DOR/ISL in HIV-1 Antiretroviral Treatment-naïve Participants (MK-8591A-053)

NCT05705349 | Active Not Recruiting Phase 3 DMC FDA Drug

• 4 other identifiers: 8591A-0532022-502099-22-00jRCT2031220720U1111-1283-2516
• Study Type: interventional
• Target: 537
• Locations: 21 countries
• Sites: 131

Brief Summary

This is a randomized, active-controlled, double-blind clinical study designed to evaluate the antiretroviral activity, safety, and tolerability of doravirine/islatravir (DOR/ISL \[MK-8591A\]) in treatment-naïve participants with human immunodeficiency virus type 1 (HIV-1) infection. It is hypothesized that DOR/ISL is non-inferior to bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) as assessed by the percentage of participants with HIV-1 ribonucleic acid (RNA) \<50 copies/mL at Week 48.

Conditions

HIV-1 Infection

Outcome Measures

Primary Outcomes (3)

• Percentage of participants with human immunodeficiency virus type 1 (HIV-1) ribonucleic acid (RNA) <50 copies/mL at Week 48

  Plasma HIV-1 RNA quantification will be performed at the central laboratory using a polymerase chain reaction (PCR) assay with a lower limit of detection of \<50 copies/mL.

  Week 48

• Percentage of participants experiencing ≥1 adverse event (AE) through Week 48

  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 48 weeks

• Percentage of participants discontinuing from study treatment due to an AE through Week 48

  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 48 weeks

Secondary Outcomes (14)

• Percentage of participants with HIV-1 RNA <50 copies/mL at Week 96

  Week 96

• Percentage of participants with HIV-1 RNA <50 copies/mL at Week 144

  Week 144

• Percentage of participants with HIV-1 RNA <200 copies/mL at Week 48

  Week 48

• Percentage of participants with HIV-1 RNA <200 copies/mL at Week 96

  Week 96

• Percentage of participants with HIV-1 RNA <200 copies/mL at Week 144

  Week 144

Study Arms (2)

DOR/ISL

EXPERIMENTAL

Participants take DOR/ISL and placebo to BIC/FTC/TAF once daily (qd) for 144 weeks.

Drug: DOR/ISL; Drug: Placebo to BIC/FTC/TAF

BIC/FTC/TAF

ACTIVE COMPARATOR

Participants take BIC/FTC/TAF and placebo to DOR/ISL qd for 144 weeks.

Drug: BIC/FTC/TAF; Drug: Placebo to DOR/ISL

Interventions

DOR/ISL DRUG

Fixed dose combination tablet containing DOR/ISL 100 mg/0.25 mg taken by mouth.

Also known as: MK-8591A

DOR/ISL

BIC/FTC/TAF DRUG

Fixed dose combination tablet containing BIC/FTC/TAF 50 mg/200 mg/25 mg taken by mouth.

BIC/FTC/TAF

Placebo to DOR/ISL DRUG

Placebo tablet matched to DOR/ISL tablet taken by mouth.

BIC/FTC/TAF

Placebo to BIC/FTC/TAF DRUG

Placebo tablet matched to BIC/FTC/TAF tablet taken by mouth.

DOR/ISL

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Is HIV-1 positive with plasma HIV-1 RNA ≥500 copies/mL at screening
• Is naïve to antiretroviral therapy (ART) defined as having received no prior therapy with any antiretroviral agent following a diagnosis of HIV-1 infection
• If female, is not a participant of childbearing potential (POCBP); or if a POCBP, is not pregnant or breastfeeding, and is willing to use an acceptable contraceptive method or abstain from heterosexual intercourse for study duration

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 AIDS-defining opportunistic infection within 30 days prior to screening
• Has active hepatitis B infection (defined as hepatitis B surface antigen \[HBsAg\]-positive or HBV deoxyribonucleic acid \[DNA\]-positive).
• Has chronic hepatitis C virus (HCV) infection (detectable HCV ribonucleic acid \[RNA\]) and lab values are 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
• Has a history or current evidence of any condition (including active tuberculosis infection), therapy, laboratory abnormality, or other circumstance (including drug or alcohol use or dependence) that might, in the opinion of the investigator, confound the results of the study or interfere with the participant's participation for the full duration of the study, such that it is not in the best interest of the participant to participate

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Study Sites (131)

Pueblo Family Physicians ( Site 5674)

Phoenix, Arizona, 85015, United States

Location

Pacific Oaks Medical Group ( Site 5681)

Beverly Hills, California, 90211, United States

Location

Ruane Clinical Research Group, Inc ( Site 5658)

Los Angeles, California, 90036, United States

Location

Vivent Health ( Site 5694)

Denver, Colorado, 80246, United States

Location

Washington Health Institute ( Site 5689)

Washington D.C., District of Columbia, 20017, United States

Location

Midway Immunology and Research Center ( Site 5657)

Ft. Pierce, Florida, 34982, United States

Location

AHF The Kinder Medical Group ( Site 5672)

Miami, Florida, 33133, United States

Location

AHF South Beach ( Site 5663)

Miami Beach, Florida, 33140, United States

Location

Orlando Immunology Center ( Site 5654)

Orlando, Florida, 32803, United States

Location

CAN Community Health - Sarasota ( Site 5668)

Sarasota, Florida, 34237, United States

Location

Triple O Research Institute, P.A ( Site 5666)

West Palm Beach, Florida, 33407, United States

Location

Emory University and Grady Health System-Medicine ( Site 5690)

Atlanta, Georgia, 30308, United States

Location

Emory University Hospital Midtown Infectious Disease Clinic ( Site 5673)

Atlanta, Georgia, 30308, United States

Location

Atlanta I.D. Group ( Site 5680)

Atlanta, Georgia, 30309, United States

Location

Metro Infectious Diseases Consultants L.L.C. ( Site 5653)

Decatur, Georgia, 30033, United States

Location

Mercer University, Department of Internal Medicine ( Site 5655)

Macon, Georgia, 31201, United States

Location

Rush University Medical Center-Infectious Disease ( Site 5671)

Chicago, Illinois, 60612, United States

Location

University of Illinois at Chicago-Project WISH ( Site 5685)

Chicago, Illinois, 60612, United States

Location

Howard Brown Health Center-Clinical Research ( Site 5665)

Chicago, Illinois, 60613, United States

Location

Be Well Medical Center ( Site 5650)

Berkley, Michigan, 48072, United States

Location

Henry Ford Hospital ( Site 5667)

Detroit, Michigan, 48202, United States

Location

KC CARE Health Center-Clinical Trials ( Site 5670)

Kansas City, Missouri, 64111, United States

Location

Jubilee Clinical Research ( Site 5679)

Las Vegas, Nevada, 89106, United States

Location

Las Vegas Research Center ( Site 5691)

Las Vegas, Nevada, 89106, United States

Location

ID Care ( Site 5676)

Hillsborough, New Jersey, 08844, United States

Location

Saint Michael's Medical Center ( Site 5682)

Newark, New Jersey, 07102, United States

Location

Columbia University Irving Medical Center-Division of Infectious Diseases ( Site 5688)

New York, New York, 10032, United States

Location

Jacobi Medical Center ( Site 5683)

The Bronx, New York, 10461, United States

Location

Atrium Health Infectious Disease Kenilworth - Charlotte ( Site 5675)

Charlotte, North Carolina, 28204, United States

Location

Regional Center for Infectious Diseases ( Site 5687)

Greensboro, North Carolina, 27401, United States

Location

University of Cincinnati Medical Center-Infectious Diseases - Outpatient ( Site 5662)

Cincinnati, Ohio, 45267-0405, United States

Location

Central Texas Clinical Research ( Site 5661)

Austin, Texas, 78705, United States

Location

St Hope Foundation ( Site 5659)

Bellaire, Texas, 77401, United States

Location

Prism Health North Texas, Oak Cliff Health Center ( Site 5660)

Dallas, Texas, 75208, United States

Location

North Texas Infectious Diseases Consultants, P.A ( Site 5651)

Dallas, Texas, 75246, United States

Location

AXCES Research - Texas - El Paso ( Site 5692)

El Paso, Texas, 79902, United States

Location

Texas Centers for Infectious Disease Associates ( Site 5656)

Fort Worth, Texas, 76104, United States

Location

DCOL Center for Clinical Research ( Site 5664)

Longview, Texas, 75605, United States

Location

Fundación Huésped ( Site 5850)

CABA, Buenos Aires, C1427CEA, Argentina

Location

Instituto de Investigaciones Clínicas Mar del Plata ( Site 5854)

Mar del Plata, Buenos Aires, B7600FZO, Argentina

Location

Instituto CAICI SRL ( Site 5852)

Rosario, Santa Fe Province, S2000PBJ, Argentina

Location

Fundación IDEAA ( Site 5851)

Buenos Aires, C1405CKC, Argentina

Location

Instituto Oulton ( Site 5853)

Córdoba, X5000JJS, Argentina

Location

Hamilton Health Sciences-Urgent Care Centre ( Site 5750)

Hamilton, Ontario, L8S 1A4, Canada

Location

Toronto General Hospital ( Site 5753)

Toronto, Ontario, M5G 2C4, Canada

Location

Clinique Medicale lActuel ( Site 5752)

Montreal, Quebec, H2L 4P9, Canada

Location

McGill University Health Centre ( Site 5751)

Montreal, Quebec, H4A 3J1, Canada

Location

Regina General Hospital ( Site 5754)

Regina, Saskatchewan, S4P 0W5, Canada

Location

Clinica Universidad Catolica del Maule ( Site 5954)

Talca, Maule Region, 3465584, Chile

Location

Biomedica Research Group-Infectology ( Site 5951)

Santiago, Region M. de Santiago, 7500710, Chile

Location

Espacio Eme ( Site 5952)

Santiago, Region M. de Santiago, 7770086, Chile

Location

Centro de Investigacion Clinicadela Universidad Catolica ( Site 5953)

Santiago, Region M. de Santiago, 8330034, Chile

Location

Universidad de Chile - Hospital Clínico Universidad de Chile-Inmunologia Alergia y VIH ( Site 5950)

Santiago, Region M. de Santiago, 8380420, Chile

Location

Hospital hernan henriquez aravena de temuco-Unidad de Investigación Clínica ( Site 5955)

Temuco, Región de la Araucanía, 4781151, Chile

Location

Ciensalud Ips S A S ( Site 6050)

Barranquilla, Atlántico, 08001, Colombia

Location

Clinica de la Costa S.A.S. ( Site 6055)

Barranquilla, Atlántico, 080020, Colombia

Location

Hospital Universitario San Ignacio-Infectious ( Site 6053)

Bogotá, Bogota D.C., 110231, Colombia

Location

Clinica Colsanitas S.A, Sede Clínica Universitaria Colombia ( Site 6051)

Bogotá, Bogota D.C., 111321, Colombia

Location

Fundación Valle del Lili ( Site 6052)

Cali, Valle del Cauca Department, 760032, Colombia

Location

Instituto Dermatológico y Cirugía de Piel "Dr. Huberto Bogaert Díaz" ( Site 8250)

Santo Domingo de Guzman, Santo Domingo Province, 10305, Dominican Republic

Location

Centre Hospitalier Universitaire de Nice - Hôpital l'Archet ( Site 6153)

Nice, Alpes-Maritimes, 06202, France

Location

Tourcoing Hospital ( Site 6150)

Tourcoing, Nord, 59200, France

Location

Hôpital Bichat - Claude-Bernard ( Site 6162)

Paris, 75018, France

Location

Hôpital Saint Antoine ( Site 6158)

Paris, 75571, France

Location

Hôpital Avicenne ( Site 6160)

Bobigny, Île-de-France Region, 93000, France

Location

Hôpital Saint-Louis ( Site 6159)

Paris, Île-de-France Region, 75010, France

Location

Pitie Salpetriere University Hospital ( Site 6156)

Paris, Île-de-France Region, 75013, France

Location

Klinikum der Ludwig-Maximilians-Universitaet Muenchen-Medizinische Klinik und Poliklinik IV, Sektio

München, Bavaria, 80336, Germany

Location

Universitaetsklinikum Freiburg ( Site 6256)

Freiburg, Brandenburg, 79106, Germany

Location

Universitätsklinikum Bonn-Immunologie ( Site 6250)

Bonn, North Rhine-Westphalia, 53127, Germany

Location

ICH Study Center GmbH & Co. KG ( Site 6259)

Hamburg, 20146, Germany

Location

Universitaetsklinikum Hamburg-Eppendorf-Infektiologie ( Site 6260)

Hamburg, 20246, Germany

Location

CLINIPHARM ( Site 8352)

Guatemala City, 01001, Guatemala

Location

Clínica Médica Especializada en Pediatría e Infectología Pediátrica - Dr. Mario Melgar ( Site 8350)

Guatemala City, 01009, Guatemala

Location

CELAN,S.A ( Site 8351)

Guatemala City, 01010, Guatemala

Location

Rambam Health Care Campus-Institute of Allergy, Clinical Immunology, ( Site 6751)

Haifa, 3109601, Israel

Location

Hadassah Medical Center-Infecious Disease ( Site 6752)

Jerusalem, 9120, Israel

Location

Sheba Medical Center-HIV unit ( Site 6753)

Ramat Gan, 5262100, Israel

Location

Sourasky Medical Center ( Site 6754)

Tel Aviv, 6423906, Israel

Location

National Hospital Organization Nagoya Medical Center ( Site 6953)

Nagoya, Aichi-ken, 460-0001, Japan

Location

Tokyo Medical University Hospital ( Site 6954)

Shinjuku-ku, Tokyo, 160-0023, Japan

Location

Center Hospital of the National Center for Global Health and Medicine ( Site 6951)

Shinjyuku-ku, Tokyo, 162-8655, Japan

Location

National Hospital Organization Osaka National Hospital ( Site 6952)

Osaka, 540-0006, Japan

Location

CCR KEMRI (Center for Clinical Research) ( Site 8652)

Nairobi, Nairobi City, 00200, Kenya

Location

PHRD KEMRI (Partners in Health Research & Development) ( Site 8651)

Nairobi, Nairobi City, 00202, Kenya

Location

KEMRI-CMR-RCTP ( Site 8650)

Kisumu, 40100, Kenya

Location

Hospital Sultanah Bahiyah ( Site 7776)

Alor Star, Kedah, 05460, Malaysia

Location

University Malaya Medical Centre-Clinical Investigation Centre (CIC) ( Site 7777)

Lembah Pantai, Kuala Lumpur, 59100, Malaysia

Location

Hospital Pulau Pinang ( Site 7779)

George Town, Pulau Pinang, 10450, Malaysia

Location

Sarawak General Hospital ( Site 7772)

Kuching, Sarawak, 93586, Malaysia

Location

Hospital Selayang ( Site 7770)

Batu Caves, Selangor, 68100, Malaysia

Location

Hospital Sungai Buloh ( Site 7778)

Sungai Buloh, Selangor, 47000, Malaysia

Location

Hospital Kuala Lumpur ( Site 7773)

Kuala Lumpur, 50586, Malaysia

Location

Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran ( Site 7251)

Mexico City, Mexico City, 14080, Mexico

Location

Ponce Medical School Foundation Inc. ( Site 7452)

Ponce, 00716, Puerto Rico

Location

Clinical Research Puerto Rico ( Site 7450)

San Juan, 00909, Puerto Rico

Location

HOPE Clinical Research ( Site 7451)

San Juan, 00909, Puerto Rico

Location

Josha Research ( Site 6652)

Bloemfontein, Free State, 9301, South Africa

Location

Perinatal HIV Research Unit (PHRU)-Adult Treatment and Research ( Site 6654)

Johannesburg, Gauteng, 2013, South Africa

Location

Helen Joseph Hospital-Clinical HIV Research Unit ( Site 6661)

Johannesburg, Gauteng, 2092, South Africa

Location

Ezintsha-Clinical Research Site ( Site 6656)

Johannesburg, Gauteng, 2193, South Africa

Location

Wentworth Hospital ( Site 6653)

Durban, KwaZulu-Natal, 4052, South Africa

Location

Qhakaza Mbokodo Research Clinic ( Site 6659)

Ladysmith, KwaZulu-Natal, 3370, South Africa

Location

Human Sciences Research Council-Centre for Community Based Research ( Site 6664)

Pietermaritzburg, KwaZulu-Natal, 3201, South Africa

Location

Madibeng Centre for Research ( Site 6660)

Brits, North West, 0250, South Africa

Location

Family Clinical Research Unit (Fam-Cru)-Adult Infectious Diseases ( Site 6657)

Cape Town, Western Cape, 7500, South Africa

Location

Desmond Tutu Health Foundation ( Site 6651)

Cape Town, Western Cape, 7925, South Africa

Location

Be Part Yoluntu Centre ( Site 6650)

Paarl, Western Cape, 7626, South Africa

Location

Hospital General Universitario de Elche-Infectius Disease ( Site 6358)

Elche, Alicante, 03202, Spain

Location

Hospital Germans Trias i Pujol-Fundació Lluita contra la Sida ( Site 6351)

Badalona, Barcelona, 08916, Spain

Location

HOSPITAL CLÍNIC DE BARCELONA-Infection Day Hospital ( Site 6350)

Barcelona, Catalonia, 08036, Spain

Location

Hospital Universitari de Bellvitge ( Site 6360)

L'Hospitalet de Llobregat,Barcelona, Catalonia, 08907, Spain

Location

HOSPITAL GENERAL UNIVERSITARIO GREGORIO MARAÑON-Unidad de Enfermedades Infecciosas ( Site 6353)

Madrid, Madrid, Comunidad de, 28007, Spain

Location

Hospital Universitario Ramón y Cajal-ENFERMEDADES INFECCIOSAS ( Site 6361)

Madrid, Madrid, Comunidad de, 28034, Spain

Location

Hospital Universitari Vall d'Hebron-Infectious Diseases: HIV unit ( Site 6352)

Barcelona, 08035, Spain

Location

Hospital Universitario Fundación Jiménez Díaz-Internal Medicine. Infectious disease ( Site 6357)

Madrid, 28015, Spain

Location

Hospital Universitario 12 de Octubre ( Site 6355)

Madrid, 28041, Spain

Location

Hospital Universitario La Paz ( Site 6354)

Madrid, 28046, Spain

Location

Hospital Universitario Virgen de la Victoria ( Site 6359)

Málaga, 29010, Spain

Location

University Hospital Basel-Infectiology ( Site 8151)

Basel, Canton of Basel-City, 4031, Switzerland

Location

Hôpitaux Universitaires de Genève (HUG)-Infectious Disease Department ( Site 8150)

Geneva, Canton of Geneva, 1205, Switzerland

Location

HIV Netherlands Australia Thailand Research Collaboration ( Site 7851)

Bangkok, Bangkok, 10330, Thailand

Location

Faculty of Medicine Siriraj Hospital-Preventive and social ( Site 7850)

Bangkok, Bangkok, 10700, Thailand

Location

Research Institute for Health Sciences-Research Institute for Health Sciences Building 1 ( Site 7852

Chiang Mai, 50200, Thailand

Location

Hacettepe Universite Hastaneleri ( Site 7650)

Altindağ, Ankara, 06230, Turkey (Türkiye)

Location

Ankara Bilkent Şehir Hastanesi-Infectious Disease and Clinical Microbiology ( Site 7659)

Ankara, 06800, Turkey (Türkiye)

Location

Southmead Hospital ( Site 7952)

Bristol, Bristol, City of, BS10 5NB, United Kingdom

Location

Royal London Hospital ( Site 7951)

London, England, E1 1BB, United Kingdom

Location

The Hathersage Centre ( Site 7953)

Manchester, England, M13 0FH, United Kingdom

Location

King's College Hospital ( Site 7950)

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

Location

The Mortimer Market Centre for Sexual Health and HIV Research ( Site 7954)

London, London, City of, WC1E 6JB, United Kingdom

Location

Related Links

• Merck Clinical Trials Information
• Plain Language Summary

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 20, 2023
• First Posted: January 30, 2023
• Study Start: March 8, 2023
• Primary Completion: October 13, 2025
• Study Completion (Estimated): August 5, 2029
• Last Updated: October 23, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will share

Locations

DO (1); US (38); CL (6); ZA (11); JP (4); GB (5); ME (1); CH (2); CA (5); MY (7); GU (3); TH (3); FR (7); DE (5); KE (3); PR (3); TU (2); CO (5); ES (11); AR (5); IL (4)