected subjects had CXCR4-using virus, compared to 4 (14.8%) subtype B and 1 (11.1%) CRF33_01B-infected subjects (P < 0.001). Among those with evidence of seroconversion within 2 years prior to study enrolment, 100% of CRF51_01B-infected subjects had CXCR4-using virus, independent of Geno2pheno FPR.

Conclusion

CRF51_01B and CRF01_AE-infected individuals have higher prevalence of CXCR4-usage compared to subtype B infected individuals. Further studies examining these differences could help optimise the use of CCR5-antagonist in populations with these subtypes, and increase our understanding of HIV-1 biology.

Keywords:
CXCR4 usage; HIV-1; treatment-naïve