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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
immunology and microbiology
Increased CXCR4 use of HIV-1 subtype C identified by population sequencing in patients failing antiretroviral treatment compared with treatment-naive patients in botswana
AIDS Research and Human Retroviruses, Volume 30, No. 5, Year 2014
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Description
HIV-1 uses the coreceptors CCR5 and/or CXCR4 for cell entry. Monotropic CCR5-using variants are found early in the infection while CXCR4-using variants may appear after progression to AIDS. CXCR4 use may consist of both monotropic and dualtropic viruses. The viral phenotype is important in evaluating the response to CCR5 inhibitors, a new class of antiviral drugs. The coreceptor use of HIV-1 was investigated using population sequencing in 24 patients from Botswana, carrying HIV-1 subtype C and failing antiretroviral treatment, while 26 treatment-naive patients acted as controls. Single genome sequencing was used to discern minor HIV-1 populations in the treatment-experienced group. The Geno2Pheno method was employed to predict the coreceptor use phenotype from HIV-1 env gp120 V3 DNA sequences. The glycan-charge model adjusted for subtype C was also used for phenotype prediction. The viral phenotype of population sequences was predicted using Geno2Pheno in 24/24 treatment-experienced patients, of whom eight (33%) were predicted to harbor CXCR4-using strains as compared to 2/26 in the treatment-naive group (p=0.03). Single genome sequencing generated 4-23 clones/patient in the treatment-experienced group. Altogether, 90/295 (31%) putative CXCR4-using clones were identified. In 10/24 (42%) treated patients at least one clone was predicted to be CXCR4-using, further increasing the amount of identified treatment-experienced patients with CXCR4 use. Although subtype C is usually associated with comparatively little CXCR4 use, the frequency of CXCR4 use in treatment-experienced patients with subtype C can be higher, which may have implications for the administration of CCR5 inhibitors in this patient group. © Copyright 2014, Mary Ann Liebert, Inc. 2014.
Authors & Co-Authors
Sollerkvist, Lotta Pramanik
Unknown Affiliation
Gaseitsiwe, Simani
Unknown Affiliation
Mine, Madisa O.
Unknown Affiliation
Sebetso, Gaseene
Unknown Affiliation
Mphoyakgosi, T.
Unknown Affiliation
Diphoko, Thabo
Unknown Affiliation
Essex, Max E.
Unknown Affiliation
Ehrnst, Anneka C.
Unknown Affiliation
Statistics
Citations: 8
Authors: 8
Affiliations: 5
Identifiers
Doi:
10.1089/aid.2013.0203
ISSN:
08892229
e-ISSN:
19318405
Research Areas
Genetics And Genomics
Health System And Policy
Infectious Diseases
Study Design
Cross Sectional Study
Study Locations
Botswana