Human Immunodeficiency Virus (HIV)Phase 3DRIVE-AHEADNCT02403674

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

A Phase 3 study testing Doravirine, Tenofovir, Lamivudine and ATRIPLA™ in people with Human Immunodeficiency Virus (HIV), run by Merck Sharp & Dohme LLC.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 years and older
Conditions the study is for: Human Immunodeficiency Virus (HIV)
What is being tested?: Doravirine, Tenofovir, Lamivudine and ATRIPLA™
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 734 participants
Where: No sites listed yet
Study dates: 5 Jun 2015to 7 Sep 2023
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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

Who cannot join

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)

Show all 9Show fewer

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

About this study

Official title: A Phase III Multicenter, Double-Blind, Randomized, Active Comparator-Controlled Clinical Trial to Evaluate the Safety and Efficacy of MK-1439A Once-Daily Versus ATRIPLA™ Once-Daily in Treatment-Naïve HIV-1 Infected Subjects

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.

Read the detailed description

Participants in Australia, Colombia, Guatemala, Honduras, Israel, New Zealand, Peru, Russia, South Africa, and Thailand who are deriving benefit from doravirine, tenofovir, lamivudine are also eligible to continue receiving study drug during additional open-label extensions which will last for 2 years or until drug is available locally, whichever comes first.

Conditions: Human Immunodeficiency Virus (HIV)
Being tested: Doravirine, Tenofovir, Lamivudine, ATRIPLA™, Placebo
Medical subject headings: Acquired Immunodeficiency Syndrome

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Doravirine, Tenofovir, LamivudineDrug
Also called MK-1439A
One doravirine, tenofovir, lamivudine tablet taken q.d. by mouth.
ATRIPLA™Drug
One ATRIPLA™ tablet taken q.d. by mouth
PlaceboDrug
Placebo tablets matched to ATRIPLA® or Doravirine, Tenofovir, Lamivudine.

Study groups in NCT02403674
Study group	Role	What they receive
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. Receives: 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. Receives: Drug: ATRIPLA™; Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 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).
Measured: Up to Week 48

Secondary outcomes (16)

Percentage of Participants With HIV-1 RNA <50 Copies/mL at Week 96
The percentage of participants in each arm with HIV-1 RNA levels <50 copies/mL at Week 96 were determined. Plasma HIV-1 RNA levels were quantified with the Abbott RealTime HIV-1 Assay. The US Food and Drug Administration (FDA) "snapshot" approach (i.e., all missing data handled as treatment failures, regardless of the reason) were used for efficacy analyses.
Measured: Week 96
Percentage of Participants With HIV-1 RNA <40 Copies/mL at Week 48
The percentage of participants in each arm with HIV-1 RNA levels <40 copies/mL (including target detected and target not detected) at Week 48 was determined. Plasma HIV 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.
Measured: Week 48
Percentage of Participants With HIV-1 RNA <40 Copies/mL at Week 96
The percentage of participants in each arm with HIV-1 RNA levels <40 copies/mL (including target detected and target not detected) at Week 96 were determined. Plasma HIV-1 RNA levels were quantified with the Abbott RealTime HIV-1 Assay. The US Food and Drug Administration (FDA) "snapshot" approach (i.e., all missing data handled as treatment failures, regardless of the reason) were used for efficacy analyses.
Measured: Week 96
Change From Baseline in CD4 Cell Counts at Week 48
The mean change from baseline in CD4 cell counts at Week 48 was assessed using the Observed Failure (OF) approach. With the OF approach, baseline values were carried forward for participants who discontinued prior to Week 48 due to lack of efficacy. Cell counts at Baseline and Week 48 were measured and expressed as cells/mm^3, and percent change was then calculated as [(Baseline counts - Week 48 counts)*100]. CD4 cell counts were quantified by a central laboratory using a commercially available assay.
Measured: Baseline (Day 1) and Week 48
Change From Baseline in CD4 Cell Counts at Week 96
The mean change from baseline in CD4 cell counts at Week 96 were assessed using the OF approach. With the OF approach, baseline values were carried forward for participants who discontinued prior to Week 96 due to lack of efficacy. Cell counts at Baseline and Week 96 were measured and expressed as cells/mm^3, and percent change was calculated as [(Baseline counts - Week 96 counts)*100]. CD4 cell counts were quantified by a central laboratory using a commercially available assay.
Measured: Baseline (Day 1) and Week 96
Percentage of Participants Experiencing ≥1 AE
An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.
Measured: Up to Week 48
Percentage of Participants Discontinuing From Study Medication Due to an AE(s)
An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.
Measured: Up to Week 48
Percentage of Participants With Tier-2 Neuropsychiatric AEs
The percentage of participants in each arm experiencing ≥1 pre-specified Tier-2 neuropsychiatric AEs was determined. The list of Tier-2 neuropsychiatric AE categories included "depression and suicide/self-injury" and "psychosis and psychotic disorders".
Measured: Up to Week 48
Change From Baseline in Fasting LDL-C at Week 48
The mean percent change from baseline in fasting (fast duration of ≥8 hours) LDL-C levels at Week 48 was determined for each arm. The Last Observation Carry Forward (LOCF) approach was applied to missing data and data collected after a participant initiated lipid-modifying therapy.
Measured: Baseline (Day 1) and Week 48
Change From Baseline in Fasting Non-HDL-C at Week 48
The mean percent change from baseline in fasting (fast duration of ≥8 hours) non-HDL-C levels at Week 48 was determined for each arm. The LOCF approach was applied to missing data and data collected after a participant initiated lipid-modifying therapy.
Measured: Baseline (Day 1) and Week 48
Change From Baseline in Fasting Cholesterol at Week 48
The mean percent change from baseline in fasting (fast duration of ≥8 hours) cholesterol levels at Week 48 was determined for each arm. The LOCF approach was applied to missing data and data collected after a participant initiated lipid-modifying therapy.
Measured: Baseline (Day 1) and Week 48
Change From Baseline in Fasting Triglycerides at Week 48
The mean percent change from baseline in fasting (fast duration of ≥8 hours) triglycerides levels at Week 48 was determined for each arm. The LOCF approach was applied to missing data and data collected after a participant initiated lipid-modifying therapy.
Measured: Baseline (Day 1) and Week 48
Change From Baseline in Fasting HDL-C at Week 48
The mean percent change from baseline in fasting (fast duration of ≥8 hours) HDL-C levels at Week 48 was determined for each arm. The LOCF approach was applied to missing data and data collected after a participant initiated lipid-modifying therapy.
Measured: Baseline (Day 1) and Week 48
Percentage of Participants With HIV-1 RNA Below the Limit of Quantification (BLoQ) at Week 48
The percentage of participants in each arm with HIV-1 RNA levels BLoQ of 40 copies/mL and target not detected at Week 48 was determined. Plasma HIV RNA levels were quantified with the Abbott RealTime HIV-1 Assay. Data were handled as observed.
Measured: Week 48
Percentage of Participants With HIV-1 RNA BLoQ at Week 96
The percentage of participants in each arm with HIV-1 RNA levels BLoQ of 40 copies/mL and target not detected at Week 96 was determined. Plasma HIV RNA levels was quantified with the Abbott RealTime HIV-1 Assay. Data was handled as observed.
Measured: Week 96
Plasma Concentration of Doravirine at Week 48
Plasma samples were collected for analysis of doravirine concentration at Week 48. A total of 2 samples were collected: 1 prior to dosing and 1 collected between 0.5 and 2 hours post-dose.
Measured: 0 hours post-dose and 2 hours post-dose on Week 48

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

5 Jun 20157 Sep 2023

First posted31 Mar 2015 (estimated)
Study start5 Jun 2015
Primary completion20 Mar 2017
Study completion7 Sep 2023

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (10)Papers the sponsor has linked to this study.
Other trials for Human Immunodeficiency Virus (HIV)Studies of the same condition, open and under way.
More trials run by Merck Sharp & Dohme LLCThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 734 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02403674
Sponsor's protocol ID: 1439A-021
Other IDs: MK-1439A-021, 2014-003382-17, 2014
Acronym: DRIVE-AHEAD
Status last verified: Nov 2024
First submitted: 26 Mar 2015
Last updated: 20 Nov 2024
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
Individual data sharing: Yes: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Publications

Molina JM, Orkin C, Paredes R, Xu ZJ, Su FH, Asante-Appiah E, Plank RM, Lahoulou R. Analysis of Viral Blips Through Week 192 of the DRIVE-FORWARD and DRIVE-AHEAD Phase 3 Studies of Doravirine-Based Regimens in Adults Living With Previously Untreated HIV-1. Open Forum Infect Dis. 2026 Jun 10;13(6):ofag258. doi: 10.1093/ofid/ofag258. eCollection 2026 Jun.
PubMed 42281892
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.
PubMed 41280318
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.
PubMed 41081774
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.
PubMed 40672760
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.
PubMed 39748155
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.
PubMed 38141637
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.
PubMed 33336698
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.
PubMed 31121015
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.
PubMed 31121013
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.
PubMed 30184165

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

Official record

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Study at a glance

From the registry record, last updated by the sponsor on 20 Nov 2024. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase III Multicenter, Double-Blind, Randomized, Active Comparator-Controlled Clinical Trial to Evaluate the Safety and Efficacy of MK-1439A Once-Daily Versus ATRIPLA™ Once-Daily in Treatment-Naïve HIV-1 Infected Subjects
ClinicalTrials.gov ID: NCT02403674
Acronym / sponsor ID: DRIVE-AHEAD / 1439A-021
Conditions: Human Immunodeficiency Virus (HIV)
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 734 participants (actual)
Lead sponsor: Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
Study start: 5 Jun 2015 (actual)
Primary completion: 20 Mar 2017 (actual)
Study completion: 7 Sep 2023 (actual)
First posted: 31 Mar 2015 (estimated)
Results: Posted 30 Apr 2018

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind (participant, investigator)
Number of arms: 2

Arm	Type	Receives
Doravirine, Tenofovir, Lamivudine	Experimental	Drug: Doravirine, Tenofovir, Lamivudine, Drug: PlaceboTreatment-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.
ATRIPLA™	Active comparator	Drug: ATRIPLA™, Drug: PlaceboTreatment-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.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (3 listed)

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

Key exclusion criteria (9 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Doravirine, Tenofovir, LamivudineAlso: MK-1439AOne doravirine, tenofovir, lamivudine tablet taken q.d. by mouth.	Drug	Doravirine, Tenofovir, Lamivudine
ATRIPLA™One ATRIPLA™ tablet taken q.d. by mouth	Drug	ATRIPLA™
PlaceboPlacebo tablets matched to ATRIPLA® or Doravirine, Tenofovir, Lamivudine.	Drug	ATRIPLA™, Doravirine, Tenofovir, Lamivudine

Primary outcome

Percentage of Participants With HIV-1 Ribonucleic Acid (RNA) <50 Copies/mL at Week 48
Time frame: 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.
Percentage of Participants With Tier-1 Neuropsychiatric Adverse Events (AEs)
Time frame: Up to Week 48
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).

16 secondary outcomes

Percentage of Participants With HIV-1 RNA <50 Copies/mL at Week 96
Time frame: Week 96
Percentage of Participants With HIV-1 RNA <40 Copies/mL at Week 48
Time frame: Week 48
Percentage of Participants With HIV-1 RNA <40 Copies/mL at Week 96
Time frame: Week 96
Change From Baseline in CD4 Cell Counts at Week 48
Time frame: Baseline (Day 1) and Week 48
Change From Baseline in CD4 Cell Counts at Week 96
Time frame: Baseline (Day 1) and Week 96
Percentage of Participants Experiencing ≥1 AE
Time frame: Up to Week 48
Percentage of Participants Discontinuing From Study Medication Due to an AE(s)
Time frame: Up to Week 48
Percentage of Participants With Tier-2 Neuropsychiatric AEs
Time frame: Up to Week 48
Change From Baseline in Fasting LDL-C at Week 48
Time frame: Baseline (Day 1) and Week 48
Change From Baseline in Fasting Non-HDL-C at Week 48
Time frame: Baseline (Day 1) and Week 48
Change From Baseline in Fasting Cholesterol at Week 48
Time frame: Baseline (Day 1) and Week 48
Change From Baseline in Fasting Triglycerides at Week 48
Time frame: Baseline (Day 1) and Week 48
Change From Baseline in Fasting HDL-C at Week 48
Time frame: Baseline (Day 1) and Week 48
Percentage of Participants With HIV-1 RNA Below the Limit of Quantification (BLoQ) at Week 48
Time frame: Week 48
Percentage of Participants With HIV-1 RNA BLoQ at Week 96
Time frame: Week 96
Plasma Concentration of Doravirine at Week 48
Time frame: 0 hours post-dose and 2 hours post-dose on Week 48

Results and safety

Results posted to the registry on 30 Apr 2018, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
MK-1439A (DOR/3TC/TDF From Day 1)	368	296
ATRIPLA™ (Switch From EFV/FTC/TDF at Week 96)	366	276

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

Time frame: Week 48. Number. Unit: Percentage of Participants

Measure	MK-1439A (DOR/3TC/TDF From Day 1) n = 364	ATRIPLA™ (Switch From EFV/FTC/TDF at Week 96) n = 364
Value	84.3	80.8

MK-1439A (DOR/3TC/TDF From Day 1) vs ATRIPLA™ (Switch From EFV/FTC/TDF at Week 96): Difference in percentages: 3.537 (95% CI -1.951 to 9.026)

Population analysed: The analysis population consists of all randomized participants who received ≥1 dose of study medication and had baseline HIV-1 RNA data available.

Primary outcome: Percentage of Participants With Tier-1 Neuropsychiatric Adverse Events (AEs)

Time frame: Up to Week 48. Number. Unit: Percentage of Participants

Measure	MK-1439A (DOR/3TC/TDF From Day 1) n = 364	ATRIPLA™ (Switch From EFV/FTC/TDF at Week 96) n = 364
Dizziness	8.8	37.1
Sleep disorders and disturbances	12.1	25.5
Altered sensorium	4.4	8.2

MK-1439A (DOR/3TC/TDF From Day 1) vs ATRIPLA™ (Switch From EFV/FTC/TDF at Week 96): Difference in percentages: -28.3 (95% CI -34.0 to -22.5), p <0.001, t-test, 2 sided
MK-1439A (DOR/3TC/TDF From Day 1) vs ATRIPLA™ (Switch From EFV/FTC/TDF at Week 96): Difference in percentages: -13.5 (95% CI -19.1 to -7.9), p <0.001, t-test, 2 sided
MK-1439A (DOR/3TC/TDF From Day 1) vs ATRIPLA™ (Switch From EFV/FTC/TDF at Week 96): Difference in percentages: -3.8 (95% CI -7.6 to -0.3), p = 0.033, t-test, 2 sided

Population analysed: The analysis population consists of all randomized participants who received ≥1 dose of study medication.

16 secondary outcomes are reported in the full results.

Adverse events

Time frame: Up to 430 weeks. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
DOR/3TC/TDF Only (From Day 1) at Base Study	22 of 364 (6%)	231 of 364 (63.5%)	1 of 368
DOR/3TC/TDF Switch at Week 96 Base Study	30 of 364 (8.2%)	281 of 364 (77.2%)	4 of 366
DOR/3TC/TDF Only (DOR/3TC/TDF From Day 1) Ext 1	19 of 291 (6.5%)	111 of 291 (38.1%)	2 of 291
DOR/3TC/TDF Switch (Switch From EFV/FTC/TDF at Week 96) Ext 1	12 of 269 (4.5%)	110 of 269 (40.9%)	0 of 269
DOR/3TC/TDF Only (DOR/3TC/TDF From Day 1) Ext 2	8 of 192 (4.2%)	0 of 0	2 of 192
DOR/3TC/TDF Switch (Switch From EFV/FTC/TDF at Week 96) Ext 2	9 of 173 (5.2%)	0 of 0	2 of 173
DOR/3TC/TDF Only (DOR/3TC/TDF From Day 1) Ext 3	2 of 121 (1.7%)	0 of 0	0 of 121
DOR/3TC/TDF Switch (Switch From EFV/FTC/TDF at Week 96) Ext 3	7 of 111 (6.3%)	0 of 0	0 of 111

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 20 Nov 2024.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 42281892Molina JM, Orkin C, Paredes R, Xu ZJ, Su FH, Asante-Appiah E, Plank RM, Lahoulou R. Analysis of Viral Blips Through Week 192 of the DRIVE-FORWARD and DRIVE-AHEAD Phase 3 Studies of Doravirine-Based Regimens in Adults Living With Previously Untreated HIV-1. Open Forum Infect Dis. 2026 Jun 10;13(6):ofag258. doi: 10.1093/ofid/ofag258. eCollection 2026 Jun.
Derived from this study: PubMed 41280318Orkin 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.
Derived from this study: PubMed 41081774Hsue 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.
Derived from this study: PubMed 40672760Walmsley 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.
Derived from this study: PubMed 39748155Moyle 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.
Derived from this study: PubMed 38141637Orkin 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.
Derived from this study: PubMed 33336698Orkin 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.
Derived from this study: PubMed 31121015Orkin 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.
Derived from this study: PubMed 31121013Thompson 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.
Derived from this study: PubMed 30184165Orkin 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.
Merck Clinical Trials InformationLink provided by the sponsor.
Individual participant dataSharing planned: Yes. http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Medical Director study director

Merck Sharp & Dohme LLC

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Doravirine, Tenofovir, Lamivudine and ATRIPLA™ in people with Human Immunodeficiency Virus (HIV), run by Merck Sharp & Dohme LLC.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 20 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 30 Apr 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage of Participants With HIV-1 Ribonucleic Acid (RNA) <50 Copies/mL at Week 48 (time frame: Week 48). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02403674, which also lists 10 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Nov 2024; AzTrials last refreshed its copy on 8 Nov 2026.