Take the pill once a week. Injections are given once a month at home. Even going to a clinic every six months to get vaccinated.
Within the next five to 10 years, these options may be available to prevent or treat HIV. Scientists are looking for long-acting alternatives to drugs that must be taken every day – and it could even be the case that in the future, HIV may only need to be taken twice a day this year, something unthinkable during the darkest decades of the epidemic.
“This period is the next wave of innovation, with new products meeting people’s needs in ways we’ve never had before, particularly in prevention,” said Mitchell Warren, executive director of HIV prevention organization AVAC Warren) said.
Long-acting treatments may eliminate the need to remember to take medications every day to prevent or treat HIV. For some patients, new drugs may reduce the stigma of the disease, which itself is a barrier to treatment.
“You don’t have to remember that every morning is a huge change for them,” said Dr. Rachel Bender Ignacio, an infectious disease physician and researcher at Fred Hutch Cancer Center in Seattle. “That shame, the inherent shame of taking this pill every morning, is what’s stopping them from taking it.”
Long-acting drugs may bring greater benefits to populations that have long been hard to reach: patients who have difficulty accessing care, or who find it difficult to take their medications every day because of their ingestion. unstable housing or transportation, struggling with substance abuse, suffering from mental illness, or facing discrimination and stigma.
By 2022, nearly 30 years after the advent of combination antiretroviral therapy, more than 9 million people 39 million people living with HIV The whole world is not receiving treatment. About 630,000 people died from AIDS-related illnesses that year.
Even in the United States, about one-third of people living with HIV do not have the virus under control. “We still haven’t solved these underlying problems with access,” said Greg Gonsalves, a longtime HIV activist and epidemiologist at the Yale School of Public Health.
“We are pleased with the scientific and clinical implications of the long-acting drug,” he added. “But for many people, that will be a distant dream.”
One barometer of excitement about long-acting treatment options was their prominence at the Retrovirus and Opportunistic Infections conference in Denver in March. The annual meeting served as the backdrop for many HIV milestones, including an exciting moment in 1996, when researchers showed: Combinations of drugs can inhibit Virus.
Dozens of studies of long-acting treatment options were presented at this year’s meeting. (While most of these drugs are very close for HIV prevention and treatment, similar options tuberculosis, hepatitis B and hepatitis C are not far behind. )
One long-acting treatment — Cabenuva, given as two injections every other month — has been on the market for nearly three years. In the United States, the annual cost is more than $39,000, although few patients pay that price. However, even with deep discounts, many patients in low-income countries still do not have access to this treatment.
Still, many researchers at the meeting were excited by the results of a study showing that Cabenuva is more effective at controlling HIV than daily medications, even in a group that typically has difficulty adhering to treatment.
“When you think about how difficult this is for some people, giving them new tools that might be able to suppress them is a big deal,” said Dr. Kimberly Smith, head of research and development at ViiV Healthcare, one of the ingredients in Cabenuva.
Long-acting drugs may be useful even in children infected with HIV. Worldwide, only about half of children diagnosed with HIV are receiving treatment.
Dr. Charles Flexner, an HIV expert at Johns Hopkins University, said in a presentation at the Denver conference that part of the problem is the lack of a version of the drug for children.
“With long-acting formulations, that will no longer be the case,” Dr. Flexner said. “Children will be able to use the same formula as adults, just at different dosages.”
Most long-acting injectables contain nanocrystals of the drug suspended in a liquid. Oral pills must pass through the stomach and intestines before entering the circulation, while so-called long-acting injections deliver the drug directly into the bloodstream. But their release is extremely slow, taking weeks or months.
Some long-acting antipsychotics are given every two to eight weeks, and the birth control pill Depo-Provera is given every three months. Cabenuva, a combination of cabotegravir made by Viiv Healthcare (a GlaxoSmithKline-owned company) and Janssen’s rilpivirine, is injected into the gluteal muscle every two months to treat HIV.
Subcutaneous injections of cabotegravir in the stomach can cause more bruising and rash than injections in the buttocks, and some people develop nodules that last for weeks or even months. But with gluteal injections, “you can’t see anything,” Dr. Smith said. “You’ll feel pain for a few days and then you can go on with your life.”
Viiv is trying to develop cabotegravir to be administered every four months and eventually every six months. The company aims to bring a four-month version to market in 2026 for HIV prevention and in 2027 for treatment.
But for people with more body fat or silicone implants in their buttocks, such as some transgender women, injecting the drug into the muscle can be challenging. Some new injections being developed are given under the skin, thus avoiding this problem.
Gilead’s lenacapavi can be administered as a subcutaneous injection into the stomach every six months, but so far Approval only For people living with HIV resistance Other medicines. The drug is in multiple late-stage trials as a long-acting HIV preventive in diverse groups, including cisgender women.
Lenacapavir is also being tested as a treatment once a week pills It is used in combination with islatravir, another drug made by Merck. Dr. Jared Baeten, a vice president at Gilead, said having multiple long-acting treatments is ideal “so that people can really choose among the options that are best for them.”
Santos Rodriguez, 28, was diagnosed with HIV in 2016 and has since taken a daily pill to suppress the virus. Mr. Rodriguez, who studies artificial intelligence at the Mayo Clinic in Florida, said taking just one pill a week was “absolutely groundbreaking for me and my persistence.”
He said the Cabernet shot required visits to a clinic every two months and there were reports that butt injections were painful, so he put off getting them. Injections every four or six months would be more attractive, he added.
To make it truly accessible to everyone, including those who live far from health care centers, researchers will also have to develop a long-acting shot that can be self-administered, some experts say.
A team is developing the technology and, with support from the Global Health Initiative UNITAID, plans to roll it out to low- and middle-income countries.
Dr. Bender Ignacio spoke about the tendency of rich countries to get first access to new treatments. She is leading the research.
The product uses a lipid matrix to suspend three HIV drugs, two of which are water-soluble and one of which is fat-soluble. Unlike long-acting injections that release the drug slowly, the so-called nanolozenges are absorbed immediately by immune cells and lymph nodes after being delivered under the skin of the stomach.
Because of this efficiency, the injections can carry smaller doses of the drug and can also be easily administered to children and teenagers, Dr. Bender Ignacio said. A single injection can maintain levels of the three drugs in the body for more than a month and can replace 150 pills.
The long-acting, self-injected vaccine has been tested on 11 people so far, including Kenneth Davis, 58, a resident of Auburn, Washington. Mr Davis, who has lost two family members to AIDS, likened the vaccine to a bee sting – short-lived and less painful than the Covid vaccine.
Because each component drug has been independently approved, Dr. Bender Ignacio estimates the injections could be used to treat 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: two daily pills, and Viiv’s cabotegravir, an injection into the buttocks every two months.
“We have been lagging behind prevention on HIV over the past decade,” said AVAC’s Mr. Warren.
A study presented at the Denver conference showed that when people were given a choice of prevention methods, more people chose long-acting cabotegravir. But the proportion choosing to take daily medication has also increased.
“The fact that we’re seeing protections improved across a range of approaches is what’s most important to me,” Mr Warren said. He added that the study “really shows that there’s evidence behind choices now, not just advocacy.”
