HESNs were defined collectively as individuals lacking anti-HIV-1 IgG seropositivity

or evidence of infection despite frequent exposure to HIV-1 and/or repeated high-risk behaviour in areas with high HIV-1 prevalence. The seronegative description addresses the possibility that some HESN subjects may have mucosal immunoglobulin (Ig)A responses to HIV-1, but by definition all HESN subjects must be anti-HIV-1 IgG seronegative and are often also tested for the presence of HIV-1 by ultra-sensitive polymerase chain reaction (PCR). In terms of documenting exposure to HIV-1, studies of HIV-1 discordant couples and haemophiliacs have had the advantage of known exposures to quantifiable amounts of HIV-1 [21]. Nevertheless, studies of commercial sex workers SAHA HDAC clinical trial and i.v. drug users have inferred exposure to HIV-1 based upon mathematical models of the frequency of high-risk activity and the prevalence of HIV-1 in the community being studied [1,18,22]. Throughout this review, we will compare and contrast the evidence for adaptive and innate responses as correlates of resistance in high-risk HESN subjects. We will also explore how mechanism(s) of innate resistance to HIV-1 in HESN subjects intersect or differ with mechanisms

of control over HIV-1 https://www.selleckchem.com/products/nu7441.html replication during chronic infection. Since the first identification of HIV-specific T cell responses in HESN subjects [23], HIV-specific T cell responses have been identified in a number of high-risk uninfected individuals from multiple cohorts [3–5,14,24]. Subsequent reports confirmed the presence of antigen-specific T cell responses to HIV-1 in HESN subjects while characterizing the functional and proliferative capacity of HIV-specific T cells in these subjects [7,25–27]. Genetically, both major histocompatibility complex (MHC) class I [28] and human leucocyte

antigen (HLA) class II [29] alleles have been associated with a reduced risk of infection with HIV-1. In terms of protection, the anti-viral mechanisms utilized by T cells against HIV-1 may come in the form of direct lysis of virally C59 infected cells or through the secretion of anti-viral factors such as chemokines/cytokines or other CD8 non-cytolytic anti-viral factors (CNAR) [30]. Together with the description of anti-HIV-specific responses in HIV-infected long-term non-progressor subjects controlling viral replication [31,32], these findings raised hope that the generation of antigen-specific T cell immune responses to HIV-1 following high-risk contact could result in protection from HIV-1 in subsequent exposures.