Study of Doravirine/Islatravir (DOR/ISL 100 mg/0.75 mg) to Evaluate the Antiretroviral Activity, Safety, and Tolerability in Treatment-Naïve Participants With Human Immunodeficiency Virus Type 1 (HIV-1) Infection (MK-8591A-020)

NCT04233879 | Completed Phase 3 Results DMC FDA Drug

• 4 other identifiers: 8591A-020MK-8591A-020jRCT20312100242019-000590-23
• Study Type: interventional
• Target: 599
• Locations: 13 countries
• Sites: 95

Brief Summary

This is a phase 3, randomized, controlled, double-blind, multisite clinical study of a once-daily fixed dose combination (FDC) of 100 mg doravirine/0.75 mg islatravir (DOR/ISL \[also known as MK-8591A\]) in treatment-naïve participants living with human immunodeficiency virus type-1 (HIV-1) infection. The primary objectives are to evaluate the antiretroviral activity, safety, and tolerability of DOR/ISL compared to bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF). The primary hypothesis is that DOR/ISL is noninferior or superior to BIC/FTC/TAF treatment based on 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 (HIV)-1 Ribonucleic Acid (RNA) <50 Copies/mL at Week 48

  The Abbott RealTime polymerase chain reaction (PCR) assay with a reliable lower limit of quantification of 40 copies/mL was used to measure the HIV-1 RNA level in blood samples obtained at each visit. The percentage of participants with HIV-1 RNA \<50 copies/mL at Week 48 was presented using the Food and Drug Administration (FDA) Snapshot missing data approach. The final analysis for this outcome is presented here.

  Week 48

• Percentage of Participants Who Experienced an Adverse Event (AE) up to Week 48

  An AE was any untoward medical occurrence in a study participant administered a study drug, which does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the study drug whether or not it is considered related to the study drug. The percentage of participants who experienced at least one AE up to Week 48 was reported. The final analysis for this outcome is presented here.

  Up to approximately 48 weeks

• Percentage of Participants Who Discontinued Study Treatment Due to an AE up to Week 48

  An AE was any untoward medical occurrence in a study participant administered a study drug, which does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the study drug whether or not it is considered related to the study drug. The percentage of participants who discontinued study treatment due to an AE up to Week 48 were reported. The final analysis for this outcome is presented here.

  Up to approximately 48 weeks

Secondary Outcomes (19)

• 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 <40 Copies/mL at Week 48

  Week 48

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

  Week 48

• Percentage of Participants With HIV-1 RNA <40 Copies/mL at Week 96

  Week 96

Study Arms (2)

Group 1: doravirine/islatravir (DOR/ISL)

EXPERIMENTAL

Treatment-naïve participants living with human immunodeficiency virus-1 (HIV-1) that had not received ≤10 days of prior antiretroviral therapy received blinded fixed dose combination (FDC) Doravirine/Islatravir (DOR/ISL) (100 mg doravirine \[DOR\]/0.75 mg islatravir \[ISL\]) and placebo to Bictegravir/Tenofovir Alafenamide/Emtricitabine (BIC/FTC/TAF) once daily (QD) from Day 1 to Week 96, and open-label DOR/ISL up to Week 144. At Week 144, participants who consent to enter the optional open-label study extension continued to receive open-label QD FDC of DOR/ISL (100 mg/0.75 mg) for an additional 24 weeks, up to Week 168.

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

Group 2: bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF)

ACTIVE COMPARATOR

Treatment-naïve participants living with HIV-1 that had not received ≤10 days of prior antiretroviral therapy received blinded BIC/FTC/TAF (50 mg bictegravir \[BIC\], 200 mg emtricitabine \[FTC\], 25 mg tenofovir alafenamide \[TAF\]) and placebo to FDC DOR/ISL QD from Day 1 to Week 96, and open-label BIC/FTC/TAF up to Week 144. At Week 144, participants who consent to enter the optional open-label study extension continued to receive QD BIC/FTC/TAF (50 mg/200 mg/25 mg) for an additional 24 weeks, up to Week 168.

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

Interventions

DOR/ISL DRUG

100 mg DOR/0.75 mg ISL FDC single tablet taken once daily by mouth.

Also known as: MK-8591A, Doravirine/islatravir

Group 1: doravirine/islatravir (DOR/ISL)

BIC/FTC/TAF DRUG

BIC/FTC/TAF 50/200/25 mg FDC single tablet taken once daily by mouth.

Also known as: Bictegravir/emtricitabine/tenofovir alafenamide

Group 2: bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF)

Placebo to BIC/FTC/TAF DRUG

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

Group 1: doravirine/islatravir (DOR/ISL)

Placebo to DOR/ISL DRUG

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

Group 2: bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF)

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 type 1 (HIV-1) positive
• Is naïve to antiretroviral therapy (ART) defined as having received ≤10 days of prior therapy with any antiretroviral agent following a diagnosis of HIV-1 infection including prevention of mother-to-child transmission up to 1 month prior to screening.
• A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies: 1) Is not a woman of childbearing potential (WOCBP); 2) Is a WOCBP and using an acceptable contraceptive method, or be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis); 3) A WOCBP must have a negative highly sensitive pregnancy test (\[urine or serum\] as required by local regulations) within 24 hours before the first dose of study intervention; 4) If a urine test cannot be confirmed as negative (eg, an ambiguous result), a serum pregnancy test is required

You may not qualify if:

• Has human immunodeficiency virus type 2 (HIV-2) infection
• Has hypersensitivity or other contraindication to any of the components of the study interventions as determined by the investigator
• Has an active diagnosis of hepatitis due to any cause, including active hepatitis B virus (HBV) infection (defined as hepatitis B surface antigen \[HBsAg\]-positive or hepatitis B virus deoxyribonucleic acid \[HBV DNA\]-positive)
• Has a history of malignancy ≤5 years prior to signing 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
• Has been treated for a viral infection other than HIV-1, such as hepatitis B, with an agent that is active against HIV-1
• Is taking or is anticipated to require systemic immunosuppressive therapy, immune modulators, or any prohibited therapy from 45 days prior to Day 1 through the study intervention period
• Is currently participating in or has participated in a clinical study with an investigational compound or device from 45 days prior to Day 1 through the study intervention period
• Has a documented or known virologic resistance to any approved HIV-1 reverse transcriptase inhibitor, or any study intervention
• Is female and is expecting to conceive or donate eggs at any time during the study

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Study Sites (95)

University of Alabama at Birmingham 1917 Research Clinic ( Site 5610)

Birmingham, Alabama, 35222, United States

Location

Pueblo Family Physicians ( Site 5606)

Phoenix, Arizona, 85015, United States

Location

Ruane Clinical Research Group, Inc. ( Site 5624)

Los Angeles, California, 90036, United States

Location

Midway Immunology and Research ( Site 5622)

Ft. Pierce, Florida, 34982, United States

Location

The Kinder Medical Group ( Site 5615)

Miami, Florida, 33133, United States

Location

Floridian Clinical Research, LLC ( Site 5625)

Miami Lakes, Florida, 33016, United States

Location

Orlando Immunology Center ( Site 5613)

Orlando, Florida, 32803, United States

Location

CAN Community Health ( Site 5627)

Sarasota, Florida, 34237, United States

Location

Triple O Research Institute, P.A. ( Site 5621)

West Palm Beach, Florida, 33407, United States

Location

Columbus Regional Research Institute ( Site 5616)

Columbus, Georgia, 31904, United States

Location

Infectious Disease Specialists Of Atlanta PC ( Site 5608)

Decatur, Georgia, 30033, United States

Location

Hennepin Healthcare-Hennepin Healthcare-ID ( Site 5633)

Minneapolis, Minnesota, 55415, United States

Location

Kansas City CARE Clinic ( Site 5607)

Kansas City, Missouri, 64111, United States

Location

University of Pennsylvania ( Site 5630)

Philadelphia, Pennsylvania, 19104, United States

Location

Saint Hope Foundation, Inc. ( Site 5629)

Bellaire, Texas, 77401, United States

Location

North Texas ID Consultants, PA ( Site 5604)

Dallas, Texas, 75246, United States

Location

Texas Centers for Infectious Disease Associates P.A. ( Site 5619)

Fort Worth, Texas, 76104, United States

Location

Helios Salud S.A. ( Site 5802)

Buenos Aires, Buenos Aires F.D., C1141ACG, Argentina

Location

IDEAA Foundation ( Site 5807)

Buenos Aires, Buenos Aires F.D., C1405CKC, Argentina

Location

Fundación Huesped ( Site 5801)

C.a.b.a, Buenos Aires F.D., C1202ABB, Argentina

Location

Instituto CAICI ( Site 5803)

Rosario, Santa Fe Province, S2000PBJ, Argentina

Location

Instituto Oulton ( Site 5804)

Córdoba, X5000JJS, Argentina

Location

Hamilton Health Sciences- Urgent Care Centre-SIS Clinic ( Site 5703)

Hamilton, Ontario, L8S 14K, Canada

Location

Toronto General Hospital - University Health Network ( Site 5705)

Toronto, Ontario, M5G 2N2, Canada

Location

Clinique Medicale L Actuel ( Site 5714)

Montreal, Quebec, H2L 4P9, Canada

Location

McGill University Health Center - Research Institute-CVIS Clinical Research Unit ( Site 5702)

Montreal, Quebec, H4A 3J1, Canada

Location

Clinica Universidad Catolica del Maule ( Site 5909)

Talca, Maule Region, 3460000, Chile

Location

Clinica Arauco Salud ( Site 5900)

Santiago, Region M. de Santiago, 7560994, Chile

Location

Hospital Clinico de la Universidad Catolica ( Site 5903)

Santiago, Region M. de Santiago, 8331150, Chile

Location

Fundacion Arriaran ( Site 5901)

Santiago, Region M. de Santiago, 8360159, Chile

Location

Centro Cardiovascular Cardiosur ( Site 5907)

Santiago, Region M. de Santiago, 8910259, Chile

Location

Hospital Dr. Hernan Henriquez Aravena ( Site 5905)

Temuco, Región de la Araucanía, 4781151, Chile

Location

Hospital Universitario San Ignacio ( Site 6005)

Bogotá, Bogota D.C., 110231, Colombia

Location

Clinica Colsanitas S.A. Sede Clinica Universitaria Colombia ( Site 6006)

Bogotá, Bogota D.C., 111321, Colombia

Location

Fundacion Valle del Lili ( Site 6001)

Cali, Valle del Cauca Department, 760032, Colombia

Location

A.P.H. Paris. Hopital Bichat Claude Bernard ( Site 6124)

Paris, Ain, 75018, France

Location

Hopital de la Croix-Rousse ( Site 6127)

Lyon, Auvergne-Rhône-Alpes, 69004, France

Location

Centre Hospitalier Regional du Orleans ( Site 6108)

Orléans, Centre-Val de Loire, 45000, France

Location

Hopital Francois Mitterrand ( Site 6119)

Dijon, Cote-d Or, 21079, France

Location

CHU de Bordeaux. Hopital Pellegrin ( Site 6116)

Bordeaux, Gironde, 33076, France

Location

Centre Hospitalier de Tourcoing ( Site 6100)

Tourcoing, Nord, 59208, France

Location

Hopital Avicenne ( Site 6102)

Bobigny, Seine-Saint-Denis, 93000, France

Location

A.P.H. Paris, Hopital Saint Louis ( Site 6114)

Paris, 75010, France

Location

Hopital Saint-Antoine ( Site 6113)

Paris, 75012, France

Location

Hopital Pitie Salpetriere ( Site 6111)

Paris, 75013, France

Location

Universitaetsklinik Freiburg ( Site 6206)

Freiburg im Breisgau, Baden-Wurttemberg, 79106, Germany

Location

Klinikum der LMU München ( Site 6204)

Munich, Bavaria, 80336, Germany

Location

MVZ Munchen am Goetheplatz ( Site 6202)

Munich, Bavaria, 80337, Germany

Location

Infektiologikum ( Site 6201)

Frankfurt am Main, Hesse, 60596, Germany

Location

Universitaetsklinikum Bonn ( Site 6200)

Bonn, North Rhine-Westphalia, 53127, Germany

Location

EPIMED- Ges. f. epidemiolog. u. klin. Forschung in der Medizin mbH ( Site 6208)

Berlin, 10787, Germany

Location

Universitaetsklinikum Hamburg- Eppendorf (UKE) ( Site 6210)

Hamburg, 20246, Germany

Location

Rambam Medical Center ( Site 6701)

Haifa, 3109601, Israel

Location

Hadassah Ein Kerem Medical Center ( Site 6702)

Jerusalem, 9112001, Israel

Location

Chaim Sheba Medical Center. ( Site 6704)

Ramat Gan, 5265601, Israel

Location

Kaplan Medical Center ( Site 6700)

Rehovot, 7610001, Israel

Location

Sourasky Medical Center ( Site 6705)

Tel Aviv, 64239, Israel

Location

A.O.R.N. dei Colli - Ospedale Cotugno ( Site 6407)

Naples, Campania, 80131, Italy

Location

Azienda Ospedaliero Universitaria di Modena Policlinico ( Site 6404)

Modena, Emilia-Romagna, 41124, Italy

Location

ASST Papa Giovanni XXIII ( Site 6411)

Bergamo, Lombardy, 24127, Italy

Location

Ospedale San Gerardo ASST Monza ( Site 6412)

Monza, Monza E Brianza, 20900, Italy

Location

Ospedale Amedeo di Savoia ( Site 6414)

Turin, Piedmont, 10149, Italy

Location

Fondazione IRCCS Ca' Granda-Ospedale Maggiore Policlinico ( Site 6401)

Milan, 20122, Italy

Location

Salute San Raffaele ( Site 6402)

Milan, 20127, Italy

Location

Azienda Ospedaliera San Paolo ( Site 6403)

Milan, 20142, Italy

Location

ASST Fatebenefratelli-Ospedale Sacco ( Site 6400)

Milan, 20157, Italy

Location

IRCCS Policlinico San Matteo ( Site 6410)

Pavia, 27100, Italy

Location

Azienda USL di Pescara-Presidio Ospedaliero di Pescara ( Site 6413)

Pescara, 65129, Italy

Location

Istituto Nazionale per Le Malattie Infettive Lazzaro Spallanzani ( Site 6405)

Roma, 00149, Italy

Location

National Hospital Organization Nagoya Medical Center ( Site 6903)

Nagoya, Aichi-ken, 460-0001, Japan

Location

Kumamoto University Hospital ( Site 6905)

Kumamoto, 860-8556, Japan

Location

National Hospital Organization - Osaka National Hospital - Institute For Clinical Research ( Site 69

Osaka, 540-0006, Japan

Location

Tokyo Medical University Hospital ( Site 6904)

Tokyo, 160-0023, Japan

Location

Center Hospital of the National Center for Global Health and Medicine ( Site 6901)

Tokyo, 162-8655, Japan

Location

JOSHA Research ( Site 6605)

Bloemfontein, Free State, 9301, South Africa

Location

Chris Hani Baragwanath Hospital - ICU ( Site 6608)

Johannesburg, Gauteng, 1862, South Africa

Location

Wits Health Consortium. Clinical HIV Research Unit ( Site 6614)

Johannesburg, Gauteng, 2041, South Africa

Location

Ezintsha ( Site 6609)

Johannesburg, Gauteng, 2193, South Africa

Location

Wentworth Hospital ( Site 6607)

Durban, KwaZulu-Natal, 4052, South Africa

Location

Family Clinical Research Unit (Fam-Cru)-Adult Infectious Diseases ( Site 6617)

Cape Town, Western Cape, 7500, South Africa

Location

Desmond Tutu HIV Foundation Clinical Trial Unit ( Site 6613)

Cape Town, Western Cape, 7925, South Africa

Location

Be Part Yoluntu Centre ( Site 6603)

Mbekweni, Paarl, Western Cape, 7646, South Africa

Location

Hospital General de Elche ( Site 6308)

Elche, Alicante, 03202, Spain

Location

Hospital Universitari Germans Trias i Pujol ( Site 6301)

Badalona, Barcelona, 08916, Spain

Location

Hospital Universitari de Bellvitge ( Site 6312)

LHospitalet de Llobregat, Barcelona, 08907, Spain

Location

Hospital Vall D Hebron ( Site 6302)

Barcelona, Catalonia, 08035, Spain

Location

Hospital Clinic i Provincial ( Site 6300)

Barcelona, Catalonia, 08036, Spain

Location

Hospital General Universitario Gregorio Maranon ( Site 6303)

Madrid, 28007, Spain

Location

Hospital Universitario Fundacion Jimenez Diaz ( Site 6307)

Madrid, 28040, Spain

Location

Hospital Universitario 12 de Octubre ( Site 6305)

Madrid, 28041, Spain

Location

Hospital Universitario La Paz ( Site 6304)

Madrid, 28046, Spain

Location

Hospital Universitario Virgen de la Victoria ( Site 6309)

Málaga, 29010, Spain

Location

Kaohsiung Veterans General Hospital ( Site 7102)

Kaohsiung City, 81362, Taiwan

Location

National Cheng Kung University Hospital ( Site 7101)

Tainan, 70403, Taiwan

Location

National Taiwan University Hospital ( Site 7100)

Taipei, 100, Taiwan

Location

Related Publications (1)

• Rockstroh JK, Paredes R, Cahn P, Molina JM, Sokhela SM, Hinestrosa F, Kassim S, Cunningham D, Ghosn J, Bogner JR, Gatanaga H, Asante-Appiah E, Zhang Y, Nwoke U, Klopfer SO, Eves K, Squires K, Correll T, Fox MC, Pisculli ML. Doravirine/Islatravir (100/0.75 mg) Once-Daily Compared With Bictegravir/Emtricitabine/Tenofovir Alafenamide as Initial HIV-1 Treatment: 48-Week Results From a Phase 3, Randomized, Controlled, Double-Blind, Noninferiority Trial. Clin Infect Dis. 2025 Sep 16;81(2):322-332. doi: 10.1093/cid/ciaf077.

  PMID: 40079835 RESULT

Related Links

• Merck Clinical Trials Information

MeSH Terms

Interventions

doravirine; islatravir; bictegravir, emtricitabine, tenofovir alafenamide, drug combination

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: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 15, 2020
• First Posted: January 18, 2020
• Study Start: February 28, 2020
• Primary Completion: November 17, 2022
• Study Completion: January 29, 2025
• Last Updated: January 28, 2026
• Results First Posted: November 21, 2023

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share

Locations

CA (4); AR (5); TW (3); ES (10); DE (7); IL (5); US (17); ZA (8); JP (5); CL (6); FR (10); IT (12); CO (3)