Abstract

Background and aim. Susceptibility to HIV and HCV is influenced by a variety of factors including host genetics. Many polymorphisms of HIV pathogenesis related genees (e.g. CCR5, CCL3L1) have been associated with susceptibility to HIV infection among sexually infected subjects. It is unknown whether the genetic variability of CCL3L1 and CCR5 influences the acquisition of multiple blood-borne infections (e.g. HCV and HIV ) occurring commonly among persons who inject drugs (PWID). We investigated whether CCR5 haplotypes and CCL3L1 gene copy number influence HIV-1 and HCV seropositivity among Caucasian PWID.

Methods. In total, 374 Caucasian PWID and 500 blood donors from Estonia (seronegative for HIV, HCV and HBV) were included in the study.The CCL3L1 copy number and nine CCR2-CCR5 polymorphisms were determined by real-time PCR. The. CCR5 haplotypes (HHA to HHG*2) were defined using an evolutionary based classification. In addition, uni- and multivariate logistic regression analysis was used to evaluate the associations of CCR5 haplotypes and CCL3L1 gene copy number with HIV and/ or HCV seropositivity.

Results and conclusions. Overall distribution of CCR5 haplotypes and CCL3L1 copy number was similar to that of other Caucasian populations. The PWID possessing CCR5 HHG*1 had decreased odds to be HCV seropositive (OR 0.37; 95% CI 0.16–0.82) compare with the PWID possessing other haplotypes. This association remained significant after adjustment for co-factors. The PWID with higher CCL3L1 copy number than population median (2) had decreased odds of HIV acquisition (OR 0.49; 95% CI 0.29–0.81); the association remained significant in a multivariate model. Among PWID with extensive exposure to HCV and HIV, CCL3L1 copy number is a risk factor for HIV seropositivity. The CCR5 HHG*1 influences HCV seropositivity so that the possession of this haplotype dimishes susceptibility to HCV. These results highlight the importance of the CCR5-CCL3L1 axis in susceptibility to HIV and HCV infections.