Viral and Immunologic Factors Contributing to the Lack of HIV Transmission Among Couples in Rakai, Uganda
Condition: HIV
Study type: Observational

Summary: 
      This study will look at viral and immunologic factors involved in protecting against sexually
      transmitted HIV infection in couples in which one partner is infected and the other is not.

      This study will include 50 couples who reside in Rakai, Uganda, and who have been together
      for at least 2 years. In some couples, both partners will be HIV-infected, in some couples
      only one partner will have HIV, and in some couples neither partner will have HIV.

      Participants undergo the following procedures at each of four study visits:

        -  HIV counseling and testing

        -  Medical history, including questions about personal behaviors such as sexual practices
           and use of condoms

        -  Blood sample collection

        -  Urine sample collection

        -  Vaginal swab for women

      Blood, urine and vaginal fluid samples are tested for HIV and other sexually transmitted
      diseases, such as syphilis. Blood and vaginal samples are also tested for HIV viral levels
      and immune response in HIV-infected individuals and for evidence of exposure to HIV in
      non-infected participants. Some blood is also tested for genetic markers to investigate
      whether certain proteins are related to resistance to HIV infection.

      ...
    

Detailed description: 
      Understanding the factors that contribute to the transmission of human immunodeficiency virus
      (HIV) infection is of great importance for the development of preventive and therapeutic
      strategies. Evidence suggests that a number of host immunologic and virologic factors play
      critical roles in protection against sexually transmitted HIV infection in HIV-discordant
      partners. Among these, the antiviral role of CD8+ T cells in HIV-infected individuals has
      been extensively studied. At least two types of CD8+ T cell-mediated antiviral activities
      have been described in HIV infection. The first is a suppressive activity against HIV
      involving lysis of infected cells in an antigen-specific, HLA-restricted fashion, while the
      second mechanism inhibits viral replication via either cell- or soluble mediated factors in
      the absence of cell killing. It has been demonstrated that cytotoxic CD8+ T lymphocytes (CTL)
      are present in both cervical and peripheral blood mononuclear cells (PBMC) from a
      subpopulation of highly-HIV-exposed but persistently seronegative individuals. However,
      studies addressing the effect of non-cytotoxic soluble factor-mediated antiviral activity by
      CD8+ T cells in preventing seroconversion in HIV-discordant couples have been lacking. This
      study proposes to examine the role of CD8+ T cell-derived CC-chemokine activities and the
      copy numbers of one of the chemokine genes, CCL3L1, along with other host anti-HIV and
      virologic factors in resistance to HIV infection in persistently seronegative HIV-discordant
      partners of HIV infected individuals.
    

Keywords: AIDS; HIV Infectiousness; Immunity; CTL; Epidemiology