Scientists develop injectable HIV drug with fewer side effects

NEW YORK

Researchers have developed an injectable new drug that blocks HIV from entering cells which offers long-lasting protection from the infection with fewer side effects.

The drug, which was tested in non-human primates, could eventually replace or supplement components of combination drug "cocktail" therapies currently used to prevent or treat the virus.

"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 study author Michael S. Kay from the University of Utah in the US.

"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," Kay added.

In this new study, published in the journal Proceedings of the National Academy of Sciences (PNAS), the researchers tested a unique drug called CPT31, based on a D-peptide that targets a critical pocket on HIV's fusion machinery that rarely mutates.

D-peptides are mirror images of naturally occurring peptides.

"To imagine it, think of right and left hands. The building blocks and overall structure of natural peptides are analogous to our left hand versus our right hand for D-peptides," the researchers said.

Because of that, CPT31 and other D-peptides are not degraded in the body. Therefore, they last much longer than natural peptides, making them especially suitable for a long-acting injectable formulation.

To see if CPT31 could prevent HIV infection, the research team first injected the drug into healthy macaque monkeys starting several days prior to exposure to a hybrid simian-human form of HIV called SHIV.

The monkeys were completely protected from this very high SHIV exposure, much higher than what humans typically encounter, and never developed signs of infection.

Subsequently, the scientists identified the minimum dose of CPT31 needed to confer complete protection, information that will help inform 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 said.

This study showed that the vast majority of circulating HIV strains from around the world are potently blocked by CPT31.

"But what about later stages of the disease when there are billions of copies of the virus circulating in the body?" the team asked.

To find out, the researchers gave CPT31 to monkeys with untreated SHIV infections and high viral loads. Over the course of 30 days, the drug significantly lowered the presence of SHIV in their bloodstreams.

In this study, CPT31 by itself effectively kept the virus at an undetectable level for months (until drug administration was discontinued).

"Upcoming human trials, scheduled for later this year, will help determine whether CPT31 is safe and effective in humans," the team noted.

--IANS

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