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

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 the preservation of 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. We believe that therapeutic approaches viewed to control BLyS levels as an adjunct treatment to ART may be promising to reduce both HIV target cells and systemic immune activation that are the hallmarks of HIV disease progression. The present proposal views to further the evidence supporting the use of anti-BLyS (Benlysta®/Belimumab) in therapies against HIV-mediated disease, through ex vivo and in vitro experimentation, which hopefully will support further validation in the SIV-infected macaques system.