BELIEVE has several teams of scientists, clinicians, and community representatives working on 4 different but synergistic approaches to cure HIV. These approaches are called Initial Research Foci or IRFs.
IRF 1
In IRF 1, scientists are studying 4 different ways of enhancing the natural immune response to HIV. White blood cells called CD8+ T cells are isolated from a participant’s blood and conditioned to target HIV infected cells. One of the major goals in this IRF is to enhance CD8+ T cell ability to kill infected cells that are harboring latent reservoirs. Reservoirs are HIV-infected cells that persist despite antiretroviral therapy. Some of these reservoirs, although infected, do not actively produce HIV proteins until the time is right. These are called latent reservoirs. Special proteins and materials called Latency Reversing Agents (LRAs) are being used to increase the number of the protective CD8+ T cells at the same time as “waking” up the latent reservoir.
IRF 2
In IRF 2, a team of scientists is investigating another type of white blood cell called a Natural Killer (NK) cell. NK cells kill infected cells in a very similar manner to CD8+ T cells. We are trying to enhance NK cell killing by adding the LRAs in addition to a protein called an antibody. Antibodies are proteins produced by another white blood cell called a B cell. The HIV field has identified several antibodies that are effective at blocking HIV from infecting human cells. These antibodies, called broadly neutralizing antibodies (bnAbs), can help target then enhanced NK cell to the HIV infected cell. IRF 2 studies build on the in vitro (experiments done in test tube like conditions) work done in IRF 1 and advance the studies into a more realistic in vivo setting (in animal models).
IRF 3
The IRF 3 group is focusing on an important reservoir called the B cell follicle in their in vivo studies. B cell follicles are located in tissues called lymph nodes. Lymph nodes are hubs where many of your white blood cells go during an infection. You have likely felt these swell when you get sick. One of the reasons HIV infected cells are protected in the B cell follicle is because CD8 T cells do not normally go to this part of the body. IRF 3 scientists are trying to enhance CD8+ T cells and reprogram them to go into the B cell follicle to kill the latent HIV reservoir residing there.
IRF 4
A major goal of BELIEVE is to eradicate HIV from the body and even though many of our preliminary experiments are done in the laboratory, we are bringing our science to the clinic. IRF 4 clinicians and scientists are attempting to enhance a participant’s own white blood cells. Blood will be taken from the participant, the killer cells (CD8+ T cells and NK cells) will be enhanced outside of the body, and the cells will be infused back into the participant. In the initial study, we are being very conservative with the safety of the participant being our highest concern. The CD8+ T and NK cells will be redirected to target HIV-infected cells. A very similar study has been done in the HIV setting and several clinical trials have been done in the cancer field with excellent safety results. If our results in IRF 1, 2, & 3 look promising, we will advance our clinical trial by modifying the CD8+ and NK cells using the LRAs, bnAbs, or B cell follicle-targeting approaches.
Support Sections and Partners
There are also three support sections (Regulatory Affairs, GMP Production, and Clinical Studies; Non-Human Primate; and Reservoir Characterization) to assist in these goals along with a Management and Operations section and a strong Community Engagement partnership. BELIEVE also leverages current NIH-funded programs of the DC Center for AIDS Research (CFAR) and of the Clinical and Translational Science Institute (CTSI) at Children’s National Research Institute in Washington DC. For more information on DC CFAR and CTSI, please visit their websites:
