A team of scientists led by the University of Utah has developed a new injectable drug that can reportedly block the HIV from entering cells.
The team also included researchers from Beth Israel Deaconess Medical Center in Boston, MA, the National Institute of Allergy and Infectious Diseases (NIAID), and pharmaceutical research company Navigen, Inc. Their study appears in the Proceedings of the National Academy of Sciences (PNAS), first published on Thursday, August 20.
"This is an exciting new HIV therapeutic option for both prevention and treatment, with a unique mechanism of action compared to other approved drugs," said Michael S. Kay, MD, Ph.D., in a press release from the University of Utah. Dr. Kay serves as the senior author of the study and a Biochemistry Professor. He added that the newly-developed drug can potentially help patients with drug resistance, and patients who could use a longer-acting anti-HIV drug.
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Testing CPT31 on Rhesus Macaques
The new medicine is based on a substance called Cholesterol - PIE12 - trimer, or CPT31. It is an HIV inhibitor based on a D-peptide, targeting a critical pocket on the human immunodeficiency virus (HIV) fusion mechanism. D-peptides are small sequences of D-amino acids that are mirror images of naturally occurring peptides. This nature makes D-peptides, like the CPT31, resistant to being degraded inside the human body.
Researchers noted that CPT31 is promising as an HIV drug due to its "high potency and breadth, the long half-life, and strong activity" in their experimental testing.
"In addition to their durability in the body, D-peptides are largely ignored by the immune system, preventing immune reactions that are a side effect often seen with traditional peptide and protein drugs," said study co-author Brett Welch, senior director of technology and strategy at Navigen, Inc. He added that they are hoping that CPT31 can offer extended viral suppression, and achieve it with loser dosage and less side effects.
To test CPT31, the research team inquired on its efficacy against rhesus macaque monkeys. They used the rhesus macaque and the R5-tropic simian-HIV AD8, or the SHIVAD8 system, because of its similarities with the human HIV disease in humans. The monkeys were first injected with the drug several days before they were exposed to SHIVAD8.
An HIV Inhibitor Than Can Be Used Alone
In the report, the research team has observed that the rhesus macaque monkeys were protected from the virus despite high exposure. The monkeys were exposed to significantly higher concentrations of the simian-human form of HIV, not displaying signs of infection. Furthermore, additional trials allowed the research team to identify the minimum dosage that can still maintain complete protection in the subjects. This will guide future clinical trials of the drug.
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Kay also noted that the drug can be administered by itself to prevent HIV infection, noting that their study demonstrates the efficacy of CPT31 against a majority of strains of the virus that are currently in existence.
To test CPT31 against the latter stages of the disease, with a significantly higher volume of the virus in the patient's body, the research team tested its efficacy after discontinuing a combination antiretroviral therapy (cART) drug cocktail in the macaques. After the 30 days, the administered drug has exhibited the capability to keep the virus at an undetectable level. It shows that even after cART administering, CPT31 alone has sufficient virus suppression capabilities. Even in humans, discontinuing cART medication often leads to a rebound in the volume of the virus in the body.
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