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Gilead and MSD (Merck & Co) have released data for their two-drug combination human immunodeficiency virus (HIV) therapy, islatravir-lenacapavir (ISL/LEN), which has shown sustained viral suppression in patients switching from triple-drug regimens – positioning the drug for potential US approval.
As per data from the Phase III ISLEND-1 study (NCT06630286), which evaluated the potential of a once-weekly, oral ISL/LEN in patients switching from treatment with mainstay HIV treatment, Biktarvy (bictegravir/emtricitabine/tenofovir alafenamide), ISL/LEN was found to be non-inferior to Biktarvy – with no patients making the switch surpassing the ‘detectable’ threshold of ≥ 50 copies/mL of HIV RNA at week 48.
Researchers observed a similar trend in the Phase III ISLEND-2 trial (NCT06630299) that pitted ISL/LEN against other daily oral standard of care (SoC) HIV therapies, with 99.7% of patients receiving ISL/LEN remaining under the detectable threshold compared with 98.7% in the SoC arm.
The tolerability profiles of ISL/LEN and the comparator SoC regimens were also similar across both ISLEND studies, as no patients in any portion of the trial experienced a downturn in CD4+ T-cell or lymphocyte counts associated with greater HIV burden. Additionally, neither group experienced clinically meaningful weight gain after 48 weeks.
Following the ISLEND programme’s positive outcome, Gilead and MSD will use the data as the foundation for their regulatory submissions for ISL/LEN in HIV. The companies originally announced the trials met their endpoints in June 2026.
Looking forward, the big pharma duo will first present data from the Phase III ISLEND programme at the 2026 International AIDS Conference, which the International AIDS Society (IAS) will host in Rio de Janeiro, Brazil from 26-31 July.
The HIV landscape shifts
As the HIV treatment paradigm continues to evolve, there have been several moves from drugmakers to create therapeutic regimens that are both less burdensome for the patient in terms of dosing and better tolerated than current SoC options.
According to GlobalData senior infectious disease analyst, Anaelle Tannen, ISL/LEN’s once-weekly dosing could boost patient quality of life and adherence compared with once-daily options like Biktarvy.
However, Tannen caveats that lenacapavir’s “low genetic barrier to the development of resistance” could present a hurdle.
“Some KOLs interviewed by GlobalData suggest that the lenacapavit shouldn’t be incorporated into single-treatment regimens (STRs); its large-scale use could promote the development of resistance, but islatravir has a high genetic barrier to resistance, meaning it could hopefully balance the drug,” Tannen commented.
If approved, ISL/LEN could become the first once-weekly STR to reach the market – potentially addressing the unmet need for longer-acting drugs in the space, and providing Gilead and MSD with a ‘first-mover’ advantage.
“There is also potential to capitalise on the appeal of two-drug regimens as being associated with lower toxicity relative to three-drug regimens, which may be particularly important for certain patient subsets, such as older patients with comorbid conditions,” Tannen added.
A factor that would make ISL/LEN even more appealing, Tannen says, would be if the drug could offer extra benefits such as reduced weight gain, as this is the main issue linked to mainstay treatment, Biktarvy.
Gilead continues to cement HIV legacy
Gilead is no stranger to success in the HIV space. In 2024, the company received a standing ovation at the International AIDS Conference as it presented data for Yeztugo (lenacapavir), the first twice-yearly injectable HIV-1 pre-exposure prophylaxis (PrEP) therapy.
99.9% of participants who received Yeztugo in the Phase III PURPOSE 1 and PURPOSE 2 trials remained HIV negative. The PrEP treatment gained approval from the US Food and Drug Administration (FDA) in June 2025.
While there have been concerns about price being a barrier to entry for patients, Gilead has allowed generic development of the therapy in third-world countries to help reduce this barrier.
Gilead is also investigating a once-yearly version of the PrEP therapy.
"Gilead, MSD chart weekly HIV med’s course to approval on SoC non-inferiority" was originally created and published by Clinical Trials Arena, a GlobalData owned brand.
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