Pilot Award Recipient: R. Brad Jones, PhD

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A Humanized Mouse for Studying the Elimination of Patient-Derived HIV Reservoirs

February 17, 2016
The development of a safe and effective cure for HIV is hampered by the lack of a predictive small animal model that could be used to test and optimize new therapies. Currently, therapies can only be tested: in cell culture - which has only a limited ability to predict in vivo effects; in SIV-infected monkeys - which are extremely expensive and available only to a few large research groups to test a small number of therapeutic approaches; and in clinical trials in people living with HIV - where only drugs with safety records that are already established in other settings (such as cancer) can be tested. For the past two years, the research group has been developing a novel approach to testing HIV cure strategies in vivo that involves injecting mice with CD4+ T-cells from people living with HIV (which contain latent virus) into immunodeficient mice. This then allows to extensively test different combination therapies to determine if we can cure HIV from these cells in the mouse. This is analogous to an approach that is commonly used in cancer where portions of a patient's tumor is engrafted in mice, therapies aimed at killing the tumor are tested in the mouse, and then successful strategies are used in the patient. In cancer this approach has been referred to as 'mouse avatars', but thus far a similar approach has not been tested in HIV.
The reserachers believe their approach will much more accurately represent real-world HIV reservoirs than other mouse models in development, which rely on engrafting mice with stemcells and attempting to generate artifical viral reservoirs. Their approach will also uniquely capture individual variation between people living with HIV, as we believe that cures may not come in a one-size-fits-all. This model will also allow for the enlisting of immune systems of people living with HIV by including their own killer T-cells in addition to latency reversing drugs in therapies to be used in mice, in the same way they hope to harness the immune system to eliminate the virus in people. If successful, it is hoped this model will allow the field to rapidly and affordibly test diverse HIV eradicaiton strategies, accelerating progress towards a cure.
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