Benefit

Technology Description

Despite significant advances in antiretroviral therapy (ART), HIV-1 infection remains a chronic, lifelong disease affecting nearly 40 million people worldwide. Current treatment paradigms require lifelong adherence and are associated with ongoing challenges including drug resistance, cumulative toxicity, treatment fatigue, and persistent quality-of-life burdens. There remains a substantial need for novel therapeutic approaches that address the limitations of existing antiviral regimens and provide alternative mechanisms of action.

Researchers in Dr. Wu's laboratory have identified the c-MET signaling pathway as a critical host factor in HIV-1 infection and demonstrated that the FDA-approved c-MET inhibitor crizotinib can suppress HIV-1 replication in primary CD4⁺ T cells. Unlike conventional therapies that directly target viral proteins, crizotinib inhibits viral entry by downregulating the cell receptors of HIV-1, namely CD4 and CXCR4. This host-directed approach offers a potentially differentiated strategy for HIV-1 treatment, with the added advantages of drug repurposing, including established clinical safety data, reduced development risk, and opportunities for accelerated clinical development and combination therapy applications. This technology may provide particular value for patients with treatment-resistant HIV-1 and offers potential opportunities for combination therapy, lifecycle management, and expansion into broader antiviral applications. ocyte specific expression of DSG2. In a murine model of ARVC, this targeted therapy rescues multiple disease phenotypes including alleviations of ventricular arrythmia, structural abnormalities, and cardiac dysfunction. This offers a potential one-time treatment capable of preventing, halting, and reversing the ARVC disease progression

UIRF Case No. 2026-102

Stage of Development

Initial pre-clinical proof of concept work has been completed using primary CD4⁺ T cells. Current and future effort is to optimize the dose and time of crizotinib treatment in inhibiting replication of clinical HIV-1 isolates and drug-resistant HIV-1 variants in primary CD4⁺ T cells.

Publications

Tripathi S, Allen MM, Wu L. HIV-1 hijacks HGF/c-MET signaling to promote viral entry and replication in primary CD4⁺ T cells. mBio. 2026 Oct 14:e0209026. doi: 10.1128/mbio.02090-26. Epub ahead of print. PMID: 42872804.