Comparison of Doravirine, Tenofovir, Lamivudine (MK-1439A) and ATRIPLA™ in Treatment-Naive Human Immunodeficiency Virus Type 1 (HIV-1)-Infected Participants (MK-1439A-021)

NCT02403674 | Completed Phase 3 Results DMC

• 3 other identifiers: 1439A-021MK-1439A-0212014-003382-17
• Study Type: interventional
• Target: 734
• Locations: 0 countries
• Sites: N/A

Brief Summary

The purpose of this study is to compare the antiretroviral activity of doravirine, tenofovir, lamivudine (MK-1439A), a single-tablet, once-daily (q.d.) fixed-dose combination (FDC) containing doravirine (MK-1439A) 100 mg + lamivudine 300 mg + tenofovir disoproxil fumarate 300 mg, with ATRIPLA™, a single-tablet FDC containing efavirenz 600 mg + emtricitabine 200 mg + tenofovir disoproxil fumarate 300 mg, in treatment-naive participants infected with human immunodeficiency virus (HIV). The primary hypothesis is that doravirine, tenofovir, lamivudine q.d. is non-inferior to ATRIPLA™ q.d. as assessed by the proportion of participants with HIV-1 ribonucleic acid (RNA) \<50 copies/mL (by the Abbott RealTime HIV-1 Assay) at Week 48. This study has a total duration of 384 weeks, including a 96-week double-blind period and an additional 288-week open-label period.

Conditions

Human Immunodeficiency Virus (HIV)

Outcome Measures

Primary Outcomes (2)

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

  The percentage of participants in each arm with HIV-1 RNA levels \<50 copies/mL at Week 48 was determined. Plasma HIV-1 RNA levels were quantified with the Abbott RealTime HIV-1 Assay. Data were handled according to the US Food and Drug Administration (FDA) "snapshot" approach in which all missing data are considered treatment failures, regardless of the reason.

  Week 48

• Percentage of Participants With Tier-1 Neuropsychiatric Adverse Events (AEs)

  The percentage of participants in each arm experiencing ≥1 pre-specified Tier-1 neuropsychiatric AEs was determined. The list of Tier-1 neuropsychiatric AE categories included "dizziness", "sleep disorders and disturbances", and "altered sensorium" (including disturbance in attention).

  Up to Week 48

Secondary Outcomes (16)

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

  Week 96

• Percentage of Participants With HIV-1 RNA <40 Copies/mL at Week 48

  Week 48

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

  Week 96

• Change From Baseline in CD4 Cell Counts at Week 48

  Baseline (Day 1) and Week 48

• Change From Baseline in CD4 Cell Counts at Week 96

  Baseline (Day 1) and Week 96

Study Arms (2)

Doravirine, Tenofovir, Lamivudine

EXPERIMENTAL

Treatment-naive HIV-infected participants will receive doravirine, tenofovir, lamivudine, a single-tablet FDC containing doravirine 100 mg + lamivudine 300 mg + tenofovir disoproxil fumarate 300 mg, q.d. by mouth for 96 weeks. Participants will also take 1 placebo tablet matched to ATRIPLA™ q.d. by mouth for 96 weeks in order to maintain blinding.

Drug: Doravirine, Tenofovir, Lamivudine; Drug: Placebo

ATRIPLA™

ACTIVE COMPARATOR

Treatment-naive HIV-infected participants will receive ATRIPLA™, a single-tablet FDC containing efavirenz 600 mg + emtricitabine 200 mg + tenofovir disoproxil fumarate 300 mg (equivalent to 245 mg tenofovir disoproxil), q.d. by mouth for 96 weeks. Participants will also take 1 placebo tablet matched to doravirine, tenofovir, lamivudine q.d. by mouth for 96 weeks in order to maintain blinding.

Drug: ATRIPLA™; Drug: Placebo

Interventions

Doravirine, Tenofovir, Lamivudine DRUG

One doravirine, tenofovir, lamivudine tablet taken q.d. by mouth.

Also known as: MK-1439A

Doravirine, Tenofovir, Lamivudine

ATRIPLA™ DRUG

One ATRIPLA™ tablet taken q.d. by mouth

ATRIPLA™

Placebo DRUG

Placebo tablets matched to ATRIPLA® or Doravirine, Tenofovir, Lamivudine.

ATRIPLA™; Doravirine, Tenofovir, Lamivudine

Eligibility Criteria

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

You may qualify if:

• Is HIV-1 positive as determined by a positive result on an enzyme-immunoassay, has screening plasma HIV-1 RNA (determined by the central laboratory) ≥1000 copies/mL within 45 days prior to the treatment phase of this study, and has HIV treatment indicated based on physician assessment
• Has never received antiretroviral therapy (ART)
• Is highly unlikely to either become pregnant or impregnate a partner

You may not qualify if:

• Has a history or current evidence of any condition, therapy, laboratory abnormality, or other circumstance that might confound results of the study
• Is a user of recreational or illicit drugs or has a recent history of alcohol/drug abuse
• Has been treated for a viral infection other than HIV-1 (e.g., hepatitis B) with an agent that is active against HIV-1
• Has participated in a study with an investigational drug/device within 30 days prior to Screening
• Has used systemic immunosuppressive therapy or immune modulators within 30 days prior to treatment in this study or is anticipated to need them during the course of the study
• Has a current (active) diagnosis of acute hepatitis due to any cause (note: participants with chronic hepatitis B and C may enter the study as long as they fulfill all entry criteria, have stable liver function tests, and have no significant impairment of hepatic synthetic function)
• Is a female who is pregnant, breastfeeding, or expecting to conceive
• Is a female and is expecting to donate eggs or is male and is expecting to donate sperm (investigators will provide appropriate guidance regarding egg and/or sperm donation after completion of the study treatment regimen)
• Has evidence of decompensated liver disease manifested by the presence of or a history of ascites, esophageal or gastric variceal bleeding, hepatic encephalopathy or other signs or symptoms of advanced liver diseases, or has liver cirrhosis and a Child-Pugh Class C score or Pugh-Turcotte (CPT) score \> 9

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Related Publications (9)

• Orkin C, Koethe JR, Kumar PN, Sklar P, Xu ZJ, Plank RM, Greaves W, Lahoulou R. Factors Associated With Weight Change After Continuing or Switching to a Doravirine-based Regimen. Open Forum Infect Dis. 2025 Nov 20;12(11):ofaf639. doi: 10.1093/ofid/ofaf639. eCollection 2025 Nov.

  PMID: 41280318 DERIVED

• Hsue PY, Behrens GMN, Xu ZJ, Zhao Y, Cmar J, Lahoulou R, Campo RE, Plank RM. Cardiovascular Risk Assessment Using the Atherosclerotic Cardiovascular Disease Risk Score Model after Continuing or Switching to a Doravirine-Based HIV Treatment Regimen. J Acquir Immune Defic Syndr. 2026 Feb 1;101(2):208-213. doi: 10.1097/QAI.0000000000003778.

  PMID: 41081774 DERIVED

• Walmsley SL, Kumar PN, Orkin C, Thompson M, Squires K, Xu ZJ, Greaves W, Plank RM, Whiteside Y, Lahoulou R. Efficacy and Safety of Doravirine-based Regimens by Sex and Race: Long-term Results From Three Phase 3 Clinical Trials. Open Forum Infect Dis. 2025 Jul 16;12(7):ofaf356. doi: 10.1093/ofid/ofaf356. eCollection 2025 Jul.

  PMID: 40672760 DERIVED

• Moyle G, Meng F, Wan H, Sklar P, Plank RM, Lahoulou R. Brief Report: Resolution of Neuropsychiatric Adverse Events After Switching to a Doravirine-Based Regimen in the Open-Label Extensions of the DRIVE-AHEAD and DRIVE-FORWARD Trials. J Acquir Immune Defic Syndr. 2025 May 1;99(1):81-86. doi: 10.1097/QAI.0000000000003599.

  PMID: 39748155 DERIVED

• Orkin C, Molina JM, Cahn P, Lombaard J, Supparatpinyo K, Kumar S, Campbell H, Wan H, Teal V, Jin Xu Z, Asante-Appiah E, Sklar P, Teppler H, Lahoulou R; DRIVE-FORWARD and DRIVE-AHEAD collaborators. Safety and efficacy of doravirine as first-line therapy in adults with HIV-1: week 192 results from the open-label extensions of the DRIVE-FORWARD and DRIVE-AHEAD phase 3 trials. Lancet HIV. 2024 Feb;11(2):e75-e85. doi: 10.1016/S2352-3018(23)00258-8. Epub 2023 Dec 20.

  PMID: 38141637 DERIVED

• Orkin C, Squires KE, Molina JM, Sax PE, Sussmann O, Lin G, Kumar S, Hanna GJ, Hwang C, Martin E, Teppler H. Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate (TDF) Versus Efavirenz/Emtricitabine/TDF in Treatment-naive Adults With Human Immunodeficiency Virus Type 1 Infection: Week 96 Results of the Randomized, Double-blind, Phase 3 DRIVE-AHEAD Noninferiority Trial. Clin Infect Dis. 2021 Jul 1;73(1):33-42. doi: 10.1093/cid/ciaa822.

  PMID: 33336698 DERIVED

• Orkin C, Molina JM, Lombaard J, DeJesus E, Rodgers A, Kumar S, Martin E, Hanna G, Hwang C. Once-daily Doravirine in Human Immunodeficiency Virus Type 1-Infected, Antiretroviral-naive Adults: An Integrated Efficacy Analysis. Clin Infect Dis. 2020 Mar 17;70(7):1344-1352. doi: 10.1093/cid/ciz424.

  PMID: 31121015 DERIVED

• Thompson M, Orkin C, Molina JM, Sax P, Cahn P, Squires K, Xu X, Rodgers A, Kumar S, Teppler H, Martin E, Hanna G, Hwang C. Once-daily Doravirine for Initial Treatment of Adults Living With Human Immunodeficiency Virus-1: An Integrated Safety Analysis. Clin Infect Dis. 2020 Mar 17;70(7):1336-1343. doi: 10.1093/cid/ciz423.

  PMID: 31121013 DERIVED

• Orkin C, Squires KE, Molina JM, Sax PE, Wong WW, Sussmann O, Kaplan R, Lupinacci L, Rodgers A, Xu X, Lin G, Kumar S, Sklar P, Nguyen BY, Hanna GJ, Hwang C, Martin EA; DRIVE-AHEAD Study Group. Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate is Non-inferior to Efavirenz/Emtricitabine/Tenofovir Disoproxil Fumarate in Treatment-naive Adults With Human Immunodeficiency Virus-1 Infection: Week 48 Results of the DRIVE-AHEAD Trial. Clin Infect Dis. 2019 Feb 1;68(4):535-544. doi: 10.1093/cid/ciy540.

  PMID: 30184165 DERIVED

Related Links

• Merck Clinical Trials Information
• Plain Language Summary

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome

Interventions

doravirine; Tenofovir; Lamivudine; Efavirenz, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination

Condition Hierarchy (Ancestors)

HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Zalcitabine; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Dideoxynucleosides; Oxazines; Emtricitabine; Drug Combinations; Pharmaceutical Preparations

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: March 26, 2015
• First Posted: March 31, 2015
• Study Start: June 5, 2015
• Primary Completion: March 20, 2017
• Study Completion: September 7, 2023
• Last Updated: November 20, 2024
• Results First Posted: April 30, 2018

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will share