New Delhi: An experimental once-weekly Human Immunodeficiency Virus (HIV) pill has been found to work as effectively as standard daily treatment at suppressing the virus in a large global Phase 3 trial, potentially offering people living with HIV a less frequent alternative to daily medication.
HIV is treated with a combination of antiretroviral medicines that stop the virus from multiplying. This lowers the amount of HIV in the blood, known as the viral load. When the viral load falls to undetectable levels, the person is said to have achieved viral suppression.
A person with an undetectable viral load cannot sexually transmit HIV, but the virus is not eliminated from the body and treatment must continue.
The Phase 3 ISLEND-2 trial, sponsored by Gilead Sciences, tested a once-weekly tablet combining Merck’s islatravir and Gilead’s lenacapavir in 626 adults across 100 sites in 14 countries and territories. The two companies are jointly developing the drug combination.
The results were first announced in June and presented at the International AIDS Conference in Rio de Janeiro in July. The full findings were published in The Lancet on 29 August.
Merck said the combination could become the first complete once-weekly oral HIV treatment, if approved.
“Single tablet regimens have transformed the outlook for millions of people living with HIV,” said Amy Colson, Research Director at the US-based Community Resource Initiative and medical director of the Zinberg Clinic at Cambridge Health Alliance in Massachusetts, who was involved in the study.
“Having a treatment option with once weekly dosing can expand choice to help address individual needs and preferences,” she said.
According to Dr Ishwar Gilada, President Emeritus of the AIDS Society of India, the findings need to be interpreted in the context of the patients enrolled in the trial.
“The trial was conducted among people who were already on treatment. So, essentially, it was a switch study, where patients were switched from one regimen to another,” said Gilada, who attended the AIDS Conference in Rio de Janeiro in July.
The trial, he explained, was therefore testing whether people already doing well on HIV treatment could move from a daily regimen to the weekly combination, rather than whether the drug could work in people starting treatment or those whose existing treatment was failing.
Chetali Rao, a Senior Scientific & Legal Researcher with Third World Network, said the findings were important because they add another potential option to the growing range of HIV treatment approaches, but the results should not be extrapolated to all people living with HIV.
What did the trial find?
Of the 626 participants in the trial, 314 switched to the once-weekly islatravir-lenacapavir tablet, while 312 continued their existing daily HIV treatment.
After 48 weeks, the weekly pill was keeping HIV under control in almost all participants, just as daily treatment was. Only one of the 314 people taking the weekly pill had a viral load of 50 copies/mL or more, compared with four of the 312 people who continued taking their daily pills.
The weekly pill worked as well as the daily pill. It was not significantly less effective at keeping the virus under control.
Adherence was also high. The median adherence to the weekly treatment was 100 percent, while 98 percent of participants took at least 90 percent of their prescribed doses.
However, the findings apply primarily to people who were already doing well on HIV treatment. All participants had suppressed HIV, had been on treatment for at least six months, and had no history of treatment failure. The study therefore shows that people with controlled HIV can switch from a daily regimen to the weekly pill and maintain viral suppression.
The results provide less information about people who have detectable virus, frequently miss their medicines or have developed resistance to HIV drugs.
The weekly combination was generally well tolerated. Treatment-related side effects were reported in 18 percent of participants receiving the weekly pill, compared with less than 1 percent among those on standard treatment. Most were mild or moderate, with headache reported in 5 percent, nausea in 3 percent and diarrhoea in 3 percent of participants.
Those who switched to the weekly pill also reported greater satisfaction with their treatment and a lower treatment burden than those who continued daily therapy.
Where would the weekly pill fit?
Modern antiretroviral therapy, or ART, prevents HIV from making new copies of itself and can reduce the virus to undetectable levels.
In India’s public ART programme, the standard first-line regimen for most adults and adolescents is TLD, a once-daily combination of medicines including tenofovir disoproxil fumarate, lamivudine and dolutegravir.
Dr Gilada explained that people living with HIV in India can broadly access treatment through government health centres or private care, with some NGOs also providing free or subsidised services.
He said India’s public programme follows a “test-and-treat” approach, under which a person who tests positive for HIV is started on treatment. Stable patients can also receive medicines for longer periods, reducing the need for frequent visits to ART centres.
On prevention, Gilada said pre-exposure prophylaxis (PrEP) is not currently part of India’s government HIV programme and is mainly accessed through private providers. Post-exposure prophylaxis (PEP) is available through government services following potential exposure to HIV.
Globally, dolutegravir-based combinations are widely used, while some countries also use regimens containing drugs such as bictegravir, tenofovir alafenamide and emtricitabine. Long-acting injectable treatments, including cabotegravir and rilpivirine, are available for appropriately selected people whose HIV is already suppressed.
Lenacapavir is already approved in the US as part of combination treatment for adults with multidrug-resistant HIV who are heavily treatment-experienced and whose current regimen is failing. After an initial loading regimen, it is given as two injections every six months.
Islatravir is not currently an approved standalone HIV treatment, and the once-weekly islatravir-lenacapavir combination remains investigational.
But Gilada said any weekly regimen may take years before it becomes widely accessible in India.
“Even if a weekly treatment comes, it might take more than five years to come to the government’s programme,” he said. He also pointed to the need for the regimen to be economical, feasible and manageable within the public health system.
In India, a Central Drugs Standard Control Organisation (CDSCO) expert panel has recommended waiving local Phase III trials for generic injectable lenacapavir being developed for HIV prevention, subject to post-approval Phase IV studies. This relates to PrEP and is separate from the experimental once-weekly islatravir-lenacapavir treatment.
Rao said the weekly pill could fill a gap between daily oral treatment and longer-acting injectable options. While daily ART requires people to remember their medicines every day, injectable regimens reduce dosing frequency but require patients to return to healthcare facilities for periodic injections.
“This kind of drug sits somewhere in between. People would not have the burden of taking a pill every day, but they also would not have to plan around clinic visits for a monthly, twice-monthly or six-monthly injection,” she said.
The combination would not replace an ineffective treatment. Instead, if approved, it could allow some people whose HIV is already suppressed to maintain control with fewer doses, reducing treatment from roughly 365 doses a year to 52.
The longer-term safety and effectiveness of the combination will also need to be established, with participants being followed through 96 weeks.
(Edited by Sugita Katyal)