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ISL/LEN

Phase 3

HIV-1-infection | Small molecule | Infectious Disease |Gilead Sciences, Inc.|Last Updated: May 29, 2026

Target and mechanism

ModalitySmall molecule

Also known as ISL

Success Probability

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Market & Valuation

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Trial Design

RandomizedDouble-BlindCONTROLLEDDMC
Total Trials2
Total Enrollment1,209

FDA Designations

No designations recorded

Clinical trial landscape

ISL/LEN · 2 trials · 1 indication

Phase 3 2
NCT06630286Study to Compare an Oral Weekly Islatravir/Lenacapavir Regimen With Bictegravir/Emtricitabine/Tenofovir Alafenamide in Virologically Suppressed People With HIV-1HIV-1-infection
ACTIVE NOT_RECRUITING609 Analytics
NCT06630299Study to Compare an Oral Weekly Islatravir/Lenacapavir Regimen With Standard of Care in Virologically Suppressed People With HIV-1HIV-1-Infection
ACTIVE NOT_RECRUITING600 Analytics
PHASE3ACTIVE NOT_RECRUITING
Study to Compare an Oral Weekly Islatravir/Lenacapavir Regimen With Bictegravir/Emtricitabine/Tenofovir Alafenamide in Virologically Suppressed People With HIV-1
HIV-1-infectionUnlock trial analytics
PHASE3ACTIVE NOT_RECRUITING
Study to Compare an Oral Weekly Islatravir/Lenacapavir Regimen With Standard of Care in Virologically Suppressed People With HIV-1
HIV-1-InfectionUnlock trial analytics

Study Endpoints

Primary Endpoints

Proportion of Participants with HIV-1 RNA ≥ 50 Copies/mL at Week 48 as Determined by the United States (US) Food and Drug Administration (FDA)-Defined Snapshot Algorithm
Week 48

Secondary Endpoints

Proportion of Participants With HIV-1 RNA ≥ 50 Copies/mL at Week 96 as Determined by the US FDA-Defined Snapshot Algorithm
Week 96
Proportion of Participants with HIV-1 RNA < 50 Copies/mL at Weeks 48 as Determined by the US FDA-Defined Snapshot Algorithm
Week 48
Proportion of Participants with HIV-1 RNA < 50 Copies/mL at Weeks 96 as Determined by the US FDA-Defined Snapshot Algorithm
Week 96
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Study Design & Arms

AllocationRANDOMIZED
MaskingDOUBLE
ModelPARALLEL
PurposeTREATMENT

Treatment Arms

ArmTypeDescription
Blinded Phase: ISL/LEN + Placebo-to-Match (PTM) B/F/TAFEXPERIMENTALParticipants 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.
Blinded Phase: PTM ISL/LEN + B/F/TAFEXPERIMENTALParticipants 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.
Open- Label Extension (OLE) PhaseEXPERIMENTALAfter 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.
ISL/LENEXPERIMENTALParticipants 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.
Standard of Care TreatmentACTIVE_COMPARATORParticipants will continue standard of care treatment with 2-3 ARVs up to Week 96: * Integrase Strand Transfer Inhibitor (INSTI) class: INSTI combined with 1 or 2 nucleoside reverse transcriptase inhibitors (NRTIs; bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF; coformulated; Biktarvy®), dolutegravir (DTG)/abacavir (ABC)/lamivudine (3TC), DTG+ TAF or TDF (TXF)/emtricitabine (FTC; Emtriva®), DTG/tenofovir disoproxil fumarate (TDF; Viread®)/3TC, DTG/3TC, raltegravir (RAL) + TXF/FTC, RAL+TDF/3TC, elvitegravir (EVG; Vitekta®)/cobicistat (c; Tybost®)/TXF/FTC), or * PI class: Boosted protease inhibitor (PI) combined with 2 NRTIs (darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF; coformulated), boosted darunavir (DRV)+TXF/FTC, boosted DRV+TDF/3TC), or * NNRTI class: Nonnucleoside reverse transcriptase inhibitor (NNRTI) combined with 2 NRTIs (doravirine (DOR)/TDF/3TC, DOR+TXF/FTC, DOR+TDF/3TC, rilpivirine (RPV)/TXF/FTC, RPV+TXF/FTC, RPV+TDF/3TC)
Extension PhaseEXPERIMENTALAt the end of randomized treatment visit, if safety and efficacy of ISL/LEN are demonstrated following review of randomized data, participants will be given the option to receive ISL/LEN tablets 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 during the randomized phase will continue to take ISL/LEN weekly. Participants receiving standard of care during the randomized phase will take an initial dose of ISL/LEN (Dose A), followed by once weekly ISL/LEN (Dose B) from Day 8 onwards.

Interventions

NameTypeDescription
ISL/LENDRUGTablet administered orally
B/F/TAFDRUGTablet administered orally
PTM B/F/TAFDRUGTablet administered orally
PTM ISL/LENDRUGTablet administered orally
Antiretroviral CombinationsDRUG2 or 3 antiretrovirals (ARVs) administered as defined by the investigator, according to the prescribing information.
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Eligibility Criteria

Age Range18 Years to N/A
SexALL
Healthy VolunteersNo
Study Sites106

Key Inclusion Criteria: * HIV-1 RNA \< 50 copies/mL for ≥ 6 months before screening, as documented by: 1. One HIV-1 RNA \< 50 copies/mL immediately preceding the 24 week period prior to screening. 2. Within 24 weeks prior to screening, if HIV-1 RNA results are available, all levels must be \< ...

Countries:United StatesArgentinaAustraliaCanadaFranceGermanyJapanPuerto RicoSpainSwitzerlandTaiwanUnited KingdomNetherlandsPolandSouth AfricaThailand
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Frequently asked questions about ISL/LEN

What is ISL used for in HIV-1 infection?

ISL, also known as ISL/LEN, is an investigational small molecule being developed for the treatment of HIV-1 infection. It is studied as a combination regimen with lenacapavir for virologically suppressed people with HIV-1. The drug is currently in Phase 2 and Phase 3 clinical trials.

What does ISL target?

ISL is a small molecule antiviral that targets HIV-1. It is being studied in combination with lenacapavir as an oral weekly regimen for the treatment of HIV-1 infection. The combination is intended to maintain viral suppression in people living with HIV-1.

Who makes ISL?

ISL is being developed by Gilead Sciences, Inc., a biopharmaceutical company traded on NASDAQ under the ticker GILD. Gilead is conducting clinical trials to evaluate the safety and efficacy of ISL in combination with lenacapavir for the treatment of HIV-1 infection.

What phase is ISL in?

ISL is in Phase 2 and Phase 3 clinical development. It is an investigational drug and has not been approved by regulatory authorities. The ongoing trials are evaluating its safety and efficacy as part of an oral weekly regimen for virologically suppressed people with HIV-1.

What clinical trials is ISL in?

ISL is being studied in three active clinical trials. NCT05052996 is a Phase 2 trial evaluating islatravir with lenacapavir in 142 participants. NCT06630286 and NCT06630299 are Phase 3 trials comparing the oral weekly regimen with standard of care in over 1,200 participants across multiple countries.

Is ISL the same as ISL/LEN?

Yes, ISL is also known as ISL/LEN. The name ISL/LEN refers to the combination of islatravir and lenacapavir, which is being studied as an oral weekly regimen for the treatment of HIV-1 infection. The drug is being developed by Gilead Sciences.