A pill taken once a week. An injection given at home once a month. Even an injection 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 toward longer-acting alternatives, perhaps even a future in which HIV requires care only twice a day. year, inconceivable in the darkest decades of the epidemic.

“This period is the next wave of innovation, newer products that meet people’s needs, particularly in prevention, in ways we’ve never had before,” said Mitchell Warren, executive director of the HIV prevention organization AVAC.

Long-acting therapies can obviate the need to remember to take a daily pill to prevent or treat HIV. And for some patients, new medications can alleviate the stigma of the disease, which itself is a barrier to treatment.

“Not having to remember every morning is a game changer 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, is what prevents them from taking it.”

Long-acting medications are likely to be of even greater help in populations that have long been difficult to reach: patients who have inconsistent access to health services, or who have trouble taking daily pills because they have a unstable housing or transportation, are struggling with substance use. consume, suffer from mental illness or suffer discrimination and stigma.

In 2022, almost 30 years after the arrival 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 that year from AIDS-related illnesses.

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

“We can be elated with the science and clinical implications” of long-acting medications, he added. “But for many people it will be a distant dream.”

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

Dozens of studies on long-acting regimens were presented at this year’s conference. (While most of these drugs are tantalizingly close for HIV prevention and treatment, similar options for tuberculosis, hepatitis B, and hepatitis C are not far behind.)

A long-acting treatment, Cabenuva, two injections given every two months, has been available for almost three years. It costs more than $39,000 a year in the United States, although few patients pay that price. However, even with a deep discount, the treatment is out of reach for many patients in low-income countries.

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

“When you think about how difficult it is for some people, giving them new tools that can suppress them is a very important thing,” said Dr. Kimberly Smith, who heads research and development at ViiV Healthcare, which makes one of the component drugs. from Cabenuva.

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

This is partly due to the lack of versions of drugs made 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, just at a different dose.”

Most long-acting injections contain drug nanocrystals suspended in a 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 they are released very slowly, 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 on 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 couple of days and then you move on with your life.”

Viiv is trying to develop a version of cabotegravir that will be administered every four months and, ultimately, one every six months. The company aims to launch 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 a significant amount of body fat or who have silicone implants in their buttocks, as some trans women do. Some newer injections in development are administered under the skin, avoiding the problem.

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

Lenacapavir is also being tested as a treatment in pill form taken once a week in combination with another drug, islatravir, made by Merck. Ideally, you want to have multiple long-acting treatments, “so people can really choose between the options that will work best for them,” said Dr. Jared Baeten, vice president of Gilead.

Santos Rodríguez, 28, was diagnosed with HIV in 2016 and has since taken a daily pill to suppress the virus. Rodriguez, who works in artificial intelligence at the Mayo Clinic in Florida, said having to take just one pill a week would be “definitely groundbreaking for me and my adherence.”

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

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

One team is developing exactly that and, with support from global health initiative Unitaid, plans to make it available to low- and middle-income countries.

“The really interesting thing about this is that the way it’s being developed, it will ideally avoid the trickle-down effect to reach the people who need it most,” said Dr. Bender Ignacio, referring to the trend in rich countries. to gain access to new therapies first. She runs the studio.

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, this so-called nanopill is absorbed by immune cells and lymph nodes immediately after administration under the skin of the stomach.

Because of this efficiency, the injections can contain smaller doses of medications and can also be easily adapted for children and adolescents, Dr. Bender Ignacio said. A single injection maintains the levels of the three drugs in the body for more than a month, replacing 150 pills.

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

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

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

“Prevention has been where we have fallen furthest behind in the AIDS response over the last decade,” said AVAC’s Mr. Warren.

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

“The fact that we saw protection increase with a variety of methods is the most important thing to me,” Warren said. The study, he added, “really shows that there is now evidence behind the election, not just the defense.”