AIDS 2026: Long-Acting Weekly Oral HIV Therapy Advances Toward Regulatory Review

A once-weekly oral HIV treatment regimen could soon offer people living with HIV a new alternative to daily antiretroviral therapy, according to late-breaking phase 3 data presented at the 26th International AIDS Society Conference on HIV Science (AIDS 2026) in Rio de Janeiro, Brazil.

Gilead Sciences and Merck announced positive results from the ISLEND-1 and ISLEND-2 phase 3 clinical trials evaluating an investigational once-weekly single-tablet regimen combining islatravir (ISL) 2 mg and lenacapavir (LEN) 300 mg in adults with virologically suppressed HIV-1. The regimen has the potential to become the first approved long-acting oral HIV treatment requiring just one dose per week.

Both studies demonstrated that participants who switched from daily oral antiretroviral therapy maintained virologic suppression through 48 weeks, at rates comparable to those of participants receiving standard daily regimens.

ISLEND-1 demonstrates noninferiority to BIKTARVY

The ISLEND-1 trial evaluated adults who switched from BIKTARVY (bictegravir/emtricitabine/tenofovir alafenamide) to once-weekly ISL/LEN.

At Week 48, investigators found the investigational regimen was statistically noninferior to continuing BIKTARVY. None (0%) of the participants who switched to ISL/LEN had HIV-1 RNA levels of 50 copies/mL or greater, compared with 0.3% of participants who remained on BIKTARVY, according to the US FDA's snapshot analysis.

Jürgen Rockstroh, MD, PhD, professor of medicine and head of the HIV Outpatient Clinic at University Hospital Bonn in Germany and primary investigator for ISLEND-1, emphasized both the clinical performance and the potential impact on patient choice.

"People living with HIV have shown strong interest in having more treatment options, including long-acting oral regimens. In the ISLEND-1 trial, switching to once-weekly oral ISL/LEN was well tolerated and maintained high rates of viral suppression. The effectiveness of the investigational combination regimen was comparable to B/F/TAF, and no treatment-emergent resistance to ISL/LEN has been seen so far. The Phase 3 results presented at AIDS 2026 and published in The New England Journal of Medicine provide strong evidence for the potential of ISL/LEN to be the first and only once-weekly oral HIV treatment option, expanding choice with a longer dosing interval that may better fit the different needs and preferences of people living with HIV."

ISLEND-2 supports switching from multiple daily regimens

The companion phase 3 ISLEND-2 trial evaluated adults with virologically suppressed HIV who switched from a variety of standard daily oral antiretroviral therapies.

Results mirrored those seen in ISLEND-1. At Week 48, the once-weekly regimen met the primary end point of statistical noninferiority. Only 0.3% of participants receiving ISL/LEN had HIV-1 RNA levels of at least 50 copies/mL compared with 1.3% of participants who continued their baseline daily therapies.

Beyond maintaining viral suppression, investigators also found that participants reported greater satisfaction with the weekly regimen. According to HIV Patient Perspective of Regimen Change assessments, most participants who switched to ISL/LEN considered the once-weekly regimen less burdensome than taking daily antiretroviral medications.

Amy Colson, MD, MPH, Medical Director of the Zinberg Clinic at Cambridge Health Alliance and primary investigator for ISLEND-2, highlighted the potential quality-of-life benefits.

"The findings in the ISLEND-2 trial represent an important advance in HIV treatment. The results show that the once-weekly oral single tablet regimen of islatravir and lenacapavir maintains virologic suppression as effectively as contemporary daily oral regimens in people with well-controlled HIV-1. A once-weekly regimen has the potential to provide enhanced privacy and greater flexibility in everyday life and to reduce daily reminders of HIV status."

Expanding treatment choice

Although modern daily antiretroviral therapy has transformed HIV into a manageable chronic condition for many patients, investigators note that treatment preferences vary considerably. Less frequent dosing may help some individuals better integrate therapy into their daily lives while reducing treatment burden.

Long-acting injectable therapies have already demonstrated that many patients value alternatives to daily pills. If approved, ISL/LEN would introduce another option by offering long-acting treatment without injections, requiring only one oral dose each week.

The findings also reinforce continued innovation in HIV care, where treatment decisions increasingly incorporate patient preferences alongside efficacy and safety.

Looking ahead

The ISLEND-1 and ISLEND-2 findings were featured during the AIDS 2026 press program and presented as late-breaking oral abstracts during the conference. The Phase 3 data were also published simultaneously in The New England Journal of Medicine.

Gilead and Merck announced they plan to include these findings in upcoming regulatory submissions. If approved, the once-weekly islatravir/lenacapavir regimen would become the first long-acting oral HIV treatment for adults with virologically suppressed HIV, offering a new option that combines durable viral suppression with a simplified weekly dosing schedule.