“BELIEVE” is short for “Bench to Bed Enhanced Lymphocyte Infusions to Engineer Viral Eradication”. One individual, known as the “Berlin patient”, is considered to be cured of HIV, with no evidence for active replication competent virus in the absence of antiretroviral (ARV) therapy. The “Mississippi” baby initially appeared to be another cure, but virus re-emerged a couple of years after ARV cessation. ARV therapy prolongs life, but a life expectancy gap shows patients on viral suppressive therapies live a shorter life, and have more co-morbidities. To help end the epidemic, an HIV cure is needed.
Current “shock and kill” strategies are limited in harnessing the power of immunity in seeking and removing latent cells. Augmentation of immunity could be performed through vaccination, although therapeutic vaccination in HIV infection has had limited efficacy to date. In addition, immune effectors in HIV infected persons are not fully recovered with ARV treatment.
There are at least three mechanisms which lead to the inability of the immune system to remove virus completely:
- A weakened and exhausted cytotoxic T- lymphocyte (CTL) response from which epitope escape has occurred
- Over activated but under performing Natural Killer cells
- Inability of effector cells to reach the right sites where latent virus resides
First, we will immediately initiate a pilot clinical study with our most promising combination of T-cell infusion and latency-reversing agents. We will compare this combination to enhanced natural and engineered T-cells to eradicate HIV reservoirs (in vitro, in mice, in non-human primates, and in additional human clinical studies), in association with novel HIV Nef small molecule inhibitors.
Second, we will develop and test enhanced Natural Killer cells with or without broadly neutralizing antibodies (in mice, in non-human primates, and in humans).
Third, we will target sites of viral latency which CTL cannot reach, by targeting CTL to home to reservoir sites. We have gathered a group of accomplished investigators, with strong collaborative histories, along with community advisors.