Islatravir + Lenacapavir for HIV

Not currently recruiting at 52 trial locations

Overseen By Gilead Clinical Study Information Center

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Gilead Sciences

Must be taking: B/F/TAF

Must not be taking: Islatravir, Lenacapavir

Disqualifiers: Hepatitis B, Hepatitis C, others

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

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

Compensation: Varies

Number of Visits: Unknown

Duration: 48 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment for individuals living with HIV who have successfully controlled the virus with their current medication. It aims to evaluate the effectiveness of a weekly combination of two drugs, islatravir (ISL) and lenacapavir (LEN, also known as Sunlenca). Participants must have been on a specific HIV medication (B/F/TAF) for at least 24 weeks and have undetectable virus levels. The trial will test various methods of switching to this new combination to determine the most effective approach. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial requires participants to have been on bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) for at least 24 weeks before joining. It does not specify if you need to stop other medications, but you must not have used islatravir or lenacapavir before.

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

Research has shown that the combination of islatravir (ISL) and lenacapavir (LEN) is generally safe for people with HIV. In studies, most participants tolerated this combination well. For instance, over a 96-week period, only about 19.2% of participants experienced treatment-related side effects, which is relatively low for HIV treatments. One study found that after 48 weeks, the treatment effectively controlled the virus and was well tolerated, with side effects similar to other treatments.

These findings suggest that ISL and LEN are promising in terms of safety. However, as they remain under study, further research is needed to confirm these results. Participants considering joining a trial can find some reassurance in these findings, but ongoing research will continue to monitor for any new safety concerns. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Islatravir and Lenacapavir for HIV because these treatments offer a unique approach compared to current therapies like antiretroviral drugs. Islatravir works by inhibiting reverse transcriptase, an enzyme crucial for HIV replication, while Lenacapavir targets the HIV capsid protein, which plays a key role in the virus's life cycle. Together, they have the potential to provide more effective viral suppression with a simpler dosing regimen, possibly requiring fewer doses than traditional daily medications. This combination could lead to better adherence and improved outcomes for people living with HIV.

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

Research has shown that the combination of islatravir and lenacapavir appears promising for people with HIV. In this trial, participants in different arms will either receive islatravir and lenacapavir or switch from B/F/TAF to islatravir and lenacapavir after 48 weeks. One study found that taking this treatment once a week by mouth kept the virus under control for up to 96 weeks. Specifically, after 48 weeks, the treatment continued to maintain low virus levels. These results suggest that islatravir and lenacapavir could help manage HIV in people who already have the virus under control. This combination remains under study and is not yet approved, but the early results are encouraging. ^{1 2 4 5 6}

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 maintained a viral load of less than 50 copies/mL and have been on B/F/TAF treatment for at least 24 weeks. They shouldn't have had previous virologic failures, exposure to ISL or LEN, serious infections within the last month, hepatitis B or C co-infections, low kidney function or certain low blood cell counts.

Inclusion Criteria

Plasma HIV-1 RNA < 50 copies/mL at screening

My HIV-1 levels have been undetectable or very low for at least 24 weeks.

I have been on B/F/TAF medication for at least 24 weeks.

Exclusion Criteria

CD4+ T-cells < 200 cells/mm^3 (Cohort 1); CD4+ T-cells < 350 cells/mm^3 (cohort 2)

I have previously used or been exposed to islatravir or lenacapavir.

My kidney function is low, with a creatinine clearance of 30 mL/min or less.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive oral weekly islatravir in combination with lenacapavir for virologically suppressed people with HIV

48 weeks

Weekly visits for drug administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Open-label extension (optional)

Participants may opt into continuation of treatment long-term

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• B/F/TAF
• Islatravir
• Lenacapavir

Trial Overview The study tests the effectiveness of taking Islatravir (ISL) orally once a week combined with Lenacapavir (LEN) in those whose HIV is already under control. The goal is to see how well this combination works after 24 weeks compared to their current treatment.

How Is the Trial Designed?

Group I: Extension Phase Cohort 2 of ISL/LEN Fixed Dose Combination (FDC) Experimental Treatment 1 Intervention

After 48 Weeks of randomized treatment, all participants will be given an option to participate in an Extension Phase to receive ISL+LEN or ISL/LEN FDC tablet (when available) until ISL/LEN becomes available or until the sponsor elects to discontinue the study, whichever occurs first. Participants receiving ISL+LEN during the randomized phase will continue to take ISL + LEN weekly. Participants receiving B/F/TAF during the randomized phase will switch to ISL+LEN: * Day 1: LEN oral 600 mg (2 x 300 mg) and ISL 2 mg (2 x 1 mg) * Day 2: LEN only oral 600 mg (2 x 300 mg) * Day 8 and weekly thereafter (ie, every 7 days): LEN oral 300 mg (1 x 300 mg) and ISL 2 mg Participants who do not switch from B/F/TAF to ISL+LEN at Week 48 will be discontinued from the study. All participants in the extension phase will be transitioned to weekly ISL/LEN FDC (Dose A) tablet when it becomes available.

Group II: Cohort 2 (ISL+LEN) Experimental Treatment 2 Interventions

Participants will receive the following for at least 48 weeks * Day 1: LEN oral 600 mg (2 x 300 mg) and ISL 2 mg (2 x 1 mg) * Day 2: LEN only oral 600 mg (2 x 300 mg) * Day 8 and weekly thereafter (ie, every 7 days): LEN oral 300 mg (1 x 300 mg) and ISL 2 mg

Group III: Cohort 2 (B/F/TAF to ISL+LEN) Experimental Treatment 3 Interventions

Participants will receive B/F/TAF 50/200/25 mg once daily for at least 48 weeks.

Group IV: Cohort 1 (ISL+LEN) Experimental Treatment 2 Interventions

Participants will receive the following for at least 48 weeks: * Day 1 and Day 2: ISL 40 and LEN 600 mg * Day 8 and weekly thereafter (ie, every 7 days): ISL 20 mg and LEN 300 mg

Group V: Cohort 1 (B/F/TAF to ISL+LEN) Experimental Treatment 3 Interventions

Participants will receive bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) 50/200/25 mg once daily for at least 48 weeks After 48 weeks, participants will switch from B/F/TAF to ISL+LEN * ISL 40 and LEN 600 mg on Day 1 and Day 2 * ISL 20 mg and LEN 300 mg weekly Participants who do not switch from B/F/TAF to ISL+LEN at Week 48 will be discontinued from the study.

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

A phase-I clinical trial involving 48 healthy Chinese subjects demonstrated that the generic version of sunitinib is bioequivalent to the original Sutent®, with pharmacokinetic parameters falling within the acceptable range for bioequivalence.

Both sunitinib and Sutent® exhibited comparable safety profiles, supporting the use of generic sunitinib as a viable alternative treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and bioequivalence of sunitinib and Sutent&#174; in Chinese healthy subjects: an open-label, randomized, crossover study. Wang, Y., Deng, Q., Gao, Z., et al.[2023]

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]

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]

Lenacapavir is the first FDA-approved capsid inhibitor for treating multidrug-resistant HIV-1, specifically for heavily treatment-experienced adults whose current therapies are failing due to resistance or safety issues.

In a phase 3 clinical trial, lenacapavir significantly reduced viral load compared to placebo, and it is administered as a long-acting injection every 6 months, although 63% of participants experienced injection site reactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenacapavir: A first-in-class capsid inhibitor for the treatment of highly treatment-resistant HIV. Prather, C., Lee, A., Yen, C.[2023]

Citations

1. eatg.org eatg.org/hiv-news/eacs-2025-weekly-oral-hiv-treatment-looks-good-at-two-years/

EACS 2025: Weekly oral HIV treatment looks good at two ... A once-weekly combination of lenacapavir and islatravir pills maintained viral suppression for 96 weeks.

2. 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 ...

3. merck.com merck.com/news/merck-to-present-new-data-from-hiv-treatment-and-prevention-pipeline-at-european-aids-conference-2025/

Merck to Present New Data from HIV Treatment and ... Patient-Reported Outcomes From People With HIV-1 Receiving Once-Weekly Oral Islatravir in Combination With Lenacapavir: Phase 2 Week 48 Results.

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. 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 ... Oral weekly islatravir plus lenacapavir in virologically suppressed people With HIV-1: 96 week outcomes from a phase 2 study. PS15.5.LB ...

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

577. Week 48 Results of a Phase 2 Study Evaluating Once- ... Oral weekly ISL + LEN maintained high rates of viral suppression at W48 and was well tolerated. There were no statistically significant between- ...