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)

A Phase 3 Randomized, Active-Controlled, Double-Blind Clinical Study to Evaluate the Antiretroviral Activity, Safety, and Tolerability of Doravirine/Islatravir Once-Daily in HIV-1 Infected Treatment-Naïve Participants

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.

Study Overview

• Status: Completed
• Conditions: HIV-1 Infection
• Intervention / Treatment: Drug: DOR/ISL; Drug: Placebo to BIC/FTC/TAF; Drug: BIC/FTC/TAF; Drug: Placebo to DOR/ISL

Detailed Description

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).

• Study Type: Interventional
• Enrollment (Actual): 599
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Córdoba, Argentina, X5000JJS
    • Instituto Oulton ( Site 5804)
  • Buenos Aires F.D.
    • Buenos Aires, Buenos Aires F.D., Argentina, C1141ACG
      • Helios Salud S.A. ( Site 5802)
    • Buenos Aires, Buenos Aires F.D., Argentina, C1405CKC
      • IDEAA Foundation ( Site 5807)
    • C.a.b.a, Buenos Aires F.D., Argentina, C1202ABB
      • Fundación Huesped ( Site 5801)
  • Santa Fe Province
    • Rosario, Santa Fe Province, Argentina, S2000PBJ
      • Instituto CAICI ( Site 5803)
• Canada
  • Ontario
    • Hamilton, Ontario, Canada, L8S 14K
      • Hamilton Health Sciences- Urgent Care Centre-SIS Clinic ( Site 5703)
    • Toronto, Ontario, Canada, M5G 2N2
      • Toronto General Hospital - University Health Network ( Site 5705)
  • Quebec
    • Montreal, Quebec, Canada, H2L 4P9
      • Clinique Medicale L Actuel ( Site 5714)
    • Montreal, Quebec, Canada, H4A 3J1
      • McGill University Health Center - Research Institute-CVIS Clinical Research Unit ( Site 5702)
• Chile
  • Araucania
    • Temuco, Araucania, Chile, 4781151
      • Hospital Dr. Hernan Henriquez Aravena ( Site 5905)
  • Maule Region
    • Talca, Maule Region, Chile, 3460000
      • Clinica Universidad Catolica del Maule ( Site 5909)
  • Region M. de Santiago
    • Santiago, Region M. de Santiago, Chile, 7560994
      • Clinica Arauco Salud ( Site 5900)
    • Santiago, Region M. de Santiago, Chile, 8331150
      • Hospital Clinico de la Universidad Catolica ( Site 5903)
    • Santiago, Region M. de Santiago, Chile, 8360159
      • Fundacion Arriaran ( Site 5901)
    • Santiago, Region M. de Santiago, Chile, 8910259
      • Centro Cardiovascular Cardiosur ( Site 5907)
• Colombia
  • Bogota D.C.
    • Bogotá, Bogota D.C., Colombia, 110231
      • Hospital Universitario San Ignacio ( Site 6005)
    • Bogotá, Bogota D.C., Colombia, 111321
      • Clinica Colsanitas S.A. Sede Clinica Universitaria Colombia ( Site 6006)
  • Valle del Cauca Department
    • Cali, Valle del Cauca Department, Colombia, 760032
      • Fundacion Valle del Lili ( Site 6001)
• France
  • Paris, France, 75010
    • A.P.H. Paris, Hopital Saint Louis ( Site 6114)
  • Paris, France, 75012
    • Hopital Saint-Antoine ( Site 6113)
  • Paris, France, 75013
    • Hopital Pitie Salpetriere ( Site 6111)
  • Ain
    • Paris, Ain, France, 75018
      • A.P.H. Paris. Hopital Bichat Claude Bernard ( Site 6124)
  • Auvergne-Rhône-Alpes
    • Lyon, Auvergne-Rhône-Alpes, France, 69004
      • Hopital de la Croix-Rousse ( Site 6127)
  • Centre-Val de Loire
    • Orléans, Centre-Val de Loire, France, 45000
      • Centre Hospitalier Regional du Orleans ( Site 6108)
  • Cote-d Or
    • Dijon, Cote-d Or, France, 21079
      • Hopital Francois Mitterrand ( Site 6119)
  • Gironde
    • Bordeaux, Gironde, France, 33076
      • CHU de Bordeaux. Hopital Pellegrin ( Site 6116)
  • Nord
    • Tourcoing, Nord, France, 59208
      • Centre Hospitalier de Tourcoing ( Site 6100)
  • Seine-Saint-Denis
    • Bobigny, Seine-Saint-Denis, France, 93000
      • Hopital Avicenne ( Site 6102)
• Germany
  • Berlin, Germany, 10787
    • EPIMED- Ges. f. epidemiolog. u. klin. Forschung in der Medizin mbH ( Site 6208)
  • Hamburg, Germany, 20246
    • Universitaetsklinikum Hamburg- Eppendorf (UKE) ( Site 6210)
  • Baden-Wurttemberg
    • Freiburg im Breisgau, Baden-Wurttemberg, Germany, 79106
      • Universitaetsklinik Freiburg ( Site 6206)
  • Bavaria
    • Munich, Bavaria, Germany, 80336
      • Klinikum der LMU München ( Site 6204)
    • Munich, Bavaria, Germany, 80337
      • MVZ Munchen am Goetheplatz ( Site 6202)
  • Hesse
    • Frankfurt am Main, Hesse, Germany, 60596
      • Infektiologikum ( Site 6201)
  • North Rhine-Westphalia
    • Bonn, North Rhine-Westphalia, Germany, 53127
      • Universitaetsklinikum Bonn ( Site 6200)
• Israel
  • Haifa, Israel, 3109601
    • Rambam Medical Center ( Site 6701)
  • Jerusalem, Israel, 9112001
    • Hadassah Ein Kerem Medical Center ( Site 6702)
  • Ramat Gan, Israel, 5265601
    • Chaim Sheba Medical Center. ( Site 6704)
  • Rehovot, Israel, 7610001
    • Kaplan Medical Center ( Site 6700)
  • Tel Aviv, Israel, 64239
    • Sourasky Medical Center ( Site 6705)
• Italy
  • Milan, Italy, 20122
    • Fondazione IRCCS Ca' Granda-Ospedale Maggiore Policlinico ( Site 6401)
  • Milan, Italy, 20127
    • Salute San Raffaele ( Site 6402)
  • Milan, Italy, 20142
    • Azienda Ospedaliera San Paolo ( Site 6403)
  • Milan, Italy, 20157
    • ASST Fatebenefratelli-Ospedale Sacco ( Site 6400)
  • Pavia, Italy, 27100
    • IRCCS Policlinico San Matteo ( Site 6410)
  • Pescara, Italy, 65129
    • Azienda USL di Pescara-Presidio Ospedaliero di Pescara ( Site 6413)
  • Roma, Italy, 00149
    • Istituto Nazionale per Le Malattie Infettive Lazzaro Spallanzani ( Site 6405)
  • Campania
    • Naples, Campania, Italy, 80131
      • A.O.R.N. dei Colli - Ospedale Cotugno ( Site 6407)
  • Emilia-Romagna
    • Modena, Emilia-Romagna, Italy, 41124
      • Azienda Ospedaliero Universitaria di Modena Policlinico ( Site 6404)
  • Lombardy
    • Bergamo, Lombardy, Italy, 24127
      • ASST Papa Giovanni XXIII ( Site 6411)
  • Monza E Brianza
    • Monza, Monza E Brianza, Italy, 20900
      • Ospedale San Gerardo ASST Monza ( Site 6412)
  • Piedmont
    • Turin, Piedmont, Italy, 10149
      • Ospedale Amedeo di Savoia ( Site 6414)
• Japan
  • Kumamoto, Japan, 860-8556
    • Kumamoto University Hospital ( Site 6905)
  • Osaka, Japan, 540-0006
    • National Hospital Organization - Osaka National Hospital - Institute For Clinical Research ( Site 69
  • Tokyo, Japan, 160-0023
    • Tokyo Medical University Hospital ( Site 6904)
  • Tokyo, Japan, 162-8655
    • Center Hospital of the National Center for Global Health and Medicine ( Site 6901)
  • Aichi-ken
    • Nagoya, Aichi-ken, Japan, 460-0001
      • National Hospital Organization Nagoya Medical Center ( Site 6903)
• South Africa
  • Free State
    • Bloemfontein, Free State, South Africa, 9301
      • JOSHA Research ( Site 6605)
  • Gauteng
    • Johannesburg, Gauteng, South Africa, 1862
      • Chris Hani Baragwanath Hospital - ICU ( Site 6608)
    • Johannesburg, Gauteng, South Africa, 2041
      • Wits Health Consortium. Clinical HIV Research Unit ( Site 6614)
    • Johannesburg, Gauteng, South Africa, 2193
      • Ezintsha ( Site 6609)
  • KwaZulu-Natal
    • Durban, KwaZulu-Natal, South Africa, 4052
      • Wentworth Hospital ( Site 6607)
  • Western Cape
    • Cape Town, Western Cape, South Africa, 7500
      • Family Clinical Research Unit (Fam-Cru)-Adult Infectious Diseases ( Site 6617)
    • Cape Town, Western Cape, South Africa, 7925
      • Desmond Tutu HIV Foundation Clinical Trial Unit ( Site 6613)
    • Mbekweni, Paarl, Western Cape, South Africa, 7646
      • Be Part Yoluntu Centre ( Site 6603)
• Spain
  • Madrid, Spain, 28007
    • Hospital General Universitario Gregorio Maranon ( Site 6303)
  • Madrid, Spain, 28040
    • Hospital Universitario Fundacion Jimenez Diaz ( Site 6307)
  • Madrid, Spain, 28041
    • Hospital Universitario 12 de Octubre ( Site 6305)
  • Madrid, Spain, 28046
    • Hospital Universitario La Paz ( Site 6304)
  • Málaga, Spain, 29010
    • Hospital Universitario Virgen de la Victoria ( Site 6309)
  • Alicante
    • Elche, Alicante, Spain, 03202
      • Hospital General de Elche ( Site 6308)
  • Barcelona
    • Badalona, Barcelona, Spain, 08916
      • Hospital Universitari Germans Trias i Pujol ( Site 6301)
    • LHospitalet de Llobregat, Barcelona, Spain, 08907
      • Hospital Universitari de Bellvitge ( Site 6312)
  • Catalonia
    • Barcelona, Catalonia, Spain, 08035
      • Hospital Vall D Hebron ( Site 6302)
    • Barcelona, Catalonia, Spain, 08036
      • Hospital Clinic i Provincial ( Site 6300)
• Taiwan
  • Kaohsiung City, Taiwan, 81362
    • Kaohsiung Veterans General Hospital ( Site 7102)
  • Tainan, Taiwan, 70403
    • National Cheng Kung University Hospital ( Site 7101)
  • Taipei, Taiwan, 100
    • National Taiwan University Hospital ( Site 7100)
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35222
      • University of Alabama at Birmingham 1917 Research Clinic ( Site 5610)
  • Arizona
    • Phoenix, Arizona, United States, 85015
      • Pueblo Family Physicians ( Site 5606)
  • California
    • Los Angeles, California, United States, 90036
      • Ruane Clinical Research Group, Inc. ( Site 5624)
  • Florida
    • Ft. Pierce, Florida, United States, 34982
      • Midway Immunology and Research ( Site 5622)
    • Miami, Florida, United States, 33133
      • The Kinder Medical Group ( Site 5615)
    • Miami Lakes, Florida, United States, 33016
      • Floridian Clinical Research, LLC ( Site 5625)
    • Orlando, Florida, United States, 32803
      • Orlando Immunology Center ( Site 5613)
    • Sarasota, Florida, United States, 34237
      • CAN Community Health ( Site 5627)
    • West Palm Beach, Florida, United States, 33407
      • Triple O Research Institute, P.A. ( Site 5621)
  • Georgia
    • Columbus, Georgia, United States, 31904
      • Columbus Regional Research Institute ( Site 5616)
    • Decatur, Georgia, United States, 30033
      • Infectious Disease Specialists Of Atlanta PC ( Site 5608)
  • Minnesota
    • Minneapolis, Minnesota, United States, 55415
      • Hennepin Healthcare-Hennepin Healthcare-ID ( Site 5633)
  • Missouri
    • Kansas City, Missouri, United States, 64111
      • Kansas City CARE Clinic ( Site 5607)
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania ( Site 5630)
  • Texas
    • Bellaire, Texas, United States, 77401
      • Saint Hope Foundation, Inc. ( Site 5629)
    • Dallas, Texas, United States, 75246
      • North Texas ID Consultants, PA ( Site 5604)
    • Fort Worth, Texas, United States, 76104
      • Texas Centers for Infectious Disease Associates P.A. ( Site 5619)

Participation Criteria

Eligibility Criteria

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

Description

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

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: 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.	Drug: DOR/ISL; 100 mg DOR/0.75 mg ISL FDC single tablet taken once daily by mouth.; Other Names: MK-8591A; Doravirine/islatravir; Drug: Placebo to BIC/FTC/TAF; Placebo single tablet matched to BIC/FTC/TAF taken by mouth.
Active Comparator: 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.	Drug: BIC/FTC/TAF; BIC/FTC/TAF 50/200/25 mg FDC single tablet taken once daily by mouth.; Other Names: Bictegravir/emtricitabine/tenofovir alafenamide; Drug: Placebo to DOR/ISL; Placebo single tablet matched to DOR/ISL taken by mouth.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With HIV-1 RNA <50 Copies/mL at Week 96	The Abbott RealTime 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 96 was presented using the FDA Snapshot missing data approach. The final analysis for this outcome is presented here.	Week 96
Percentage of Participants With HIV-1 RNA <50 Copies/mL at Week 144	The Abbott RealTime 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 144 was presented using the Data as Observed (DAO) missing data approach. The final analysis for this outcome is presented here.	Week 144
Percentage of Participants With HIV-1 RNA <40 Copies/mL at Week 48	The percentage of participants with HIV-1 RNA <40 copies/mL was determined. The Abbott RealTime 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 <40 copies/mL at Week 48 was presented using the FDA Snapshot missing data approach. The final analysis for this outcome is presented here.	Week 48
Percentage of Participants With HIV-1 RNA <200 Copies/mL at Week 48	The percentage of participants with HIV-1 RNA <200 copies/mL was determined. The Abbott RealTime 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 <200 copies/mL at Week 48 was presented using the FDA Snapshot missing data approach. The final analysis for this outcome is presented here.	Week 48
Percentage of Participants With HIV-1 RNA <40 Copies/mL at Week 96	The Abbott RealTime 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 <40 copies/mL at Week 96 was presented using the FDA Snapshot missing data approach. The final analysis for this outcome is presented here.	Week 96
Percentage of Participants With HIV-1 RNA <200 Copies/mL at Week 96	The Abbott RealTime 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 <200 copies/mL at Week 96 was presented using the FDA Snapshot missing data approach. The final analysis for this outcome is presented here.	Week 96
Percentage of Participants With HIV-1 RNA <40 Copies/mL at Week 144	The Abbott RealTime 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 <40 copies/mL at Week 144 was presented using the DAO missing data approach. The final analysis for this outcome is presented here.	Week 144
Percentage of Participants With HIV-1 RNA <200 Copies/mL at Week 144	The Abbott RealTime 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 <200 copies/mL at Week 144 was presented using the DAO missing data approach. The final analysis for this outcome is presented here.	Week 144
Mean Change From Baseline in Cluster of Differentiation 4+ (CD4+) T-Cell Counts at Week 48	Plasma CD4+ T-cell count was measured in cells/mm^3 for baseline and at Week 48 by a central laboratory. Baseline measurements were defined as the Day 1 value of each participant. The mean change from baseline in CD4+ T-cell count at Week 48 using the Data as Observed (DAO) approach was presented. The final analysis for this outcome is presented here.	Baseline (Day 1) and Week 48
Mean Change From Baseline in Cluster of Differentiation 4+ (CD4+) T-Cell Counts at Week 96	Plasma CD4+ T-cell count was measured in cells/mm^3 for baseline and at Week 96 by a central laboratory. Baseline measurements were defined as the Day 1 value of each participant. The mean change from baseline in CD4+ T-cell count at Week 96 using the Data as Observed (DAO) approach was presented. The final analysis for this outcome is presented here.	Baseline (Day 1) and Week 96
Mean Change From Baseline in Cluster of Differentiation 4+ (CD4+) T-Cell Counts at Week 144	Plasma CD4+ T-cell count was measured in cells/mm^3 for baseline and at Week 144 by a central laboratory. Baseline measurements were defined as the Day 1 value of each participant. The mean change from baseline in CD4+ T-cell count at Week 144 using the Data as Observed (DAO) approach was presented. The final analysis for this outcome is presented here.	Baseline (Day 1) and Week 144
Incidence of Viral Resistance-Associated Substitutions (RASs) at Week 48	RASs was defined as participants with confirmed HIV-1 RNA ≥200 copies/mL and/or genotypic or phenotypic analysis of data showing evidence of resistance to the study drug administered. The number of participants who demonstrated RASs at Week 48 was presented. The final analysis for this outcome is presented here.	Week 48
Incidence of Viral RASs at Week 96	RASs was defined as participants with confirmed HIV-1 RNA ≥200 copies/mL and/or genotypic or phenotypic analysis of data showing evidence of resistance to the study drug administered. The number of participants who demonstrated RASs at Week 96 was presented. The final analysis for this outcome is presented here.	Week 96
Incidence of Viral RASs at Week 144	RASs was defined as participants with confirmed HIV-1 RNA ≥200 copies/mL and/or genotypic or phenotypic analysis of data showing evidence of resistance to the study drug administered. The number of participants who demonstrated RASs at Week 144 was presented. The final analysis for this outcome is presented here.	Week 144
Mean Change From Baseline in Body Weight at Week 48	Body weight was measured at baseline and at Week 48. Participants removed their shoes and wore a single layer of clothing at each measurement. Baseline measurements were defined as the Day 1 value of each participant. The mean change from baseline in body weight at Week 48 was presented. The final analysis for this outcome is presented here.	Baseline (Day 1) and Week 48
Mean Change From Baseline in Body Weight at Week 96	Body weight was measured at baseline and at Week 96. Participants removed their shoes and wore a single layer of clothing at each measurement. Baseline measurements were defined as the Day 1 value of each participant. The mean change from baseline in body weight at Week 96 was presented. The final analysis for this outcome is presented here.	Baseline (Day 1) and Week 96
Mean Change From Baseline in Body Weight at Week 144	Body weight was measured at baseline and at Week 144. Participants removed their shoes and wore a single layer of clothing at each measurement. Baseline measurements were defined as the Day 1 value of each participant. The mean change from baseline in body weight at Week 144 was presented. The final analysis for this outcome is presented here.	Baseline (Day 1) and Week 144
Percentage of Participants Who Experienced an Adverse Event (AE)	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 or more AEs is presented. Per protocol, pregnancy-related AEs collected for enrolled participants are reported separately and are presented in the AE module. The final analysis for this outcome is presented here.	Up to approximately 47 months
Percentage of Participants Who Discontinued Study Treatment Due to an AE	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 intervention due to an AE is presented. Per protocol, pregnancy-related AEs collected for enrolled participants are reported separately and are presented in the AE module. The final analysis for this outcome is presented here.	Up to approximately 38 months

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC
• Investigators: Study Director: Medical Director, Merck Sharp & Dohme LLC

Publications and helpful links

General Publications

• 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.

Helpful Links

• Merck Clinical Trials Information
• Plain Language Summary

Study record dates

Study Major Dates

• Study Start (Actual): February 28, 2020
• Primary Completion (Actual): November 17, 2022
• Study Completion (Actual): January 29, 2025

Study Registration Dates

• First Submitted: January 15, 2020
• First Submitted That Met QC Criteria: January 15, 2020
• First Posted (Actual): January 18, 2020

Study Record Updates

• Last Update Posted (Actual): June 3, 2026
• Last Update Submitted That Met QC Criteria: June 1, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; 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-020; MK-8591A-020 (Other Identifier: MSD Protocol Number); jRCT2031210024 (Registry Identifier: jRCT); 2019-000590-23 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: https://trialstransparency.msdclinicaltrials.com/pdf/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
• product manufactured in and exported from the U.S.: No