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CompletedNCT02397096DRIVE-SHIFTUpdated Nov 20, 2024Results posted

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)

A Phase 3 interventional study of Doravirine, Tenofovir, Lamivudine and Baseline regimen of ritonavir- or cobicistat-boosted protease inhibitor in HIV-1 Infection, sponsored by Merck Sharp & Dohme LLC. Completed. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2024-11-20.

Sponsored by Merck Sharp & Dohme LLC · Phase 3, Interventional, and Treatment

Phase
Phase 3
Study type
Interventional
Enrollment
673
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study 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.

Read the detailed description

Three optional study extensions are planned. Study Extension 1 will evaluate safety of the switch to doravirine, tenofovir, lamivudine for an additional 2 years beyond the Base Study. Study Extensions 2 and 3 will evaluate safety of the switch to doravirine, tenofovir, lamivudine until doravirine, tenofovir, lamivudine becomes locally available, or 4 years beyond Study Extension 1, whichever comes first.

02

Conditions studied

  • HIV-1 Infection
03

In context

Lead sponsor

Merck Sharp & Dohme LLC is the lead sponsor of 2,114 studies on the registry; 133 are open to participants now.

Of its 489 completed or terminated interventional studies of FDA-regulated products, 362 (74%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

Inclusion Criteria include, but are not limited to:

  • 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
  • For inclusion in Study Extension 1 (optional): completed the Week 48 visit; considered to have derived benefit from study participation up to Week 48; considered to be a clinically appropriate candidate for an additional 2 years treatment with study drug
  • For inclusion in Study Extension 2 (optional): completed the Week 144 visit; considered to have derived benefit from study participation up to Week 144; considered to be a clinically appropriate candidate for an additional 2 years treatment with study drug
  • For inclusion in Study Extension 3 (optional): completed the Week 240 visit; considered to have derived benefit from study participation up to Week 240; considered to be a clinically appropriate candidate for an additional 2 years treatment with study drug

Exclusion criteria

Exclusion Criteria:

Exclusion Criteria include, but are not limited to:

  • 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
05

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
673 participants (actual)

Study arms

  • Experimental
    Immediate Switch to Doravirine, Tenofovir, Lamivudine

    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

  • Active comparator
    Delayed Switch to Doravirine, Tenofovir, Lamivudine

    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

  • DrugDoravirine, Tenofovir, Lamivudine

    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

  • DrugBaseline regimen of ritonavir- or cobicistat-boosted protease inhibitor

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

  • DrugBaseline regimen of cobicistat-boosted elvitegravir

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

  • DrugBaseline regimen of a non-nucleoside reverse transcriptase inhibitor

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

  • DrugBaseline regimen of two nucleoside reverse transcriptase inhibitors

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

06

What researchers measure

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.

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

Secondary outcomes

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

    To evaluate the effect on fasting LDL-C of an immediate switch to DOR/3TC/TDF on Study Day 1 compared with continuation of a ritonavir-boosted, PI-based regimen, as measured by mean change from baseline in each treatment group. The Last Observation Carry Forward (LOCF) approach was applied to missing data and data collected after a participant initiated lipid-modifying therapy.

    Time frame: Baseline and Week 24

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

    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 Last Observation Carry Forward (LOCF) approach was applied for missing data or data collected after modifying lipid lowering therapy.

    Time frame: Baseline and Week 24

  3. Percentage of Participants Maintaining 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.

    Time frame: Week 24

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

    The mean change from baseline in CD4 cell counts was assessed using the Observed Failure (OF) approach. With the OF approach, baseline values were carried forward for participants who discontinued due to lack of efficacy. Cell counts were measured and expressed as cells/mm\^3, and percent change was then calculated. CD4 cell counts were quantified by a central laboratory using a commercially available assay.

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

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

    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 due to lack of efficacy. Cell counts were measured and expressed as cells/mm\^3, and percent change was then calculated. CD4 cell counts were quantified by a central laboratory using a commercially available assay.

    Time frame: Baseline and Week 24

  6. Percentage of Participants Maintaining HIV-1 RNA <40 Copies/mL

    The percentage of participants in each arm achieving HIV-1 RNA levels \<40 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.

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

  7. Percentage of Participants Maintaining HIV-1 RNA <40 Copies/mL

    To evaluate the immunological effect of an immediate switch to MK -1439A on Study Day 1 compared with continuation of a ritonavir boosted, PI-based regimen, as measured by the proportion of subjects maintaining HIV-1 RNA below the limit of quantification (BLoQ) by the Abbott RealTime HIV-1 Assay (\<40 copies/mL) in both treatment groups.

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

  8. Percentage of Participants With 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.

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

  9. Percentage of Participants Experiencing ≥1 Adverse Event (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.

    Time frame: Up to week 24

  10. Percentage of Participants Experiencing ≥1 Serious Adverse Event (SAE)

    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.

    Time frame: Up to 24 weeks

  11. 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.

    Time frame: Up to Week 24

07

Results

Posted Apr 3, 2019

Participant flow

Day 1 to Week 24
Participant flow — Day 1 to Week 24
MilestoneImmediate Switch Group (ISG)Delayed Switch Group (DSG)
Started450223
Treated447223
Completed427209
Not completed2314
Withdrew: Adverse event71
Withdrew: Death10
Withdrew: Lack of efficacy01
Withdrew: Lost to follow-up34
Withdrew: Physician decision23
Withdrew: Protocol violation14
Withdrew: Withdrawal by subject61
Withdrew: Randomized, not treated30
Week 24 to Week 48
Participant flow — Week 24 to Week 48
MilestoneImmediate Switch Group (ISG)Delayed Switch Group (DSG)
Started427209
Completed407202
Not completed207
Withdrew: Adverse event62
Withdrew: Lack of efficacy51
Withdrew: Non-compliance with study drug01
Withdrew: Physician decision21
Withdrew: Withdrawal by subject52
Withdrew: Lost to follow-up20
Study Extension 1
Participant flow — Study Extension 1
MilestoneImmediate Switch Group (ISG)Delayed Switch Group (DSG)
Started398202
Completed357179
Not completed4123
Withdrew: Adverse event75
Withdrew: Death10
Withdrew: Lack of efficacy25
Withdrew: Lost to follow-up23
Withdrew: Non-compliance with study drug30
Withdrew: Physician decision42
Withdrew: Pregnancy10
Withdrew: Protocol violation01
Withdrew: Withdrawal by subject217
Study Extension 2
Participant flow — Study Extension 2
MilestoneImmediate Switch Group (ISG)Delayed Switch Group (DSG)
Started303154
Completed12978
Not completed17476
Withdrew: Adverse event33
Withdrew: Availability of study medication locally15264
Withdrew: Death20
Withdrew: Lack of efficacy10
Withdrew: Lost to follow-up21
Withdrew: Non-compliance with study drug10
Withdrew: Physician decision25
Withdrew: Pregnancy10
Withdrew: Withdrawal by subject103
Study Extension 3
Participant flow — Study Extension 3
MilestoneImmediate Switch Group (ISG)Delayed Switch Group (DSG)
Started8443
Completed6939
Not completed154
Withdrew: Adverse event10
Withdrew: Availability of study medication locally113
Withdrew: Lost to follow-up10
Withdrew: Withdrawal by subject21

Outcome measures

PrimaryPercentage 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.

Time frame:
Immediate Switch to MK-1439A arm: Week 48; Delayed Switch to MK-1439A arm: Week 24
Reported as:
Number · Percentage of Participants
Percentage of Participants Maintaining Human Immunodeficiency Virus-1 Ribonucleic Acid (HIV-1 RNA) <50 Copies/mL
Percentage of ParticipantsImmediate Switch Group (ISG)Delayed Switch Group (DSG)
Percentage of Participants Maintaining Human Immunodeficiency Virus-1 Ribonucleic Acid (HIV-1 RNA) <50 Copies/mL90.894.6
Statistical analysis
  • Immediate Switch Group (ISG) vs Delayed Switch Group (DSG) · Treatment difference: -3.784 · 95% CI -7.877 to 0.310Stratum-adjusted Mantel-Haenszel method with the difference weighted by the harmonic mean of sample size per arm for each stratum.
SecondaryMean Change From Baseline in Fasting Low-density Lipoprotein Cholesterol (LDL-C)

To evaluate the effect on fasting LDL-C of an immediate switch to DOR/3TC/TDF on Study Day 1 compared with continuation of a ritonavir-boosted, PI-based regimen, as measured by mean change from baseline in each treatment group. The Last Observation Carry Forward (LOCF) approach was applied to missing data and data collected after a participant initiated lipid-modifying therapy.

Time frame:
Baseline and Week 24
Reported as:
Mean · mg/dL
Mean Change From Baseline in Fasting Low-density Lipoprotein Cholesterol (LDL-C)
mg/dLImmediate Switch (Ritonavir--boosted, PI-based) Group (ISG)Delayed Switch (Ritonavir-boosted, PI-based) Group (DSG)
Baseline108.82 ± 34.21109.00 ± 33.58
Change from Baseline-16.54 ± 23.10-1.94 ± 25.74
Statistical analysis
  • Immediate Switch (Ritonavir--boosted, PI-based) Group (ISG) vs Delayed Switch (Ritonavir-boosted, PI-based) Group (DSG) · ANCOVA · p = <0.0001 · Treatment difference: -14.65 · 95% CI -18.92 to -10.3895% CIs and 2-sided p-values were calculated from an ANCOVA model with terms for baseline lipid level, use of lipid-lowering therapy at Study Day 1 and treatment.
SecondaryMean Change From Baseline in Fasting Non-high-density Lipoprotein Cholesterol (Non-HDL-C)

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 Last Observation Carry Forward (LOCF) approach was applied for missing data or data collected after modifying lipid lowering therapy.

Time frame:
Baseline and Week 24
Reported as:
Mean · mg/dL
Mean Change From Baseline in Fasting Non-high-density Lipoprotein Cholesterol (Non-HDL-C)
mg/dLImmediate Switch (Ritonavir--boosted, PI-based) Group (ISG)Delayed Switch (Ritonavir-boosted, PI-based) Group (DSG)
Baseline139.14 ± 42.12137.99 ± 38.46
Change from Baseline-24.74 ± 29.26-1.31 ± 28.45
Statistical analysis
  • Immediate Switch (Ritonavir--boosted, PI-based) Group (ISG) vs Delayed Switch (Ritonavir-boosted, PI-based) Group (DSG) · ANCOVA · p = <0.0001 · Treatment difference: -23.03 · 95% CI -28.00 to -18.0595% CIs and 2-sided p-values were calculated from an ANCOVA model with terms for baseline lipid level, use of lipid-lowering therapy at Study Day 1 and treatment.
SecondaryPercentage of Participants Maintaining 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.

Time frame:
Week 24
Reported as:
Number · Percentage of Participants
Percentage of Participants Maintaining HIV-1 RNA <50 Copies/mL
Percentage of ParticipantsImmediate Switch Group (ISG)Delayed Switch Group (DSG)
Percentage of Participants Maintaining HIV-1 RNA <50 Copies/mL93.794.6
Statistical analysis
  • Immediate Switch Group (ISG) vs Delayed Switch Group (DSG) · Treatment difference: -0.877 · 95% CI -4.706 to 2.952Stratum-adjusted Mantel-Haenszel method with the difference weighted by the harmonic mean of sample size per arm for each stratum.
SecondaryMean Change From Baseline in Cluster of Differentiation (CD4) Cell Counts

The mean change from baseline in CD4 cell counts was assessed using the Observed Failure (OF) approach. With the OF approach, baseline values were carried forward for participants who discontinued due to lack of efficacy. Cell counts were measured and expressed as cells/mm\^3, and percent change was then calculated. CD4 cell counts were quantified by a central laboratory using a commercially available assay.

Time frame:
Immediate Switch to MK-1439A arm: Baseline and Week 48; Delayed Switch to MK-1439A arm: Baseline and Week 24
Reported as:
Mean · cells/mm^3
Mean Change From Baseline in Cluster of Differentiation (CD4) Cell Counts
cells/mm^3Immediate Switch Group (ISG)Delayed Switch Group (DSG)
Baseline660.5 ± 293.4655.6 ± 279.3
Change from Baseline13.9 ± 168.118.0 ± 157.7
Statistical analysis
  • Immediate Switch Group (ISG) vs Delayed Switch Group (DSG) · Mean difference (final values): -4.0 · 95% CI -31.6 to 23.595% CIs were calculated based on t-distribution.
SecondaryMean Change From Baseline in Cluster of Differentiation (CD4) Cell Counts

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 due to lack of efficacy. Cell counts were measured and expressed as cells/mm\^3, and percent change was then calculated. CD4 cell counts were quantified by a central laboratory using a commercially available assay.

Time frame:
Baseline and Week 24
Reported as:
Geometric mean · cells/mm^3
Mean Change From Baseline in Cluster of Differentiation (CD4) Cell Counts
cells/mm^3Immediate Switch Group (ISG)Delayed Switch Group (DSG)
Baseline664.5 ± 300.7655.6 ± 279.3
Change from Baseline5.1 ± 174.918.0 ± 157.7
Statistical analysis
  • Immediate Switch Group (ISG) vs Delayed Switch Group (DSG) · Mean difference (final values): -12.8 · 95% CI -41.1 to 15.495% Confidence Intervals were based on t-distribution.
SecondaryPercentage of Participants Maintaining HIV-1 RNA <40 Copies/mL

The percentage of participants in each arm achieving HIV-1 RNA levels \<40 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.

Time frame:
Immediate Switch to MK-1439A arm: Week 48; Delayed Switch to MK-1439A arm: Week 24
Reported as:
Number · Percentage of Participants
Percentage of Participants Maintaining HIV-1 RNA <40 Copies/mL
Percentage of ParticipantsImmediate Switch Group (ISG)Delayed Switch Group (DSG)
Percentage of Participants Maintaining HIV-1 RNA <40 Copies/mL89.793.3
Statistical analysis
  • Immediate Switch Group (ISG) vs Delayed Switch Group (DSG) · Treatment difference: -3.556 · 95% CI -7.977 to 0.864Stratum-adjusted Mantel-Haenszel method with the difference weighted by the harmonic mean of sample size per arm for each stratum.
SecondaryPercentage of Participants Maintaining HIV-1 RNA <40 Copies/mL

To evaluate the immunological effect of an immediate switch to MK -1439A on Study Day 1 compared with continuation of a ritonavir boosted, PI-based regimen, as measured by the proportion of subjects maintaining HIV-1 RNA below the limit of quantification (BLoQ) by the Abbott RealTime HIV-1 Assay (\<40 copies/mL) in both treatment groups.

Time frame:
Immediate Switch to MK-1439A arm: Week 24; Delayed Switch to MK-1439A arm: Week 24
Reported as:
Number · Percentage of Participants
Percentage of Participants Maintaining HIV-1 RNA <40 Copies/mL
Percentage of ParticipantsImmediate Switch Group (ISG)Delayed Switch Group (DSG)
Percentage of Participants Maintaining HIV-1 RNA <40 Copies/mL92.893.3
Statistical analysis
  • Immediate Switch Group (ISG) vs Delayed Switch Group (DSG) · Treatment difference: -0.427 · 95% CI -4.591 to 3.738Stratum-adjusted Mantel-Haenszel method with the difference weighted by the harmonic mean of sample size per arm for each stratum.
SecondaryPercentage of Participants With 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.

Time frame:
Immediate Switch to MK-1439A arm: Week 48; Delayed Switch to MK-1439A arm: Week 24
Reported as:
Number · Percentage of Participants
Percentage of Participants With HIV-1 RNA >=50 Copies/mL
Percentage of ParticipantsImmediate Switch Group (ISG)Delayed Switch Group (DSG)
Percentage of Participants With HIV-1 RNA >=50 Copies/mL1.61.8
Statistical analysis
  • Immediate Switch Group (ISG) vs Delayed Switch Group (DSG) · Treatment difference: -0.232 · 95% CI -2.529 to 2.064Stratum-adjusted Mantel-Haenszel method with the difference weighted by the harmonic mean of sample size per arm for each stratum.
SecondaryPercentage of Participants Experiencing ≥1 Adverse Event (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.

Time frame:
Up to week 24
Reported as:
Number · Percentage of Participants
Percentage of Participants Experiencing ≥1 Adverse Event (AE)
Percentage of ParticipantsImmediate Switch Group (ISG)Delayed Switch Group (DSG)
Percentage of Participants Experiencing ≥1 Adverse Event (AE)68.952.5
SecondaryPercentage of Participants Experiencing ≥1 Serious Adverse Event (SAE)

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.

Time frame:
Up to 24 weeks
Reported as:
Number · Percentage of Participants
Percentage of Participants Experiencing ≥1 Serious Adverse Event (SAE)
Percentage of ParticipantsImmediate Switch Group (ISG)Delayed Switch Group (DSG)
Percentage of Participants Experiencing ≥1 Serious Adverse Event (SAE)2.93.6
SecondaryPercentage 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.

Time frame:
Up to Week 24
Reported as:
Number · Percentage of Participants
Percentage of Participants Discontinuing From Study Medication Due to an AE(s)
Percentage of ParticipantsImmediate Switch Group (ISG)Delayed Switch Group (DSG)
Percentage of Participants Discontinuing From Study Medication Due to an AE(s)2.50.4

Adverse events

Collected over Up to ~338 weeks. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
ISG Base Study Weeks 0-241/450 (0.2%)13/447 (2.9%)100/447 (22.4%)
DSG Base Study Weeks 0-240/223 (0%)8/223 (3.6%)28/223 (12.6%)
ISG Base Study Weeks 24-480/427 (0%)11/427 (2.6%)63/427 (14.8%)
DSG Base Study Weeks 24-480/209 (0%)4/209 (1.9%)33/209 (15.8%)
ISG Study Extension 11/398 (0.3%)37/398 (9.3%)107/398 (26.9%)
DSG Study Extension 10/202 (0%)13/202 (6.4%)57/202 (28.2%)
ISG Study Extension 23/303 (1%)13/303 (4.3%)24/303 (7.9%)
DSG Study Extension 20/154 (0%)7/154 (4.5%)11/154 (7.1%)
ISG Study Extension 30/84 (0%)3/84 (3.6%)9/84 (10.7%)
DSG Study Extension 30/43 (0%)1/43 (2.3%)3/43 (7%)
Most frequent serious events
Showing 10 of 93
Most frequent serious events
EventISG Base Study Weeks 0-24DSG Base Study Weeks 0-24ISG Base Study Weeks 24-48DSG Base Study Weeks 24-48ISG Study Extension 1DSG Study Extension 1ISG Study Extension 2DSG Study Extension 2ISG Study Extension 3DSG Study Extension 3
Tendon ruptureInjury, poisoning and procedural complications0/4470/2230/4270/2090/3980/2020/3030/1540/841/43
PneumoniaInfections and infestations1/4473/2230/4270/2091/3982/2021/3030/1540/840/43
COVID-19Infections and infestations0/4470/2230/4270/2090/3980/2020/3031/1541/840/43
Bowen's diseaseNeoplasms benign, malignant and unspecified (incl cysts and polyps)0/4470/2230/4270/2091/3980/2020/3030/1541/840/43
NephrolithiasisRenal and urinary disorders0/4470/2230/4270/2091/3980/2020/3030/1541/840/43
AppendicitisInfections and infestations0/4470/2231/4271/2091/3982/2021/3030/1540/840/43
Basal cell carcinomaNeoplasms benign, malignant and unspecified (incl cysts and polyps)0/4470/2230/4270/2093/3980/2020/3030/1540/840/43
Coronary artery stenosisCardiac disorders0/4470/2230/4270/2090/3980/2020/3031/1540/840/43
Myocardial infarctionCardiac disorders0/4470/2230/4270/2090/3980/2020/3031/1540/840/43
Retinal detachmentEye disorders0/4470/2230/4270/2090/3980/2020/3031/1540/840/43
Most frequent other events
Most frequent other events
EventISG Base Study Weeks 0-24DSG Base Study Weeks 0-24ISG Base Study Weeks 24-48DSG Base Study Weeks 24-48ISG Study Extension 1DSG Study Extension 1ISG Study Extension 2DSG Study Extension 2ISG Study Extension 3DSG Study Extension 3
NasopharyngitisInfections and infestations33/44712/22319/4279/20951/39829/2025/3032/1540/840/43
COVID-19Infections and infestations0/4470/2230/4270/2090/3980/2024/3036/1547/843/43
HeadacheNervous system disorders29/4475/22311/42714/20922/39813/2022/3033/1540/840/43
DiarrhoeaGastrointestinal disorders20/4475/22313/4279/20918/39811/2023/3030/1541/840/43
ArthralgiaMusculoskeletal and connective tissue disorders14/4475/2238/4273/20921/3984/2025/3031/1541/840/43
Back painMusculoskeletal and connective tissue disorders9/4474/22316/4271/20921/3989/2027/3032/1540/840/43

Baseline characteristics

Age, Continuous
Age, Continuous(Years)Immediate Switch Group (ISG)Delayed Switch Group (DSG)Total
Mean43.1 ± 10.143.7 ± 10.643.3 ± 10.3
Sex: Female, Male
Sex: Female, Male(Participants)Immediate Switch Group (ISG)Delayed Switch Group (DSG)Total
Female7529104
Male375194569
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)Immediate Switch Group (ISG)Delayed Switch Group (DSG)Total
Hispanic or Latino9843141
Not Hispanic or Latino347177524
Unknown or Not Reported538
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Immediate Switch Group (ISG)Delayed Switch Group (DSG)Total
American Indian or Alaska Native527
Asian17825
Native Hawaiian or Other Pacific Islander101
Black or African American563490
White346168514
More than one race251136
Unknown or Not Reported000
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Study locations

No study locations are listed for this record.

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References and documents

Publications

  • 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. PubMed 33633036 ↗
  • 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. PubMed 32868326 ↗
  • 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. PubMed 30985556 ↗

Study documents

  • Protocol and statistical analysis plan · Oct 31, 2022

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: Yes — http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

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Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Nov 20, 2024, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
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Registry details

Key details

Study ID
NCT02397096
Lead sponsor
Merck Sharp & Dohme LLC
Responsible party
Sponsor
First posted
Mar 24, 2015
Start date
Jun 9, 2015
Primary completion
Feb 22, 2018
Completion
Sep 5, 2023
Results posted
Apr 3, 2019
Last update
Nov 20, 2024

Study contacts

Medical Director
study director · Merck Sharp & Dohme LLC

Oversight

Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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