Association between TLR3 rs3775291 and resistance to HIV among highly exposed Caucasian intravenous drug users

Infect Genet Evol. 2013 Dec;20:78-82. doi: 10.1016/j.meegid.2013.08.008. Epub 2013 Aug 17.


Background: TLR3 recognizes dsRNA and triggers immune responses against RNA and DNA viruses. A polymorphism in TLR3, rs3775291 (Leu412Phe), has been associated with the increased susceptibility to enteroviral myocarditis, protection against tick-borne encephalitis virus and HIV-1 infection. We investigated Caucasian intravenous drug users (IDUs) and blood donors in order to evaluate the associations between TLR3 genotypes and susceptibility to HIV infection.

Materials and methods: A total of 345 Caucasian IDUs were recruited, 50% of them were HIV positive, 89% HCV and 77% HBV positive. Based on their history of needle sharing, 20 of the HIV negative IDUs were classified as highly exposed HIV seronegatives (HESNs), 68 as non-HESNs and 85 as unexposed. The control group consisting of 497 blood donors tested negative for all three viruses. TLR3 rs3775291 were determined by using TaqMan Allelic Discrimination Assay.

Results: The TLR3 rs3775291 T allele frequency was similar among the HIV negative and HIV positive IDUs and blood donors - 36%, 31% and 34%, respectively. The frequency of persons possessing at least one TLR3 rs3775291 T allele was significantly higher in HESNs compared with blood donors and HIV positive IDUs (80% vs. 55%; p=0.037 and 80% vs. 53%; p=0.031, respectively). In the univariate analysis, persons who possessed at least one T allele had reduced odds of being HIV seropositive (OR=0.29, 95% CI=0.09-0.90). This association remained significant (OR=0.25, 95% CI=0.07-0.87) after the adjustment for other co-variates (HCV, HBV serostatus and duration of intravenous drug use).

Conclusions: The TLR3 rs3775291 T allele has a protective effect against HIV infection among HESNs IDUs.

Keywords: Highly exposed HIV seronegatives; Intravenous drug users; Leu412Phe; TLR3.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Blood Donors
  • Drug Users*
  • Estonia
  • Female
  • Genetic Predisposition to Disease
  • Genotype
  • HIV Infections / genetics*
  • HIV Infections / immunology
  • HIV Infections / transmission
  • HIV Seropositivity / genetics*
  • Humans
  • Male
  • Polymorphism, Single Nucleotide
  • Substance Abuse, Intravenous / genetics
  • Substance Abuse, Intravenous / immunology
  • Substance Abuse, Intravenous / virology*
  • Surveys and Questionnaires
  • Toll-Like Receptor 3 / genetics*
  • Toll-Like Receptor 3 / immunology*
  • White People / genetics
  • Young Adult


  • TLR3 protein, human
  • Toll-Like Receptor 3