Grant: Catalyst Grant: Innovation in HIV Vaccine and HIV Cure Research

34 million people are currently HIV infected world-wide and require treatment with anti-retroviral drugs to avoid disease progression, AIDS and death. There are obstacles to treating all those who are HIV infected, including access, side effects and cost. These impediments provide the impetus for investigating ways to either eradicate HIV or find a functional cure for this infection. A functional cure is defined as one where HIV in controlled without treatment. Around 0.25% of HIV infected individuals exhibit such a profile and are called Elite Controllers (EC). Half of EC express protective HLA antigens. CD8 T cell mediated immune responses are important in viral control in some EC because they recognize HIV peptide/HLA complexes leading to viral suppression or the emergence of unfit virus. However, many EC, expressing protective HLA or not, have normal CD8 numbers and low or undetectable HIV-specific CD8 responses. We plan to investigate how EC with weak CD8 T cell immunity control their infection by examining whether they do so through Natural Killer (NK) cell responses. NK cells are important in anti-viral immunity and have not yet been studied as potential mediators of viral control in EC. For this project we have access to a cohort of 188 untreated HIV infected slow progressers recruited across Canada of which 40 are EC. Samples collected longitudinally on these subjects are available. We will assess whether one or the other of these anti-viral responses predominates in EC and how they evolve from early infection. Understanding why EC control HIV as well as they do is a step towards devising strategies that can be applied to HIV infected progressors so that they too can control their HIV infected long term without treatment.