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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
Association of chemokine receptor gene (CCR2-CCR5) haplotypes with acquisition and control of HIV-1 infection in Zambians
Retrovirology, Volume 8, Article 22, Year 2011
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Description
Background: Polymorphisms in chemokine (C-C motif) receptors 2 and 5 genes (CCR2 and CCR5) have been associated with HIV-1 infection and disease progression. We investigated the impact of CCR2-CCR5 haplotypes on HIV-1 viral load (VL) and heterosexual transmission in an African cohort. Between 1995 and 2006, cohabiting Zambian couples discordant for HIV-1 (index seropositive and HIV-1 exposed seronegative {HESN}) were monitored prospectively to determine the role of host genetic factors in HIV-1 control and heterosexual transmission. Genotyping for eight CCR2 and CCR5 variants resolved nine previously recognized haplotypes. By regression and survival analytic techniques, controlling for non-genetic factors, we estimated the effects of these haplotypic variants on a) index partner VL, b) seroconverter VL, c) HIV-1 transmission by index partners, d) HIV-1 acquisition by HESN partners.Results: Among 567 couples, 240 virologically linked transmission events had occurred through 2006. HHF*2 homozygosity was associated with significantly lower VL in seroconverters (mean beta = -0.58, log10 P = 0.027) and the HHD/HHE diplotype was associated with significantly higher VL in the seroconverters (mean beta = 0.54, log10 P = 0.014) adjusted for age and gender in multivariable model. HHD/HHE was associated with more rapid acquisition of infection by the HESNs (HR = 2.0, 95% CI = 1.20-3.43, P = 0.008), after adjustments for index partner VL and the presence of genital ulcer or inflammation in either partner in Cox multivariable models. The HHD/HHE effect was stronger in exposed females (HR = 2.1, 95% CI = 1.14-3.95, P = 0.018).Conclusions: Among Zambian discordant couples, HIV-1 coreceptor gene haplotypes and diplotypes appear to modulate HIV-1 VL in seroconverters and alter the rate of HIV-1 acquisition by HESNs. These associations replicate or resemble findings reported in other African and European populations. © 2011 Malhotra et al; licensee BioMed Central Ltd.
Available Materials
https://efashare.b-cdn.net/share/pmc/articles/PMC3075214/bin/1742-4690-8-22-S1.DOC
https://efashare.b-cdn.net/share/pmc/articles/PMC3075214/bin/1742-4690-8-22-S2.DOC
Authors & Co-Authors
Malhotra, Rakhi
United States, Birmingham
The University of Alabama at Birmingham
Hu, Liangyuan
United States, Birmingham
The University of Alabama at Birmingham
Song, Wei
United States, Birmingham
The University of Alabama at Birmingham
Brill, Ilene K.
United States, Birmingham
The University of Alabama at Birmingham
Mulenga, Joseph
Zambia, Lusaka
Rwanda Zambia Hiv Research Group
Allen, Susan A.
Zambia, Lusaka
Rwanda Zambia Hiv Research Group
United States, Atlanta
Emory University
Hunter, Eric
United States, Atlanta
Emory University
Shrestha, Sadeep
United States, Birmingham
The University of Alabama at Birmingham
Tang, Jianming
United States, Birmingham
The University of Alabama at Birmingham
Kaslow, Richard A.
United States, Birmingham
The University of Alabama at Birmingham
Statistics
Citations: 31
Authors: 10
Affiliations: 3
Identifiers
Doi:
10.1186/1742-4690-8-22
Research Areas
Genetics And Genomics
Infectious Diseases
Sexual And Reproductive Health
Study Design
Cohort Study
Participants Gender
Female