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Objective  The role of CC chemokine receptor 5 (CCR5) and its ligand CCL5 on the pathogenesis of HIV infection has been well studied but not for HCV infection. Here, we investigated whether  CCL5  haplotypes influence HIV and HCV seropositivity among 373 Caucasian people who inject drugs (PWID) from Estonia.    Methods  Study included 373 PWID; 56% were HIV seropositive, 44% HCV seropositive and 47% co-infected. Four  CCL5  haplotypes (A-D) were derived from three  CCL5  polymorphisms (rs2107538/rs2280788/rs2280789) typed by Taqman allelic discrimination assays. The data of  CCR5  haplotypes were used from our previous study. The association between  CCL5  haplotypes with HIV and/or HCV seropositivity was determined using logistic regression analysis.    Results  Possessing  CCL5  haplotype D (defined by rs2107538A/rs2280788G/rs2280789C) decreased the odds of HCV seropositivity compared to those not possessing it (OR = 0.19; 95% CI 0.09–0.40), which remained significant after adjustment to co-variates (OR = 0.08; 95% CI 0.02–0.29). An association of this haplotype with HIV seropositivity was not found. In step-wise logistic regression with backward elimination  CCL5  haplotype D and  CCR5  HHG*1 had reduced odds for HCV seropositivity (OR = 0.28 95% CI 0.09–0.92; OR = 0.23 95% CI 0.08–0.68, respectively) compared to those who did not possess these haplotypes, respectively.    Conclusions  Our results suggest that among PWID  CCL5  haplotype D and  CCR5  HHG*1 independently protects against HCV. Our findings highlight the importance of CCL5 genetic variability and CCL5-CCR5 axis on the susceptibility to HCV.

A CCL5 Haplotype Is Associated with Low Seropositivity Rate of HCV Infection in People Who Inject Drugs