Association of chemokine receptor gene (CCR2-CCR5) haplotypes with acquisition and control of HIV-1 infection in Zambians

• Published in: Retrovirology 2011-03, Vol.8 (1), p.22-22, Article 22
• Main Authors: Malhotra, Rakhi, Hu, Liangyuan, Song, Wei, Brill, Ilene, Mulenga, Joseph, Allen, Susan, Hunter, Eric, Shrestha, Sadeep, Tang, Jianming, Kaslow, Richard A
• Format: Article
• Language: English
• Subjects: Adult; African Continental Ancestry Group - genetics; Analysis; Chemokine receptors; Chemokines; Confidence intervals; Control; Data collection; Development and progression; Disease Progression; Family Characteristics; Female; Frequency distribution; Gene Frequency; Genes; Genetic aspects; Genotype; Haplotypes; HIV; HIV infection; HIV Infections - genetics; HIV Infections - prevention & control; HIV Infections - transmission; HIV Infections - virology; HIV-1 - pathogenicity; HIV-1 - physiology; Human immunodeficiency virus; Humans; Male; Physiological aspects; Polymorphism, Genetic; Public health; Receptors, CCR2 - genetics; Receptors, CCR5 - genetics; Risk factors; Studies; Teaching hospitals; Viral Load; Young Adult; Zambia
• ISSN: 1742-4690; 1742-4690
• DOI: 10.1186/1742-4690-8-22

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. 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). 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.