Researchers affiliated with the University of Utah have devised a peptide-based injectable drug that prevents HIV from infecting cells. Unlike other drugs available on the market, the novel therapy offers long-lasting protection and has few side effects. Experiments on non-human primates also showed that the drug can be used to dramatically reduce the amount of HIV circulating in the bloodstream when the infection is already present.
“This is an exciting new HIV therapeutic option for both prevention and treatment, with a unique mechanism of action compared to other approved drugs,” Michael S. Kay, a senior author of the study and a professor of biochemistry at the University of Utah, said in a statement. “It has great potential to help patients who suffer from drug resistance as well as those who would benefit from a longer-acting, injectable anti-HIV drug cocktail.”
Better preventive medicine for HIV?
The human immunodeficiency virus (HIV) is one tough nut to crack. Its M.O. is to attack the very immune cells that are designed to target invaders such as HIV. When enough of these T helper cells are destroyed by the virus, the body is defenseless against HIV itself, as well as other infections. When this happens, the HIV-infected person develops acquired immune deficiency syndrome (AIDS).
Scientists first discovered HIV and AIDS in the early 1980s. By 1987, there were 32,000 people infected with HIV in the United States alone, more than half of whom had died.
Today, there are more than 38 million people currently living with the infection. Fortunately, these people can now take modern antiretroviral therapy (cART), a cocktail of drugs that dramatically enhance survivability and prevent the onset of AIDS. HIV drugs also stop people who have the virus from passing it to their partner during sex.
On the flipside, cART is very expensive, can have serious side effects that negatively impact quality of life, and requires patients to take pills daily.
While it’s remarkable that we now have drugs that can manage HIV infections, there’s always room for improvement. And Kay and colleagues believe their new HIV therapy is a promising avenue of research.
Their therapy is based on a drug called CPT31, which is based on D-peptides that target a crucial mechanism in the HIV fusion machinery that rarely mutates.
Proteins and most naturally occurring peptides are composed of amino acids in the L-configuration. D-peptides are basically the mirror version of L-peptides, sort of like your left hand and right hand — they’re both the same but in different configurations.
Since D-peptides are so analogous to natural peptides, they are largely ignored by the immune system, preventing unwanted immune reactions that are often a side effect of traditional HIV drugs. Additionally, CPT31 lasts longer in the body compared to natural peptides, making them particularly suitable for long-acting injectable formulations.
“As a D-peptide, our hope is that CPT31 will provide extended viral suppression with a lower dose and reduced side effects,” said Brett Welch, a co-author of the study and senior director of technology and strategy at Navigen, Inc., the company that manufacturing CPT31 and is currently managing upcoming clinical trials.
The researchers injected CPT31 into healthy macaque monkeys several days prior to exposing them to a hybrid simian-human form of HIV called SHIV. Although the monkeys were exposed to a very high dose of SHIV, they never developed any obvious signs of infection.
These experiments allowed the researchers to determine the minimum dose of CPT31 that is required for effective therapy, which will help inform upcoming clinical trials.
“We think this drug could be used by itself to prevent HIV infection because initial HIV exposure typically involves a relatively small amount of virus,” Kay says. “This study showed that the vast majority of circulating HIV strains from around the world are potently blocked by CPT31.”
Additionally, the researchers also injected CPT31 into monkeys that were already infected with SHIV and had received no prior treatment. Over the span of 30 days, the drug significantly lowered the presence of SHIV in the bloodstream. Unfortunately, the viral levels rebounded two to three weeks after the shot was administered.
“Such a simplified ‘maintenance therapy’ could present patients with a new option for viral control that is more cost-effective, convenient to take, and has fewer side effects,” Kay says.
Navigen is also working on a longer-acting formulation of CPT31. The goal is to have people take an injection once every three months.
“Long-acting injectable formulations appear to be greatly preferred by both patients and physicians compared to current daily drug regimens that can be challenging to maintain,” Welch says. “Additionally, the steady therapeutic drug levels provided by such a formulation would reduce the risk of drug resistance caused by missed daily pills, as well as reduce side effects.”
The findings appeared in the Proceedings of the National Academy of Sciences (PNAS).