Safety and Efficacy of a Switch to Doravirine, Tenofovir, Lamivudine (MK-1439A) in Human Immunodeficiency Virus (HIV-1)-Infected Participants Virologically Suppressed on an Anti-retroviral Regimen in Combination With Two Nucleoside Reverse Transcriptase Inhibitors (MK-1439A-024)

NCT02397096 | Completed Phase 3 Results FDA Drug

• 3 other identifiers: 1439A-024MK-1439A-0242014-005550-18
• Study Type: interventional
• Target: 673
• Locations: 0 countries
• Sites: N/A

Brief Summary

The multicenter, open label, randomized study will evaluate the safety and efficacy of a switch to MK-1439A (MK-1439 \[doravirine\] plus lamivudine and tenofovir disoproxil fumarate) in HIV-1-infected participants virologically suppressed on a protocol-specified antiretroviral regimen. The primary hypothesis is that a switch to doravirine, tenofovir, lamivudine will be non-inferior to continuation of the regimen at Screening for 24 weeks, as assessed by the proportion of participants maintaining HIV-1 ribonucleic acid (RNA) \<50 copies/mL. The Base Study results will be based on the first 48 weeks of this ongoing study.

Conditions

HIV-1 Infection

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants Maintaining Human Immunodeficiency Virus-1 Ribonucleic Acid (HIV-1 RNA) <50 Copies/mL

  The percentage of participants in each arm achieving HIV-1 RNA levels \<50 copies/mL 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 and all missing data were considered treatment failures, regardless of the reason.

  Immediate Switch to MK-1439A arm: Week 48; Delayed Switch to MK-1439A arm: Week 24

Secondary Outcomes (11)

• Mean Change From Baseline in Fasting Low-density Lipoprotein Cholesterol (LDL-C)

  Baseline and Week 24

• Mean Change From Baseline in Fasting Non-high-density Lipoprotein Cholesterol (Non-HDL-C)

  Baseline and Week 24

• Percentage of Participants Maintaining HIV-1 RNA <50 Copies/mL

  Week 24

• Mean Change From Baseline in Cluster of Differentiation (CD4) Cell Counts

  Immediate Switch to MK-1439A arm: Baseline and Week 48; Delayed Switch to MK-1439A arm: Baseline and Week 24

• Mean Change From Baseline in Cluster of Differentiation (CD4) Cell Counts

  Baseline and Week 24

Study Arms (2)

Immediate Switch to Doravirine, Tenofovir, Lamivudine

EXPERIMENTAL

Participants receiving continuous antiretroviral therapy with a ritonavir- or cobicistat-boosted protease inhibitor (atazanavir, darunavir, or lopinavir) or cobicistat-boosted elvitegravir or a non nucleoside reverse transcriptase inhibitor (NNRTI) (specifically, efavirenz, nevirapine, or rilpivirine) in combination with 2 NRTIs for \>=6 months with undetectable HIV-1 RNA will switch on Day 1 to doravirine, tenofovir, lamivudine single tablet by mouth once daily for 48 weeks in the Base Study and, optionally, for up to an additional 6 years in the Study Extensions

Drug: Doravirine, Tenofovir, Lamivudine; Drug: Baseline regimen of ritonavir- or cobicistat-boosted protease inhibitor; Drug: Baseline regimen of cobicistat-boosted elvitegravir; Drug: Baseline regimen of a non-nucleoside reverse transcriptase inhibitor; Drug: Baseline regimen of two nucleoside reverse transcriptase inhibitors

Delayed Switch to Doravirine, Tenofovir, Lamivudine

ACTIVE COMPARATOR

Participants receiving continuous antiretroviral therapy with a ritonavir- or cobicistat-boosted protease inhibitor (atazanavir, darunavir, or lopinavir) or cobicistat-boosted elvitegravir or a NNRTI (specifically, efavirenz, nevirapine, or rilpivirine) in combination with 2 NRTIs for \>=6 months with undetectable HIV-1 RNA will continue on this therapy until Week 24, at which time they will switch to doravirine, tenofovir, lamivudine single tablet by mouth once daily for 24 weeks in the Base Study and, optionally, for up to an additional 6 years in the Study Extensions

Drug: Doravirine, Tenofovir, Lamivudine; Drug: Baseline regimen of ritonavir- or cobicistat-boosted protease inhibitor; Drug: Baseline regimen of cobicistat-boosted elvitegravir; Drug: Baseline regimen of a non-nucleoside reverse transcriptase inhibitor; Drug: Baseline regimen of two nucleoside reverse transcriptase inhibitors

Interventions

Doravirine, Tenofovir, Lamivudine DRUG

Single tablet containing MK-1439 (doravirine) 100 mg, lamivudine 300 mg, and tenofovir disoproxil fumarate 300 mg

Also known as: Doravirine (PIFELTRO™), Doravirine/Lamivudine/Tenofovir disoproxil fumarate (DELSTRIGO™), MK-1439A

Delayed Switch to Doravirine, Tenofovir, Lamivudine; Immediate Switch to Doravirine, Tenofovir, Lamivudine

Baseline regimen of ritonavir- or cobicistat-boosted protease inhibitor DRUG

Baseline regimen of antiretroviral therapy with a ritonavir- or cobicistat-boosted protease inhibitor (atazanavir, darunavir, or lopinavir) administered according to the product circular

Delayed Switch to Doravirine, Tenofovir, Lamivudine; Immediate Switch to Doravirine, Tenofovir, Lamivudine

Baseline regimen of cobicistat-boosted elvitegravir DRUG

Baseline regimen of antiretroviral therapy with cobicistat-boosted elvitegravir administered according to the product circular

Delayed Switch to Doravirine, Tenofovir, Lamivudine; Immediate Switch to Doravirine, Tenofovir, Lamivudine

Baseline regimen of a non-nucleoside reverse transcriptase inhibitor DRUG

Baseline regimen of antiretroviral therapy with a NNRTI (efavirenz, nevirapine, or rilpivirine) administered according to the product circular

Delayed Switch to Doravirine, Tenofovir, Lamivudine; Immediate Switch to Doravirine, Tenofovir, Lamivudine

Baseline regimen of two nucleoside reverse transcriptase inhibitors DRUG

Baseline regimen of antiretroviral therapy with two NRTIs administered according to the product circular

Delayed Switch to Doravirine, Tenofovir, Lamivudine; Immediate Switch to 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:

• Have plasma Human Immunodeficiency Virus-1 Ribonucleic Acid (HIV-1 RNA) levels below the limit of quantification (BLoQ) (\<40 copies/mL by the Abbott RealTime HIV-1 Assay as determined by the central laboratory) at the screening visit.
• Receiving antiretroviral therapy with a ritonavir- or cobicistat-boosted protease inhibitor (atazanavir, darunavir, or lopinavir) or cobicistat-boosted elvitegravir or a NNRTI (specifically, efavirenz, nevirapine, or rilpivirine) in combination with 2 Nucleoside Reverse Transcriptase Inhibitor (NRTIs) (and no other antiretroviral therapy) continuously for \>= 6 months.
• Receiving first or second retroviral regimen (participants receiving a NNRTI at Screening must be on their first retroviral regimen)
• No history of using an experimental NNRTI
• Has a genotype prior to starting his/her initial antiretroviral regimen and no known resistance to any of the study agents
• Not receiving lipid lowering therapy or on a stable dose of lipid lowering therapy at the time of enrollment
• Has the following laboratory values at screening within 30 days prior to the treatment phase of this study: Alkaline phosphatase ≤ 3.0 x upper limit of normal (ULN), Serum aspartate aminotransferase (AST) and serum alanine aminotransferase (ALT) ≤ 5.0 x ULN, and Hemoglobin ≥9.0 g/dL (if female) or ≥10.0 g/dL (if male)
• Has a calculated creatinine clearance at the time of screening ≥ 50 mL/min, based on the Cockcroft-Gault equation
• Male or female participant not of reproductive potential or, if of reproductive potential, agrees to avoid becoming pregnant or impregnating a partner while receiving study drug and for 14 days after the last dose of study drug by complying with one of the following: 1) practice abstinence from heterosexual activity, or 2) use acceptable contraception during heterosexual activity

You may not qualify if:

• Uses recreational or illicit drugs or has a recent history of drug or alcohol abuse or dependence
• Received treatment for a viral infection other than HIV-1, such as hepatitis B, with an agent that is active against HIV-1 such as adefovir, emtricitabine, lamivudine, or tenofovir
• Has documented or known resistance to study drugs including doravirine, lamivudine, and/or tenofovir
• Participated in a study with an investigational compound or device within 30 days or anticipates doing so during the course of this study
• Used systemic immunosuppressive therapy or immune modulators within 30 days or anticipates needing them during the course of this study (short courses of corticosteroids will be allowed)
• Current, active diagnosis of acute hepatitis due to any cause (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 function)
• Has evidence of decompensated liver disease or has liver cirrhosis and a Child-Pugh Class C score or Pugh-Turcotte score \>9
• Pregnant, breastfeeding, or expecting to conceive at any time during the study
• Female and is expecting to donate eggs or male and is expecting to donate sperm during the study

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Related Publications (5)

• 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

• 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

• Kumar P, Johnson M, Molina JM, Rizzardini G, Cahn P, Bickel M, Wan H, Xu ZJ, Morais C, Sklar P, Greaves W; DRIVE-SHIFT Study Group. Brief Report: Switching to DOR/3TC/TDF Maintains HIV-1 Virologic Suppression Through Week 144 in the DRIVE-SHIFT Trial. J Acquir Immune Defic Syndr. 2021 Jun 1;87(2):801-805. doi: 10.1097/QAI.0000000000002642.

  PMID: 33633036 DERIVED

• Vaddady P, Kandala B, Yee KL. Population Pharmacokinetic and Pharmacodynamic Analysis To Evaluate a Switch to Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate in People Living with HIV-1. Antimicrob Agents Chemother. 2020 Oct 20;64(11):e00590-20. doi: 10.1128/AAC.00590-20. Print 2020 Oct 20.

  PMID: 32868326 DERIVED

• Johnson M, Kumar P, Molina JM, Rizzardini G, Cahn P, Bickel M, Mallolas J, Zhou Y, Morais C, Kumar S, Sklar P, Hanna GJ, Hwang C, Greaves W; DRIVE-SHIFT Study Group. Switching to Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate (DOR/3TC/TDF) Maintains HIV-1 Virologic Suppression Through 48 Weeks: Results of the DRIVE-SHIFT Trial. J Acquir Immune Defic Syndr. 2019 Aug 1;81(4):463-472. doi: 10.1097/QAI.0000000000002056.

  PMID: 30985556 DERIVED

Related Links

• Merck Clinical Trials Information
• Plain Language Summary

MeSH Terms

Interventions

doravirine; Tenofovir; Lamivudine

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

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: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 18, 2015
• First Posted: March 24, 2015
• Study Start: June 9, 2015
• Primary Completion: February 22, 2018
• Study Completion: September 5, 2023
• Last Updated: November 20, 2024
• Results First Posted: April 3, 2019

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will share