The biology of how circumcision reduces HIV susceptibility: broader implications for the prevention field

AIDS Res Ther. 2017 Sep 12;14(1):49. doi: 10.1186/s12981-017-0167-6.


Circumcision reduces heterosexual HIV-1 acquisition in men by at least 60%. However, the biological mechanisms by which circumcision is protective remain incompletely understood. We test the hypothesis that the sub-preputial microenvironment created by the foreskin drives immune activation in adjacent foreskin tissues, facilitating HIV-1 infection through a combination of epithelial barrier disruption, enhanced dendritic cell maturation, and the recruitment/activation of neutrophils and susceptible CD4 T cell subsets such as Th17 cells. Furthermore, we provide evidence that the genital microbiome may be an important driver of this immune activation. This suggests that new modalities to reduce genital immune activation and/or alter the genital microbiome, used alone or in combination with topical microbicides, may be of significant benefit to HIV prevention.

Keywords: Chemokines; Circumcision; Foreskin; HIV-1; Microbiome; T-cells.

Publication types

  • Review

MeSH terms

  • Adult
  • Animals
  • CD4-Positive T-Lymphocytes / immunology
  • Chemokines / immunology
  • Circumcision, Male*
  • Disease Susceptibility*
  • Foreskin / immunology
  • Foreskin / virology
  • HIV Infections / immunology
  • HIV Infections / prevention & control*
  • HIV Infections / virology
  • HIV-1 / isolation & purification
  • HIV-1 / physiology*
  • Heterosexuality
  • Humans
  • Lymphocyte Activation
  • Male
  • Microbiota / immunology
  • Penis / cytology
  • Penis / immunology
  • Penis / virology
  • Primates
  • Simian Acquired Immunodeficiency Syndrome / immunology
  • Simian Immunodeficiency Virus / immunology
  • Simian Immunodeficiency Virus / physiology
  • Th17 Cells / immunology
  • Th17 Cells / virology


  • Chemokines