Irja Lutsar, University of Tartu
Tõnis Karki, University of Tartu
Marie-Anne Shaw, University of Leeds
The injecting drug use and the spread of blood-borne viruses (e.g. HIV and HCV) due to contaminated syringes are a major concern worldwide. In Estonia, the HIV-1 epidemic started in 2000 when rare recombinant form CRF06_cpx entered into the intravenous drug users (IDUs) population. One of the factors that influence the susceptibility to HIV is host genetic factors. These factors have been studies mainly among persons infected or exposed by sexual transmission. How these factors influence the susceptibility to HIV among IDUs is largely unknown. The aim of current study was to assess the influence of genetic variability of HIV co-receptor CCR5 and its ligand (CCL3L1 and CCL5) and TLR3 on susceptibility to HIV and HCV in IDUs population. For that 374 IDUs were recruited from two syringe exchange programmes and three prisons (during 2006 - 2007) and 345 IDUs from one syringe exchange programmes (in 2010) in Estonia. The single nucleotide polymorphisms of CCR5, CCL5 and TLR3, and copy number of CCL3L1 were determined by real-time PCR. CCR5 and CCL5 halpotypes were defined using literature.
The results showed that CCR5 haplotype G*1 had protective effect against the susceptibility to HCV (ORadjusted = 0.07; 95% CI = 0.03 - 0.20) compared to other haplotypes. In addition, IDUs who possessed CCL5 haplotype D had decreased odds of being HCV positive (ORadjusted = 0.12; 95% CI = 0.03 - 0.42) than IDUs without this haplotype. However, CCR5 and CCL5 haplotyped did not influence the susceptibility to HIV. IDUs who had higher CCL3L1 copy number than population median had decreased odds of being HIV positive (ORadjusted = 0.20; 95% CI = 0.09 - 0.45) compared to IDUs with lower copy number. The possession of TLR3 rs3775291 T allele gave a protective effect against HIV infection (ORadjusted = 0.25; 95% CI = 0.07 - 0.87) compared to IDUs not possessing this allele. In summary, current study showed that in IDUs population the variability of CCL3L1 and TLR3 influence the susceptibility to HIV, and the variability of CCR5 and CCL5 influence the susceptibility to HCV.