Behavioral risk exposure and host genetics of susceptibility to HIV-1 infection

Sadeep Shrestha, Steffanie A. Strathdee, Noya Galai, Taras Oleksyk, M. Daniele Fallin, Shruti Mehta, Daniel Schaid, David Vlahov, Stephen J. O'Brien, Michael W. Smith

Research output: Contribution to journalArticlepeer-review

44 Scopus citations


Background. Some individuals are readily infected with low human immunodeficiency virus type 1 (HIV-1) exposure, whereas others appear less susceptible, suggesting that host genetics plays a role in the viral entry pathway. The matched case-control study design with measured risk exposures provides an avenue for discovering genes involved in susceptibility to infection. Methods. We conducted a nested case-control study of African Americans (266 HIV-1 seroconverter cases and 532 seronegative controls from the AIDS Link to Intravenous Experience cohort), to examine the association between 50 single-nucleotide polymorphisms (SNPs) in 9 candidate genes (CCR5, CCR2, RANTES, MIP1A, MCP2, IL10, IFNG, MCSF, and IL2) and susceptibility to HIV-1 infection. To account for differential exposure propensities, risk behavior self-reported during semiannual visits was used to estimate a standardized cumulative risk exposure (SCRE). Individual SNPs were evaluated using conditional logistic-regression models, and the inferred haplotypes were assessed in the haplotype trend regression analyses after adjusting for age and SCRE. Results. Four SNPs (CCR2-V64I, CCR5-2459, MIP1A+954, and IL2+3896) and specific haplotypes in the IL2 and CCR2/CCR5 regions were significantly associated with HIV-1 infection susceptibility in different genetic models. Conclusions. Our results suggest that genetic variants in associated host genes may play an important role in susceptibility to HIV-1 infection.

Original languageEnglish (US)
Pages (from-to)16-26
Number of pages11
JournalJournal of Infectious Diseases
Issue number1
StatePublished - Jan 1 2006

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases


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