Long-Acting Drugs May Revolutionize H.I.V. Prevention and Treatment

One pill to take once a week. An injection administered at home once a month. Even a vaccine given in a clinic every six months.

In the next five to ten years, these options may be available to prevent or treat HIV. Instead of medications that must be taken daily, scientists are moving closer to longer-acting alternatives — perhaps even a future in which HIV might require attention only twice a year. year, inconceivable in the darkest decades of the epidemic.

“This period is the next wave of innovation, new products meeting people’s needs, especially around prevention, in a way we’ve never had before,” said Mitchell Warren, executive director of the HIV prevention organization AVAC.

Long-acting therapies can avoid having to think about taking a daily pill to prevent or treat HIV. And for some patients, new medications can ease the stigma of the disease, itself a barrier to treatment.

“Not having to remember that every morning changes the planet for them,” said Dr. Rachel Bender Ignacio, director of UW Positive at the University of Washington, a clinical research site focused on HIV. “That stigma, that internalized stigma of taking that pill every morning, that’s what keeps them from taking it.”

Long-acting medications are likely to be even more beneficial for populations that have long been hard to reach: patients who have patchy access to health services, or who struggle to take their daily pills. due to unstable housing or transportation, are struggling with substance abuse. consumption, suffer from mental illness or face discrimination and stigma.

In 2022, almost 30 years after the advent of combination antiretroviral therapy, more than nine million of the 39 million people living with HIV worldwide were not receiving treatment. About 630,000 people died from AIDS-related illnesses that year.

Even in the United States, about a third of people diagnosed with HIV do not control the virus. “We still haven’t solved these kinds of underlying issues around access,” said Gregg Gonsalves, a longtime HIV activist and epidemiologist at the Yale School of Public Health.

“We can be excited about the science and clinical implications” of long-acting drugs, he added. “But for many people, this remains a distant dream.”

A barometer of the enthusiasm for long-acting regimens was their prominence at the Retroviruses and Opportunistic Infections Conference in Denver in March. The annual meeting has served as the backdrop for many HIV-related milestones, including the electric moment of 1996, when researchers showed that a combination of drugs could suppress the virus.

Dozens of studies on long-acting diets were presented at the conference this year. (Although most of these drugs are very close to preventing and treating HIV, similar options for tuberculosis, hepatitis B, and hepatitis C are not far behind.)

A long-acting treatment – ​​Cabenuva, two injections administered every two months – has been available for almost three years. In the United States, it costs more than $39,000 a year, although few patients pay that price. However, even with a significant reduction, treatment remains out of reach for many patients in low-income countries.

Still, many researchers at the conference were excited by study results showing that Cabenuva was more effective than daily pills in controlling HIV, even in groups that typically have trouble adhering to treatment.

“When you think about how difficult it is for some people, giving them new tools that could help remove them is a big deal,” said Dr. Kimberly Smith, who leads research and development at ViiV Healthcare, which makes one of the component drugs of Cabenuva.

Long-acting medications could be helpful even for children living with HIV. Worldwide, only about half of children diagnosed with HIV receive treatment.

That’s partly due to a lack of versions of the drugs designed for children, said Dr. Charles Flexner, an HIV expert at Johns Hopkins University, in a presentation at the Denver conference.

“With long-acting formulations, that will no longer be the case,” Dr. Flexner said. “Children will be able to use the same formulation as adults, but at a different dose. »

Most long-acting injections contain drug nanocrystals suspended in liquid. While oral pills must pass through the stomach and intestinal tract before entering the circulation, so-called depot injections deliver medications directly into the bloodstream. But their release is extremely slow, over weeks or months.

Some depot antipsychotics are given every two to eight weeks, and the contraceptive Depo-Provera is given once every three months. Cabenuva — a combination of cabotegravir, made by ViiV Healthcare (majority owned by GSK), and Janssen’s rilpivirine — is injected into the gluteal muscles every two months to treat HIV

Cabotegravir administered under the skin of the stomach caused more bruising and rashes than in the buttocks, and some people developed nodules that persisted for weeks or even months. But with buttock injections, “you don’t see anything,” Dr. Smith said. “You feel pain for a few days, then you move on with your life. »

ViiV is trying to develop a version of cabotegravir to be administered every four months and, ultimately, once every six months. The company aims to commercialize the four-month version for HIV prevention in 2026 and for treatment in 2027.

But injecting drugs into muscles is a challenge for people who have significant body fat or have silicone implants in their buttocks, as some trans women do. Some newer injections under development are administered under the skin, circumventing the problem.

Gilead’s lenacapavir can be given by subcutaneous injection into the stomach once every six months, but it is so far only approved for HIV-positive people who are resistant to other drugs. The drug is in several late-stage trials as a long-acting HIV preventative among diverse groups, including cisgender women.

Lenacapavir is also being tested as a once-weekly pill treatment in combination with another drug, islatravir, made by Merck. Ideally, there should be multiple long-acting treatments available, “so patients can really choose the options that work best for them,” said Dr. Jared Baeten, vice president of Gilead.

Santos Rodriguez, 28, was diagnosed with HIV in 2016 and has been taking a daily pill to suppress the virus ever since. Mr Rodriguez, who works on artificial intelligence at the Mayo Clinic in Florida, said having to take just one pill a week would be “definitely revolutionary for me and my membership”.

He said he was discouraged by the bimonthly clinic visits required for Cabenuva injections and by reports that buttock injections are painful. An injection every four or six months would be much more attractive, he added.

To make it truly accessible to everyone, including those who live far from a health center, researchers also need to come up with a long-acting injection that can be self-administered, some experts noted.

That’s exactly what a team is developing and, with support from global health initiative Unitaid, plans to make it available in low- and middle-income countries.

“What’s really exciting is that the way it’s being developed, it will ideally bypass the fallout to reach the people who need it most,” said Dr. Bender Ignacio, referring to the trend of rich countries to have first access to new therapies. She directs the study.

The product uses a lipid base to suspend three anti-HIV drugs, two water-soluble and one fat-soluble. Unlike depot injections, which release drugs slowly, so-called nanolozenge is absorbed by immune cells and lymph nodes immediately after administration under the skin of the stomach.

The injections can contain smaller doses of medication because of their effectiveness, and they can also be easily adapted for children and adolescents, Dr. Bender Ignacio said. A single injection maintains the levels of all three drugs in the body for over a month, replacing 150 tablets.

So far, the long-acting, self-administered vaccine has only been tested on 11 people, including Kenneth Davis, 58, a resident of Auburn, Washington. Mr. Davis, who lost two family members to AIDS, compared the vaccine to a bee. injection – fleeting and less painful than Covid vaccines.

Since the component drugs have each been approved independently, Dr. Bender Ignacio estimated that the injections could be available to treat HIV in less than five years.

Many products, including those in Dr. Bender Ignacio’s study, can be adjusted to prevent HIV. There are currently only three options for this: two types of daily pills and ViiV’s cabotegravir, which is injected into the buttocks once every two months.

“It is in the area of ​​prevention where we have fallen furthest behind in the AIDS response over the past decade,” said AVAC’s Warren.

A study presented at the Denver conference showed that when people were offered a choice of prevention methods, more of them chose long-acting cabotegravir. But the percentage opting for daily pills has also increased.

“The fact that we’ve seen protection increase through a whole range of methods is the most important thing to me,” Mr Warren said. The study, he added, “really shows that there is now evidence behind choice, not just for advocacy.”

News Source :
Gn Health

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