Once-Weekly HIV Pill Matches Daily Treatment in Phase 3 Trial

Trial Results

A once-weekly HIV pill has been shown to be as effective as daily antiretroviral therapy at maintaining viral suppression, according to findings from the Phase 3 ISLEND-2 trial published in The Lancet on 29 August. The study, sponsored by Gilead Sciences, tested a tablet combining Merck's islatravir and Gilead's lenacapavir in 626 adults across 100 sites in 14 countries and territories. The results were first announced in June and presented at the International AIDS Conference in Rio de Janeiro in July.

Of the participants, 314 switched to the once-weekly tablet, while 312 continued their existing daily HIV treatment. After 48 weeks, only one of the 314 people receiving the weekly pill had a viral load of 50 copies/mL or more, compared with four of the 312 who remained on daily therapy. The weekly regimen was therefore not significantly less effective than daily treatment.

Adherence to the weekly pill was high, with median adherence reaching 100 percent, and nearly all participants took at least 90 percent of their prescribed doses. Participants who switched to the weekly pill also reported greater satisfaction with their treatment and a lower perceived treatment burden than those who continued daily therapy.

The 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 side effects were mild or moderate, with headache reported in 5 percent, nausea in 3 percent, and diarrhoea in 3 percent of participants.

Merck said the combination could become the first complete once-weekly oral HIV treatment if approved.

Expert Perspectives

Dr Ishwar Gilada, President Emeritus of the AIDS Society of India, who attended the AIDS Conference in Rio de Janeiro, said 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," he said. The trial 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.

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, said: "Single tablet regimens have transformed the outlook for millions of people living with HIV. Having a treatment option with once weekly dosing can expand choice to help address individual needs and preferences."

Implications for India

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. In India, the standard first-line regimen for most adults and adolescents in the public ART programme 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. India's public programme follows a "test-and-treat" approach, under which a person who tests positive for HIV is started on treatment.

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. 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.

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, pointing to the need for the regimen to be economical, feasible and manageable within the public health system.

Separately, 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 recommendation relates to PrEP and is separate from the experimental once-weekly islatravir-lenacapavir treatment.

Outlook

Rao said the weekly pill could fill a gap between daily oral treatment and longer-acting injectable options. The combination 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.

Participants in the ISLEND-2 trial are being followed through 96 weeks for longer-term safety and effectiveness.