A once-weekly tablet for HIV has kept the virus suppressed as effectively as a widely used daily treatment in a large clinical trial.

If longer-term results remain reassuring and regulators approve it, the option could reduce the burden of taking HIV medicine every day for some people.

The weekly tablet combines two antiretroviral medicines, islatravir and lenacapavir. It is not yet a routine treatment option, and the study did not include people who were struggling to take daily HIV medication consistently.

Still, the findings offer evidence that less-frequent oral treatment may be possible for people whose HIV is already well controlled.

HIV treatment has become simpler, but daily dosing can still be difficult

Modern antiretroviral therapy, often called ART, can reduce the amount of HIV in the blood to very low, undetectable levels. This is known as viral suppression.

When HIV remains suppressed, it protects the person’s immune system and prevents sexual transmission of the virus. This principle is commonly described as “undetectable equals untransmittable”, or U=U.

Many people now take a single HIV tablet each day. One widely prescribed option is Biktarvy, which contains three medicines: bictegravir, emtricitabine and tenofovir alafenamide.

Daily treatment is effective, but taking medicine every day for years or decades can be tiring. Some people experience “pill fatigue”, meaning the mental, emotional or practical strain of regular dosing. Daily tablets may also be an unwanted reminder of HIV, particularly where stigma remains a concern.

Long-acting HIV treatments already exist, including injections given at scheduled clinic visits. However, injections do not suit everyone. A weekly tablet could provide another option between daily pills and regular injections.

What the new trial found

The evidence comes from a phase 3 human clinical trial called ISLEND-1, published in The New England Journal of Medicine.

Phase 3 trials are large studies designed to test whether a treatment works well enough, and is safe enough, to support possible regulatory approval. ISLEND-1 involved 607 adults at 106 sites in 12 countries.

All participants had already taken daily Biktarvy and had maintained viral suppression, with fewer than 50 copies of HIV per millilitre of blood, for at least six months. They had no previous virological treatment failure, meaning no previous HIV treatment had stopped controlling their virus.

Researchers randomly assigned participants either to switch to the once-weekly islatravir-lenacapavir tablet or to continue taking Biktarvy once daily. Neither participants nor most study staff knew which treatment had been assigned during the main part of the trial.

After 48 weeks:

• None of the 304 people taking the weekly treatment had a viral load of 50 copies per millilitre or above.
• One of the 303 people continuing daily Biktarvy reached that threshold.
• More than 93% of participants in both groups remained virally suppressed according to the study’s main assessment.
• No participant in either group experienced confirmed virological failure.
• Measures of immune health, including CD4-positive T-cell counts, remained broadly stable.

In plain terms, the once-weekly tablet controlled HIV at least as well as the established daily regimen over one year in this group of participants.

How the two-drug weekly treatment works

HIV reproduces by entering immune cells and using several steps to make copies of itself. Antiretroviral medicines interrupt different parts of this process.

Islatravir is a type of medicine known as a nucleoside reverse transcriptase inhibitor. It interferes with reverse transcriptase, an enzyme HIV needs to turn its genetic material into a form that can be copied inside human cells.

Lenacapavir works differently. It targets HIV’s capsid, the protein shell that surrounds the virus’s genetic material. The capsid is needed at several stages of the virus’s life cycle, including when HIV enters cells and when new virus particles are assembled.

Using medicines that act at different stages helps prevent the virus from multiplying. The drugs are designed to remain at effective levels in the body long enough to allow weekly dosing.

Side effects were broadly similar over 48 weeks

Adverse events, meaning health problems reported during the study whether or not they were caused by treatment, were common in both groups. They were reported by 79.3% of people receiving the weekly tablet and 78.5% of those receiving daily Biktarvy.

Most were mild or moderate. Reported problems included upper respiratory infections, diarrhoea, headache and nausea.

Serious adverse events occurred in 5.3% of the weekly-treatment group and 4.6% of the daily-treatment group. Six people taking the weekly treatment and five taking daily Biktarvy stopped their assigned treatment because of adverse events.

These figures do not by themselves show that the weekly medicine caused all reported events. Clinical trials record events occurring during treatment so that researchers can look for meaningful differences between groups.

How strong is the evidence?

This was a large, randomised and double-blind phase 3 trial, which provides relatively strong evidence for the specific question it studied: whether people with already suppressed HIV could switch from daily Biktarvy to the weekly tablet and maintain viral control for 48 weeks.

The trial was designed to test whether weekly islatravir-lenacapavir was “non-inferior” to daily Biktarvy. This means researchers were assessing whether it was not meaningfully less effective than the standard treatment, rather than trying to prove it was better.

However, the findings have important limits.

Most importantly, participants had already kept their HIV suppressed for at least six months and appeared to have high medication adherence. Pill counts suggested adherence of nearly 99% in the weekly group and about 96% in the daily-treatment group.

That means the study does not yet show how well the weekly tablet works for people who regularly miss daily doses, even though they may be among those most likely to benefit from a less-frequent oral treatment.

The trial also lasted 48 weeks. Longer follow-up is needed to identify uncommon or delayed side effects, assess the durability of viral suppression and monitor for the emergence of drug resistance.

The study was funded by Gilead Sciences and Merck Sharp & Dohme, the companies developing lenacapavir and islatravir. Industry funding does not invalidate results, but it makes independent review, transparent reporting and further research especially important.

Hepatitis B remains an important consideration

The weekly combination does not treat hepatitis B virus. This matters because HIV and hepatitis B can occur together.

Two components of Biktarvy, emtricitabine and tenofovir alafenamide, are active against both HIV and hepatitis B. Stopping them in someone with chronic hepatitis B could allow hepatitis B to become active or worsen.

For this reason, people with active hepatitis B were excluded from ISLEND-1. During the study, one unvaccinated participant taking the weekly tablet developed hepatitis B.

Any future use of the weekly treatment would therefore require hepatitis B testing, vaccination where appropriate and careful selection of patients. People living with HIV should not change treatment without discussing it with their HIV specialist.

What this means now

The study does not change current HIV treatment guidance. The weekly islatravir-lenacapavir tablet remains under development and would need regulatory review before becoming available for routine care.

For people currently taking effective HIV treatment, the key message remains unchanged: continue taking prescribed medicine as directed and discuss any concerns about side effects, missed doses, privacy or treatment burden with an HIV clinician.

If approved, a weekly tablet may give some people another way to manage HIV without daily pills or clinic-based injections.

The best treatment will still depend on individual circumstances, including other health conditions, hepatitis B status, possible drug interactions, preferences and the ability to take doses reliably.

Longer-term results will be important

The ISLEND-1 trial is continuing and is expected to provide results through 96 weeks. These data should give a clearer picture of longer-term safety and whether viral suppression remains durable.

Researchers will also need studies involving more varied groups, including people with previous treatment difficulties, co-existing hepatitis B and different patterns of adherence.

Evidence on how people manage a weekly schedule outside the close support of a clinical trial will be particularly useful.

The main finding is encouraging but specific: among adults whose HIV was already well controlled on daily treatment, a weekly oral combination of islatravir and lenacapavir maintained viral suppression over 48 weeks as effectively as daily Biktarvy.

It is an important addition to the continuing effort to make lifelong HIV treatment effective, manageable and suited to individual needs.