Islatravir + Lenacapavir for HIV

(ISLEND-1 Trial)

Not currently recruiting at 125 trial locations

Overseen By Gilead Clinical Study Information Center

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Gilead Sciences

Must be taking: B/F/TAF

Must not be taking: ISL, LEN

Disqualifiers: Virologic failure, Active infections, Hepatitis B, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new once-a-week pill combining islatravir and lenacapavir for people living with HIV. Researchers aim to determine if this weekly regimen is as safe and effective as the current daily treatment of bictegravir, emtricitabine, and tenofovir alafenamide. Participants must have been on the existing daily treatment for at least six months and have very low HIV levels (less than 50 copies/mL). As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to the development of a potentially groundbreaking treatment.

Will I have to stop taking my current medications?

The trial requires participants to switch from their current HIV medication (B/F/TAF) to the new study medication (ISL/LEN) if they choose to participate. You will need to stop taking B/F/TAF and start the new regimen.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the combination of islatravir and lenacapavir is generally well-tolerated by people with HIV. In earlier studies, most participants maintained low virus levels in their blood, and their CD4+ T-cells, crucial for a healthy immune system, did not significantly decrease.

At Week 24 of one study, 94.2% of participants using islatravir and lenacapavir successfully suppressed the virus, similar to those on standard treatments. This suggests the new treatment works as well as current options.

The studies did not identify any major safety issues, indicating this treatment might be safe for people. However, individual experiences can differ, so participants should discuss any concerns with their healthcare provider. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for HIV?

Researchers are excited about the combination of Islatravir and Lenacapavir for treating HIV because it introduces a novel way to combat the virus. Unlike traditional daily regimens, which often include a combination of reverse transcriptase inhibitors and integrase inhibitors, this treatment uses Islatravir, a nucleoside reverse transcriptase translocation inhibitor, and Lenacapavir, a capsid inhibitor. This unique approach not only targets the virus differently but also allows for a more flexible dosing schedule, with once-weekly administration. This could significantly enhance adherence and quality of life for patients, making it a promising option in HIV management.

What evidence suggests that this trial's treatments could be effective for HIV?

Research has shown that the combination of islatravir and lenacapavir holds promise for treating HIV. In this trial, participants in the blinded phase will receive either ISL/LEN with a placebo-to-match B/F/TAF or PTM ISL/LEN with B/F/TAF. After 48 weeks, 94.2% of participants who switched to this treatment maintained very low HIV levels. Remarkably, after 96 weeks, all participants on this combination had undetectable virus levels, indicating well-controlled HIV. This once-a-week pill has proven safe and effective in suppressing the virus over time. ^{4 6 7 8 9}

Who Is on the Research Team?

Gilead Study Director

Principal Investigator

Gilead Sciences

Are You a Good Fit for This Trial?

This trial is for people with HIV who have had low virus levels (<50 copies/mL) for at least 6 months while on B/F/TAF treatment. They must be willing to continue their current treatment until the start of the study and, if they can become pregnant, agree to use certain birth control methods.

Inclusion Criteria

My HIV viral load is under 50 copies/mL.

I have been on B/F/TAF for at least 6 months and can continue it.

My HIV-1 level was below 50 copies/mL before the last 24 weeks.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Blinded Phase

Participants receive either ISL/LEN with PTM B/F/TAF or PTM ISL/LEN with B/F/TAF for 96 weeks

96 weeks

Open-label Extension

Participants may opt into continuation of ISL/LEN treatment until it becomes available or the study is discontinued

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Islatravir/Lenacapavir

Trial Overview The study compares a once-weekly oral tablet regimen of islatravir/lenacapavir (ISL/LEN) against continuing the standard daily bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF). The main goal is to see if switching treatments maintains low HIV levels after 48 weeks.

How Is the Trial Designed?

Group I: Open- Label Extension (OLE) Phase Experimental Treatment 1 Intervention

After the end of Blinded Phase at Week 96, if safety and efficacy of ISL/LEN are demonstrated following review of unblinded data, all participants will be given an option to enter the open-label extension phase to receive ISL/LEN in an extension phase until ISL/LEN becomes available or until the sponsor elects to discontinue the study, whichever occurs first. Participants receiving ISL/LEN and PTM B/F/TAF during the blinded phase will continue to take ISL/LEN weekly. Participants receiving B/F/TAF and PTM ISL/LEN during the blinded phase will take an initial dose of ISL/LEN (Dose A), followed by once weekly ISL/LEN (Dose B) from Day 8 onwards.

Group II: Blinded Phase: PTM ISL/LEN + B/F/TAF Experimental Treatment 2 Interventions

Participants will receive an initial dose of PTM ISL/LEN (Dose A), followed by once weekly PTM ISL/LEN (Dose B) from Day 8 onwards up to Week 96. Participants will also receive B/F/TAF (50/200/25 mg) once daily up from Day 1 up to Week 96.

Group III: Blinded Phase: ISL/LEN + Placebo-to-Match (PTM) B/F/TAF Experimental Treatment 2 Interventions

Participants will receive an initial dose of ISL/LEN (Dose A), followed by once weekly ISL/LEN (Dose B) from Day 8 onwards up to Week 96. Participants will also receive PTM B/F/TAF once daily from Day 1 up to Week 96.

Islatravir/Lenacapavir is already approved in European Union, United States for the following indications:

Approved in European Union as Sunlenca for:

• HIV-1 infection in heavily treatment-experienced patients with multi-drug resistance

Approved in United States as Sunlenca for:

• HIV-1 infection in heavily treatment-experienced patients with multi-drug resistance

Who Is Running the Clinical Trial?

Gilead Sciences

Lead Sponsor

Trials

1,150

Recruited

878,000+

Daniel O'Day

Gilead Sciences

Chief Executive Officer since 2019

MBA from Columbia University

Dietmar Berger

Gilead Sciences

Chief Medical Officer

MD and PhD from Albert-Ludwigs University School of Medicine

Merck Sharp & Dohme LLC

Industry Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Published Research Related to This Trial

Islatravir, a new treatment for HIV-1, was found to be generally well tolerated in a phase 1b trial with 30 treatment-naive adults, showing that it can significantly reduce HIV-1 RNA levels by more than 1.0 log after just 7 days, even at low doses of 0.5 mg.

The study demonstrated that islatravir has a long intracellular half-life of 78.5-128.0 hours, which may contribute to its prolonged effects against the virus, and no serious adverse events or signs of viral resistance were reported, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, pharmacokinetics, and antiretroviral activity of islatravir (ISL, MK-8591), a novel nucleoside reverse transcriptase translocation inhibitor, following single-dose administration to treatment-naive adults infected with HIV-1: an open-label, phase 1b, consecutive-panel trial. Schürmann, D., Rudd, DJ., Zhang, S., et al.[2020]

Islatravir (MK-8591) was found to be generally well-tolerated in two Phase 1 trials involving 32 participants, with no serious adverse events reported, indicating a favorable safety profile for this potential HIV treatment.

The pharmacokinetics of islatravir showed rapid absorption and a long half-life, with intracellular levels of its active form comparable to those associated with efficacy in preclinical studies, supporting its potential effectiveness in treating and preventing HIV-1.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, tolerability, and pharmacokinetics of single- and multiple-dose administration of islatravir (MK-8591) in adults without HIV. Matthews, RP., Ankrom, W., Friedman, E., et al.[2022]

Islatravir, a novel nucleoside analog for HIV treatment and prevention, demonstrated potent antiviral activity with a long intracellular half-life, achieving therapeutic concentrations in both plasma and tissue after daily administration for up to 6 weeks.

The study involving 36 adults showed that islatravir was generally well tolerated at doses up to 5 mg, with effective levels of its active form (ISL-TP) reached after just one dose, indicating its potential for effective HIV treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Pharmacokinetics of Once-Daily Multiple-Dose Administration of Islatravir in Adults Without HIV. Matthews, RP., Jackson Rudd, D., Zhang, S., et al.[2023]

Lenacapavir (LEN) is a novel capsid inhibitor that offers a unique treatment option for heavily treatment-experienced (HTE) HIV-1 patients, demonstrating efficacy in achieving viral suppression and immune restoration when combined with other antiretrovirals.

Administered subcutaneously twice a year, lenacapavir provides a convenient dosing schedule, making it a well-tolerated and effective addition to existing HIV treatment regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenacapavir: A Novel Long-Acting Capsid Inhibitor for HIV. Tailor, MW., Chahine, EB., Koren, D., et al.[2023]

Lenacapavir (LEN) is the first HIV-1 capsid inhibitor approved for multidrug-resistant HIV-1 infection, showing efficacy with a low level of drug-related mutations and no cross-resistance to other anti-HIV drugs.

LEN can be administered as a long-acting treatment, making it suitable for patients with limited access to healthcare, and it has demonstrated potential for synergistic effects when combined with other anti-HIV medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Highlights on the Development, Related Patents, and Prospects of Lenacapavir: The First-in-Class HIV-1 Capsid Inhibitor for the Treatment of Multi-Drug-Resistant HIV-1 Infection. Dzinamarira, T., Almehmadi, M., Alsaiari, AA., et al.[2023]

In the CAPELLA study, lenacapavir (LEN) combined with an optimized background regimen (OBR) achieved viral suppression in 81% of heavily treatment-experienced individuals with multidrug-resistant HIV after 26 weeks, demonstrating its efficacy in a challenging patient population.

However, resistance mutations to lenacapavir were observed in 8 participants, indicating that using LEN as an unintended monotherapy can lead to the development of resistance, highlighting the importance of proper treatment adherence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Resistance Analyses in Highly Treatment-Experienced People With Human Immunodeficiency Virus (HIV) Treated With the Novel Capsid HIV Inhibitor Lenacapavir. Margot, NA., Naik, V., VanderVeen, L., et al.[2022]

In a study involving 24 adult participants, the coadministration of islatravir and doravirine did not significantly affect the pharmacokinetics of either drug, indicating that they can be safely combined without altering their effectiveness.

All treatment regimens were well tolerated, suggesting that islatravir and doravirine can be further investigated together for the treatment of HIV-1 infection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase 1 Study to Evaluate the Drug Interaction Between Islatravir (MK-8591) and Doravirine in Adults Without HIV. Matthews, RP., Jackson Rudd, D., Fillgrove, KL., et al.[2021]

In a phase 2b trial involving 121 treatment-naive participants, islatravir combined with doravirine maintained HIV-1 RNA levels below 50 copies per milliliter in 81.1% of participants over 96 weeks, demonstrating its efficacy in viral suppression.

The safety profile of islatravir was favorable, with only 7.8% of participants experiencing drug-related adverse events, compared to 22.6% in the DOR/3TC/TDF group, indicating better tolerability for the islatravir regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brief Report: Efficacy and Safety of Oral Islatravir Once Daily in Combination With Doravirine Through 96 Weeks for Treatment-Naive Adults With HIV-1 Infection Receiving Initial Treatment With Islatravir, Doravirine, and Lamivudine. Molina, JM., Yazdanpanah, Y., Afani Saud, A., et al.[2023]

Citations

1. gilead.com gilead.com/news/news-details/2025/gilead-presents-new-hiv-research-data-at-eacs-2025--driving-scientific-innovation-in-treatment-and-prevention

Gilead Presents New HIV Research Data at EACS 2025 The combination of islatravir and lenacapavir is investigational. Use in combination for the treatment of HIV has not been approved by any regulatory authority.

2. eatg.org eatg.org/hiv-news/eacs-2025-once-weekly-hiv-pill-maintains-viral-suppression-for-96-weeks/

EACS 2025: Once-weekly HIV pill maintains viral ... At 96 weeks, all participants on the islatravir-lenacapavir combination maintained undetectable viral loads, and mean adherence-assessed by pill ...

3. merck.com merck.com/news/gilead-and-merck-announce-phase-2-data-showing-a-treatment-switch-to-an-investigational-oral-once-weekly-combination-regimen-of-islatravir-and-lenacapavir-maintained-viral-suppression-in-adults-at-wee/

Gilead and Merck Announce Phase 2 Data Showing a ... At 48 weeks, the novel investigational combination maintained a high rate (n=49; 94.2%) of viral suppression (HIV-1 RNA <50 copies/mL) in ...

4. hivglasgow.org hivglasgow.org/once-weekly-combination-of-islatravir-and-lenacapavir-safe-and-effective-in-48-week-study/

Once-weekly combination of islatravir and lenacapavir safe ... A once-weekly oral combination of two investigational antiretrovirals, islatravir and lenacapavir, maintained high rates of viral suppression 48 weeks after a ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT05052996?tab=results

Study Evaluating the Safety and Efficacy of Islatravir in ... Study Evaluating the Safety and Efficacy of Islatravir in Combination With Lenacapavir in Virologically Suppressed People With HIV. ClinicalTrials.gov ID ...

6. gilead.com gilead.com/news/news-details/2024/gilead-and-merck-announce-phase-2-data-showing-an-investigational-oral-once-weekly-combination-regimen-of-islatravir-and-lenacapavir-maintained-viral-suppression-at-week-24

Gilead and Merck Announce Phase 2 Data Showing an ... Results of the primary endpoint (HIV-1 RNA ≥50 copies/mL (c/mL) showed that one participant (1.9%) treated with islatravir and lenacapavir had a viral load of > ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11777299/

577. Week 48 Results of a Phase 2 Study Evaluating Once- ... Weekly oral ISL 2 mg + LEN 300 mg maintained high rates of viral suppression (HIV-1 RNA < 50 copies/mL) with no clinically relevant decreases in CD4+ T-cells ...

8. gileadclinicaltrials.com gileadclinicaltrials.com/study?id=GS-US-563-6041

Study Evaluating the Safety and Efficacy of Islatravir in ... The primary objective of this study is to evaluate the efficacy of oral weekly islatravir (ISL) in combination with lenacapavir (LEN) in virologically ...

9. askgileadmedical.com askgileadmedical.com/docs/sunlenca/lenacapavir-investigational-use-with-islatravir

For HCP's | Lenacapavir Investigational Use with Islatravir Results. At Week 24, 94.2% of participants in both the ISL + LEN and BIC/FTC/TAF groups achieved HIV-1 RNA ...