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)

NCT ID: NCT04233879

Last Updated: 2026-01-28

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

599 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-02-28

Study Completion Date

2025-01-29

Brief Summary

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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.

Detailed Description

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Double-blind treatment with the assigned intervention occurs from Day 1 to Week 96, followed by an open-label portion up to Week 144. Participants who benefit from treatment in the opinion of the Investigator may continue their assigned intervention up to Week 168 (or until they have the option to enroll in a DOR/ISL 100 mg/0.25 mg study, whichever is sooner).

Conditions

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HIV-1 Infection

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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Group 1: doravirine/islatravir (DOR/ISL)

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.

Group Type EXPERIMENTAL

DOR/ISL

Intervention Type DRUG

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

Placebo to BIC/FTC/TAF

Intervention Type DRUG

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

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

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.

Group Type ACTIVE_COMPARATOR

BIC/FTC/TAF

Intervention Type DRUG

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

Placebo to DOR/ISL

Intervention Type DRUG

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

Interventions

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DOR/ISL

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

Intervention Type DRUG

BIC/FTC/TAF

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

Intervention Type DRUG

Placebo to BIC/FTC/TAF

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

Intervention Type DRUG

Placebo to DOR/ISL

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

Intervention Type DRUG

Other Intervention Names

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MK-8591A Doravirine/islatravir Bictegravir/emtricitabine/tenofovir alafenamide

Eligibility Criteria

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Inclusion Criteria

* 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

Exclusion Criteria

* 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
* Has exclusionary laboratory values within 45 days prior to Day 1
* Is female and is expecting to conceive or donate eggs at any time during the study
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Medical Director

Role: STUDY_DIRECTOR

Merck Sharp & Dohme LLC

Locations

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

Birmingham, Alabama, United States

Site Status

Pueblo Family Physicians ( Site 5606)

Phoenix, Arizona, United States

Site Status

Ruane Clinical Research Group, Inc. ( Site 5624)

Los Angeles, California, United States

Site Status

Midway Immunology and Research ( Site 5622)

Ft. Pierce, Florida, United States

Site Status

The Kinder Medical Group ( Site 5615)

Miami, Florida, United States

Site Status

Floridian Clinical Research, LLC ( Site 5625)

Miami Lakes, Florida, United States

Site Status

Orlando Immunology Center ( Site 5613)

Orlando, Florida, United States

Site Status

CAN Community Health ( Site 5627)

Sarasota, Florida, United States

Site Status

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

West Palm Beach, Florida, United States

Site Status

Columbus Regional Research Institute ( Site 5616)

Columbus, Georgia, United States

Site Status

Infectious Disease Specialists Of Atlanta PC ( Site 5608)

Decatur, Georgia, United States

Site Status

Hennepin Healthcare-Hennepin Healthcare-ID ( Site 5633)

Minneapolis, Minnesota, United States

Site Status

Kansas City CARE Clinic ( Site 5607)

Kansas City, Missouri, United States

Site Status

University of Pennsylvania ( Site 5630)

Philadelphia, Pennsylvania, United States

Site Status

Saint Hope Foundation, Inc. ( Site 5629)

Bellaire, Texas, United States

Site Status

North Texas ID Consultants, PA ( Site 5604)

Dallas, Texas, United States

Site Status

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

Fort Worth, Texas, United States

Site Status

Helios Salud S.A. ( Site 5802)

Buenos Aires, Buenos Aires F.D., Argentina

Site Status

IDEAA Foundation ( Site 5807)

Buenos Aires, Buenos Aires F.D., Argentina

Site Status

Fundación Huesped ( Site 5801)

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

Site Status

Instituto CAICI ( Site 5803)

Rosario, Santa Fe Province, Argentina

Site Status

Instituto Oulton ( Site 5804)

Córdoba, , Argentina

Site Status

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

Hamilton, Ontario, Canada

Site Status

Toronto General Hospital - University Health Network ( Site 5705)

Toronto, Ontario, Canada

Site Status

Clinique Medicale L Actuel ( Site 5714)

Montreal, Quebec, Canada

Site Status

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

Montreal, Quebec, Canada

Site Status

Clinica Universidad Catolica del Maule ( Site 5909)

Talca, Maule Region, Chile

Site Status

Clinica Arauco Salud ( Site 5900)

Santiago, Region M. de Santiago, Chile

Site Status

Hospital Clinico de la Universidad Catolica ( Site 5903)

Santiago, Region M. de Santiago, Chile

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Fundacion Arriaran ( Site 5901)

Santiago, Region M. de Santiago, Chile

Site Status

Centro Cardiovascular Cardiosur ( Site 5907)

Santiago, Region M. de Santiago, Chile

Site Status

Hospital Dr. Hernan Henriquez Aravena ( Site 5905)

Temuco, Región de la Araucanía, Chile

Site Status

Hospital Universitario San Ignacio ( Site 6005)

Bogotá, Bogota D.C., Colombia

Site Status

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

Bogotá, Bogota D.C., Colombia

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Fundacion Valle del Lili ( Site 6001)

Cali, Valle del Cauca Department, Colombia

Site Status

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

Paris, Ain, France

Site Status

Hopital de la Croix-Rousse ( Site 6127)

Lyon, Auvergne-Rhône-Alpes, France

Site Status

Centre Hospitalier Regional du Orleans ( Site 6108)

Orléans, Centre-Val de Loire, France

Site Status

Hopital Francois Mitterrand ( Site 6119)

Dijon, Cote-d Or, France

Site Status

CHU de Bordeaux. Hopital Pellegrin ( Site 6116)

Bordeaux, Gironde, France

Site Status

Centre Hospitalier de Tourcoing ( Site 6100)

Tourcoing, Nord, France

Site Status

Hopital Avicenne ( Site 6102)

Bobigny, Seine-Saint-Denis, France

Site Status

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

Paris, , France

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Hopital Saint-Antoine ( Site 6113)

Paris, , France

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Hopital Pitie Salpetriere ( Site 6111)

Paris, , France

Site Status

Universitaetsklinik Freiburg ( Site 6206)

Freiburg im Breisgau, Baden-Wurttemberg, Germany

Site Status

Klinikum der LMU München ( Site 6204)

Munich, Bavaria, Germany

Site Status

MVZ Munchen am Goetheplatz ( Site 6202)

Munich, Bavaria, Germany

Site Status

Infektiologikum ( Site 6201)

Frankfurt am Main, Hesse, Germany

Site Status

Universitaetsklinikum Bonn ( Site 6200)

Bonn, North Rhine-Westphalia, Germany

Site Status

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

Berlin, , Germany

Site Status

Universitaetsklinikum Hamburg- Eppendorf (UKE) ( Site 6210)

Hamburg, , Germany

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Rambam Medical Center ( Site 6701)

Haifa, , Israel

Site Status

Hadassah Ein Kerem Medical Center ( Site 6702)

Jerusalem, , Israel

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Chaim Sheba Medical Center. ( Site 6704)

Ramat Gan, , Israel

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Kaplan Medical Center ( Site 6700)

Rehovot, , Israel

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Sourasky Medical Center ( Site 6705)

Tel Aviv, , Israel

Site Status

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

Napoli, Campania, Italy

Site Status

Azienda Ospedaliero Universitaria di Modena Policlinico ( Site 6404)

Modena, Emilia-Romagna, Italy

Site Status

ASST Papa Giovanni XXIII ( Site 6411)

Bergamo, Lombardy, Italy

Site Status

Ospedale San Gerardo ASST Monza ( Site 6412)

Monza, Monza E Brianza, Italy

Site Status

Ospedale Amedeo di Savoia ( Site 6414)

Turin, Piedmont, Italy

Site Status

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

Milan, , Italy

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Salute San Raffaele ( Site 6402)

Milan, , Italy

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Azienda Ospedaliera San Paolo ( Site 6403)

Milan, , Italy

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ASST Fatebenefratelli-Ospedale Sacco ( Site 6400)

Milan, , Italy

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IRCCS Policlinico San Matteo ( Site 6410)

Pavia, , Italy

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

Pescara, , Italy

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

Roma, , Italy

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National Hospital Organization Nagoya Medical Center ( Site 6903)

Nagoya, Aichi-ken, Japan

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Kumamoto University Hospital ( Site 6905)

Kumamoto, , Japan

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

Osaka, , Japan

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Tokyo Medical University Hospital ( Site 6904)

Tokyo, , Japan

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

Tokyo, , Japan

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JOSHA Research ( Site 6605)

Bloemfontein, Free State, South Africa

Site Status

Chris Hani Baragwanath Hospital - ICU ( Site 6608)

Johannesburg, Gauteng, South Africa

Site Status

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

Johannesburg, Gauteng, South Africa

Site Status

Ezintsha ( Site 6609)

Johannesburg, Gauteng, South Africa

Site Status

Wentworth Hospital ( Site 6607)

Durban, KwaZulu-Natal, South Africa

Site Status

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

Cape Town, Western Cape, South Africa

Site Status

Desmond Tutu HIV Foundation Clinical Trial Unit ( Site 6613)

Cape Town, Western Cape, South Africa

Site Status

Be Part Yoluntu Centre ( Site 6603)

Mbekweni, Paarl, Western Cape, South Africa

Site Status

Hospital General de Elche ( Site 6308)

Elche, Alicante, Spain

Site Status

Hospital Universitari Germans Trias i Pujol ( Site 6301)

Badalona, Barcelona, Spain

Site Status

Hospital Universitari de Bellvitge ( Site 6312)

LHospitalet de Llobregat, Barcelona, Spain

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Hospital Vall D Hebron ( Site 6302)

Barcelona, Catalonia, Spain

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Hospital Clinic i Provincial ( Site 6300)

Barcelona, Catalonia, Spain

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Hospital General Universitario Gregorio Maranon ( Site 6303)

Madrid, , Spain

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Hospital Universitario Fundacion Jimenez Diaz ( Site 6307)

Madrid, , Spain

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Hospital Universitario 12 de Octubre ( Site 6305)

Madrid, , Spain

Site Status

Hospital Universitario La Paz ( Site 6304)

Madrid, , Spain

Site Status

Hospital Universitario Virgen de la Victoria ( Site 6309)

Málaga, , Spain

Site Status

Kaohsiung Veterans General Hospital ( Site 7102)

Kaohsiung City, , Taiwan

Site Status

National Cheng Kung University Hospital ( Site 7101)

Tainan, , Taiwan

Site Status

National Taiwan University Hospital ( Site 7100)

Taipei, , Taiwan

Site Status

Countries

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United States Argentina Canada Chile Colombia France Germany Israel Italy Japan South Africa Spain Taiwan

References

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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.

Reference Type RESULT
PMID: 40079835 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

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http://www.merckclinicaltrials.com

Merck Clinical Trials Information

Other Identifiers

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MK-8591A-020

Identifier Type: OTHER

Identifier Source: secondary_id

jRCT2031210024

Identifier Type: REGISTRY

Identifier Source: secondary_id

2019-000590-23

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

8591A-020

Identifier Type: -

Identifier Source: org_study_id

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