Our Research
Despite the success of standard antiretroviral therapy, the need for an HIV cure remains compelling, both to improve the lives of people living with HIV and to bring about the end of the pandemic. The “REACH: Research Enterprise to Advance a Cure for HIV” Martin Delaney Collaboratory comprehensive scientific plan aims to uncover mechanisms driving HIV persistence, including intrinsic resistance to cellular-mediated killing, to guide the development of novel combination approaches that can harness cellular immune responses to achieve durable remission and eradication of HIV reservoirs.
Research Focus 1 - Basic Science
Overarching aim: To redefine the three-way relationship between the persistent HIV reservoir, CD8+ T cells, and rebound virus at the levels of single cells, individuals, and diverse populations.
Overarching hypothesis: We posit that the HIV reservoir remains partially visible to CD8+ T cells on ART and that persistence is enabled, to a degree, by the selection of reservoir cells that are intrinsically resistant to cytolysis. The strategy of our REACH program enables evaluation of this central question alongside additional discrete hypotheses.
Research Focus 2 - Viral Control
Overarching aim: To harness conventional and unconventional (bNAb-induced) CD8+ T cell responses, in combination with bNAbs and next-generation biologics, to achieve durable control of HIV replication.
Overarching hypothesis: CD8+ T cells can be enlisted to enforce durable control of HIV replication, where progress stands to be made by: i) understanding and recreating/enhancing the mechanisms of CD8-mediated control following bNAb treatment, ii) optimizing strategies to block immune escape, and iii) designing combinations to mediate cell-mediated and humoral immunity.
Research Focus 3 - Eradication of Reservoirs
Overarching aim: To develop a discovery-to-translation pipeline to overcome multiple barriers to the eradication of HIV reservoirs by CTL/NK cells.
Overarching hypothesis: Consistent and robust reductions in the HIV reservoirs present in ex vivo CD4+ T cells and in macrophages can be achieved through: i) optimal combinations of latency reversing agents (existing or novel), ii) enhanced CTL or NK effectors, and iii) novel cytopathicity enhancing agents - designed to overcome resistance to cytolysis in reservoir-harboring cells.
Integrative Strategy
Our strategy addresses research questions through interconnected and synergistic projects
Promising approaches will be selected for animal model studies and human clinical trials