A Switch to Doravirine/Islatravir (DOR/ISL) in Participants With Human Immunodeficiency Virus Type 1 (HIV-1) Who Are Virologically Suppressed on Antiretroviral Therapy (ART) (MK-8591A-051)

A Phase 3, Randomized, Active-Controlled, Open-Label Clinical Study to Evaluate a Switch to Doravirine/Islatravir (DOR/ISL 100 mg/0.25 mg) Once-Daily in Participants With HIV-1 Who Are Virologically Suppressed on Antiretroviral Therapy

The primary objectives of this study are to evaluate the safety and tolerability of a switch to Doravirine/Islatravir (DOR/ISL) compared with continued baseline antiretroviral therapy (ART), through Week 48; and to evaluate the antiretroviral activity of a switch to DOR/ISL compared with continued baseline ART at Week 48. The primary hypothesis is that DOR/ISL is non-inferior to continued baseline ART, as assessed by the percentage of participants with HIV-1 ribonucleic acid (RNA) ≥50 copies/mL at Week 48, with a margin of 4 percentage points used to define non-inferiority.

Study Overview

• Status: Active, not recruiting
• Conditions: HIV-1 Infection
• Intervention / Treatment: Drug: ART; Drug: DOR/ISL

• Study Type: Interventional
• Enrollment (Actual): 553
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Darlinghurst, New South Wales, Australia, 2010
      • Holdsworth House Medical Practice ( Site 4200)
    • Sydney, New South Wales, Australia, 2010
      • St Vincent's Hospital-IBAC ( Site 4203)
  • Queensland
    • Brisbane, Queensland, Australia, 4006
      • Holdsworth House Medical Practice - Brisbane ( Site 4201)
    • Brisbane, Queensland, Australia, 4029
      • Royal Brisbane and Women's Hospital-Infectious Diseases Research ( Site 4204)
  • Victoria
    • Melbourne, Victoria, Australia, 3181
      • Prahran Market Clinic ( Site 4202)
• Canada
  • Ontario
    • Hamilton, Ontario, Canada, L8S 1A4
      • Hamilton Health Sciences- Urgent Care Centre-SIS Clinic ( Site 3104)
    • Toronto, Ontario, Canada, M5G 1K2
      • Maple Leaf Research ( Site 3103)
    • Toronto, Ontario, Canada, M5G 2M1
      • Toronto General Hospital ( Site 3102)
  • Quebec
    • Montreal, Quebec, Canada, H2L 4E9
      • Clinique de médecine Urbaine du Quartier Latin ( Site 3101)
    • Montreal, Quebec, Canada, H2L 4P9
      • Clinique Medicale lActuel-Clinical Research ( Site 3100)
• Colombia
  • Atlántico
    • Barranquilla, Atlántico, Colombia, 08001
      • Ciensalud Ips S A S ( Site 3300)
    • Barranquilla, Atlántico, Colombia, 080020
      • Clinica de la Costa S.A.S. ( Site 3305)
  • Valle del Cauca Department
    • Cali, Valle del Cauca Department, Colombia, 760032
      • Fundacion Valle del Lili- CIC ( Site 3302)
• Japan
  • Aichi-ken
    • Nagoya, Aichi-ken, Japan, 460-0001
      • National Hospital Organization Nagoya Medical Center ( Site 4403)
  • Tokyo
    • Shinjuku-ku, Tokyo, Japan, 160-0023
      • Tokyo Medical University Hospital ( Site 4404)
    • Shinjyuku-ku, Tokyo, Japan, 162-8655
      • Center Hospital of the National Center for Global Health and Medicine ( Site 4401)
• South Africa
  • Free State
    • Bloemfontein, Free State, South Africa, 9300
      • Josha Research ( Site 3903)
  • Gauteng
    • Johannesburg, Gauteng, South Africa, 2013
      • Perinatal HIV Research Unit (PHRU)-Adult Treatment and Research ( Site 3905)
    • Johannesburg, Gauteng, South Africa, 2092
      • Helen Joseph Hospital ( Site 3910)
    • Johannesburg, Gauteng, South Africa, 2193
      • Ezintsha-Clinical Research Site ( Site 3907)
    • Pretoria, Gauteng, South Africa, 0007
      • Private Practice Dr. Marleen de Jager ( Site 3900)
  • KwaZulu-Natal
    • Durban, KwaZulu-Natal, South Africa, 4052
      • Wentworth Hospital ( Site 3904)
  • Western Cape
    • Cape Town, Western Cape, South Africa, 7505
      • Family Clinical Research Unit (Fam-Cru)-Adult Infectious Diseases ( Site 3908)
    • Cape Town, Western Cape, South Africa, 7925
      • Desmond Tutu Health Foundation ( Site 3902)
    • Paarl, Western Cape, South Africa, 7646
      • Be Part Yoluntu Centre ( Site 3901)
• Switzerland
  • Bern, Switzerland, 3010
    • Inselspital Bern-Inselspital Infektiologie ( Site 4003)
  • Canton Ticino
    • Lugano, Canton Ticino, Switzerland, 6903
      • Ospedale Regionale di Lugano, Sede Civico-Servizio Malattie Infettive ( Site 4005)
  • Canton of Basel-City
    • Basel, Canton of Basel-City, Switzerland, 4031
      • University Hospital Basel-Infectiology ( Site 4002)
  • Canton of Geneva
    • Geneva, Canton of Geneva, Switzerland, 1211
      • Hôpitaux Universitaires de Genève (HUG)-Infectious Disease Department ( Site 4004)
  • Canton of Vaud
    • Lausanne, Canton of Vaud, Switzerland, 1011
      • CHUV (centre hospitalier universitaire vaudois) ( Site 4006)
  • Canton of Zurich
    • Zurich, Canton of Zurich, Switzerland, 8091
      • UniversitätsSpital Zürich ( Site 4000)
• United Kingdom
  • Birmingham, United Kingdom, B9 5SS
    • Heartlands Hospital ( Site 4102)
  • Brighton And Hove
    • East Sussex, Brighton And Hove, United Kingdom, BN2 1ES
      • Brighton and Sussex University Hospitals NHS Trust ( Site 4104)
  • England
    • Crumpsall, England, United Kingdom, M8 5RB
      • North Manchester General Hospital ( Site 4107)
    • London, England, United Kingdom, E1 1BB
      • Royal London Hospital ( Site 4100)
    • London, England, United Kingdom, NW32QG
      • Royal Free Hospital ( Site 4101)
    • Newcastle upon Tyne, England, United Kingdom, NE1 4LP
      • Royal Victoria Infirmary ( Site 4105)
  • London, City of
    • London, London, City of, United Kingdom, SE5 9RL
      • King's College Hospital ( Site 4108)
• United States
  • California
    • Los Angeles, California, United States, 90027
      • Kaiser Permanente-Infectious Disease ( Site 3014)
    • Palm Springs, California, United States, 92262
      • Palmtree Clinical Research ( Site 3032)
    • San Francisco, California, United States, 94110
      • Zuckerberg San Francisco General Hospital and Trauma Center-UCSF ID Clinical Trials Center ( Site 30
  • District of Columbia
    • Washington D.C., District of Columbia, United States, 20007
      • Georgetown University Medical Center ( Site 3006)
  • Florida
    • Ft. Pierce, Florida, United States, 34982
      • Midway Immunology and Research Center ( Site 3009)
    • Orlando, Florida, United States, 32803
      • Orlando Immunology Center ( Site 3004)
    • Sarasota, Florida, United States, 34237
      • CAN Community Health - Sarasota ( Site 3017)
    • West Palm Beach, Florida, United States, 33407
      • Triple O Research Institute, P.A ( Site 3026)
  • Georgia
    • Decatur, Georgia, United States, 30033
      • Infectious Disease Specialists of Atlanta ( Site 3003)
    • Savannah, Georgia, United States, 31401
      • Chatham County Health Department - Chatham CARE Center-Infectious Disease ( Site 3028)
  • New Jersey
    • Hillsborough, New Jersey, United States, 08844
      • ID Care ( Site 3041)
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Penn Medicine: University of Pennsylvania Health System-Perelman Center for Advanced Medicine ( Site
  • Texas
    • Austin, Texas, United States, 78705
      • Central Texas Clinical Research ( Site 3015)
    • Houston, Texas, United States, 77098
      • The Crofoot Research Center ( Site 3040)
    • Longview, Texas, United States, 75605
      • DCOL Center for Clinical Research ( Site 3022)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Is Human Immunodeficiency Virus-1 (HIV-1) positive with plasma HIV-1 Ribonucleic Acid (RNA) <50 copies/mL at screening
• Has been receiving continuous, stable oral 2-drug or 3-drug combination (± PK booster) antiretroviral therapy ART with documented viral suppression (HIV-1 RNA <50 copies/mL) for ≥3 consecutive months prior to providing documented informed consent and has no history of prior virologic treatment failure on any past or current regimen
• Female is not a participant of childbearing potential (POCBP); or if a POCBP uses an acceptable contraceptive method or abstains from penile-vaginal intercourse as their preferred and usual lifestyle; has a negative highly sensitive pregnancy test; and whose medical history, menstrual history, and recent sexual activity has been reviewed by the investigator

Exclusion Criteria:

• Has HIV-2 infection
• Has hypersensitivity or other contraindication to any of the components of the study interventions as determined by the investigator
• Has a diagnosis of an active acquired immunodeficiency syndrome (AIDS)-defining opportunistic infection within 30 days prior to screening
• Has active hepatitis B virus (HBV) infection
• Has chronic hepatitis C virus (HCV) infection consistent with cirrhosis
• Has a ≤5 years prior history of malignancy
• Is taking or is anticipated to require systemic immunosuppressive therapy, immune modulators, or strong and moderate cytochrome P450 3A (CYP3A) inducers
• Has taken long-acting HIV therapy at any time
• Is currently participating in or has participated in a clinical study and received (or is receiving) an investigational compound or device from 45 days prior to Day 1 through the study treatment period
• Has a documented or known virologic resistance to Doravine (DOR)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: DOR/ISL; Participants with Human Immunodeficiency Virus-1 (HIV-1) that have been virologically suppressed for ≥3 consecutive months who were previously treated with continuous baseline antiretroviral therapy (ART) receive doravine/islatravir (DOR/ISL), a fixed dose combination (FDC) of 100 mg DOR/0.25 mg ISL orally once daily (qd) for 144 weeks. At Week 144, participants who consent to enter the optional study extension will continue to receive DOR/ISL qd (100 mg/0.25 mg) for an additional 96 weeks or until it is commercially accessible (whichever comes first).	Drug: DOR/ISL; Single tablet combination of 100 mg doravirine (DOR) with 0.25 mg Islatravir (ISL) in tablet form, taken orally, once daily.; Other Names: MK-8591A
Active Comparator: ART + DOR/ISL; Participants with HIV-1 that has been virologically suppressed for ≥3 consecutive months who were previously treated with continuous baseline ART received standard of care (SOC) ART for 48 weeks, followed by treatment with DOR/ISL as a FDC of 100 mg DOR/0.25 mg ISL orally qd until Week 144. At Week 144, participants who consent to enter the optional study extension will continue to receive DOR/ISL qd (100 mg/0.25 mg) for an additional 96 weeks or until it is commercially accessible (whichever comes first).	Drug: ART; Standard of care ART, per approved product list, taken orally

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With HIV-1 RNA ≥50 Copies/mL at Week 48	HIV-1 RNA levels in plasma were measured by polymerase chain reaction (PCR) assay with a reliable lower limit of quantification of <50 copies/mL. The percentage of participants with HIV-1 RNA ≥50 copies/mL at Week 48 is presented using the FDA Snapshot missing data approach.	Week 48
Percentage of Participants With One or More Adverse Events (AEs) at Week 48	An AE is defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The percentage of participants who experienced at least one AE from Day 1 up to Week 48 are reported.	Up to Week 48
Percentage of Participants With an AE Leading to Discontinuation of Study Intervention at Week 48	An AE is defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The percentage of participants who experienced at least one AE leading to discontinuation of study intervention from Day 1 up to Week 48 are reported.	Up to Week 48

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With HIV-1 RNA <200 Copies/mL at Week 48	HIV-1 RNA levels in plasma were measured by a polymerase chain reaction (PCR) assay with a reliable lower limit of quantification of <50 copies/mL. The percentage of participants with HIV-1 RNA <200 copies/mL at Week 48 is presented using the FDA Snapshot missing data approach.	Week 48
Percentage of Participants With HIV-1 RNA <50 Copies/mL at Week 48	HIV-1 RNA levels in plasma were measured by a polymerase chain reaction (PCR) assay with a reliable lower limit of quantification of <50 copies/mL. The percentage of participants with HIV-1 RNA <50 copies/mL at Week 48 is presented using the FDA Snapshot missing data approach.	Week 48
Percentage of Participants With HIV-1 RNA <200 Copies/mL at Week 96	HIV-1 RNA levels in plasma were measured by a polymerase chain reaction (PCR) assay with a reliable lower limit of quantification of <50 copies/mL. The percentage of participants with HIV-1 RNA <200 copies/mL at Week 96 is presented using the FDA Snapshot missing data approach.	Week 96
Participants With HIV-1 RNA <200 Copies/mL at Week 144	HIV-1 RNA levels in plasma were measured by a polymerase chain reaction (PCR) assay with a reliable lower limit of quantification of <50 copies/mL. The percentage of participants with HIV-1 RNA <200 copies/mL at Week 144 is presented using the FDA Snapshot missing data approach.	Week 144
Percentage of Participants With HIV-1 RNA ≥50 Copies/mL at Week 96	HIV-1 RNA levels in plasma were measured by a polymerase chain reaction (PCR) assay with a reliable lower limit of quantification of <50 copies/mL. The percentage of participants with HIV-1 RNA ≥50 copies/mL at Week 96 is presented using the FDA Snapshot missing data approach.	Week 96
Percentage of Participants With HIV-1 RNA ≥50 Copies/mL at Week 144	HIV-1 RNA levels in plasma were measured by a polymerase chain reaction (PCR) assay with a reliable lower limit of quantification of <50 copies/mL. The percentage of participants with HIV-1 RNA ≥50 copies/mL at Week 144 is presented using the FDA Snapshot missing data approach.	Week 144
Percentage of Participants With HIV-1 RNA <50 Copies/mL at Week 96	HIV-1 RNA levels in plasma were measured by a polymerase chain reaction (PCR) assay with a reliable lower limit of quantification of <50 copies/mL. The percentage of participants with HIV-1 RNA <50 copies/mL at Week 96 is presented using the FDA Snapshot missing data approach.	Week 96
Percentage of Participants With HIV-1 RNA <50 Copies/mL at Week 144	HIV-1 RNA levels in plasma were measured by a polymerase chain reaction (PCR) assay with a reliable lower limit of quantification of <50 copies/mL. The percentage of participants with HIV-1 RNA <50 copies/mL at Week 144 is presented using the FDA Snapshot missing data approach.	Week 144
Mean Change of Plasma Cluster of Differentiation 4 (CD4+) T-Cell Count From Baseline Day 1 to Week 48	Plasma CD4+ T-Cell Count was measured in cells/mm^3 for baseline and 48 weeks. Baseline measurements were defined as the Day 1 value of each participant. The mean change of plasma CD4+ T-Cell count from baseline to Week 48 is presented.	Baseline at Day 1 and Week 48
Mean Change of Plasma CD4+ T-Cell Count From Baseline Week 48 to Week 96	Mean change from baseline at Week 48 in CD4+ T-cell count at Week 96. This outcome measure is applicable to participants who were randomized to switch to DOR/ISL at Week 48.	Baseline at Week 48 and Week 96
Mean Change of Plasma CD4+ T-Cell Count From Baseline Day 48 to Week 144	Mean change from baseline at Week 48 in CD4+ T-cell count at Week 144. This outcome measure is applicable to participants who were randomized to switch to DOR/ISL at Week 48.	Baseline at Week 48 and Week 144
Mean Change of Plasma CD4+ T-Cell Count From Baseline Day 1 to Week 96	Mean change from baseline at Day 1 in CD4+ T-cell count at Week 96. This outcome measure is applicable to those randomized to start DOR/ISL on Day 1.	Baseline at Day 1 and Week 96
Mean Change of Plasma CD4+ T-Cell Count From Baseline Day 1 to Week 144	Mean change from baseline at Day 1 in CD4+ T-cell count at Week 144. This outcome measure is applicable to those randomized to start DOR/ISL on Day 1.	Baseline at Day 1 and Week 144
Percentage of Participants With Treatment-Emergent, Resistance-associated Substitutions at Week 48	Participants with clinically significant confirmed viremia [2 consecutive occurences 4 weeks (+-1 week) apart of HIV-1 RNA >=200 copies/mL at any time during the study] or who discontinue study intervention for another reason with HIV-1 RNA >=200 copies/mL at the time of discontinuation met the criteria for post-baseline resistance testing. Participants with HIV-1 RNA >=400 copies/mL or any participant for whom available genotypic or phenotypic data show evidence of resistance, irrespective of viral load were included in the resistance analysis subset. Plasma samples were collected for genotypic and phenotypic HIV-1 viral drug resistance testing and used to assess resistance-associated substitutions and virus susceptibility to study intervention. The percentage of participants in the resistance analysis subset with treatment-emergent resistance-associated substitutions to the study intervention is presented.	Up to Week 48
Mean Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) at Week 48	Blood serum samples were taken at baseline and Week 48. The mean change from baseline in fasting Low density lipoprotein cholesterol (LDL-C) at Week 48 is presented for PI-containing regimens (including PI- + InSTI-containing regimens), non-PI- and non-InSTI-containing regimens, and InSTI-containing regimens (non-PI-containing regimens) are presented.	Baseline and Week 48
Mean Change From Baseline in Fasting Non-High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 48	Blood serum samples were taken at baseline and Week 48. The mean change from baseline in fasting Non-HDL-C at Week 48 is presented for PI-containing regimens (including PI- + InSTI-containing regimens), non-PI- and non-InSTI-containing regimens, and InSTI-containing regimens (non-PI-containing regimens) are presented.	Baseline and Week 48
Participants With One or More AEs at Week 96	An AE is defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The percentage of participants who experienced at least one AE from Day 1 up to Week 96 is reported.	Up to Week 96
Participants With One or More AEs at Week 144	An AE is defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The percentage of participants who experienced at least one AE from Day 1 up to Week 144 is reported.	Up to Week 144
Percentage of Participants With AEs Leading to Discontinuation of Study Intervention at Week 96	An AE is defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The percentage of participants who experienced at least one AE leading to discontinuation of study intervention from Day 1 up to Week 96 are reported.	Up to Week 96
Percentage of Participants With AEs Leading to Discontinuation of Study Intervention at Week 144	An AE is defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The percentage of participants who experienced at least one AE leading to discontinuation of study intervention from Day 1 up to Week 144 are reported.	Up to Week 144
Percentage of Participants With One or More AEs From Week 48 up to Week 96	An AE is defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The percentage of participants who experienced at least one AE from Week 48 up to Week 96 is reported.	Week 48 up to Week 96
Percentage of Participants With One or More AEs From Week 48 up to Week 144	An AE is defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The percentage of participants who experienced at least one AE from Week 48 up to Week 144 is presented.	Week 48 up to Week 144
Percentage of Participants With AEs Leading to Discontinuation of Study Intervention From Week 48 up to Week 96	An AE is defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The percentage of participants who experienced at least one AE leading to discontinuation of study intervention from Week 48 up to Week 96 are reported.	Week 48 up to Week 96
Percentage of Participants With AEs Leading to Discontinuation of Study Intervention From Week 48 up to Week 144	An AE is defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The percentage of participants who experienced at least one AE leading to discontinuation of study intervention from Week 48 up to Week 144 are reported.	Week 48 up to Week 144

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC
• Investigators: Study Director: Medical Director, Merck Sharp & Dohme LLC

Publications and helpful links

Helpful Links

• Merck Clinical Trials Information
• Plain Language Summary

Study record dates

Study Major Dates

• Study Start (Actual): February 20, 2023
• Primary Completion (Actual): October 10, 2024
• Study Completion (Estimated): July 11, 2028

Study Registration Dates

• First Submitted: November 18, 2022
• First Submitted That Met QC Criteria: November 18, 2022
• First Posted (Actual): November 30, 2022

Study Record Updates

• Last Update Posted (Actual): November 21, 2025
• Last Update Submitted That Met QC Criteria: November 11, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Anti-Infective Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Nucleic Acid Synthesis Inhibitors; Antiviral Agents; Reverse Transcriptase Inhibitors; Anti-Retroviral Agents; Islatravir
• Other Study ID Numbers: 8591A-051; MK-8591A-051 (Other Identifier: MSD); 2022-502127-22 (EudraCT Number); jRCT2031220698 (Registry Identifier: jRCT); U1111-1283-3894 (Registry Identifier: UTN); 2022-502127-22-00 (Registry Identifier: EU CT)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: https://trialstransparency.msdclinicaltrials.com/pdf/ProcedureAccessClinicalTrialData.pdf

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No