Therapeutics/Drugs

Ekaterina Dadachova of the Albert Einstein College of Medicine in the U.S., in collaboration with Arturo Casadevall, proposes to use radioimmunotherapy as a strategy to eliminate HIV-infected cells in patients on anti-retroviral therapy. Targeting viral antigens on these cells with radioactivity-armed antibodies could lead to HIV eradication. This project's Phase I research demonstrated that radioimmunotherapy can kill HIV-infected primary human cells in conjunction with anti-retroviral therapy (ART) and that this antibody can also reach HIV-infected cells in the central nervous system.

Amalio Telenti of the Institute of Microbiology in Switzerland proposes to identify biomarkers specific to HIV latency using high-throughput screening of RNA sequences and a customized screening tool for validating HIV positive individuals. If successful, the biomarkers could be used in the study of HIV latency reservoirs and aid eradication efforts.

Sara Richter of the University of Padua in Italy will develop a therapeutic to completely clear HIV from the body by targeting a proviral DNA structural motif found in both actively and latently infected host cells. In Phase I they analyzed a highly conserved DNA structural motif of four guanine nucleotides (G-4) found in the integrated HIV-1 proviral DNA and found that it regulates proviral transcription and is likely involved in latent infection.

Jerome Zack of the University of California, Los Angeles in the U.S. will test nanoparticles for their ability to specifically activate HIV from latently infected cells. Once the latent cells express viral proteins, host immune responses and targeted therapies can be used to kill the cell. If successful, this project could provide an effective approach to eliminate an important viral reservoir from HIV infected individuals.

Alex Deiters of North Carolina State University in the U.S. will work to discover small molecule inhibitors of short ribonucleic acids (microRNAs) that cause HIV latency in resting T-lymphocytes. Inhibiting the function of these microRNAs could reverse HIV latency, purge HIV reservoirs, and ultimately represent a chemotherapeutic approach to eradicating HIV infection.

Joao Goncalves of ADEIM - Faculdade de Farmacia Lisboa in Portugal proposes to develop molecular sensor strategies using nanoparticles to target memory T cells to deliver a toxin that will be expressed when zinc-finger proteins detect HIV-1 sequences.

Gero Hütter of Red Cross Germany proposes to use stem cells transplants to cure HIV. He is planning to develop a program that generates a registry of stem cells that lack the CCR5 protein, which is used by HIV to enter into a cell. If successful these adult stem cells could be transplanted into a HIV patient and effectively "cure" HIV.

Daniel Kavanagh of Massachusetts General Hospital in the U.S. proposes to use a novel class of molecular probes to identify and characterize individual cells latently infected with HIV. If successful, this project will identify new markers that may be used to target and eliminate HIV-infected cells.

Adam Spivak from Johns Hopkins University School of Medicine in the U.S. will perform a high-throughput screen to identify novel compounds able to selectively induce cell death in chronically HIV-1 infected cells. Understanding the mechanism of action of such compounds will inform efforts to target and eradicate remaining HIV-1 reservoirs in patients receiving antiretroviral therapy.

Steven R. King of the University of Michigan in the U.S. proposes to engineer HIV proteins that can target and destroy HIV in latently infected cells. If successful, these new anti-viral drugs together with conventional treatments could completely clear the virus from people, resulting in a cure for HIV infection.