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ISL

Phase 3

HIV-1 Infection | Small molecule | Infectious Disease |Merck & Company, Inc.|Last Updated: Aug 10, 2026

Success Probability

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Trial Design

RandomizedDouble-BlindPLACEBO_CONTROLLEDDMC
Total Trials1
Total Enrollment35

FDA Designations

No designations recorded

Clinical trial landscape

ISL · 3 trials · 2 indications

Phase 3 1Phase 2 2
NCT04233216Doravirine/Islatravir (DOR/ISL) in Heavily Treatment-Experienced (HTE) Participants for Human Immunodeficiency Virus Type 1 (HIV-1) Infection (MK-8591A-019)HIV-1 Infection
COMPLETED35 Analytics
PHASE3COMPLETED
Doravirine/Islatravir (DOR/ISL) in Heavily Treatment-Experienced (HTE) Participants for Human Immunodeficiency Virus Type 1 (HIV-1) Infection (MK-8591A-019)
HIV-1 InfectionUnlock trial analytics

Study Endpoints

Primary Endpoints

Percentage of Participants Receiving Doravirine/Islatravir (DOR/ISL) With ≥0.5 log10 Change From Day 1 Baseline to Day 8 in Human Immunodeficiency Virus Type 1 (HIV-1) Ribonucleic Acid (RNA) Compared to Placebo Treatment
Day 1 (baseline) and Day 8

Participants with a ≥0.5 log10 decrease from Day 1 baseline to Day 8 in HIV-1 RNA were identified by the central laboratory with an Abbott Real Time Polymerase Chain Reaction (PCR) assay which has a lower limit of detection (LLOD) of 40 copies/mL Only participants treated with DOR/ISL FDC or placebo were analyzed in this outcome measure.

Percentage of Participants With ≥1 AEs Through Week 49
Up to 49 weeks

An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.

Percentage of Participants Withdrawing From Study Treatment Due to AE(s) Through Week 25
Up to 25 weeks

An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.

Percentage of Participants With ≥1 Adverse Events (AEs) Through Week 25
Up to 25 weeks

An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.

Percentage of Participants Withdrawing From Study Treatment Due to AE(s) Through Week 49
Up to 49 weeks

An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.

Phase 2: Percentage of Participants With Human Immunodeficiency Virus Type 1 (HIV-1) Ribonucleic Acid (RNA) <50 Copies/mL at Week 24
Week 24

Plasma HIV-1 ribonucleic acid (RNA) quantification will be performed at the central laboratory using a polymerase chain reaction (PCR) assay. Percentage of participants with HIV-1 RNA \<50 copies/mL will be reported at week 24.

Phase 2: Percentage of Participants Who Experience an Adverse Event (AE) at Week 24
Week 24

An AE is defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment.

Phase 2: Percentage of Participants Who Discontinue Study Intervention Due to an AE at Week 24
Week 24

An AE is defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment.

Phase 3: Percentage of Participants With HIV-1 RNA <50 Copies/mL at Week 48
Week 48

Plasma HIV-1 RNA quantification will be performed at the central laboratory using a PCR assay. Percentage of participants with HIV-1 RNA \<50 copies/mL will be reported at week 48.

Phase 3: Percentage of Participants Who Experience an AE at Week 48
Week 48

An AE is defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment.

Phase 3: Percentage of Participants Who Discontinue Study Intervention Due to an AE at Week 48
Week 48

An AE is defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment.

Percentage of Participants With HIV-1 RNA ≥50 copies/mL at Week 24
Week 24

Plasma HIV-1 ribonucleic acid (RNA) quantification will be performed at the central laboratory using a polymerase chain reaction (PCR) assay. Percentage of participants with HIV-1 RNA ≥50 copies/mL will be reported at week 24.

Percentage of Participants who Experience an Adverse Event (AE)
Up to ~ 96 weeks

An AE is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The percentage of participants who experience an AE will be reported.

Percentage of Participants Discontinuing Study Treatment due to AEs
Up to ~ 96 weeks

An AE is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The percentage of participants who discontinue study treatment due to an AE will be reported.

Secondary Endpoints

Percentage of Participants With ≥1 Adverse Events (AEs) Through Week 97
Up to 97 weeks
Percentage of Participants Discontinuing From Study Therapy Due to AE(s) Through Week 97
Up to 97 weeks
Percentage of Participants Receiving DOR or ISL (Given With Antiretroviral Therapy [ART]) With ≥0.5 log10 Change From Day 1 Baseline to Day 8 HIV-1 RNA Compared to Placebo Treatment
Day 1 (baseline) and Day 8
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Study Design & Arms

AllocationRANDOMIZED
MaskingDOUBLE
ModelPARALLEL
PurposeTREATMENT

Treatment Arms

ArmTypeDescription
ISL + ARTEXPERIMENTALHTE participants with HIV-1 infection take ISL 0.75 mg once daily (QD) in combination with failing ART from Day 1 to Day 7; followed by open-label 100 mg DOR/0.75 mg ISL fixed dose combination (FDC) QD + OBT from Day 8 to Week 97.
DOR + ARTEXPERIMENTALHTE participants with HIV-1 infection take DOR 100 mg QD in combination with failing ART from Day 1 to Day 7; followed by open-label 100 mg DOR/0.75 mg ISL FDC QD + OBT from Day 8 to Week 97.
DOR/ISL + ARTEXPERIMENTALHTE participants with HIV-1 infection take 100 mg DOR/0.75 mg ISL FDC QD in combination with failing ART from Day 1 to Day 7; followed by open-label 100 mg DOR/0.75 mg ISL FDC QD + OBT from Day 8 to Week 97.
Placebo + ARTPLACEBO_COMPARATORHTE participants with HIV-1 infection take placebo QD in combination with failing ART from Day 1 to Day 7; followed by open-label 100 mg DOR/0.75 mg ISL FDC QD + OBT from Day 8 to Week 97.
Phase 2: ISL + ULOEXPERIMENTALIslatravir (ISL) 2mg and Ulonivirine (ULO) 200mg administered orally once weekly (qw) for 96 weeks
Phase 2: BIC/FTC/TAFACTIVE_COMPARATORBictegravir/Emtricitabine/Tenofovir Alafenamide (BIC/FTC/TAF) 50/200/25 mg, administered orally once daily (qd) for 96 weeks
Phase 3: ISL/ULO and Placebo to BIC/FTC/TAFEXPERIMENTALISL/ULO fixed dose combination (2/200 mg), administered orally qw, and matching placebo to BIC/FTC/TAF administered orally qd for 96 weeks
Phase 3: BIC/FTC/TAF and Placebo to ISL/ULOACTIVE_COMPARATORBIC/FTC/TAF 50/200/25 mg, administered orally qd, and matching placebo to ISL/ULO administered orally qw for 96 weeks
ISL + ULO in Group 1EXPERIMENTALIn part 1 of the study, participants will receive ISL 2mg + ULO 200mg orally once a week (QW) for 48 weeks. In part 2 (2nd 48 weeks), participants will continue to receive ISL 2mg + ULO 200mg once a week till week 96.
BIC/FTC/TAF in Group 2ACTIVE_COMPARATORIn part 1 of the study, participants will receive BIC 50mg/FTC 200mg/TAF 25mg orally once daily (QD) for 48 weeks.
ISL + ULO in Group 2EXPERIMENTALIn part 2 of the study, participants previously on BIC/FTC/TAF (for the 1st 48 weeks, or part 1) will switch to ISL + ULO, to week 96.

Interventions

NameTypeDescription
ISLDRUGISL 0.75 mg capsule taken by mouth.
DORDRUGDOR 100 mg tablet taken by mouth.
DOR/ISLDRUG100 mg DOR/0.75 mg ISL FDC taken by mouth.
Placebo to ISLDRUGPlacebo capsule matched to ISL taken by mouth.
Placebo to DORDRUGPlacebo tablet matched to DOR taken by mouth.
ULODRUGULO 2 x 100 mg oral tablets administered qw for 96 weeks
BIC/FTC/TAFDRUGBIC/FTC/TAF 50/200/25 mg oral tablet administered qd for 96 weeks
Placebo for BIC/FTC/TAFDRUGBIC/FTC/TAF-matching placebo oral tablet administered qd for 96 weeks
Placebo to ISL/ULODRUGISL/ULO-matching placebo oral tablets administered qw for 96 weeks
ISL/ULODRUGISL/ULO fixed-dose combination 2 mg/200 mg oral tablet administered qw for 96 weeks
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Eligibility Criteria

Age Range18 Years to N/A
SexALL
Healthy VolunteersNo
Study Sites98

Inclusion Criteria: * Is HIV-1 positive. * Has been receiving the same baseline ART for ≥3 months prior to signing the Informed Consent Form/Assent Form. * Weighs ≥35 kg. * Has at least triple-class resistance (must include nucleoside reverse transcriptase inhibitor \[NRTI\], non-nucleoside reverse...

Countries:United StatesAustraliaCanadaChileColombiaFranceGermanyItalyJapanPeruPortugalPuerto RicoRussiaSouth AfricaSouth KoreaSpainUkraineUnited KingdomArgentinaGuatemalaMexicoSwitzerland
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Recent Changes (Last 90 Days)

LOWAug 11, 2026NCT07266831lastUpdatePostDate: changed
LOWAug 11, 2026NCT07266831lastUpdatePostDate: changed
LOWAug 11, 2026NCT07266831lastUpdatePostDate: changed
LOWAug 4, 2026NCT07266831lastUpdatePostDate: changed
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LOWJul 13, 2026NCT07266831lastUpdatePostDate: changed
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LOWJun 8, 2026NCT07266831lastUpdatePostDate: changed
LOWJun 8, 2026NCT07266831lastUpdatePostDate: changed
LOWJun 8, 2026NCT07266831lastUpdatePostDate: changed

Frequently asked questions about ISL

What is ISL used for in HIV-1 Infection?

ISL, also known as islatravir, is an investigational small molecule being developed for the treatment of Human Immunodeficiency Virus Type 1 (HIV-1) Infection. It is being studied in combination with other antiretroviral agents for both treatment-experienced and treatment-naive adults with HIV-1.

Who makes ISL?

ISL is being developed by Merck & Company, Inc., which trades under the ticker symbol MRK. The company is conducting clinical trials to evaluate the drug's safety and efficacy in treating HIV-1 infection.

What phase is ISL in?

ISL is in Phase 3 clinical development for HIV-1 Infection. One Phase 3 trial has been completed, and additional Phase 2 studies are ongoing or active but not recruiting. The drug is investigational and has not been approved by regulatory authorities.

What clinical trials is ISL in?

ISL is being studied in several clinical trials. NCT04233216 is a completed Phase 3 study of Doravirine/Islatravir in heavily treatment-experienced participants. NCT06891066 is an active Phase 2 trial of ISL with Ulonivirine once weekly in virologically suppressed adults. NCT07266831 is a recruiting Phase 2 study in treatment-naive people with HIV-1.

How does ISL work?

ISL is a nucleoside reverse transcriptase translocation inhibitor that works by blocking the action of reverse transcriptase, an enzyme HIV-1 needs to replicate. By inhibiting this enzyme, ISL helps reduce the viral load in people infected with HIV-1.

Is ISL the same as islatravir?

Yes, ISL is the same as islatravir. The drug is referred to by the abbreviation ISL in clinical trial names and is also known by its full name, islatravir. It is being studied in combination with other antiretrovirals for HIV-1 treatment.