Grant: Project Grant

The depletion of CD4 T cells is a hallmark of HIV infection. A newly characterized population of CD4 T cells (T follicular helper, Tfh), which is essential for maintaining an efficient B cell immunity and for the maturation of HIV-specific antibodies, is depleted in different anatomical immune tissues after HIV infection. Despite early antiretroviral therapy (ART), HIV persists in sanctuaries that permit viral rebound after ART interruption. Simian immunodeficiency virus (SIV) is closely related to HIV, and it causes a disease in rhesus macaques that is similar to AIDS in people, including the depletion of CD4 T and Tfh cells, and the constitution of ART-resistant reservoirs. We have tested a new compound that prevent SIV-induced CD4 T cell depletion in the absence of ART. We have also demonstrated that this protective effect was associated with both a reduction in the size of the SIV reservoirs and a delay in disease progression to simian AIDS. The main objective of this proposal is to test if combining this new anti-apoptotic agent with ART can both reduce the SIV reservoirs and improve the immune response against SIV. We hypothesize that combining this anti-apoptotic compound with ART will restore Tfh cells, improve B-cell immunity compared to ART alone, and help produce better antibodies capable of controlling viremia and broadening the immune response against SIV reservoirs. Thus, we also expect this beneficial effect to last beyond ART interruption. The project will include treatment-naïve and ART-treated SIV-infected macaques that will receive this anti-apoptotic compound. We will analyze extensively T and B cell dynamics, tissue distribution, and antibody production in relation to the size of viral reservoirs. Overall, our main objective is to contribute to the improvement of cure strategies for people living with HIV.