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

Kah Ying Ng, Kuan Kiat Chew, Palvinder Kaur, Joe Yap Kwan, Wei Xin Khong, Li Lin, Arlene Chua, Mei Ting Tan, Thomas C Quinn, Oliver B. Laeyendecker, Yee Sin Leo, Oon Tek Ng

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Article number90
JournalBMC Infectious Diseases
Volume13
Issue number1
DOIs
StatePublished - Feb 19 2013

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Singapore
HIV-1
Tropism
Viruses
HIV
Therapeutics
Infection
Population

Keywords

  • CXCR4 usage
  • HIV-1
  • treatment-naïve

ASJC Scopus subject areas

  • Infectious Diseases

Cite this

High prevalence of CXCR4 usage among treatment-naive CRF01_AE and CRF51_01B-infected HIV-1 subjects in Singapore. / Ng, Kah Ying; Chew, Kuan Kiat; Kaur, Palvinder; Kwan, Joe Yap; Khong, Wei Xin; Lin, Li; Chua, Arlene; Tan, Mei Ting; Quinn, Thomas C; Laeyendecker, Oliver B.; Leo, Yee Sin; Ng, Oon Tek.

In: BMC Infectious Diseases, Vol. 13, No. 1, 90, 19.02.2013.

Research output: Contribution to journalArticle

Ng, Kah Ying ; Chew, Kuan Kiat ; Kaur, Palvinder ; Kwan, Joe Yap ; Khong, Wei Xin ; Lin, Li ; Chua, Arlene ; Tan, Mei Ting ; Quinn, Thomas C ; Laeyendecker, Oliver B. ; Leo, Yee Sin ; Ng, Oon Tek. / High prevalence of CXCR4 usage among treatment-naive CRF01_AE and CRF51_01B-infected HIV-1 subjects in Singapore. In: BMC Infectious Diseases. 2013 ; Vol. 13, No. 1.
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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-na{\"i}ve 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-na{\"i}ve 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.",
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T1 - High prevalence of CXCR4 usage among treatment-naive CRF01_AE and CRF51_01B-infected HIV-1 subjects in Singapore

AU - Ng, Kah Ying

AU - Chew, Kuan Kiat

AU - Kaur, Palvinder

AU - Kwan, Joe Yap

AU - Khong, Wei Xin

AU - Lin, Li

AU - Chua, Arlene

AU - Tan, Mei Ting

AU - Quinn, Thomas C

AU - Laeyendecker, Oliver B.

AU - Leo, Yee Sin

AU - Ng, Oon Tek

PY - 2013/2/19

Y1 - 2013/2/19

N2 - 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.

AB - 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.

KW - CXCR4 usage

KW - HIV-1

KW - treatment-naïve

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