Once Weekly Oral HIV Regimen Maintains Suppression Through Week 48

Gilead Sciences and Merck announced detailed outcomes from the phase 3 ISLEND-1 (NCT06630286) and ISLEND-2 (NCT06630299) trials evaluating the once weekly oral single-tablet regimen of islatravir 2 mg/lenacapavir 300 mg (ISL/LEN) in adults with virologically suppressed HIV. The data, to be presented in late-breaking sessions at the 26th International AIDS Conference (AIDS 2026) on July 29, showed that participants who switched to ISL/LEN maintained suppression at rates statistically similar to those who continued daily therapy.¹

The companies said the week 48 results will form the basis of upcoming regulatory submissions.¹

Detailed Week 48 Data Confirm Noninferiority

“Once-daily, combination, single-tablet antiretroviral therapy is the cornerstone of HIV treatment today. However, the treatment landscape is evolving,” Jürgen Rockstroh, MD, professor of medicine and head of the HIV Outpatient Clinic at University Hospital Bonn in Germany, said in a news release.¹ “Long-acting therapies provide an alternative to daily pills. The ISLEND-1 study results show the potential of ISL/LEN as the first once-weekly oral single-tablet treatment option.”

In the double-blind ISLEND-1 trial, no participants (0%) who switched to ISL/LEN had HIV-1 RNA of 50 copies/mL or higher at week 48, compared with 0.3% of participants who remained on bictegravir/emtricitabine/tenofovir alafenamide (Biktarvy), as measured by the FDA-defined snapshot algorithm.¹

In the open-label ISLEND-2 trial, 0.3% of participants receiving ISL/LEN had HIV-1 RNA of 50 copies/mL or higher at week 48, versus 1.3% of those who remained on standard-of-care regimens that included integrase strand transfer inhibitors, boosted protease inhibitors, or nonnucleoside reverse transcriptase inhibitors. Both results met the trials' noninferiority thresholds.¹

“Single tablet regimens have transformed the outlook for millions of people living with HIV,” Amy Colson, research director at Community Resource Initiative and medical director of the Zinberg Clinic at Cambridge Health Alliance, said in the news release.¹ “Having a treatment option with once weekly dosing can expand choice to help address individual needs and preferences. The 48-week findings provide the evidence for ISL/LEN as the potential first once weekly oral treatment option to help support long-term treatment needs and be responsive to the preferences of people living with HIV.”

Participants who switched to ISL/LEN also reported higher treatment satisfaction and lower treatment burden than those on daily standard-of-care therapy, based on HIV Patient Perspective of Regimen Change outcomes reporting.¹

Safety Profile Comparable Across Trials

In the blinded ISLEND-1 trial, treatment-related adverse events occurred in 13.5% of participants on ISL/LEN and 13.2% of those on bictegravir/emtricitabine/tenofovir alafenamide, with nausea and headache (3% each) most common in both groups.¹

Serious adverse events occurred in 5.3% of the ISL/LEN group versus 4.6% of the comparator group, and discontinuations due to adverse events were low in both arms (2% vs 1.7%, respectively).¹

In the open-label ISLEND-2 trial, treatment-related adverse events were reported in 18% of participants on ISL/LEN, compared with fewer than 1% of those on standard-of-care regimens.¹

The most common events with ISL/LEN (occurring in 2% or more of participants) were headache (5%), nausea (3%), and diarrhea (3%). Discontinuations due to adverse events remained low in both groups (1% vs less than 1%).¹

Across both trials, CD4+ T-cell and lymphocyte counts stayed stable through week 48, and body weight showed no clinically meaningful difference between treatment groups. The companies reported no new safety concerns.¹

Pharmacist Considerations as Long-Acting Oral Options Expand

For pharmacists, the detailed dataset adds substance to the topline results announced in June, which first signaled the potential for a once weekly oral option to bridge the gap between daily pills and long-acting injectable therapies.²

Islatravir works through translocation inhibition and other reverse-transcriptase-related mechanisms, while lenacapavir, a first-in-class capsid inhibitor, disrupts HIV at multiple stages of its life cycle with no known cross-resistance to other existing drug classes in vitro.¹

The regimen remains investigational and is not approved for use by any regulatory authority. Both ISLEND trials specifically enrolled participants who were already virologically suppressed on a stable regimen for at least 6 months, underscoring that any future switch to ISL/LEN—if approved—would apply to patients already achieving suppression rather than those starting treatment.¹

For counseling, the distinction will matter because sustained viral suppression, whether on a daily or weekly regimen, is what prevents both disease progression and onward transmission of HIV. Public health guidance emphasizes that adherence remains the determining factor in maintaining an undetectable viral load, regardless of dosing frequency, and that interrupted therapy allows viral load to rebound.^3,4

As once weekly oral regimens move toward potential approval, pharmacists may play an increasing role in counseling patients on adherence expectations and monitoring schedules specific to less-frequent dosing intervals.

REFERENCES

1. Gilead Sciences, Inc.; Merck. Investigational once-weekly oral HIV treatment regimen of islatravir and lenacapavir maintained virological suppression in adults with HIV who switched antiretroviral therapy. News release. Gilead Sciences, Inc. July 21, 2026. Accessed July 22, 2026. https://www.gilead.com/news/news-details/2026/investigational-once-weekly-oral-hiv-treatment-regimen-of-islatravir-and-lenacapavir-maintained-virological-suppression-in-adults-with-hiv-who-switched-antiretroviral-therapy

2. Gallagher A. Once weekly oral HIV regimen maintains viral suppression. Drug Topics. June 9, 2026. Accessed July 22, 2026. https://www.drugtopics.com/view/once-weekly-oral-hiv-regimen-maintains-viral-suppression

3. Centers for Disease Control and Prevention. HIV treatment as prevention. HIV Partners. October 24, 2024. Accessed July 22, 2026. https://www.cdc.gov/hivpartners/php/hiv-treatment/index.html

4. National Institute of Allergy and Infectious Diseases. 10 things to know about HIV suppression. NIAID. Accessed July 22, 2026. https://www.niaid.nih.gov/diseases-conditions/10-things-know-about-hiv-suppression