HIV-1Phase 3DRIVE-FORWARDNCT02275780
Safety and Efficacy of Doravirine (MK-1439) in Participants With Human Immunodeficiency Virus 1 (HIV-1) (MK-1439-018)
A Phase 3 study testing Doravirine, Darunavir and Ritonavir in people with HIV-1, run by Merck Sharp & Dohme LLC.
Trial summary
To establish a new treatment option for treatment-naïve participants with HIV-1, the efficacy and safety of doravirine will be determined relative to a protease inhibitor (PI). Participants will receive double-blind treatment during the 96-week Base Study. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- HIV-1
- What is being tested?
- Doravirine, Darunavir and Ritonavir
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 769 participants
- Where
- No sites listed yet
- Study dates
- 1 Dec 2014to 6 Mar 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 and has HIV treatment indicated based on physician assessment.
- Has received no (0 days of) antiretroviral therapy (ART), including investigational antiretroviral agents.
- Is considered clinically stable with no signs or symptoms of active infection for at least 2 weeks prior to the start of treatment.
- Female is highly unlikely to become pregnant, or male is highly unlikely to impregnate a partner because they are not of reproductive potential, or agree to practice abstinence or use acceptable contraception for up to 14 days after the last dose of study drug.
- Eligibility for the Study Extension 1 at the Week 96 visit: 1) completed the Week 96 visit, 2) derived benefit from participation through Week 96 in the opinion of the investigator, 3) is a clinically-appropriate candidate for an additional 96 weeks of treatment with the Study Extension regimen.
- Eligibility for the Study Extension 2 at the Week 192 visit: 1) completed the Week 192 visit, 2) derived benefit from participation through Week 192 in the opinion of the investigator, 3) is a clinically-appropriate candidate for 96 weeks of treatment with the Study Extension regimen.
Who cannot join
- Uses or has had a recent history of using recreational or illicit drugs.
- Has been treated for a viral infection other than HIV-1, such as hepatitis B, with an agent that is active against HIV-1.
- Has documented or known resistance to study drugs including doravirine, darunavir, ritonavir, emtricitabine, tenofovir, abacavir and/or lamivudine.
- Has participated in a study with an investigational compound/device within the prior month, or anticipates doing so during this study.
- Has used systemic immunosuppressive therapy or immune modulators within the prior 30 days, or anticipates doing so during this study.
- Has significant hypersensitivity or other contraindication to any of the components of the study drugs.
Show all 9Show fewer
- Has a current (active) diagnosis of acute hepatitis due to any cause.
- Is pregnant, breastfeeding or expecting to conceive at any time during the study.
- Female who expects to donate eggs, or male who expects to donate sperm at any time during the study.
About this study
Official title: A Phase 3 Multicenter, Double-Blind, Randomized, Active Comparator-Controlled Clinical Trial to Evaluate the Safety and Efficacy of Doravirine (MK-1439) 100 mg Once Daily Versus Darunavir 800 mg Once Daily Plus Ritonavir 100 mg Once Daily, Each in Combination With TRUVADA™ or EPZICOM™/KIVEXA™, in Treatment-Naïve HIV-1 Infected Subjects
To establish a new treatment option for treatment-naïve participants with HIV-1, the efficacy and safety of doravirine will be determined relative to a protease inhibitor (PI). Participants will receive double-blind treatment during the 96-week Base Study. Eligible participants in either of the Base Study groups will continue to receive the doravirine-containing regimen open label for an additional 96 weeks in the Study Extension 1. Eligible participants who are deriving benefit will continue in Study Extension 2 to receive the doravirine-containing regimen open label until doravirine becomes locally available or for an additional 96 weeks, whichever comes first. The primary hypothesis is that doravirine 100 mg once a day (q.d.) is non-inferior to darunavir/ritonavir (800 mg/100 mg) q.d., each in combination with TRUVADA™ or EPZICOM™/KIVEXA™, as assessed by the proportion of participants with HIV-1 ribonucleic acid (RNA) <50 copies/mL at Week 48. If non-inferiority is established, then the superiority of doravirine 100 mg q.d. compared to darunavir/ ritonavir (800 mg/100 mg) q.d. will be assessed.
Read the detailed description
Participants in Australia, Russia, and South Africa who are deriving benefit from MK-1439A are also eligible to continue receiving study drug during Study Extension 3, which will last for 2 years or until drug is available locally, whichever comes first.
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DoravirineDrug
Doravirine 100 mg tablet administered p.o. q.d.
DarunavirDrug
Darunavir 800 mg tablet administered p.o. q.d.
RitonavirDrug
Ritonavir 100 mg tablet administered p.o. q.d.
TRUVADA™ or EPZICOM™/KIVEXA™Drug
The investigator selects either TRUVADA™, a tablet containing 200 mg emtricitabine and 300 mg tenofovir disoproxil fumarate p.o. q.d. or EPZICOM™/KIVEXA™, a tablet containing 600 mg abacavir sulfate and 300 mg lamivudine, p.o. q.d.
| Study group | Role | What they receive |
|---|---|---|
| Doravirine 100 mg | Experimental | Double-blind Doravirine 100 mg administered orally (p.o.) once daily (q.d.) + investigator selected TRUVADA™ or EPZICOM™/KIVEXA™ administered p.o. q.d. for 96 weeks in the Base Study. Eligible participants may continue in Study Extension 1 with open-label Doravirine 100 mg administered p.o. q.d. + investigator selected TRUVADA™ or EPZICOM™/KIVEXA™ administered p.o., q.d. for an additional 96 weeks. Eligible participants may continue to receive the Doravirine regimen in Study Extension 2 until Doravirine becomes locally available, or for an additional 96 weeks, whichever comes first. Eligible participants may continue to receive the Doravirine regimen in Study Extension 3 until Doravirine becomes locally available, or for an additional 96 weeks, whichever comes first. Receives: Drug: Doravirine; Drug: TRUVADA™ or EPZICOM™/KIVEXA™ |
| Darunavir 800 mg and Ritonavir 100 mg | Active comparator | Double-blind Darunavir 800 mg and Ritonavir 100 mg administered p.o. q.d. + investigator selected TRUVADA™ or EPZICOM™/KIVEXA™ administered p.o. q.d. for 96 weeks. Eligible participants may continue in Study Extension 1 with open-label Doravirine 100 mg administered p.o. q.d. + investigator selected TRUVADA™ or EPZICOM™/KIVEXA™ administered p.o. q.d. for an additional 96 weeks. Eligible participants may continue to receive the Doravirine regimen in Study Extension 2 until Doravirine becomes locally available, or for an additional 96 weeks, whichever comes first. Eligible participants may continue to receive the Doravirine regimen in Study Extension 3 until Doravirine becomes locally available, or for an additional 96 weeks, whichever comes first. Receives: Drug: Doravirine; Drug: Darunavir; Drug: Ritonavir; Drug: TRUVADA™ or EPZICOM™/KIVEXA™ |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants Achieving Plasma HIV-1 RNA <50 Copies/mL at Week 48
The percentage of participants in each arm achieving 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 and all missing data were considered treatment failures, regardless of the reason.
Measured: Week 48
Secondary outcomes (15)
Percentage of Participants Achieving Plasma HIV-1 RNA <50 Copies/mL at Week 96
The percentage of participants in each arm achieving HIV-1 RNA levels <50 copies/mL at Week 96 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.
Measured: Week 96
Change From Baseline in Mean CD4+ T-cell Count at Week 48
CD4+ T-cell counts were quantified by a central laboratory using a commercially available assay.
Measured: Baseline and Week 48
Change From Baseline in Mean CD4+ T-cell Count at Week 96
CD4+ T-cell counts were quantified by a central laboratory using a commercially available assay.
Measured: Baseline and Week 96
Mean Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) at Week 48
Serum LDL-C was determined after an overnight fast. Change from Baseline was analyzed using ANCOVA models with terms for Baseline lipid level and treatment group. The Last Observation Carry Forward (LOCF) approach was applied for missing data or data collected after modifying lipid-lowering therapy.
Measured: Baseline and Week 48
Mean Change From Baseline in Fasting Non-High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 48
Serum non-HDL-C was determined after an overnight fast. Change from Baseline was analyzed using ANCOVA models with terms for Baseline lipid level and treatment group. The LOCF approach was applied for missing data or data collected after modifying lipid-lowering therapy.
Measured: Baseline and Week 48
Mean Change From Baseline in Fasting High Density Lipoprotein Cholesterol (HDL-C) at Week 48
Serum HDL-C was determined after an overnight fast. Change from Baseline was analyzed using ANCOVA models with terms for Baseline lipid level and treatment group. The LOCF approach was applied for missing data or data collected after modifying lipid-lowering therapy.
Measured: Baseline and Week 48
Mean Change From Baseline in Fasting Total Cholesterol at Week 48
Serum total cholesterol was determined after an overnight fast. Change from Baseline was analyzed using ANCOVA models with terms for Baseline lipid level and treatment group. The LOCF approach was applied for missing data or data collected after modifying lipid-lowering therapy.
Measured: Baseline and Week 48
Mean Change From Baseline in Fasting Triglyceride at Week 48
Serum triglyceride was determined after an overnight fast. Change from Baseline was analyzed using ANCOVA models with terms for Baseline lipid level and treatment group. The LOCF approach was applied for missing data or data collected after modifying lipid-lowering therapy.
Measured: Baseline and Week 48
Percentage of Participants With Any Adverse Event
An adverse event (AE) is defined as any untoward medical occurrence in a study participant and which does not necessarily have to have a causal relationship to treatment. An adverse event can therefore be any unfavourable and unintended sign, symptom, or disease temporally associated with the study treatment or protocol-specified procedure, whether or not considered related to study treatment or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the study treatment is also an AE. The percentage of participants with any AE was assessed.
Measured: Up to 98 weeks
Percentage of Participants With Any Serious Adverse Event
A serious adverse event is an AE that results in death, is life threatening, results in persistent or significant disability or incapacity, results in or prolongs a hospitalization, is a congenital anomaly or birth defect, is a cancer, is associated with an overdose, or is another important medical event. The percentage of participants with any SAE was assessed.
Measured: Up to 98 weeks
Percentage of Participants With Any Drug-related Adverse Event
The investigator was to determine if an AE had a reasonable possibility of a relationship to the study drug. The percentage of participants with any drug-related AE was assessed.
Measured: Up to 98 weeks
Percentage of Participants With Any Drug-related Serious Adverse Event
The percentage of participants with any drug-related SAE was assessed.
Measured: Up to 98 weeks
Percentage of Participants Who Discontinued Study Treatment Due to an Adverse Event
The percentage of participants who discontinued study treatment due to an AE was assessed.
Measured: Up to 96 weeks
Percentage of Participants Achieving Plasma HIV-1 RNA <40 Copies/mL at Week 48
The percentage of participants in each arm achieving HIV-1 RNA levels <40 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 and all missing data were considered treatment failures, regardless of the reason.
Measured: Week 48
Percentage of Participants Achieving Plasma HIV-1 RNA <40 Copies/mL at Week 96
The percentage of participants in each arm achieving HIV-1 RNA levels <40 copies/mL at Week 96 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.
Measured: Week 96
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Oct 2014 (estimated)
- Study start1 Dec 2014
- Primary completion29 Sep 2016
- Study completion6 Mar 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 HIV-1Studies 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
- 769 participants (actual)
Sponsor and investigators
- Lead sponsor
- Merck Sharp & Dohme LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Director, Study director, Merck Sharp & Dohme LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02275780
- Sponsor's protocol ID
- 1439-018
- Other IDs
- MK-1439-018, 2014-001127-69, 2014
- Acronym
- DRIVE-FORWARD
- Status last verified
- Sep 2024
- First submitted
- 23 Oct 2014
- Last updated
- 1 Oct 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 42281892Orkin 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 41280318Hsue 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 41081774Walmsley 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 40672760Moyle 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 39748155Orkin 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 38141637Molina JM, Squires K, Sax PE, Cahn P, Lombaard J, DeJesus E, Lai MT, Rodgers A, Lupinacci L, Kumar S, Sklar P, Hanna GJ, Hwang C, Martin EA; DRIVE-FORWARD trial group. Doravirine versus ritonavir-boosted darunavir in antiretroviral-naive adults with HIV-1 (DRIVE-FORWARD): 96-week results of a randomised, double-blind, non-inferiority, phase 3 trial. Lancet HIV. 2020 Jan;7(1):e16-e26. doi: 10.1016/S2352-3018(19)30336-4. Epub 2019 Nov 15.
PubMed 31740348Orkin 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 31121015Thompson 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 31121013Molina JM, Squires K, Sax PE, Cahn P, Lombaard J, DeJesus E, Lai MT, Xu X, Rodgers A, Lupinacci L, Kumar S, Sklar P, Nguyen BY, Hanna GJ, Hwang C; DRIVE-FORWARD Study Group. Doravirine versus ritonavir-boosted darunavir in antiretroviral-naive adults with HIV-1 (DRIVE-FORWARD): 48-week results of a randomised, double-blind, phase 3, non-inferiority trial. Lancet HIV. 2018 May;5(5):e211-e220. doi: 10.1016/S2352-3018(18)30021-3. Epub 2018 Mar 25.
PubMed 29592840
Study at a glance
From the registry record, last updated by the sponsor on 1 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 3 Multicenter, Double-Blind, Randomized, Active Comparator-Controlled Clinical Trial to Evaluate the Safety and Efficacy of Doravirine (MK-1439) 100 mg Once Daily Versus Darunavir 800 mg Once Daily Plus Ritonavir 100 mg Once Daily, Each in Combination With TRUVADA™ or EPZICOM™/KIVEXA™, in Treatment-Naïve HIV-1 Infected Subjects
- ClinicalTrials.gov ID
- NCT02275780
- Acronym / sponsor ID
- DRIVE-FORWARD / 1439-018
- Conditions
- HIV-1
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 769 participants (actual)
- Lead sponsor
- Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
- Study start
- 1 Dec 2014 (actual)
- Primary completion
- 29 Sep 2016 (actual)
- Study completion
- 6 Mar 2023 (actual)
- First posted
- 27 Oct 2014 (estimated)
- Results
- Posted 23 Oct 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
To establish a new treatment option for treatment-naïve participants with HIV-1, the efficacy and safety of doravirine will be determined relative to a protease inhibitor (PI). Participants will receive double-blind treatment during the 96-week Base Study. Eligible participants in either of the Base Study groups will continue to receive the doravirine-containing regimen open label for an additional 96 weeks in the Study Extension 1. Eligible participants who are deriving benefit will continue in Study Extension 2 to receive the doravirine-containing regimen open label until doravirine becomes locally available or for an additional 96 weeks, whichever comes first. The primary hypothesis is that doravirine 100 mg once a day (q.d.) is non-inferior to darunavir/ritonavir (800 mg/100 mg) q.d., each in combination with TRUVADA™ or EPZICOM™/KIVEXA™, as assessed by the proportion of participants with HIV-1 ribonucleic acid (RNA) <50 copies/mL at Week 48. If non-inferiority is established, then the superiority of doravirine 100 mg q.d. compared to darunavir/ ritonavir (800 mg/100 mg) q.d. will be assessed.
Detailed description
Participants in Australia, Russia, and South Africa who are deriving benefit from MK-1439A are also eligible to continue receiving study drug during Study Extension 3, which will last for 2 years or until drug is available locally, whichever comes first.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Doravirine 100 mg | Experimental | Drug: Doravirine, Drug: TRUVADA™ or EPZICOM™/KIVEXA™Double-blind Doravirine 100 mg administered orally (p.o.) once daily (q.d.) + investigator selected TRUVADA™ or EPZICOM™/KIVEXA™ administered p.o. q.d. for 96 weeks in the Base Study. Eligible participants may continue in Study Extension 1 with open-label Doravirine 100 mg administered p.o. q.d. + investigator selected TRUVADA™ or EPZICOM™/KIVEXA™ administered p.o., q.d. for an additional 96 weeks. Eligible participants may continue to receive the Doravirine regimen in Study Extension 2 until Doravirine becomes locally available, or for an additional 96 weeks, whichever comes first. Eligible participants may continue to receive the Doravirine regimen in Study Extension 3 until Doravirine becomes locally available, or for an additional 96 weeks, whichever comes first. |
| Darunavir 800 mg and Ritonavir 100 mg | Active comparator | Drug: Doravirine, Drug: Darunavir, Drug: Ritonavir, Drug: TRUVADA™ or EPZICOM™/KIVEXA™Double-blind Darunavir 800 mg and Ritonavir 100 mg administered p.o. q.d. + investigator selected TRUVADA™ or EPZICOM™/KIVEXA™ administered p.o. q.d. for 96 weeks. Eligible participants may continue in Study Extension 1 with open-label Doravirine 100 mg administered p.o. q.d. + investigator selected TRUVADA™ or EPZICOM™/KIVEXA™ administered p.o. q.d. for an additional 96 weeks. Eligible participants may continue to receive the Doravirine regimen in Study Extension 2 until Doravirine becomes locally available, or for an additional 96 weeks, whichever comes first. Eligible participants may continue to receive the Doravirine regimen in Study Extension 3 until Doravirine becomes locally available, or for an additional 96 weeks, whichever comes first. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Is HIV-1 positive and has HIV treatment indicated based on physician assessment.
- Has received no (0 days of) antiretroviral therapy (ART), including investigational antiretroviral agents.
- Is considered clinically stable with no signs or symptoms of active infection for at least 2 weeks prior to the start of treatment.
- Female is highly unlikely to become pregnant, or male is highly unlikely to impregnate a partner because they are not of reproductive potential, or agree to practice abstinence or use acceptable contraception for up to 14 days after the last dose of study drug.
- Eligibility for the Study Extension 1 at the Week 96 visit: 1) completed the Week 96 visit, 2) derived benefit from participation through Week 96 in the opinion of the investigator, 3) is a clinically-appropriate candidate for an additional 96 weeks of treatment with the Study Extension regimen.
Key exclusion criteria (9 listed)
- Uses or has had a recent history of using recreational or illicit drugs.
- Has been treated for a viral infection other than HIV-1, such as hepatitis B, with an agent that is active against HIV-1.
- Has documented or known resistance to study drugs including doravirine, darunavir, ritonavir, emtricitabine, tenofovir, abacavir and/or lamivudine.
- Has participated in a study with an investigational compound/device within the prior month, or anticipates doing so during this study.
- Has used systemic immunosuppressive therapy or immune modulators within the prior 30 days, or anticipates doing so during this 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 |
|---|---|---|
| DoravirineDoravirine 100 mg tablet administered p.o. q.d. | Drug | Darunavir 800 mg and Ritonavir 100 mg, Doravirine 100 mg |
| DarunavirDarunavir 800 mg tablet administered p.o. q.d. | Drug | Darunavir 800 mg and Ritonavir 100 mg |
| RitonavirRitonavir 100 mg tablet administered p.o. q.d. | Drug | Darunavir 800 mg and Ritonavir 100 mg |
| TRUVADA™ or EPZICOM™/KIVEXA™The investigator selects either TRUVADA™, a tablet containing 200 mg emtricitabine and 300 mg tenofovir disoproxil fumarate p.o. q.d. or EPZICOM™/KIVEXA™, a tablet containing 600 mg abacavir sulfate and 300 mg lamivudine, p.o. q.d. | Drug | Darunavir 800 mg and Ritonavir 100 mg, Doravirine 100 mg |
Primary outcome
Percentage of Participants Achieving Plasma HIV-1 RNA <50 Copies/mL at Week 48
Time frame: Week 48
The percentage of participants in each arm achieving 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 and all missing data were considered treatment failures, regardless of the reason.
15 secondary outcomes
Percentage of Participants Achieving Plasma HIV-1 RNA <50 Copies/mL at Week 96
Time frame: Week 96
Change From Baseline in Mean CD4+ T-cell Count at Week 48
Time frame: Baseline and Week 48
Change From Baseline in Mean CD4+ T-cell Count at Week 96
Time frame: Baseline and Week 96
Mean Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) at Week 48
Time frame: Baseline and Week 48
Mean Change From Baseline in Fasting Non-High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 48
Time frame: Baseline and Week 48
Mean Change From Baseline in Fasting High Density Lipoprotein Cholesterol (HDL-C) at Week 48
Time frame: Baseline and Week 48
Mean Change From Baseline in Fasting Total Cholesterol at Week 48
Time frame: Baseline and Week 48
Mean Change From Baseline in Fasting Triglyceride at Week 48
Time frame: Baseline and Week 48
Percentage of Participants With Any Adverse Event
Time frame: Up to 98 weeks
Percentage of Participants With Any Serious Adverse Event
Time frame: Up to 98 weeks
Percentage of Participants With Any Drug-related Adverse Event
Time frame: Up to 98 weeks
Percentage of Participants With Any Drug-related Serious Adverse Event
Time frame: Up to 98 weeks
Percentage of Participants Who Discontinued Study Treatment Due to an Adverse Event
Time frame: Up to 96 weeks
Percentage of Participants Achieving Plasma HIV-1 RNA <40 Copies/mL at Week 48
Time frame: Week 48
Percentage of Participants Achieving Plasma HIV-1 RNA <40 Copies/mL at Week 96
Time frame: Week 96
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Oct 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 31740348Molina JM, Squires K, Sax PE, Cahn P, Lombaard J, DeJesus E, Lai MT, Rodgers A, Lupinacci L, Kumar S, Sklar P, Hanna GJ, Hwang C, Martin EA; DRIVE-FORWARD trial group. Doravirine versus ritonavir-boosted darunavir in antiretroviral-naive adults with HIV-1 (DRIVE-FORWARD): 96-week results of a randomised, double-blind, non-inferiority, phase 3 trial. Lancet HIV. 2020 Jan;7(1):e16-e26. doi: 10.1016/S2352-3018(19)30336-4. Epub 2019 Nov 15.
- 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 29592840Molina JM, Squires K, Sax PE, Cahn P, Lombaard J, DeJesus E, Lai MT, Xu X, Rodgers A, Lupinacci L, Kumar S, Sklar P, Nguyen BY, Hanna GJ, Hwang C; DRIVE-FORWARD Study Group. Doravirine versus ritonavir-boosted darunavir in antiretroviral-naive adults with HIV-1 (DRIVE-FORWARD): 48-week results of a randomised, double-blind, phase 3, non-inferiority trial. Lancet HIV. 2018 May;5(5):e211-e220. doi: 10.1016/S2352-3018(18)30021-3. Epub 2018 Mar 25.
- 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, Darunavir and Ritonavir in people with HIV-1, 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 6 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 1 Oct 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 23 Oct 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 Achieving Plasma HIV-1 RNA <50 Copies/mL at Week 48 (time frame: Week 48). 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 NCT02275780, 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 1 Oct 2024.