DRIVE-SHIFT: 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)

• Sponsor: Merck Sharp & Dohme LLC (Industry)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT02397096
• Collaborator: (none)
• Enrollment: 673
• Arms: 2
• Anticipated Duration (Months): 98.6

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
HIV-1 Infection	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	Phase 3

Detailed Description

Two 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 Extension 2 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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 673 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase III Multicenter, Open-Label, Randomized Study to Evaluate a Switch to MK-1439A in HIV-1-Infected Subjects Virologically Suppressed on a Regimen of a Ritonavir-boosted Protease Inhibitor and Two Nucleoside Reverse Transcriptase Inhibitors (NRTIs)
• Actual Study Start Date: Jun 9, 2015
• Actual Primary Completion Date: Feb 22, 2018
• Anticipated Study Completion Date: Aug 26, 2023

Arms and Interventions

Arm	Intervention/Treatment
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; Single tablet containing MK-1439 (doravirine) 100 mg, lamivudine 300 mg, and tenofovir disoproxil fumarate 300 mg; Other Names: Doravirine (PIFELTRO™) Doravirine/Lamivudine/Tenofovir disoproxil fumarate (DELSTRIGO™) MK-1439A ; Drug: Baseline 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; Drug: Baseline regimen of cobicistat-boosted elvitegravir; Baseline regimen of antiretroviral therapy with cobicistat-boosted elvitegravir administered according to the product circular; Drug: Baseline 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; Drug: Baseline regimen of two nucleoside reverse transcriptase inhibitors; Baseline regimen of antiretroviral therapy with two NRTIs administered according to the product circular
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; Single tablet containing MK-1439 (doravirine) 100 mg, lamivudine 300 mg, and tenofovir disoproxil fumarate 300 mg; Other Names: Doravirine (PIFELTRO™) Doravirine/Lamivudine/Tenofovir disoproxil fumarate (DELSTRIGO™) MK-1439A ; Drug: Baseline 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; Drug: Baseline regimen of cobicistat-boosted elvitegravir; Baseline regimen of antiretroviral therapy with cobicistat-boosted elvitegravir administered according to the product circular; Drug: Baseline 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; Drug: Baseline regimen of two nucleoside reverse transcriptase inhibitors; Baseline regimen of antiretroviral therapy with two NRTIs administered according to the product circular

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants Maintaining Human Immunodeficiency Virus-1 Ribonucleic Acid (HIV-1 RNA) <50 Copies/mL [Immediate Switch to MK-1439A arm: Week 48; Delayed Switch to MK-1439A arm: Week 24]

   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.

Secondary Outcome Measures

1. Mean Change From Baseline in Fasting Low-density Lipoprotein Cholesterol (LDL-C) [Baseline and Week 24]

   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.

2. Mean Change From Baseline in Fasting Non-high-density Lipoprotein Cholesterol (Non-HDL-C) [Baseline and Week 24]

   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.

3. Percentage of Participants Maintaining HIV-1 RNA <50 Copies/mL [Week 24]

   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.

4. Mean Change From Baseline in Cluster of Differentiation (CD4) Cell Counts [Immediate Switch to MK-1439A arm: Baseline and Week 48; Delayed Switch to MK-1439A arm: Baseline and Week 24]

   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.

5. Mean Change From Baseline in Cluster of Differentiation (CD4) Cell Counts [Baseline and Week 24]

   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.

6. Percentage of Participants Maintaining HIV-1 RNA <40 Copies/mL [Immediate Switch to MK-1439A arm: Week 48; Delayed Switch to MK-1439A arm: Week 24]

   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.

7. Percentage of Participants Maintaining HIV-1 RNA <40 Copies/mL [Immediate Switch to MK-1439A arm: Week 24; Delayed Switch to MK-1439A arm: Week 24]

   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.

8. Percentage of Participants With HIV-1 RNA >=50 Copies/mL [Immediate Switch to MK-1439A arm: Week 48; Delayed Switch to MK-1439A arm: Week 24]

   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.

9. Percentage of Participants Experiencing ≥1 Adverse Event (AE) [Up to week 24]

   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.

10. Percentage of Participants Experiencing ≥1 Serious Adverse Event (SAE) [Up to 24 weeks]

    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.

11. Percentage of Participants Discontinuing From Study Medication Due to an AE(s) [Up to Week 24]

    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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• At least 18 years of age on the day of signing the informed consent.

• Understand the study procedures and voluntarily agree to participate by giving written informed consent for the trial.

• Have plasma 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 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

Exclusion Criteria:

• 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

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Merck Sharp & Dohme LLC

Investigators

• Study Director: Medical Director, Merck Sharp & Dohme LLC

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Dec 14, 2017

More Information

Publications

None provided.

• Responsible Party: Merck Sharp & Dohme LLC
• ClinicalTrials.gov Identifier: NCT02397096
• Other Study ID Numbers: 1439A-024; 2014-005550-18; MK-1439A-024
• First Posted: Mar 24, 2015
• Last Update Posted: May 26, 2021
• Last Verified: May 1, 2021

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Ritonavir; HIV Protease Inhibitors; Tenofovir; Lamivudine; Cobicistat; Elvitegravir; Reverse Transcriptase Inhibitors; Protease Inhibitors

Study Results

Participant Flow

Recruitment Details	Out of 852 participants screened, 673 were randomized to study treatment, and 670 were treated. There were 122 global study sites utilized.
Pre-assignment Detail	This report covers results for the 48-week base study plus follow-up (up to 50 weeks). Results for the ongoing open-label study extensions will be reported when the extensions are completed.

Arm/Group Title	Immediate Switch Group (ISG)	Delayed Switch Group (DSG)
Arm/Group Description	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 (nuceloside/nucleotide reverse transcriptase inhibitors) NRTIs for >=6 months with undetectable HIV-1 RNA will switch on Day 1 to MK-1439A 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.	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 MK-1439A 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.
Period Title: Day 1 to Week 24
STARTED	447	223
COMPLETED	427	209
NOT COMPLETED	20	14
Period Title: Day 1 to Week 24
STARTED	427	209
COMPLETED	407	202
NOT COMPLETED	20	7
Period Title: Day 1 to Week 24
STARTED	399	202
COMPLETED	0	0
NOT COMPLETED	399	202

Baseline Characteristics

Arm/Group Title	Immediate Switch Group (ISG)	Delayed Switch Group (DSG)	Total
Arm/Group Description	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 (nuceloside/nucleotide reverse transcriptase inhibitors) NRTIs for >=6 months with undetectable HIV-1 RNA will switch on Day 1 to MK-1439A 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.	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 MK-1439A 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.	Total of all reporting groups
Overall Participants	447	223	670
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	43.1 (10.1)	43.7 (10.6)	43.3 (10.3)
Sex: Female, Male (Count of Participants)
Female	75 16.8%	29 13%	104 15.5%
Male	372 83.2%	194 87%	566 84.5%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	99 22.1%	45 20.2%	144 21.5%
Not Hispanic or Latino	341 76.3%	175 78.5%	516 77%
Unknown or Not Reported	7 1.6%	3 1.3%	10 1.5%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	5 1.1%	2 0.9%	7 1%
Asian	17 3.8%	8 3.6%	25 3.7%
Native Hawaiian or Other Pacific Islander	1 0.2%	0 0%	1 0.1%
Black or African American	56 12.5%	34 15.2%	90 13.4%
White	344 77%	168 75.3%	512 76.4%
More than one race	24 5.4%	11 4.9%	35 5.2%
Unknown or Not Reported	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug.

Arm/Group Title	Immediate Switch Group (ISG)	Delayed Switch Group (DSG)
Arm/Group Description	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 (nuceloside/nucleotide reverse transcriptase inhibitors) NRTIs for >=6 months with undetectable HIV-1 RNA will switch on Day 1 to MK-1439A 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.	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 MK-1439A 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.
Measure Participants	447	223
Number [Percentage of Participants]	90.8 20.3%	94.6 42.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Immediate Switch Group (ISG), Delayed Switch Group (DSG)
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate (DOR/3TC/TDF) once daily (QD) ISG is concluded to be non-inferior to baseline regimen DSG if the lower bound of the 95% CI for the difference in percent response is above -8 percentage points.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Treatment Difference
	Estimated Value	-3.784
	Confidence Interval	(2-Sided) 95%; -7.877 to 0.310
	Parameter Dispersion	Type: Value:
	Estimation Comments	Stratum-adjusted Mantel-Haenszel method with the difference weighted by the harmonic mean of sample size per arm for each stratum.
Other Statistical Analysis		Superiority of an immediate switch to DOR/3TC/TDF over continuation of the baseline regimen was defined by a lower bound of the two-sided 95% CI for the difference in response rates being greater than zero (contingent upon satisfying the multiplicity criteria).

2. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

All randomized participants in the ritonavir-boosted PI-based regimen who received at least 1 dose of study drug and had a measurement at baseline and had at least one post baseline time point assessed.

Arm/Group Title	Immediate Switch (Ritonavir--boosted, PI-based) Group (ISG)	Delayed Switch (Ritonavir-boosted, PI-based) Group (DSG)
Arm/Group Description	Participants receiving continuous antiretroviral therapy with a ritonavir-boosted, PI-based regimen for >=6 months with undetectable HIV-1 RNA will switch on Day 1 to MK-1439A 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.	Participants receiving continuous antiretroviral therapy with a ritonavir-boosted, PI-based regimen for >=6 months with undetectable HIV-1 RNA will continue on this therapy until Week 24, at which time they will switch to MK-1439A 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.
Measure Participants	256	125
Baseline	108.82 (34.21)	109.00 (33.58)
Change from Baseline	-16.54 (23.10)	-1.94 (25.74)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Immediate Switch Group (ISG), Delayed Switch Group (DSG)
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Treatment Difference
	Estimated Value	-14.65
	Confidence Interval	(2-Sided) 95%; -18.92 to -10.38
	Parameter Dispersion	Type: Value:
	Estimation Comments	95% 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.

3. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

All randomized participants who received the ritonavir-boosted PI-based regimen at least 1 dose of study drug and had a measurement at baseline and had at least one post baseline time point assessed.

Arm/Group Title	Immediate Switch (Ritonavir--boosted, PI-based) Group (ISG)	Delayed Switch (Ritonavir-boosted, PI-based) Group (DSG)
Arm/Group Description	Participants receiving continuous antiretroviral therapy with a ritonavir-boosted, PI-based regimen for >=6 months with undetectable HIV-1 RNA will switch on Day 1 to MK-1439A 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.	Participants receiving continuous antiretroviral therapy with a ritonavir-boosted, PI-based regimen for >=6 months with undetectable HIV-1 RNA will continue on this therapy until Week 24, at which time they will switch to MK-1439A 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.
Measure Participants	266	133
Baseline	139.14 (42.12)	137.99 (38.46)
Change from Baseline	-24.74 (29.26)	-1.31 (28.45)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Immediate Switch Group (ISG), Delayed Switch Group (DSG)
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Treatment Difference
	Estimated Value	-23.03
	Confidence Interval	(2-Sided) 95%; -28.00 to -18.05
	Parameter Dispersion	Type: Value:
	Estimation Comments	95% 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.

4. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug.

Arm/Group Title	Immediate Switch Group (ISG)	Delayed Switch Group (DSG)
Arm/Group Description	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 (nuceloside/nucleotide reverse transcriptase inhibitors) NRTIs for >=6 months with undetectable HIV-1 RNA will switch on Day 1 to MK-1439A 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.	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 MK-1439A 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.
Measure Participants	447	223
Number [Percentage of Participants]	93.7 21%	94.6 42.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Immediate Switch Group (ISG), Delayed Switch Group (DSG)
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	DOR/3TC/TDF QD ISG is concluded to be non-inferior to baseline regimen DSG if the lower bound of the 95% CI for the difference in percent response is above -8 percentage points.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Treatment Difference
	Estimated Value	-0.877
	Confidence Interval	(2-Sided) 95%; -4.706 to 2.952
	Parameter Dispersion	Type: Value:
	Estimation Comments	Stratum-adjusted Mantel-Haenszel method with the difference weighted by the harmonic mean of sample size per arm for each stratum.
Other Statistical Analysis		Superiority of an immediate switch to DOR/3TC/TDF over continuation of the baseline regimen was defined by a lower bound of the two-sided 95% CI for the difference in response rates being greater than zero (contingent upon satisfying the multiplicity criteria).

5. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug and had a measurement at baseline and had at least one post baseline time point assessed.

Arm/Group Title	Immediate Switch Group (ISG)	Delayed Switch Group (DSG)
Arm/Group Description	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 (nuceloside/nucleotide reverse transcriptase inhibitors) NRTIs for >=6 months with undetectable HIV-1 RNA will switch on Day 1 to MK-1439A 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.	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 MK-1439A 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.
Measure Participants	402	209
Baseline	660.5 (293.4)	655.6 (279.3)
Change from Baseline	13.9 (168.1)	18.0 (157.7)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Immediate Switch Group (ISG), Delayed Switch Group (DSG)
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-4.0
	Confidence Interval	(2-Sided) 95%; -31.6 to 23.5
	Parameter Dispersion	Type: Value:
	Estimation Comments	95% CIs were calculated based on t-distribution.

6. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug and had a measurement at baseline and had at least one post baseline time point assessed.

Arm/Group Title	Immediate Switch Group (ISG)	Delayed Switch Group (DSG)
Arm/Group Description	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 (nuceloside/nucleotide reverse transcriptase inhibitors) NRTIs for >=6 months with undetectable HIV-1 RNA will switch on Day 1 to MK-1439A 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.	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 MK-1439A 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.
Measure Participants	412	209
Baseline	664.5 (300.7)	655.6 (279.3)
Change from Baseline	5.1 (174.9)	18.0 (157.7)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Immediate Switch Group (ISG), Delayed Switch Group (DSG)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-12.8
	Confidence Interval	(2-Sided) 95%; -41.1 to 15.4
	Parameter Dispersion	Type: Value:
	Estimation Comments	95% Confidence Intervals were based on t-distribution.

7. Secondary Outcome

Title	Percentage of Participants Maintaining HIV-1 RNA <40 Copies/mL
Description	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

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug.

Arm/Group Title	Immediate Switch Group (ISG)	Delayed Switch Group (DSG)
Arm/Group Description	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 (nuceloside/nucleotide reverse transcriptase inhibitors) NRTIs for >=6 months with undetectable HIV-1 RNA will switch on Day 1 to MK-1439A 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.	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 MK-1439A 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.
Measure Participants	447	223
Number [Percentage of Participants]	89.7 20.1%	93.3 41.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Immediate Switch Group (ISG), Delayed Switch Group (DSG)
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Treatment Difference
	Estimated Value	-3.556
	Confidence Interval	(2-Sided) 95%; -7.977 to 0.864
	Parameter Dispersion	Type: Value:
	Estimation Comments	Stratum-adjusted Mantel-Haenszel method with the difference weighted by the harmonic mean of sample size per arm for each stratum.

8. Secondary Outcome

Title	Percentage of Participants Maintaining HIV-1 RNA <40 Copies/mL
Description	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

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug.

Arm/Group Title	Immediate Switch Group (ISG)	Delayed Switch Group (DSG)
Arm/Group Description	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 (nuceloside/nucleotide reverse transcriptase inhibitors) NRTIs for >=6 months with undetectable HIV-1 RNA will switch on Day 1 to MK-1439A 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.	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 MK-1439A 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.
Measure Participants	447	223
Number [Percentage of Participants]	92.8 20.8%	93.3 41.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Immediate Switch Group (ISG), Delayed Switch Group (DSG)
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Treatment Difference
	Estimated Value	-0.427
	Confidence Interval	(2-Sided) 95%; -4.591 to 3.738
	Parameter Dispersion	Type: Value:
	Estimation Comments	Stratum-adjusted Mantel-Haenszel method with the difference weighted by the harmonic mean of sample size per arm for each stratum.

9. Secondary Outcome

Title	Percentage of Participants With HIV-1 RNA >=50 Copies/mL
Description	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

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug.

Arm/Group Title	Immediate Switch Group (ISG)	Delayed Switch Group (DSG)
Arm/Group Description	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 (nuceloside/nucleotide reverse transcriptase inhibitors) NRTIs for >=6 months with undetectable HIV-1 RNA will switch on Day 1 to MK-1439A 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.	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 MK-1439A 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.
Measure Participants	447	223
Number [Percentage of Participants]	1.6 0.4%	1.8 0.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Immediate Switch Group (ISG), Delayed Switch Group (DSG)
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	DOR/3TC/TDF QD ISG is concluded to be non-inferior to baseline regimen DSG if the lower bound of the 95% CI for the difference in percent response is above -4 percentage points.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Treatment Difference
	Estimated Value	-0.232
	Confidence Interval	(2-Sided) 95%; -2.529 to 2.064
	Parameter Dispersion	Type: Value:
	Estimation Comments	Stratum-adjusted Mantel-Haenszel method with the difference weighted by the harmonic mean of sample size per arm for each stratum.

10. Secondary Outcome

Title	Percentage of Participants Experiencing ≥1 Adverse Event (AE)
Description	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

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug.

Arm/Group Title	Immediate Switch Group (ISG)	Delayed Switch Group (DSG)
Arm/Group Description	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 (nuceloside/nucleotide reverse transcriptase inhibitors) NRTIs for >=6 months with undetectable HIV-1 RNA will switch on Day 1 to MK-1439A 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.	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 MK-1439A 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.
Measure Participants	447	223
Number [Percentage of Participants]	68.9 15.4%	52.5 23.5%

11. Secondary Outcome

Title	Percentage of Participants Experiencing ≥1 Serious Adverse Event (SAE)
Description	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

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug.

Arm/Group Title	Immediate Switch Group (ISG)	Delayed Switch Group (DSG)
Arm/Group Description	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 (nuceloside/nucleotide reverse transcriptase inhibitors) NRTIs for >=6 months with undetectable HIV-1 RNA will switch on Day 1 to MK-1439A 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.	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 MK-1439A 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.
Measure Participants	447	223
Number [Percentage of Participants]	2.9 0.6%	3.6 1.6%

12. Secondary Outcome

Title	Percentage of Participants Discontinuing From Study Medication Due to an AE(s)
Description	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

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug.

Arm/Group Title	Immediate Switch Group (ISG)	Delayed Switch Group (DSG)
Arm/Group Description	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 (nuceloside/nucleotide reverse transcriptase inhibitors) NRTIs for >=6 months with undetectable HIV-1 RNA will switch on Day 1 to MK-1439A 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.	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 MK-1439A 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.
Measure Participants	447	223
Number [Percentage of Participants]	2.5 0.6%	0.4 0.2%

Adverse Events

Time Frame	48 week base study plus follow-up (Up to 50 weeks)
Adverse Event Reporting Description	The at-risk population is all participants who received at least 1 dose of study drug during the base study.
Arm/Group Title	Baseline Regimen DSG (Study Weeks 0-24)		DOR/3TC/TDF QD DSG (Study Weeks 24-48)		DOR/3TC/TDF QD ISG (Study Weeks 0-48)		ALL DOR: DOR/3TC/TDF ISG (Weeks 0-48)+DSG (Weeks 24-48)
Arm/Group Description	Participants in the delayed switch group (DSG) that received the baseline regimen of continuous antiretroviral therapy with a ritonavir- or cobicistat-boosted protease inhibitor (atazanavir, darunavir, or lopinavir) or cobicistat-boosted elvitegravir (EVG) or a NNRTI (specifically, efavirenz, nevirapine, or rilpivirine) in combination with 2 NRTIs for 24 weeks.		Participants in the delayed switch group (DSG) that received continuous antiretroviral therapy with an oral tablet of doravirine (DOR)/lamivudine (3TC) /tenofovir disoproxil fumarate (TDF) once daily from study week 24 to week 48.		Participants in the immediate switch group (ISG) that received continuous antiretroviral therapy with an oral tablet of doravirine (DOR)/lamivudine (3TC) /tenofovir disoproxil fumarate (TDF) once daily for 48 weeks.		Participants in the immediate switch group (ISG) that received continuous antiretroviral therapy with an oral tablet of doravirine (DOR)/lamivudine (3TC) /tenofovir disoproxil fumarate (TDF) once daily for 48 weeks. AND Participants in the delayed switch group (DSG) that received continuous antiretroviral therapy with an oral tablet of doravirine (DOR)/lamivudine (3TC) /tenofovir disoproxil fumarate (TDF) once daily from study week 24 to week 48.
All Cause Mortality
	Baseline Regimen DSG (Study Weeks 0-24)		DOR/3TC/TDF QD DSG (Study Weeks 24-48)		DOR/3TC/TDF QD ISG (Study Weeks 0-48)		ALL DOR: DOR/3TC/TDF ISG (Weeks 0-48)+DSG (Weeks 24-48)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/223 (0%)		0/209 (0%)		1/447 (0.2%)		1/656 (0.2%)
Serious Adverse Events
	Baseline Regimen DSG (Study Weeks 0-24)		DOR/3TC/TDF QD DSG (Study Weeks 24-48)		DOR/3TC/TDF QD ISG (Study Weeks 0-48)		ALL DOR: DOR/3TC/TDF ISG (Weeks 0-48)+DSG (Weeks 24-48)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/223 (3.6%)		4/209 (1.9%)		23/447 (5.1%)		27/656 (4.1%)
Cardiac disorders
Angina pectoris	0/223 (0%)	0	0/209 (0%)	0	1/447 (0.2%)	1	1/656 (0.2%)	1
Atrial fibrillation	0/223 (0%)	0	0/209 (0%)	0	1/447 (0.2%)	1	1/656 (0.2%)	1
Gastrointestinal disorders
Gastrooesophageal reflux disease	0/223 (0%)	0	0/209 (0%)	0	1/447 (0.2%)	1	1/656 (0.2%)	1
General disorders
Death	0/223 (0%)	0	0/209 (0%)	0	1/447 (0.2%)	1	1/656 (0.2%)	1
Infections and infestations
Appendicitis	0/223 (0%)	0	1/209 (0.5%)	1	1/447 (0.2%)	1	2/656 (0.3%)	2
Endocarditis	0/223 (0%)	0	0/209 (0%)	0	1/447 (0.2%)	1	1/656 (0.2%)	1
Pneumonia	3/223 (1.3%)	3	0/209 (0%)	0	1/447 (0.2%)	1	1/656 (0.2%)	1
Respiratory syncytial virus infection	0/223 (0%)	0	0/209 (0%)	0	1/447 (0.2%)	1	1/656 (0.2%)	1
Shigella infection	0/223 (0%)	0	0/209 (0%)	0	1/447 (0.2%)	1	1/656 (0.2%)	1
Tuberculous pleurisy	1/223 (0.4%)	1	0/209 (0%)	0	0/447 (0%)	0	0/656 (0%)	0
Injury, poisoning and procedural complications
Foot fracture	0/223 (0%)	0	0/209 (0%)	0	1/447 (0.2%)	1	1/656 (0.2%)	1
Hand fracture	0/223 (0%)	0	1/209 (0.5%)	1	0/447 (0%)	0	1/656 (0.2%)	1
Hip fracture	0/223 (0%)	0	0/209 (0%)	0	1/447 (0.2%)	1	1/656 (0.2%)	1
Investigations
Alanine aminotransferase increased	0/223 (0%)	0	0/209 (0%)	0	2/447 (0.4%)	2	2/656 (0.3%)	2
Amylase increased	0/223 (0%)	0	0/209 (0%)	0	1/447 (0.2%)	1	1/656 (0.2%)	1
Aspartate aminotransferase increased	0/223 (0%)	0	0/209 (0%)	0	2/447 (0.4%)	2	2/656 (0.3%)	2
Blood creatine phosphokinase increased	0/223 (0%)	0	0/209 (0%)	0	2/447 (0.4%)	2	2/656 (0.3%)	2
CD4 lymphocytes decreased	0/223 (0%)	0	0/209 (0%)	0	1/447 (0.2%)	1	1/656 (0.2%)	1
Lipase increased	0/223 (0%)	0	0/209 (0%)	0	2/447 (0.4%)	2	2/656 (0.3%)	2
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion	0/223 (0%)	0	0/209 (0%)	0	1/447 (0.2%)	1	1/656 (0.2%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Squamous cell carcinoma	1/223 (0.4%)	1	0/209 (0%)	0	0/447 (0%)	0	0/656 (0%)	0
Nervous system disorders
Amyotrophic lateral sclerosis	0/223 (0%)	0	0/209 (0%)	0	1/447 (0.2%)	1	1/656 (0.2%)	1
Headache	0/223 (0%)	0	0/209 (0%)	0	1/447 (0.2%)	1	1/656 (0.2%)	1
Lacunar infarction	0/223 (0%)	0	0/209 (0%)	0	1/447 (0.2%)	1	1/656 (0.2%)	1
Psychiatric disorders
Depression	1/223 (0.4%)	1	0/209 (0%)	0	1/447 (0.2%)	1	1/656 (0.2%)	1
Suicidal ideation	1/223 (0.4%)	1	0/209 (0%)	0	0/447 (0%)	0	0/656 (0%)	0
Suicide attempt	0/223 (0%)	0	0/209 (0%)	0	1/447 (0.2%)	1	1/656 (0.2%)	1
Renal and urinary disorders
Nephrolithiasis	1/223 (0.4%)	1	0/209 (0%)	0	0/447 (0%)	0	0/656 (0%)	0
Renal cyst	1/223 (0.4%)	1	0/209 (0%)	0	0/447 (0%)	0	0/656 (0%)	0
Renal failure	0/223 (0%)	0	1/209 (0.5%)	1	1/447 (0.2%)	1	2/656 (0.3%)	2
Respiratory, thoracic and mediastinal disorders
Asthma	0/223 (0%)	0	0/209 (0%)	0	1/447 (0.2%)	1	1/656 (0.2%)	1
Chronic obstructive pulmonary disease	1/223 (0.4%)	1	0/209 (0%)	0	0/447 (0%)	0	0/656 (0%)	0
Cough	1/223 (0.4%)	1	0/209 (0%)	0	0/447 (0%)	0	0/656 (0%)	0
Sleep apnoea syndrome	0/223 (0%)	0	1/209 (0.5%)	1	0/447 (0%)	0	1/656 (0.2%)	1
Skin and subcutaneous tissue disorders
Rash maculo-papular	0/223 (0%)	0	0/209 (0%)	0	1/447 (0.2%)	1	1/656 (0.2%)	1
Other (Not Including Serious) Adverse Events
	Baseline Regimen DSG (Study Weeks 0-24)		DOR/3TC/TDF QD DSG (Study Weeks 24-48)		DOR/3TC/TDF QD ISG (Study Weeks 0-48)		ALL DOR: DOR/3TC/TDF ISG (Weeks 0-48)+DSG (Weeks 24-48)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	25/223 (11.2%)		30/209 (14.4%)		126/447 (28.2%)		156/656 (23.8%)
Gastrointestinal disorders
Diarrhoea	5/223 (2.2%)	5	9/209 (4.3%)	10	31/447 (6.9%)	33	40/656 (6.1%)	43
Infections and infestations
Nasopharyngitis	12/223 (5.4%)	14	9/209 (4.3%)	10	45/447 (10.1%)	55	54/656 (8.2%)	65
Musculoskeletal and connective tissue disorders
Back pain	4/223 (1.8%)	4	1/209 (0.5%)	1	23/447 (5.1%)	24	24/656 (3.7%)	25
Nervous system disorders
Headache	5/223 (2.2%)	5	14/209 (6.7%)	14	38/447 (8.5%)	43	52/656 (7.9%)	57

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The SPONSOR must have the opportunity to review all proposed abstracts, manuscripts, or presentations regarding this study 60 days prior to submission for publication/presentation. Any information identified by the SPONSOR as confidential must be deleted prior to submission. SPONSOR review can be expedited to meet publication timelines.