A team of University of Nebraska Medical Center researchers has changed the chemical structure of an existing HIV drug to help it reach cells and tissues where the virus resides.
The work, which the scientists said could hasten an eventual HIV cure, is detailed in the Feb. 5 issue of the journal Nature Communications. The study was led by Dr. Howard Gendelman, professor and chairman of UNMC’s Department of Pharmacology and Neurosciences, and Benson Edagwa, an assistant professor in the department.
Using a scheme that alters the properties of the antiviral drug dolutegravir, the UNMC scientists took the modified drug and placed it into nanocrystals. The drug crystals easily distributed throughout the body to tissue reservoirs of HIV infection.
While such drugs have been successful at keeping HIV at bay, the virus is able to hide out in tissues such as lymph nodes, bone marrow, the gastrointestinal tract and spleen. The virus can still replicate in these reservoirs, even when it’s been driven to undetectable levels in the blood. Researchers, including Gendelman and his colleagues, have been working to devise treatments that would eliminate them. They’ve also been working to change the course of treatment so patients have to take the drugs less often than the current daily routine.
In mice, the UNMC team’s drug scheme extended the life of the drug itself and facilitated its entry into hidden body compartments when injected while increasing its action in reducing viral growth.
“The strength of this system is that it not only can be effective in improving HIV care and prevention,” Edagwa said in a statement, “but it can be applied to many classes of drugs beyond HIV, such as drugs used to treat cancer, other infectious diseases and degenerative diseases that affect the brain.”
Edagwa designed the drug chemical modifications. Also instrumental in the discovery were graduate student Brady Sillman and Aditya Bade, an instructor in the department.
UNMC has plans to complete a nanomedicine production plant that will make it possible to produce the drugs and others like it on campus beginning this fall. Patents have been filed and supported by UNeMed, UNMC’s technology transfer arm, and ViiV Healthcare, a subsidiary of drug maker GlaxoSmithKline. The research was funded by ViiV Healthcare and research grants from four institutes of the National Institutes of Health.