Antimicrobial Agents and Infectious Diseases

Vorinostat Can Help Clear Dormant HIV Infections

The drug vorinostat (Zolinza), originally developed as a third-line treatment for cutaneous T cell lymphoma, can stimulate dormant HIV into activity again and make it prey for two types of killer immunotherapy.  Finding and eliminating dormant HIV infections is a critical and unresolved problem in HIV therapy today.

The process was developed by a team at the University of North Carolina at Chapel Hill led by Julia Sung, and builds on their previous research in the field.

Sung and her colleagues took blood samples from people who were HIV-positive but showed no detectable levels of virus, extracted some of their CD8 killer T cells, created cell cultures from the blood samples, and introduced Vorinostat into the cell culture growth medium.  After incubating the cells with Vorinostat, they changed the culture medium and replaced it with a solution that was Vorinostat-free.

The next step was adding the two immunotherapeutic agents.  One set of cultures received antibody-based molecules called DART that sought out CD8 cells and bound them to cells that were producing HIV antigens.  The antigens indicated that these cells now contained active HIV virus Vorinistat had awakened from its dormant state.  The other set of cultures received CD8 cells that had been incubated with cytokines and HIV peptides, then multiplied.  These enhanced T cells, called HXTC cells, are superior killers of the HIV virus.  Both immunotherapies killed the virus-laden cells and successfully cleared the cultures of dormant HIV.

The researchers called their new process the Latency Clearance Assay and hope it will be used to evaluate the effectiveness of different combinations of HIV-awakening agents and immunotherapeutic clearance strategies to create therapies that can eliminate dormant HIV.

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