Combination Therapy Rids Immune Cells of HIV

Researchers hope new treatment delivery system will reduce administration down to once or twice per year.

Researchers may be on the verge of developing a new HIV treatment that controls the virus for extended periods.

HIV is typically treated with a class of antiviral drugs called protease inhibitors.

Recently, scientists at the University of Nebraska Medical Center designed a new delivery mechanism for protease inhibitors that, when combined with an investigative medication at the University of Rochester School of Medicine and Dentistry, exterminates HIV in immune cells to keep the virus under control.

Current HIV treatments are taken daily in the form of pills, but researchers hope this new delivery system will cut the administration down to once or twice per year.

Nebraska researcher Howard E. Gendelman designed the investigational drug delivery system — a so-called “nanoforumulated” protease inhibitor. Nanoformulation of a drug involves making it into a crystal.

After this process is completed, the crystal drug is placed into a fat and protein coat, which protects the drug from being degraded by the liver and removed by the kidney.

The nanoformulated protease inhibitor completely wiped out significant quantities of HIV when it was combined with URMC-099, a new drug discovered in the laboratory of UR scientist Harris A. Gelbard MD, PhD.

The experimental drug worked to boost the concentration of the nanoformulated drug in immune cells and slowed the rate at which it was disposed of, thereby extending its therapeutic effect.

“The chemical marriage between URMC-099 and antiretroviral drug nanoformulations could increase drug longevity, improve patient compliance, and reduce general toxicities,” said Gendelman, lead study author and professor and chair of the Department of Pharmacology and Experimental Neuroscience at Nebraska. “We are excited about pursuing this research for the treatment and eradication of HIV infections.”

The separate therapies were tested together in lab experiments that used human immune cells and in mice engineered to have a human immune system.

The researchers believe the nanoformulation technology helps to keep protease inhibitors in white blood cells longer and that URMC-099 prolongs the lifespan even more.

URMC-099 was developed by Gelbard to treat HIV-associated neurocognitive disorders, such as memory loss and overall mental fog that affects half of all patients living with HIV.

The drug was tested with several protease inhibitors, due to the fact that any patient prescribed treatment with URMC-099 would also be taking antiretroviral therapy.

The primary endpoint of the investigation was to see whether the drugs could be safely taken together. To the surprise of Gelbard and Gendelman, URMC-099 was found to increase the effectiveness of the nanoformulated drug.

“Our ultimate hope is that we’re able to create a therapy that could be given much less frequently than the daily therapy that is required today,” Gelbard said. “If a drug could be given once every six months or longer that would greatly increase compliance, reduce side effects and help people manage the disease, because they won’t have to think about taking medication every day.”