HIV IMMUNE RESPONSE IN RWANDAN RAPID AND NON-PROGRESSORS

University Of Alabama At Birmingham, Birmingham AL

Investigators

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Abstract

Description (adapted from applicant's abstract): Multiple immunologic and genetic factors are involved in protection from disease progression with HIV-1 infection. The PI proposes to study humoral and cellular immune responses and b-chemokine production in a cohort of epidemiologically and genetically well-characterized HIV-positive women from Kigali, Rwanda, who have remained asymptomatic after 10 years of infection contrasted to women who progressed rapidly to disease and death. They will determine humoral immune responses (HIV-specific antibody and neutralization titers, antibody avidity and conformational dependence). These will be correlated with disease progression, development of mature antibody responses and HLA markers. They will also determine the level of enhancing antibodies, and how these correlate with disease progression. They will examine CD4+ T cell proliferation and CTL activity in long-term survivors and rapid progressors and relate these to the presence of protective HLA markers. They will also determine the relationship between an intact cellular immune response and development and maintenance of a mature antibody response. This will provide a better understanding of the development and functioning of the antibody response in relation to the integrity of the cellular immune system. The effectiveness of the CD4+ T cell proliferative response in decreasing viral load in the subjects will be examined and specific epitopes targeted by PBMC from individuals demonstrating virus-specific responses mapped. They will also measure b-chemokine production by in vitro stimulated PBMC. These will be related to viral load, CD4 proliferative response, and disease progression. They will measure CCR5 receptor expression and determine the relationship between b-chemokine production, CCR5 expression, and polymorphisms in the CCR5 promoter.