Phase 3
Completed N=734
Comparison of Doravirine, Tenofovir, Lamivudine (MK-1439A) and ATRIPLA™ in Treatment-Naive Human Immunodeficiency Virus Type 1 (HIV-1)-Infected Participants (MK-1439A-021)
Source: ClinicalTrials.gov NCT02403674 ↗Enrolled (actual)
734
Serious AEs
5.8%
Results posted
Apr 2018
Primary outcomePrimary: Percentage of Participants With HIV-1 Ribonucleic Acid (RNA) <50 Copies/mL at Week 48 — 84.3; 80.8 Percentage of Participants
◆ Published Evidence
Established
31citations · ~16 / year
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.
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.
Linked Publications (5)
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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.
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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.
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Factors Associated With Weight Change After Continuing or Switching to a Doravirine-based Regimen.
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Cardiovascular Risk Assessment Using the Atherosclerotic Cardiovascular Disease Risk Score Model after Continuing or Switching to a Doravirine-Based HIV Treatment Regimen.
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Efficacy and Safety of Doravirine-based Regimens by Sex and Race: Long-term Results From Three Phase 3 Clinical Trials.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percentage of Participants With HIV-1 Ribonucleic Acid (RNA) <50 Copies/mL at Week 48 |
84.3; 80.8 | — |
| PRIMARY Percentage of Participants With Tier-1 Neuropsychiatric Adverse Events (AEs) |
8.8; 37.1; 12.1; 25.5; 4.4; 8.2 | <0.001 sig |
| SECONDARY Percentage of Participants With HIV-1 RNA <50 Copies/mL at Week 96 |
77.5; 73.6 | — |
| SECONDARY Percentage of Participants With HIV-1 RNA <40 Copies/mL at Week 48 |
83.8; 79.7 | — |
| SECONDARY Percentage of Participants With HIV-1 RNA <40 Copies/mL at Week 96 |
76.1; 72.8 | — |
| SECONDARY Change From Baseline in CD4 Cell Counts at Week 48 |
198.4; 188.4 | — |
| SECONDARY Change From Baseline in CD4 Cell Counts at Week 96 |
237.7; 223.0 | — |
| SECONDARY Percentage of Participants Experiencing ≥1 AE |
82.7; 90.7 | — |
| SECONDARY Percentage of Participants Discontinuing From Study Medication Due to an AE(s) |
3.0; 6.6 | — |
| SECONDARY Percentage of Participants With Tier-2 Neuropsychiatric AEs |
4.1; 6.6; 0.3; 1.1 | <0.001 sig |
| SECONDARY Change From Baseline in Fasting LDL-C at Week 48 |
-1.58; 8.74 | <0.0001 sig |
| SECONDARY Change From Baseline in Fasting Non-HDL-C at Week 48 |
-3.83; 13.26 | <0.0001 sig |
| SECONDARY Change From Baseline in Fasting Cholesterol at Week 48 |
-1.97; 21.77 | — |
| SECONDARY Change From Baseline in Fasting Triglycerides at Week 48 |
-12.40; 22.01 | — |
| SECONDARY Change From Baseline in Fasting HDL-C at Week 48 |
1.86; 8.51 | — |
| SECONDARY Percentage of Participants With HIV-1 RNA Below the Limit of Quantification (BLoQ) at Week 48 |
59.6; 55.5 | — |
| SECONDARY Percentage of Participants With HIV-1 RNA BLoQ at Week 96 |
59.3; 59.1 | — |
| SECONDARY Plasma Concentration of Doravirine at Week 48 |
1290; 2330 | — |
Eligibility Criteria
Inclusion Criteria
- 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
Exclusion Criteria
- 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
Data sourced from ClinicalTrials.gov (NCT02403674) and the linked publication. Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.