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)

NCT05631093 | Active Not Recruiting Phase 3 Results DMC FDA Drug

• 6 other identifiers: 8591A-051MK-8591A-051jRCT2031220698U1111-1283-38942022-502127-22-002022-502127-22
• Study Type: interventional
• Target: 553
• Locations: 8 countries
• Sites: 53

Brief Summary

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.

Conditions

HIV-1 Infection

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (24)

• Percentage of Participants With HIV-1 RNA <200 Copies/mL at Week 48

  Week 48

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

  Week 48

• Percentage of Participants With HIV-1 RNA <200 Copies/mL at Week 96

  Week 96

• Participants With HIV-1 RNA <200 Copies/mL at Week 144

  Week 144

• Percentage of Participants With HIV-1 RNA ≥50 Copies/mL at Week 96

  Week 96

Study Arms (2)

DOR/ISL

EXPERIMENTAL

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

ART + DOR/ISL

ACTIVE COMPARATOR

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

Interventions

ART DRUG

Standard of care ART, per approved product list, taken orally

ART + DOR/ISL

DOR/ISL DRUG

Single tablet combination of 100 mg doravirine (DOR) with 0.25 mg Islatravir (ISL) in tablet form, taken orally, once daily.

Also known as: MK-8591A

DOR/ISL

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Study Sites (53)

Kaiser Permanente-Infectious Disease ( Site 3014)

Los Angeles, California, 90027, United States

Location

Palmtree Clinical Research ( Site 3032)

Palm Springs, California, 92262, United States

Location

Zuckerberg San Francisco General Hospital and Trauma Center-UCSF ID Clinical Trials Center ( Site 30

San Francisco, California, 94110, United States

Location

Georgetown University Medical Center ( Site 3006)

Washington D.C., District of Columbia, 20007, United States

Location

Midway Immunology and Research Center ( Site 3009)

Ft. Pierce, Florida, 34982, United States

Location

Orlando Immunology Center ( Site 3004)

Orlando, Florida, 32803, United States

Location

CAN Community Health - Sarasota ( Site 3017)

Sarasota, Florida, 34237, United States

Location

Triple O Research Institute, P.A ( Site 3026)

West Palm Beach, Florida, 33407, United States

Location

Infectious Disease Specialists of Atlanta ( Site 3003)

Decatur, Georgia, 30033, United States

Location

Chatham County Health Department - Chatham CARE Center-Infectious Disease ( Site 3028)

Savannah, Georgia, 31401, United States

Location

ID Care ( Site 3041)

Hillsborough, New Jersey, 08844, United States

Location

Penn Medicine: University of Pennsylvania Health System-Perelman Center for Advanced Medicine ( Site

Philadelphia, Pennsylvania, 19104, United States

Location

Central Texas Clinical Research ( Site 3015)

Austin, Texas, 78705, United States

Location

The Crofoot Research Center ( Site 3040)

Houston, Texas, 77098, United States

Location

DCOL Center for Clinical Research ( Site 3022)

Longview, Texas, 75605, United States

Location

Holdsworth House Medical Practice ( Site 4200)

Darlinghurst, New South Wales, 2010, Australia

Location

St Vincent's Hospital-IBAC ( Site 4203)

Sydney, New South Wales, 2010, Australia

Location

Holdsworth House Medical Practice - Brisbane ( Site 4201)

Brisbane, Queensland, 4006, Australia

Location

Royal Brisbane and Women's Hospital-Infectious Diseases Research ( Site 4204)

Brisbane, Queensland, 4029, Australia

Location

Prahran Market Clinic ( Site 4202)

Melbourne, Victoria, 3181, Australia

Location

Hamilton Health Sciences- Urgent Care Centre-SIS Clinic ( Site 3104)

Hamilton, Ontario, L8S 1A4, Canada

Location

Maple Leaf Research ( Site 3103)

Toronto, Ontario, M5G 1K2, Canada

Location

Toronto General Hospital ( Site 3102)

Toronto, Ontario, M5G 2M1, Canada

Location

Clinique de médecine Urbaine du Quartier Latin ( Site 3101)

Montreal, Quebec, H2L 4E9, Canada

Location

Clinique Medicale lActuel-Clinical Research ( Site 3100)

Montreal, Quebec, H2L 4P9, Canada

Location

Ciensalud Ips S A S ( Site 3300)

Barranquilla, Atlántico, 08001, Colombia

Location

Clinica de la Costa S.A.S. ( Site 3305)

Barranquilla, Atlántico, 080020, Colombia

Location

Fundacion Valle del Lili- CIC ( Site 3302)

Cali, Valle del Cauca Department, 760032, Colombia

Location

National Hospital Organization Nagoya Medical Center ( Site 4403)

Nagoya, Aichi-ken, 460-0001, Japan

Location

Tokyo Medical University Hospital ( Site 4404)

Shinjuku-ku, Tokyo, 160-0023, Japan

Location

Center Hospital of the National Center for Global Health and Medicine ( Site 4401)

Shinjyuku-ku, Tokyo, 162-8655, Japan

Location

Josha Research ( Site 3903)

Bloemfontein, Free State, 9300, South Africa

Location

Perinatal HIV Research Unit (PHRU)-Adult Treatment and Research ( Site 3905)

Johannesburg, Gauteng, 2013, South Africa

Location

Helen Joseph Hospital ( Site 3910)

Johannesburg, Gauteng, 2092, South Africa

Location

Ezintsha-Clinical Research Site ( Site 3907)

Johannesburg, Gauteng, 2193, South Africa

Location

Private Practice Dr. Marleen de Jager ( Site 3900)

Pretoria, Gauteng, 0007, South Africa

Location

Wentworth Hospital ( Site 3904)

Durban, KwaZulu-Natal, 4052, South Africa

Location

Family Clinical Research Unit (Fam-Cru)-Adult Infectious Diseases ( Site 3908)

Cape Town, Western Cape, 7505, South Africa

Location

Desmond Tutu Health Foundation ( Site 3902)

Cape Town, Western Cape, 7925, South Africa

Location

Be Part Yoluntu Centre ( Site 3901)

Paarl, Western Cape, 7646, South Africa

Location

University Hospital Basel-Infectiology ( Site 4002)

Basel, Canton of Basel-City, 4031, Switzerland

Location

Hôpitaux Universitaires de Genève (HUG)-Infectious Disease Department ( Site 4004)

Geneva, Canton of Geneva, 1211, Switzerland

Location

CHUV (centre hospitalier universitaire vaudois) ( Site 4006)

Lausanne, Canton of Vaud, 1011, Switzerland

Location

UniversitätsSpital Zürich ( Site 4000)

Zurich, Canton of Zurich, 8091, Switzerland

Location

Ospedale Regionale di Lugano, Sede Civico-Servizio Malattie Infettive ( Site 4005)

Lugano, Canton Ticino, 6903, Switzerland

Location

Inselspital Bern-Inselspital Infektiologie ( Site 4003)

Bern, 3010, Switzerland

Location

Brighton and Sussex University Hospitals NHS Trust ( Site 4104)

East Sussex, Brighton And Hove, BN2 1ES, United Kingdom

Location

North Manchester General Hospital ( Site 4107)

Crumpsall, England, M8 5RB, United Kingdom

Location

Royal London Hospital ( Site 4100)

London, England, E1 1BB, United Kingdom

Location

Royal Free Hospital ( Site 4101)

London, England, NW32QG, United Kingdom

Location

Royal Victoria Infirmary ( Site 4105)

Newcastle upon Tyne, England, NE1 4LP, United Kingdom

Location

King's College Hospital ( Site 4108)

London, London, City of, SE5 9RL, United Kingdom

Location

Heartlands Hospital ( Site 4102)

Birmingham, B9 5SS, United Kingdom

Location

Related Links

• Merck Clinical Trials Information
• Plain Language Summary

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme LLC

ClinicalTrialsDisclosure@MSD.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 18, 2022
• First Posted: November 30, 2022
• Study Start: February 20, 2023
• Primary Completion: October 10, 2024
• Study Completion (Estimated): July 11, 2028
• Last Updated: November 21, 2025
• Results First Posted: November 21, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will share

Locations

US (15); AU (5); CO (3); GB (7); ZA (9); CA (5); CH (6); JP (3)