One pill taken once a week. Inject at home once a month. There is even an injection that is given at the clinic every six months.
Within the next 5 to 10 years, these options may become available to prevent or treat HIV. Instead of drugs that have to be taken daily, scientists are moving closer to longer-acting alternatives — perhaps even a future in which HIV may need attention just twice a year. years, unimaginable during the darkest decades of the epidemic.
“This phase is the next wave of innovation, newer products that meet people's needs, especially around prevention,” said Mitchell Warren, executive director of HIV prevention organization AVAC. ways we never had before.”
Long-acting therapies can help eliminate the need to remember to take daily pills to prevent or treat HIV. And for some patients, new drugs may reduce stigma about the disease, itself an obstacle to treatment.
“There's no need to remember that every morning is earth-shattering for them,” said Dr. Rachel Bender Ignacio, an infectious disease physician and researcher at the Fred Hutch Cancer Center in Seattle. “That stigma, that internalized stigma about taking that pill every morning, is what prevents them from taking it.”
Long-acting drugs offer even greater benefits to long-hard-to-reach populations: patients with limited access to health services or those who have difficulty taking daily medications because they are sick. Unstable housing or transportation, are struggling with substance use, have a mental illness, or face discrimination and stigma.
In 2022, nearly 30 years after the introduction of combination antiretroviral therapy, more than nine million people 39 million people are infected with HIV untreated worldwide. About 630,000 people died from AIDS-related illnesses that year.
Even in the United States, about one-third of people diagnosed with HIV do not have the virus under control. “We still haven't solved the underlying problems 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 significance” of long-acting drugs, he added. “But for many people, that will be a distant dream.”
One barometer of the excitement about long-acting regimens is their prominence at the Conference on Retroviruses and Opportunistic Infections in Denver in March. This annual meeting has played a was the foundation for many important HIV milestones, including the electric moment in 1996 when researchers demonstrated that combination of drugs can prevent it virus.
Dozens of studies on long-acting regimens were presented at this year's conference. (While most of these medications come very close to preventing and treating HIV, similar options for tuberculosisHepatitis B and hepatitis C are not far behind.)
A long-acting treatment – Cabenuva, two injections given one month apart – has been available for nearly three years. It costs more than $39,000 per year in the United States, although few patients pay that price. Yet even with steep discounts, treatment remains out of reach for many patients in low-income countries.
Still, many researchers at the conference were excited about results from a study showing that Cabenuva was more effective than a daily pill in controlling HIV even in groups that typically have difficulty adhering to treatment. treat.
“When you think about how difficult it is for some people, giving them new tools can causing them to be inhibited is a big problem.” one of the medicinal ingredients in Cabenuva.
Long-acting medications can be helpful even for children with HIV. Worldwide, only about half of children diagnosed with HIV receive treatment.
That's partly due to a lack of a pediatric version of the drug, Dr. Charles Flexner, an HIV expert at Johns Hopkins University, said in a presentation at the Denver conference.
“With long-acting formulations, that no longer happens,” says Dr. Flexner. “Children will be able to use the same formulation as adults, just at a different dosage.”
Most long-acting injections contain drug nanocrystals suspended in a liquid. While oral medications must pass through the stomach and intestinal tract before entering the circulatory system, so-called depot injections deliver the medication directly into the bloodstream. But they are released extremely slowly, over several weeks or months.
Some antipsychotic medications are taken every two to eight weeks, and the birth control pill Depo-Provera is taken every three months. Cabenuva – a combination of cabotegraver, majority owned by Viiv Healthcare (GSK) and Janssen's rilpivirine – is injected into the gluteal muscle every two months to treat HIV
Cabotegravir injected under the skin of the stomach causes more bruising and rash on the buttocks, and some people develop welts that last for weeks or even months. But with gluteal injections, “you won't see anything,” Dr. Smith says. “You feel pain for a few days and then you move on with your life.”
Viiv is trying to develop a version of Cabotegravir to be given every four months and eventually every six months. The company aims to bring a four-month version to market for HIV prevention in 2026 and treatment in 2027.
But intramuscular injections are challenging for people with significant amounts of body fat or who have silicone implants in their buttocks, as some trans women do. Some newer injections being developed are given subcutaneously, which avoids the problem.
Gilead's Lenacapavir can be injected subcutaneously into the stomach every six months, but so far that hasn't been enough. approved only for people infected with HIV against other medications. The drug is in late-stage testing as a long-acting HIV prevention measure in various groups, including transgender women.
Lenacapavir is also being tested as a treatment pill once a week in combination with another drug, islatravir, manufactured by Merck. Having a variety of long-acting treatments is ideal, said Dr. Jared Baeten, Gilead's vice president, “so people can really make a choice among the most appropriate options.” with them”.
Santos Rodriguez, 28, was diagnosed with HIV in 2016 and has since taken daily medication to suppress the virus. Mr. Rodriguez, who works on artificial intelligence at the Mayo Clinic in Florida, said taking just one pill a week would “definitely be a breakthrough for me and my compliance.”
He said he was put off by his bimonthly clinic visits for Cabenuva injections, and by reports that the buttock injections were painful. A shoot every four months or six months would be much more appealing, he added.
Some experts note that to truly be accessible to everyone, including those who live far from health care centers, researchers must also find a long-acting injectable drug that can be self-administered. .
A team is developing exactly that and, with support from the global health initiative Unitaid, plans to make it available in low- and middle-income countries.
“What's really exciting about this is the way it's being developed, ideally it will bypass the trickle-down effect to get to the people who need it most,” said Dr. Bender Ignacio. get access to new therapies first. She is leading the research.
The product uses a lipid matrix to suspend three HIV drugs, two water-soluble and one fat-soluble. Unlike depot injections, which release the drug slowly, this so-called nanolozenge is absorbed by immune cells and lymph nodes immediately after it is inserted under the skin of the stomach.
The shots can deliver smaller doses of medication because of this effect, and they can also be easily adjusted for children and teens, Dr. Bender Ignacio said. A single injection maintains the concentration of these three drugs in the body for more than a month, replacing 150 pills.
So far, the self-administered long-acting shot has been tested on just 11 people, including Kenneth Davis, 58, of Auburn, Wash. Mr Davis, who lost two family members to AIDS, likened the shot to a bee sting – fleeting and less painful than the Covid vaccine.
Because the component drugs have all been independently approved, Dr. Bender Ignacio estimates the shots could cure HIV in less than five years.
Many products, including those in Dr. Bender Ignacio's study, can be adapted to prevent HIV. There are currently only three options for that: two daily oral medications and Viiv's Cabotegravir, which is given as a one-time injection into the buttocks every two months.
“It's prevention where we've fallen the most behind in the AIDS response over the past decade,” said Mr. Warren, of AVAC.
A study presented at the Denver conference found that when people were given a choice of prevention methods, many of them chose long-acting Cabotegravir. But the proportion choosing to take daily medication also increased.
“The fact that we see increased protection through multiple methods — to me that's the most important thing,” Mr. Warren said. The study, he added, “really shows that there is now evidence behind choice, not just support.”
