Research Moves Toward Once-Yearly HIV Treatment

The idea is to free people from needing daily pills.

Oral medications for HIV, which came to market in the 1990s, have changed the face of the epidemic. They are no cure, but when people can stick with their medication regimen, the virus can be suppressed for years.

“The main challenge we face today is adherence,” said Dr. Melanie Thompson, former chairwoman of the HIV Medicine Association.

Taking pills every day, for life, is “not so easy,” noted Thompson, who was not involved in the new study. People can simply forget, she said, or fail to bring their medication on a trip. They can also run out of pills, or have trouble paying for them.

Longer-acting medications could be helpful in that regard. On the other hand, Thompson said, safety becomes an even bigger concern if a drug is going to persist in the body for a long time.

“If you take it and you don’t do well, you’re stuck with it,” she said. “You can’t take it away.”

Another question, Thompson said, is what happens toward the end of the drug’s life in the body. Does it suddenly shut off? Or do levels of the drug wane to where they would no longer be protective, but possibly allow the virus to develop resistance to it?

The safety concerns also include possible drug interactions: What if someone on a long-acting drug develops an infection and needs medication? Or, Thompson said, what if she becomes pregnant?

With a yearly formulation, instead of every two months, those issues loom even larger.

“The idea of moving toward something that’s given once a year is exciting,” Thompson said. But, she stressed, many unknowns would have to be addressed.

Gendelman said that while the cabotegravir injections currently in trials could free people from daily pills, they would still require frequent doctor visits — and a regular jab into the buttocks muscle, which can be uncomfortable for days.

That’s what led him and colleague Benson Edagwa, an assistant professor, to the current project.

Edagwa, a chemist, designed the modifications necessary to turn cabotegravir into a “nanocrystal.” After it’s injected, much of that modified substance takes up residence in muscle, some of it in the liver and spleen, Gendelman said. Over time, the body’s own enzymes “very slowly” convert it into active drug.

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