Gilead and Merck Report Positive Phase 3 Results for Once-Weekly Oral HIV Treatment

The way HIV is treated has changed dramatically over the last few decades. Daily antiretroviral therapy has helped millions of people achieve long-term viral suppression and live healthier lives. Now, researchers are working on the next step in HIV treatment—reducing how often patients need to take their medication.

Gilead Sciences and Merck, known as MSD outside the United States and Canada, have announced positive results from two Phase 3 clinical trials evaluating an investigational once-weekly oral HIV treatment regimen. The studies, known as ISLEND-1 and ISLEND-2, achieved their primary efficacy endpoints at Week 48, bringing the potential of a once-weekly HIV pill one step closer to reality.

A New Approach to HIV Treatment

The investigational treatment combines two medicines, islatravir and lenacapavir, into a single tablet that is taken once a week.

The goal is simple. Instead of taking HIV medication every day, patients could potentially maintain viral suppression with just one pill per week.

If approved, this would represent one of the first long-acting oral HIV treatment options available and could offer greater flexibility and convenience for people living with HIV.

According to Gilead and Merck, the combination is designed to provide effective viral control while reducing the treatment burden associated with daily medication schedules.

What Were the ISLEND Trials Designed to Study?

The Phase 3 ISLEND program consists of two separate studies evaluating the safety and effectiveness of the once-weekly islatravir and lenacapavir combination.

ISLEND-1 focused on people living with HIV who were already virologically suppressed while taking Biktarvy.

ISLEND-2 evaluated people who were virologically suppressed while taking various standard-of-care daily antiretroviral therapy regimens.

Both studies investigated whether participants could successfully switch from their daily treatment to the once-weekly regimen while maintaining viral suppression.

Positive Results from ISLEND-1

ISLEND-1 was a randomized, double-blind Phase 3 trial that compared the once-weekly regimen against continued treatment with Biktarvy.

The primary goal of the study was to measure the percentage of participants whose HIV-1 RNA levels remained below the threshold used by the U.S. Food and Drug Administration's Snapshot Algorithm at Week 48.

The results showed that the once-weekly regimen was statistically non-inferior to Biktarvy.

In simple terms, patients taking the once-weekly treatment maintained viral suppression at rates comparable to those who continued taking their daily medication.

The safety profile was also generally comparable to Biktarvy, and researchers reported no new safety concerns.

Positive Results from ISLEND-2

ISLEND-2 evaluated people living with HIV who were receiving a variety of standard daily antiretroviral treatments.

Participants either switched to the once-weekly islatravir and lenacapavir tablet or continued their existing daily treatment regimen.

The study achieved its primary endpoint at Week 48 and demonstrated that the once-weekly regimen was statistically non-inferior to standard daily HIV therapies.

Researchers also reported a safety profile comparable to existing treatment options.

These findings suggest that the investigational therapy may offer a viable alternative for a broad range of patients currently taking daily HIV medications.

Why Less Frequent Dosing Matters

Although daily HIV medications are highly effective, maintaining lifelong adherence can still be challenging for some patients.

Busy schedules, privacy concerns, travel, and treatment fatigue can all affect medication routines over time.

A once-weekly oral option could help address some of these challenges by reducing the number of doses patients need to remember each month.

Jared Baeten, Senior Vice President and Head of Clinical Development for Virology at Gilead Sciences, noted that long-acting oral therapies represent a new wave of innovation in HIV treatment and could provide greater flexibility and discretion for people living with the virus.

How Islatravir and Lenacapavir Work Together

One reason researchers are excited about this combination is that the two medicines target different stages of HIV replication.

Lenacapavir has a unique multi-stage mechanism of action that differs from existing classes of antiretroviral therapies. Rather than acting on a single stage of the viral lifecycle, it is designed to interfere with HIV replication at multiple points.

Researchers have also reported that lenacapavir has shown no known cross-resistance in laboratory studies to currently available HIV drug classes.

Islatravir is a next-generation nucleoside analog developed by Merck. It blocks HIV replication through multiple mechanisms, including interruption of reverse transcriptase activity and disruption of viral DNA formation.

Together, these two compounds provide the scientific foundation for a long-acting oral treatment strategy.

Safety Findings Remain Encouraging

Safety remains one of the most important considerations in any HIV treatment program.

Across both ISLEND studies, the safety profile of the investigational regimen was generally comparable to the therapies used as comparators.

Researchers did not identify any new safety concerns during the trials.

This consistency is important because it suggests that less frequent dosing may be achieved without compromising overall tolerability.

What Happens Next?

Following the positive Phase 3 results, Gilead and Merck plan to submit the ISLEND data to regulatory authorities around the world.

The companies also intend to present detailed trial findings at future scientific conferences.

Regulatory review will determine whether the once-weekly regimen can move closer to becoming an approved treatment option for people living with HIV.

Understanding the Potential Impact

If approved, islatravir and lenacapavir could become the first once-weekly oral HIV treatment regimen available to patients.

This would represent a significant shift in HIV care.

For decades, treatment innovation has focused on improving efficacy, reducing side effects, and simplifying therapy. The introduction of a once-weekly oral regimen would add another layer of convenience and flexibility that many patients may find valuable.

While injectable long-acting therapies are already available for some patients, an oral once-weekly option could provide another choice for those who prefer tablets over injections.

Gilead's Ongoing HIV Leadership

Gilead has played a major role in HIV treatment innovation for nearly four decades.

The company has developed multiple HIV medicines, including the first single-tablet HIV regimen and the first pre-exposure prophylaxis treatment designed to help reduce new HIV infections.

More recently, Gilead introduced long-acting injectable HIV prevention therapies and continues to invest heavily in both treatment and prevention research.

Lenacapavir is being studied across multiple HIV treatment and prevention programs, including both oral and injectable long-acting approaches.

Merck's Continued HIV Research Efforts

Merck is also advancing several HIV research programs centered around islatravir.

Beyond the once-weekly islatravir and lenacapavir combination, the company is evaluating islatravir in several additional clinical trials, including once-daily and once-weekly treatment regimens with other investigational HIV medicines.

The goal is to provide more treatment options that address the diverse needs of people living with HIV.

The positive Phase 3 results from the ISLEND-1 and ISLEND-2 studies mark an important milestone in the development of long-acting oral HIV therapies. The investigational once-weekly combination of islatravir and lenacapavir successfully maintained viral suppression while demonstrating a safety profile comparable to existing treatment options.

Although the therapy is still under regulatory review and has not yet been approved, the findings suggest that a future where HIV treatment may require only one pill per week is becoming increasingly possible. For many people living with HIV, that could mean greater flexibility, reduced treatment burden, and another important option for managing their health.