A Switch to Doravirine/Islatravir (DOR/ISL) in Participants With Human Immunodeficiency Virus Type 1 (HIV-1) Who Are Virologically Suppressed on Bictegravir/Emtricitabine/Tenofovir Alafenamide (BIC/FTC/TAF) (MK-8591A-052)

A Phase 3, Randomized, Active-Controlled, Double-Blind 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 Bictegravir/Emtricitabine/Tenofovir Alafenamide (BIC/FTC/TAF)

The primary objectives of this study are to evaluate the antiretroviral activity of a switch to Doravirine/Islatravir (DOR/ISL) compared with continued Bictegravir/Emtricitabine/Tenofovir Alafenamide (BIC/FTC/TAF) at Week 48; and to evaluate the safety and tolerability of a switch to DOR/ISL compared with continued BIC/FTC/TAF, through Week 48. The primary hypotheses are that (1) DOR/ISL is non-inferior to continued BIC/FTC/TAF, 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; and (2) DOR/ISL is superior to BIC/FTC/TAF, as assessed by the percentage of participants with HIV-1 RNA ≥50 copies/mL at Week 48.

Study Overview

• Status: Active, not recruiting
• Conditions: HIV-1 Infection
• Intervention / Treatment: Drug: DOR/ISL; Drug: Placebo to BIC/FTC/TAF; Drug: BIC/FTC/TAF; Drug: Placebo to DOR/ISL

• Study Type: Interventional
• Enrollment (Actual): 514
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Darlinghurst, New South Wales, Australia, 2010
      • Holdsworth House Medical Practice ( Site 6200)
    • Sydney, New South Wales, Australia, 2010
      • St Vincent's Hospital-IBAC ( Site 6203)
  • Queensland
    • Brisbane, Queensland, Australia, 4006
      • Holdsworth House Medical Practice - Brisbane ( Site 6201)
    • Brisbane, Queensland, Australia, 4029
      • Royal Brisbane and Women's Hospital-Infectious Diseases Research ( Site 6204)
  • Victoria
    • Melbourne, Victoria, Australia, 3181
      • Prahran Market Clinic ( Site 6202)
• Chile
  • Maule Region
    • Talca, Maule Region, Chile, 3465584
      • Clinica Universidad Catolica del Maule ( Site 2204)
  • Region M. de Santiago
    • Santiago, Region M. de Santiago, Chile, 7620001
      • Clínica Universidad de Los Andes ( Site 2206)
    • Santiago, Region M. de Santiago, Chile, 8380420
      • Universidad de Chile - Hospital Clínico Universidad de Chile-Inmunologia Alergia y VIH ( Site 2200)
  • Región de la Araucanía
    • Temuco, Región de la Araucanía, Chile, 4781151
      • Hospital hernan henriquez aravena de temuco-Unidad de Investigación Clínica ( Site 2205)
• Israel
  • Haifa, Israel, 3109601
    • Rambam Health Care Campus-Institute of Allergy, Clinical Immunology, ( Site 4801)
  • Jerusalem, Israel, 9120
    • Hadassah Medical Center-Infecious Disease ( Site 4802)
  • Ramat Gan, Israel, 5262100
    • Sheba Medical Center-HIV unit ( Site 4803)
  • Tel Aviv, Israel, 64239
    • Sourasky Medical Center ( Site 4804)
• Japan
  • Osaka, Japan, 540-0006
    • National Hospital Organization - Osaka National Hospital - Institute For Clinical Research ( Site 66
  • Aichi-ken
    • Nagoya, Aichi-ken, Japan, 460-0001
      • National Hospital Organization Nagoya Medical Center ( Site 6603)
  • Tokyo
    • Shinjyuku-ku, Tokyo, Japan, 162-8655
      • Center Hospital of the National Center for Global Health and Medicine ( Site 6601)
• United Kingdom
  • Reading, United Kingdom, RG1 5AN
    • Royal Berkshire Hospital ( Site 5813)
  • Bristol, City of
    • Bristol, Bristol, City of, United Kingdom, BS10 5NB
      • Southmead Hospital ( Site 5805)
  • England
    • Birmingham, England, United Kingdom, B15 2TH
      • Queen Elizabeth Hospital Birmingham ( Site 5809)
    • Liverpool, England, United Kingdom, L7 8XP
      • Royal Liverpool University Hospital ( Site 5812)
    • London, England, United Kingdom, E1 1BB
      • Royal London Hospital ( Site 5800)
    • London, England, United Kingdom, NW32QG
      • Royal Free Hospital ( Site 5801)
  • London, City of
    • London, London, City of, United Kingdom, SE1 9RT
      • Guy's & St Thomas' NHS Foundation Trust ( Site 5808)
    • London, London, City of, United Kingdom, WC1E 6JB
      • The Mortimer Market Centre for Sexual Health and HIV Research ( Site 5810)
  • Wales
    • Cardiff, Wales, United Kingdom, CF14 4XW
      • University Hospital of Wales ( Site 5803)
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85015
      • Pueblo Family Physicians ( Site 1425)
  • California
    • Beverly Hills, California, United States, 90211
      • Pacific Oaks Medical Group ( Site 1400)
    • Los Angeles, California, United States, 90036
      • Ruane Clinical Research Group, Inc ( Site 1414)
    • Los Angeles, California, United States, 90069
      • Mills Clinical Research ( Site 1433)
  • District of Columbia
    • Washington D.C., District of Columbia, United States, 20005
      • Whitman-Walker Institute ( Site 1431)
  • Florida
    • Fort Lauderdale, Florida, United States, 33308
      • Therafirst Medical Center ( Site 1402)
    • Ft. Pierce, Florida, United States, 34982
      • Midway Immunology and Research Center ( Site 1401)
    • Miami, Florida, United States, 33133
      • AHF The Kinder Medical Group ( Site 1426)
    • Orlando, Florida, United States, 32803
      • Orlando Immunology Center ( Site 1407)
    • West Palm Beach, Florida, United States, 33407
      • Triple O Research Institute, P.A ( Site 1417)
  • Georgia
    • Decatur, Georgia, United States, 30033
      • Infectious Disease Specialists of Atlanta ( Site 1403)
    • Macon, Georgia, United States, 31201
      • Mercer University, Department of Internal Medicine ( Site 1411)
  • Massachusetts
    • Boston, Massachusetts, United States, 02129
      • AccessHealth MA ( Site 1419)
  • Michigan
    • Berkley, Michigan, United States, 48072
      • Be Well Medical Center ( Site 1408)
  • Missouri
    • Kansas City, Missouri, United States, 64111
      • KC CARE Health Center-Clinical Trials ( Site 1422)
  • Nevada
    • Las Vegas, Nevada, United States, 89106
      • Las Vegas Research Center ( Site 1436)
  • North Carolina
    • Greensboro, North Carolina, United States, 27401
      • Regional Center for Infectious Disease Research ( Site 1435)
  • Texas
    • Austin, Texas, United States, 78705
      • Central Texas Clinical Research ( Site 1413)
    • Bellaire, Texas, United States, 77401
      • St Hope Foundation ( Site 1410)
    • Dallas, Texas, United States, 75205
      • Prism Health North Texas, Oak Cliff Health Center ( Site 1409)
    • Dallas, Texas, United States, 75246
      • North Texas Infectious Diseases Consultants, P.A ( Site 1404)
    • Fort Worth, Texas, United States, 76104
      • Texas Centers for Infectious Disease Associates ( Site 1406)
    • Houston, Texas, United States, 77098
      • The Crofoot Research Center ( Site 1424)
    • Longview, Texas, United States, 75605
      • DCOL Center for Clinical Research ( Site 1415)

Participation Criteria

Eligibility Criteria

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

Description

The key inclusion and exclusion criteria include but are not limited to the following:

Inclusion Criteria:

• Is HIV-1 positive with plasma HIV-1 RNA <50 copies/mL
• Has been receiving BIC/FTC/TAF therapy 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 participant of childbearing potential, not pregnant or breastfeeding, and is willing to use an acceptable contraceptive method or abstain from heterosexual intercourse for study duration

Exclusion Criteria:

• Has HIV-2 infection
• 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 with laboratory values consistent with cirrhosis
• Has a history of malignancy ≤5 years prior to providing documented informed consent except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or cutaneous Kaposi's sarcoma
• Is taking or is anticipated to require systemic immunosuppressive therapy, immune modulators, or strong and moderate cytochrome P450 3A (CYP3A) inducers
• Has a documented or known virologic resistance to DOR
• Has taken long-acting HIV therapy at any time (e.g., cabotegravir, lenacapavir)
• 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 except those currently enrolled in the comparator arm of an ongoing DOR/ISL study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: DOR/ISL and Placebo to BIC/FTC/TAF; Participants will receive DOR/ISL 100 mg/0.25 mg and Placebo to BIC/FTC/TAF once daily (QD) orally from day 1 to week 144. After week 144, eligible participants may continue on DOR/ISL and continue study treatment until week 240 or to when DOR/ISL becomes commercially accessible (whichever comes first).	Drug: DOR/ISL; DOR/ISL 100 mg/0.25 mg oral tablets once daily; Other Names: MK-8591A; Doravirine/Islatravir; Drug: Placebo to BIC/FTC/TAF; 0 mg oral tablets once daily
Active Comparator: BIC/FTC/TAF and Placebo to DOR/ISL; Participants will receive BIC/FTC/TAF 50 mg/200 mg/25 mg and Placebo to DOR/ISL once daily (QD) orally from day 1 to week 144. After week 144, eligible participants may switch to DOR/ISL and continue study treatment until week 240 or to when DOR/ISL becomes commercially accessible (whichever comes first).	Drug: BIC/FTC/TAF; BIC/FTC/TAF 50 mg/200 mg/25 mg oral tablets once daily; Other Names: Bictegravir/Emtricitabine/Tenofovir Alafenamide; Drug: Placebo to DOR/ISL; 0 mg oral tablets once daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Human Immunodeficiency Virus Type 1 (HIV-1) Ribonucleic Acid (RNA) ≥50 Copies/mL at Week 48	HIV-1 RNA levels in blood samples taken at each visit were measured 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 Who Experience Adverse Events (AEs) Through Week 48	An AE was 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 is reported.	Up to Week 48
Percentage of Participants Who Discontinue Study Intervention Due to AEs Through Week 48	An AE was 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 discontinued study intervention due to an AE is 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 blood samples taken at each visit were measured 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 blood samples taken at each visit were measured 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
Change From Baseline in Cluster of Differentiation 4-positive (CD4+) T-cell Count at 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 change from baseline to Week 48 and corresponding 2-sided 95% confidence intervals were calculated based on cLDA models adjusted by treatment group, time, and the interaction of time-by-treatment group.	Baseline at Day 1 and Week 48
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. Per protocol, 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
Percentage of Participants With HIV-1 RNA ≥50 Copies/mL at Week 96	Percentage of participants with HIV-1 RNA ≥50 copies/mL at Week 96 will be reported.	Week 96
Percentage of Participants With HIV-1 RNA <200 Copies/mL at Week 96	Percentage of participants with HIV-1 RNA <200 copies/mL at Week 96 will be reported.	Week 96
Percentage of Participants With HIV-1 RNA <50 Copies/mL at Week 96	Percentage of participants with HIV-1 RNA <50 copies/mL at Week 96 will be reported.	Week 96
Change From Baseline in CD4+ T-cell Count at Week 96	Mean change from baseline at Day 1 in CD4+ T-cell count at Week 96 will be reported.	Baseline at Day 1 and Week 96
Number of Participants With Viral Drug Resistance Mutations at Week 96	Number of participants with evidence of viral drug resistance-associated substitutions at Week 96 will be reported.	Week 96
Percentage of Participants With HIV-1 RNA ≥50 Copies/mL at Week 144	Percentage of participants with HIV-1 RNA ≥50 copies/mL at Week 144 will be reported.	Week 144
Percentage of Participants With HIV-1 RNA <200 Copies/mL at Week 144	Percentage of participants with HIV-1 RNA <200 copies/mL at Week 144 will be reported.	Week 144
Percentage of Participants With HIV-1 RNA <50 Copies/mL at Week 144	Percentage of participants with HIV-1 RNA <50 copies/mL at Week 144 will be reported.	Week 144
Change From Baseline in CD4+ T-cell Count at Week 144	Mean change from baseline at Day 1 in CD4+ T-cell count at Week 144 will be reported.	Baseline at Day 1 and Week 144
Number of Participants With Viral Drug Resistance Mutations at Week 144	Number of participants with evidence of viral drug resistance-associated substitutions at Week 144 will be reported.	Week 144
Percentage of Participants Who Experience AEs Through Week 144	An AE is 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.	Up to Week 144
Percentage of Participants Who Discontinue Study Intervention Due to AEs Through Week 144	An AE is 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.	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 17, 2023
• Primary Completion (Actual): October 25, 2024
• Study Completion (Estimated): August 4, 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 (Estimated): November 18, 2025
• Last Update Submitted That Met QC Criteria: November 4, 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-HIV Agents; Anti-Retroviral Agents; doravirine; bictegravir, emtricitabine, tenofovir alafenamide, drug combination; islatravir
• Other Study ID Numbers: 8591A-052; MK-8591A-052 (Other Identifier: MSD); 2022-502079-49-00 (Registry Identifier: EU CT); jRCT2051230003 (Registry Identifier: jRCT); U1111-1283-0949 (Registry Identifier: UTN)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: http://engagezone.msd.com/doc/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