B-101 Prospects and Strategies for an HIV Cure

Abstract

Two highly-publicized cures of HIV infection, 1 in an adult who received an allogeneic hematopoietic stem cell transplant for leukemia from a CCR5 delta 32 homozygous donor, and 1 in an infant started on ART within 2 days of birth, have inspired worldwide efforts to cure HIV infection. The recent relapse of HIV infection 3–8 months after stopping ART in 2 allogeneic bone marrow transplant recipients who had cleared HIV from blood is a sobering reminder of the difficulty of eliminating all replication-competent HIV from an infected host. In this special lecture, I will first review major obstacles to curing HIV infection including: (1) persistent viremia despite effective HIV, (2) latent replication-competent proviruses in CD4+ T-cells, (3) HIV diversity and immune escape variants, (4) clonal expansion of HIV-infected cells, and (5) highly-variable and incompletely effective host immune responses to HIV. I will then highlight curative approaches that are being explored: (1) immediate ART after birth in HIV-infected infants, (2) ART in adults during acute/early HIV infection to prevent reservoir expansion and induce post-treatment immune control, (3) latency reversing agents to deplete HIV reservoirs (e.g., romidepsin), (4) reversal of exhaustion of HIV-specific through immune response by targeting inhibitory receptors on T-cells (e.g. anti-PD-L1), (5) antibody- , cell-, and vaccine-based immunotherapies to enhance HIV immune responses, and (6) host modification to confer cellular resistance to HIV replication. Progress towards a cure of HIV infection will undoubtedly occur, but the challenge of developing and delivering effective and scalable therapies for most HIV-infected persons worldwide is a very formidable 1.