Grant: Operating Grant - PA: HIV/AIDS Bridge Funding - Biomedical/Clinical Stream

Although the vast majority of HIV-infected individuals can now achieve and maintain viral suppression with modern antiretroviral therapy (ART), their life expectancy remains limited and they continue to be at much higher risk for diseases commonly associated with aging. B lymphocyte dysregulations are often observed during HIV infection, and not fully restored by ART, contributing to abnormal levels of immune activation and inflammation that may drive these clinical events, sustaining a global impairment of the humoral immune compartment and favouring the development of autoimmune manifestations and malignancies, as well as promoting HIV reservoirs. Dendritic cells (DCs) are involved in the outcome of B-cell development, differentiation and survival, mainly through production of growth factors such as B lymphocyte stimulator (BLyS/BAFF). We have recently demonstrated that BLyS over-expressing DCs are increased in the blood of HIV-infected progressors, as soon as in the acute phase of infection and persisting despite successful therapy, being concomitant with B-cell dysregulations. The present proposal aims to further determine the impact and the mechanisms by which BLyS/BAFF affect immune activation and viral reservoirs expansion during HIV/SIV infection. We believe that these studies will provide strong evidence to support novel therapeutic approaches viewed to control BLyS levels as an adjunct treatment to ART to reduce both HIV target cells and systemic immune activation that are the hallmarks of HIV disease progression. .