Vorinostat renders dormant HIV infection vulnerable to clearance
Chapel Hill, NC – The ability for HIV to hide in the body in a dormant state makes curing the 40 million people living with the virus a challenge. Researchers at the University of North Carolina at Chapel Hill have shown the drug Vorinostat reverses this latency, causing resting CD4 T-cells to express HIV. The investigators have developed an assay that detects antigen production and includes immune effectors capable of clearing the virus. These results were published in EBioMedicine.
Vorinostat produces a window of vulnerability in the HIV reservoir by triggering viral antigen production. The team developed the latency clearance assay (LCA) to measure the amount of antigen activity Vorinostat produces. The assay also includes immune effectors capable of clearing the cells expressing the viral antigen.
"Measuring a latency reversing agent's ability to induce relevant HIV production is technically challenging," said Julia Sung, M.D., the study's lead author and an assistant professor of medicine in the UNC Division of Infectious Diseases. "Using a latency clearance assay, we have detected the ability of Vorinostat, a latency reversing agent under clinical investigation, to induce recognizable levels of HIV protein on the cell surface allowing for subsequent clearance of infected cells."
The optimal combination of latency-reversing agents and clearance strategies will be needed to cure HIV. The team says their assay can be used to evaluate these combinations in future studies.
The team at UNC collaborated with colleagues at MacroGenics, Inc., and Children's National Medical Center on this study. The National Institutes of Health funded this research.
The mission of UNC's Institute for Global Health & Infectious Diseases is to harness the full resources of the University and its partners to solve global health problems, reduce the burden of disease, and cultivate the next generation of global health leaders. Learn more at http://www.globalhealth.unc.edu.