Once Weekly Oral HIV Regimen Maintains Viral Suppression

Gilead Sciences and Merck announced positive topline results from 2 phase 3 clinical trials, ISLEND-1 (NCT06630286) and ISLEND-2 (NCT06630299), evaluating an investigational oral once-weekly combination of islatravir and lenacapavir. This novel treatment regimen met its primary efficacy end points at week 48, demonstrating that it is as effective as daily antiretroviral therapy for maintaining viral suppression in people living with HIV.¹

For pharmacists, these results represent a potential shift toward long-acting oral therapies that could simplify treatment adherence and offer patients greater discretion and flexibility.

“Long-acting oral therapies represent a new wave of transformational innovation in HIV drug development, with the potential to reshape the landscape of care,” Jared Baeten, MD, PhD, senior vice president of clinical development and virology therapeutic area head at Gilead Sciences, said in a news release.¹ “Innovative oral HIV treatment options that allow for less frequent dosing may make a meaningful difference in the lives of people living with the virus, potentially offering more flexibility and discretion”.

The investigational regimen combines islatravir, a next-generation nucleoside analog with multiple mechanisms of action, including translocation inhibition, with lenacapavir, a first-in-class capsid inhibitor. Lenacapavir is designed to inhibit HIV at multiple stages of its lifecycle and has no known cross-resistance to other existing drug classes in vitro. The unique pharmacokinetic profiles of both agents enable them to remain potent enough for once-weekly oral dosing, distinguishing them from current daily oral treatments.¹

In the double-blind ISLEND-1 trial, the once-weekly single-tablet regimen of islatravir/lenacapavir was found to be statistically noninferior to Biktarvy in virologically suppressed participants. Simultaneously, the open-label ISLEND-2 trial showed the regimen was noninferior to a variety of daily standard-of-care antiretroviral regimens, which included integrase strand transfer inhibitors, boosted protease inhibitors, and nonnucleoside reverse transcriptase inhibitors. The primary efficacy end point for both trials was based on the percentage of participants with HIV-1 RNA levels of 50 copies per milliliter or higher at week 48, using the FDA snapshot algorithm.^1-3

The safety profile of the islatravir/lenacapavir combination was generally comparable to the comparator daily regimens in both trials, and no new safety concerns were identified during the study period. Current long-acting HIV treatments are predominantly injectable medications administered by health care providers at intervals ranging from every 2 weeks to every 6 months, so a once-weekly oral option would bridge the gap between traditional daily pills and clinical injections.^1,4

Although these results are promising, pharmacists should be aware that the islatravir and lenacapavir combination remains investigational and is not yet approved for use by regulatory authorities. Current clinical guidelines emphasize that switching HIV treatment should only occur after careful consultation, as inappropriate switches can lead to drug resistance. Eligibility for the ISLEND trials specifically required participants to be virologically suppressed on a stable regimen for at least 6 months prior to screening, with no history of virologic failure.^1-4

As the landscape of HIV care evolves, Gilead and Merck have stated their intention to file the phase 3 data with global regulatory authorities and present detailed findings at future scientific congresses. This development reflects a broader industry trend toward transformational innovation, aimed at ensuring that people living with HIV are not defined by their condition and have access to treatment options that align with their individual lifestyles and preferences.¹

For the pharmacy community, the potential approval of the first once-weekly oral regimen would add a tool to the antiretroviral arsenal, further transforming HIV into a manageable chronic condition.

“These results underscore the shared focus and commitment that we and our collaborators at Gilead have on continuing research to help people living with HIV,” Eliav Barr, MD, senior vice president, head of global clinical development, and chief medical officer for Merck Research Laboratories, said in the news release.¹ “By advancing this investigational novel once-weekly oral regimen of islatravir and lenacapavir, we aim to bring forward a new long-acting oral option that, if approved, would represent the first of its kind with less frequent dosing and further expand options for people living with HIV.”

READ MORE: HIV Resource Center

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REFERENCES

1. Gilead and Merck announce positive topline results from 2 phase 3 studies evaluating islatravir/lenacapavir, an oral once-weekly HIV treatment. News release. Merck. June 8, 2026. June 9, 2026. https://www.merck.com/news/gilead-and-merck-announce-positive-topline-results-from-two-phase-3-studies-evaluating-islatravir-lenacapavir-an-oral-once-weekly-hiv-treatment/

2. Study to compare an oral weekly islatravir/​lenacapavir regimen with bictegravir/​emtricitabine/​tenofovir alafenamide in virologically suppressed people with HIV-1 (ISLEND-1). ClinicalTrials.gov identification: NCT06630286. Updated April 30, 2026. Accessed June 9, 2026. https://clinicaltrials.gov/study/NCT06630286

3. Study to compare an oral weekly islatravir/​lenacapavir regimen with standard of care in virologically suppressed people with HIV-1 (ISLEND-2). ClinicalTrials.gov identification: NCT06630299. Updated May 29, 2026. Accessed June 9, 2026. https://clinicaltrials.gov/study/NCT06630299

4. Long-acting HIV medicine. HIVinfo.NIH.gov. April 17, 2026. Accessed June 9, 2026. https://hivinfo.nih.gov/understanding-hiv/fact-sheets/long-acting-hiv-medicine