Long-acting medicines have proved as effective as daily pills in preventing HIV from replicating, according to results from twin trials that enrolled more than 1,000 people in 16 countries.
The drugs tested, cabotegravir and rilpivirine, are given once a month as an injection. They are the first of several long-acting antiretroviral HIV medicines in development, which researchers hope will tackle one of the toughest challenges in the fight against HIV: how to ensure that people consistently take the drugs that can prevent the virus from replicating in their cells. Skipped doses put people with HIV, and their sexual partners, at risk.
Researchers say long-acting medicines could ensure that the vast majority of people who are prescribed antiretroviral drugs — the standard treatment for HIV — successfully suppress the virus, in line with goals set by the United Nations. And it could help the US government to meet its aim of reducing HIV transmission in the country by 90% in the next decade. Researchers hope that long-acting drugs might prevent HIV, too.
“The combination is paradigm shifting,” says Chloe Orkin, an HIV researcher at Queen Mary University of London, who reported the trial findings on 7 March at the Conference on Retroviruses and Opportunistic Infections in Seattle, Washington. “Instead of being reminded that you have HIV 365 days a year, it’s reduced to just 12,” she says. “That gives people a kind of freedom.”
In the 1990s, researchers devised combinations of antiretroviral drugs that transformed HIV from a death sentence into a chronic condition kept in check by daily pills. But sticking to the daily pill schedule can prove tricky. Some people can’t easily reach clinics to get a regular supply of drugs, for instance — a problem that longer-lasting medications could ease.
The antiretroviral injections tested in the trials include a mixture of cabotegravir and rilpivirine, which each block HIV from replicating but in different ways. The medicines remain in the body’s tissues and leach out over weeks. The combination was developed by ViiV Healthcare, a drug company in London that was spun off from pharmaceutical giants GlaxoSmithKline and Pfizer.
One of the clinical trials compared virus levels in blood samples from 556 people with HIV who had not previously taken antiretroviral drugs. For 11 months, participants took either monthly injections or daily doses of three common antiretroviral pills. The other trial had a similar design, but enrolled 616 people who had been taking the standard combination of antiretroviral pills for at least six months before the study started. Not only did the injections keep HIV in check as effectively as pills in both studies, but in each study more than 85% of people on injections said they preferred the monthly regimen.
That doesn’t surprise Orkin. Daily doses grow tiresome, especially for adolescents, she says — and become toxic as people grow old. “Putting three drugs into your body every day for 40 years is a long cumulative exposure,” she says. Some drugs also interact badly with other medications that people might take as they age, such as treatments for high blood pressure. Orkin expects periodic injections of two HIV drugs to take less of a toll than a daily three-drug dose.
The fight continues
ViiV and other groups are now conducting trials to see whether cabotegravir or rilpivirine injections can prevent HIV transmission. Preventive therapy using existing antiretrovirals, called pre-exposure prophylaxis (PrEP), is effective — but it can be a hard sell for people without HIV who don’t like the side effects, stigma or burden of the daily pills. Many HIV researchers hope that the development of long-acting injectable drugs could increase adherence to PrEP.
And scientists are still searching for a cure for HIV infection. A study1 published in Nature on 5 March reports that a person with HIV seems to be clear of the virus after receiving a stem-cell transplant that replaced their white blood cells with those from a person with natural resistance to the virus. This is only the second time that this method has been shown to remove all traces of the virus from a person.
But scientists warn that it is too soon to say that the person, known as the ‘London patient’, has been cured. And stem-cell transplants are complicated, expensive and risky compared with long-acting antiretroviral drugs. The two patients who appear to have been cleared of HIV by such transplants received them to treat advanced cancer, rather than as a possible HIV cure.
“To be honest, the reality is that long-acting drugs are infinitely more relevant than is the cure,” said Anthony Fauci, director of the US National Institute of Allergy and Infectious Diseases in Bethesda, Maryland, after news of the London patient broke.