Immunogenetic Modulators of Mucosal Protection From HIV-1
Condition: HIV Infections; HSV-2 Infection
MeSH terms: Infections; Communicable Diseases
Study type: Observational

Summary: 
      This is a single site, prospective, observational study that seeks to assess changes in
      mucosal immunity that occur as a result of HIV-1 exposure, HSV-2 infection, and/or
      pre-exposure prophylaxis (PrEP) usage to prevent HIV-1 acquisition. The study will collect
      mucosal and peripheral blood samples for a detailed analysis of longitudinal immune
      responses, while also obtaining samples for genetic characterization to understand how
      variants in CD101 and UBE2V1 may modulate host mucosal responses and HIV-1 infection risk.
    

Detailed description: 
      A challenge to development of HIV-1 vaccines is to better understand the natural immune
      mechanisms for protection from HIV-1 infection. To this end, immunologists have increasingly
      appreciated the importance of regulatory T cells in peripheral blood that modulate the
      magnitude and characteristics of the host inflammatory response including against infectious
      diseases. The investigators have recently identified specific host genetic variants in the
      genes CD101 and UBE2V1 that appear to strongly predispose to HIV-1 infection risk and may act
      through regulatory T cells and other immunologic pathways. Most studies of individuals who
      are repeatedly HIV-1 exposed but remain seronegative (HESN) have focused on immunological
      correlates in peripheral blood rather than mucosal immune responses. However, with genital
      mucosal tissues being the portal of entry for heterosexually transmitted HIV-1 infection, it
      is critical to understand the role of immunological responses to HIV-1 that occur in the
      genital mucosa. A valuable model to carry out such studies is offered by evaluation of
      HIV-Exposed SeroNegative (HESN) individuals, particularly in the context of heterosexual sex
      with a stable HIV-1 infected partner e.g., HIV-1 serodiscordant couples (SDC). In order to
      understand how genital exposure to HIV-1 may modulate these immune pathways, HIV-1
      serodiscordant couples should be compared to heterosexual partners in concordant HIV-1
      negative couples (CNC) where neither partner has HIV-1. This study seeks to address this
      important knowledge gap by enrolling high-risk HESN with defined heterosexual HIV-1 exposures
      in the context of serodiscordant partnerships compared to unexposed concordant seronegative
      controls. The study will prospectively collect mucosal and peripheral blood samples for a
      detailed analysis of longitudinal immune responses, while also obtaining samples for genetic
      characterization to understand how variants in CD101 and UBE2V1 may modulate host mucosal
      responses and HIV-1 infection risk.

      Primary Objectives:

        -  To identify mucosal immunoregulatory mechanisms mediating host response to heterosexual
           exposure to HIV-1.

        -  To determine how high priority variants in CD101 and UBE2V1 modify host mucosal
           responses in HIV-1 exposure and infection.

      Secondary Objectives:

        -  Identify factors (including HIV-1 exposure, host genetic and microbiota) that modify
           immunoregulatory mechanisms mediating host response to HIV-1

        -  Evaluate how these immunogenetic regulatory mechanisms influence other infectious and
           immunological outcomes

        -  Evaluate the effect of PrEP on early HIV-1 disease
    

Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        African heterosexual HIV-serodiscordant (SDC) and HIV-1 concordant negative couples (CNC)
      
Biospecimen description: 
      Genital samples Blood samples Urine samples Saliva samples
    
Keywords: HIV prevention; Tenofovir Disoproxil Fumarate (TDF)/Emtricitabine (FTC); PrEP