Grant: Fellowship - PA: Biomedical / Clinical HIV/AIDS Research

HIV infection is one of three most significant infectious disease killers in man. An estimated 34 million people are currently infected with HIV world-wide. The standard of care for HIV infection is life-long treatment with combinations of anti-retroviral drugs. There continue to be barriers to treating all HIV infected subjects for the rest of their lives, including access to drugs, side effects and cost. There is a great deal of interest in developing strategies to achieve a functional cure for HIV, which is defined as control of viral load without treatment. A rare subset of HIV infected individuals known as Elite Controllers (EC) exhibit the characteristics of a functional cure. About half of ECs express HLA molecules that are considered to be protective. The mechanism of protection is thought to involve CD8+ T cell recognition of these protective HLAs forming a complex with fragments of HIV on the surface of infected cells thus leading to their being killed. However, many EC do not express these protective HLAs. EC who either do or do not express these HLAs are EC with very low levels of HIV-specific CD8+ T cell immune responses. In this project I will explore the role of other mechanisms for viral control in EC. I will investigate whether and how Natural Killer (NK) cells may be suppressing their HIV viral load. NK cells are also kill virally infected cells either directly or via an antibody response that bridges infected cells and NK cells known as ADCC. Antibodies that are ADCC competent have been described in ECs. NK cells may also exert an anti-viral effect via the secretion of factors that block HIV entry into new cells or interfere with other parts of the HIV replication cycle. In summary, this project will deepen our understanding of how EC spontaneously control HIV without treatment. This knowledge will contribute to the development of strategies aiming to achieve a functional cure for large numbers of infected individuals worldwide.