Placebo to Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate
Doravirine/Islatravir
Countries
United States
Chile
France
United Kingdom
Protocol Section
Identification Module
NCT ID
NCT03272347
Obsolete or Duplicate NCT IDs
Not provided
Organization Study
8591-011
Secondary IDs
ID
Type
Description
Link
2017-000437-32
EudraCT Number
Brief Title
Islatravir (MK-8591) With Doravirine and Lamivudine in Participants Infected With Human Immunodeficiency Virus Type 1 (MK-8591-011)
Official Title
A Phase 2B, Randomized, Double-Blind, Active-Comparator-Controlled, Dose-Ranging Clinical Trial to Evaluate the Safety, Tolerability, Antiretroviral Activity, and Pharmacokinetics of MK-8591 Given in Combination With Doravirine (DOR) and Lamivudine (3TC) in HIV-1-Infected Treatment-Naïve Adults
Acronym
Not provided
Organization
Merck Sharp & Dohme LLCINDUSTRY
Status Module
Record Verification Date
Feb 2023
Overall Recruitment Status or Expanded Access Status
Completed
Last Known Status
Not provided
Delayed Posting
Not provided
Why Stopped
Not provided
Expanded Access Info
No
Start Date
Nov 27, 2017Actual
Primary Completion Date
Mar 8, 2021Actual
Completion Date
Mar 9, 2022Actual
First Submitted Date
Sep 1, 2017
First Submission Date that Met QC Criteria
Sep 1, 2017
First Posted Date
Sep 5, 2017Actual
Results Waived
Not provided
Results First Submitted Date
Feb 23, 2022
Results First Submitted that Met QC Criteria
Mar 31, 2022
Results First Posted Date
Apr 27, 2022Actual
Certification/Extension (aka Delayed Results) First Submitted Date
Not provided
Certification/Extension First Submitted that Passed QC Review
Not provided
Certification/Extension First Posted Date
Not provided
Last Update Submitted Date
Mar 3, 2023
Last Update Posted Date
Mar 29, 2023Actual
Sponsor/Collaborators Module
Responsible Party, by Official Title
Sponsor
Lead Sponsor
Merck Sharp & Dohme LLCINDUSTRY
Collaborators
Not provided
Oversight Module
Has Data Monitoring Committee (DMC)
Yes
Is FDA Regulated Drug
Yes
Is FDA Regulated Device
No
Is Unapproved Device
Not provided
Pediatric Postmarket Surveillance of a Device Product
Not provided
Product Exported from US
Not provided
FDAAA801 Violation
Not provided
Description Module
Brief Summary
This study will evaluate the safety, tolerability, antiretroviral activity, and pharmacokinetics of 3 doses of islatravir (MK-8591) in combination with doravirine (DOR) and lamivudine (3TC) administered to antiretroviral treatment-naïve adult participants with human immunodeficiency virus type 1 (HIV-1) infection.
Detailed Description
Not provided
Conditions Module
Conditions
HIV-1 Infection
Keywords
Not provided
Design Module
Study Type
Interventional
Number of References to an Expanded Access Study
Not provided
Expanded Access Types
Not provided
Patient Registry
Not provided
Target Follow-Up Duration
Not provided
Phases
Phase 2
Interventional Study Design
Allocation
Biospecimen
No data available
No data is available for this block.
Enrollment
123Actual
Arms/Interventions Module
Arm Groups
Label
Type
Description
Intervention Names
Islatravir 0.25 mg
Experimental
Participants will be treated once daily (QD) with 0.25 mg islatravir, 100 mg DOR, 300 mg 3TC, and placebo to doravirine/lamivudine/tenofovir disoproxil fumarate (DOR/3TC/TDF) for a minimum of 24 weeks. Between week 24 through week 52, 3TC and placebo to DOR/3TC/TDF may be discontinued. Around Week 60, participants may be switched to a selected open label dose of islatravir and DOR 100 mg QD and continue treatment until Week 144. At Week 144 participants will receive the fixed dose combination of doravirine (100mg)/islatravir (0.75mg) QD open label and will continue treatment until Week 192.
Drug: Islatravir
Drug: Doravirine
Drug: Lamivudine
Drug: Placebo to Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate
Drug: Doravirine/Islatravir
Islatravir 0.75 mg
Experimental
Participants will be treated QD with 0.75 mg islatravir, 100 mg DOR, 300 mg 3TC, and placebo to DOR/3TC/TDF for a minimum of 24 weeks. Between week 24 through week 52, 3TC and placebo to DOR/3TC/TDF may be discontinued. Around Week 60, participants may be switched to a selected open label dose of islatravir and DOR 100 mg QD and will continue treatment until Week 144. At Week 144 participants will receive the fixed dose combination of doravirine (100mg)/islatravir (0.75mg) QD open label and will continue treatment until Week 192.
Drug: Islatravir
Drug: Doravirine
Drug: Lamivudine
Drug: Placebo to Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate
Drug: Doravirine/Islatravir
Islatravir 2.25 mg
Experimental
Participants will be treated QD with 2.25 mg islatravir, 100 mg DOR, 300 mg 3TC, and placebo to DOR/3TC/TDF for a minimum of 24 weeks. Between week 24 through week 52, 3TC and placebo to DOR/3TC/TDF may be discontinued. Around Week 60, participants may be switched to a selected open label dose of islatravir and DOR 100 mg QD and will continue treatment until Week 144. At Week 144 participants will receive the fixed dose combination of doravirine (100mg)/islatravir (0.75mg) QD open label and will continue treatment until Week 192.
Interventions
Name
Type
Description
Arm Group Labels
Other Names
Islatravir
Drug
Islatravir at 0.25 mg, 0.75 mg or 2.25 mg is orally administered QD in capsule form for up to 52 weeks. After Week 60 a selected open label dose may be administered.
Outcomes Module
Primary Outcomes
Measure
Description
Time Frame
Percentage of Participants With HIV-1 RNA <50 Copies/mL at Week 24
Blood samples were collected and plasma human immunodeficiency virus 1 (HIV-1) ribonucleic acid (RNA) were quantified using a real time polymerase chain reaction (PCR) assay with a lower limit of detection of 40 copies/mL. Missing values were counted as failure.
Week 24
Percentage of Participants With HIV-1 RNA <50 Copies/mL at Week 48
Blood samples were collected and plasma HIV-1 RNA were quantified using a real time PCR assay with a lower limit of detection of 40 copies/mL. Missing values were counted as failure.
Week 48
Number of Participants Experiencing Adverse Events (AEs) up to Week 144
An adverse event (AE) is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study treatment.
Up to 144 weeks
Number of Participants Discontinuing Study Drug Due to AEs up to Week 144
An AE is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study treatment.
Up to 144 weeks
Secondary Outcomes
Measure
Description
Time Frame
Percentage of Participants With HIV-1 RNA <50 Copies/mL up to 24 Weeks After 3TC and Placebo Are Discontinued From the Regimen
Blood samples were collected and plasma HIV-1 RNA were quantified using a real time PCR assay with a lower limit of detection of 40 copies/mL, and missing values were counted as failure. 3TC and placebo are discontinued from the regimen from Week 24 up to Week 52.
Up to 24 weeks after 3TC and Placebo are discontinued from the regimen (up to approximately 60 weeks after initiating treatment)
Other Outcomes
Not provided
Eligibility Module
Eligibility Criteria
Inclusion Criteria:
Has HIV-1 infection
Is naïve to anti-retroviral therapy (ART).
Is clinically stable, with no signs or symptoms of acute infection, at the time of entry into the study
Female is not pregnant, not breastfeeding, not a woman of childbearing potential (WOCBP); but if WOCBP agrees to follow the contraceptive guidance
All participants, male and female, agree to use barrier methods of contraception when engaged in any sexual activity during treatment and for 6 weeks following treatment.
Exclusion Criteria:
Is a user of recreational or illicit drugs or has had a history of drug or alcohol abuse or dependence that may interfere with trial participation
Has significant hypersensitivity or other contraindication to any of the components of the study drugs
Has a history of malignancy ≤5 years prior
Female expects to donate eggs at any time during the study
Is breastfeeding or expecting to conceive
A WOCBP who has a positive urine pregnancy test on Day 1 before the first dose of study treatment
Has been treated for a viral infection other than HIV-1, such as hepatitis B, with an agent that is active against HIV-1
Has used systemic immunosuppressive therapy or immune modulators within 30 days prior to treatment in this study or is anticipated to need them during the course of the study
Requires any of the following prohibited medications: Carbamazepine, Phenobarbital, Phenytoin, Rifabutin, Rifampin, Herbal remedies, St. John's Wort, Modafinil, Bosentan, Nafcillin, Pentostatin
Is currently participating in or has participated in an interventional clinical trial with an investigational compound or device within 30 days of signing informed consent to participate in this current trial
Has a documented or known virologic resistance to any approved HIV-1 reverse transcriptase inhibitor, protease inhibitor, integrase inhibitor
Has active hepatitis C virus (HCV) coinfection defined as detectable HCV RNA or HBV co-infection defined as hepatitis B surface antigen [HBsAg]-positive
Has a current (active) diagnosis of acute hepatitis due to any cause
Has previously been randomized in a study and received islatravir (MK-8591), DOR, Doravirine, Tenofovir, Lamivudine, or 3TC.
Molina JM, Yazdanpanah Y, Afani Saud A, Bettacchi C, Chahin Anania C, Klopfer SO, Grandhi A, Eves K, Hepler D, Robertson MN, Hwang C, Hanna GJ, Correll T. Brief Report: Efficacy and Safety of Oral Islatravir Once Daily in Combination With Doravirine Through 96 Weeks for Treatment-Naive Adults With HIV-1 Infection Receiving Initial Treatment With Islatravir, Doravirine, and Lamivudine. J Acquir Immune Defic Syndr. 2022 Sep 1;91(1):68-72. doi: 10.1097/QAI.0000000000002879. Epub 2021 Dec 8.
Treatment-naïve participants ≥18 years of age with human immunodeficiency virus type 1 (HIV-1) were enrolled in this study.
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
FG000
Islatravir 0.25 mg
In Part 1, participants were treated once daily (QD) with 0.25 mg islatravir, 100 mg doravirine (DOR), 300 mg lamivudine (3TC), and placebo to doravirine/lamivudine/tenofovir disoproxil fumarate (DOR/3TC/TDF) for a minimum of 24 weeks. In part 2, after receiving at least 24 weeks of study intervention, participants with HIV-1 RNA <50 copies/mL and no Protocol-defined Virologic Failure (PDVF) discontinued treatment of 3TC and placebo to DOR/3TC/TDF. Part 2 assessed ISL 0.25 mg (blind maintained) + DOR QD. After all participants had received at least 48 weeks of study intervention and the islatravir dose was selected, all participants in the islatravir group were switched to the selected dose 0.75 mg (between week 60 and week 84). Part 3 assessed Islatravir 0.75 mg + DOR QD open label through Week 144. In Part 4, beginning with Week 144, participants received the fixed dose combination of doravirine (100 mg)/islatravir (0.75 mg) QD open label and continued treatment until Week 192.
Periods
Title
Milestones
Reasons Not Completed
Overall Study
Type
Comment
Milestone Data
STARTED
Baseline Characteristics Module
Baseline Analysis Population Description
Not provided
Outcome Measures Module
Outcome Measures
Adverse Events Module
Frequency Threshold
5
More Info Module
Limitations and Caveats
Not provided
Annotation Section
No data available
No data is available for this block.
Document Section
Large Document Module
Document Has No Statistical Analysis Plan (SAP)
Not provided
Uploaded Document Information
Type
Includes Protocol
Includes SAP
Includes ICF
Document Label
Document Date
Document Uploaded Date
Document File Name
Prot_SAP
Yes
Yes
No
Study Protocol and Statistical Analysis Plan
Jul 6, 2020
Derived Section
Miscellaneous Info Module
Version Holder
Jul 10, 2026
Removed Countries
Not provided
Submission Tracking
No data available
No data is available for this block.
Condition Browse Module
No data available
No data is available for this block.
Intervention Browse Module
MeSH Terms
Randomized
Intervention Model
Parallel Assignment
Intervention Model Description
Not provided
Primary Purpose
Treatment
Observational Model
Not provided
Time Perspective
Not provided
Masking Info
Masking
Double
Masking Description
Masking in Part 1, including matching placebo. Masking only to dose in Part 2. No masking in Parts 3 and 4.
Who Masked
ParticipantInvestigator
Drug: Islatravir
Drug: Doravirine
Drug: Lamivudine
Drug: Placebo to Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate
Drug: Doravirine/Islatravir
DOR/3TC/TDF
Active Comparator
Participants will be treated QD with placebo to islatravir, placebo to DOR, placebo to 3TC, and a fixed dose combination of DOR/3TC/TDF consisting of 100 mg DOR + 300 mg 3TC + 300 mg TDF for a minimum of 24 weeks. Between week 24 through week 52 placebo treatments may be discontinued and participants will receive only DOR/3TC/TDF QD open label up to Week 144. At Week 144 participants will receive the fixed dose combination of doravirine (100mg)/islatravir (0.75mg) QD open label and will continue treatment until Week 192.
Fixed dose combination of 100 mg doravirine + 300 mg lamivudine + 300 mg tenofovir disoproxil fumarate is orally administered QD in tablet form for up to 144 weeks.
DOR/3TC/TDF
MK-1439A
Placebo to Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate
Drug
Placebo to doravirine/lamivudine/tenofovir disoproxil fumarate is orally administered QD in tablet form for up to 52 weeks
Islatravir 0.25 mg
Islatravir 0.75 mg
Islatravir 2.25 mg
Doravirine/Islatravir
Drug
Fixed dose combination of islatravir 0.75 mg/doravirine 100 mg orally administered QD in tablet form for 48 weeks
DOR/3TC/TDF
Islatravir 0.25 mg
Islatravir 0.75 mg
Islatravir 2.25 mg
MK-8591A
Percentage of Participants With HIV-1 RNA <50 Copies/mL up to 48 Weeks After 3TC and Placebo Are Discontinued From the Regimen
Blood samples were collected and plasma HIV-1 RNA were quantified using a real time PCR assay with a lower limit of detection of 40 copies/mL, and missing values were counted as failure. 3TC and placebo are discontinued from the regimen from Week 24 up to Week 52.
Up to 48 weeks
Percentage of Participants With HIV-1 RNA <50 Copies/mL up to 48 Weeks After Starting Open-label Doravirine/Islatravir Regimen (Part 4)
Blood samples were collected and plasma HIV-1 RNA were quantified using a real time PCR assay with a lower limit of detection of 40 copies/mL. Missing values were counted as failure. The percentage of participants with HIV-1 RNA <50 copies in Part 4 are reported.
Up to Week 192
Change From Baseline in Mature T-helper (CD4+ T)-Cell Count at Week 24
Blood samples were collected and cluster of differentiation (CD4)+ T-cell counts were performed, where baseline measurements are defined as the Day 1 value, and baseline values were carried forward for participants who discontinue due to lack of efficacy. Post-baseline data were collected after the first dose of study medication through 14 days after the last dose of study medication.
Baseline and Week 24
Change From Baseline in CD4+ T-cell Count at Week 48
Blood samples were collected and CD4+ T-cell counts were performed, where baseline measurements are defined as the Day 1 value, and baseline values were carried forward for participants who discontinue due to lack of efficacy. Post-baseline data were collected after the first dose of study medication through 14 days after the last dose of study medication.
Baseline and Week 48
Change From Baseline in CD4+ T-cell Count at Week 96
Blood samples were collected and CD4+ T-cell counts were performed, where baseline measurements are defined as the Day 1 value, and baseline values were carried forward for participants who discontinue due to lack of efficacy. Post-baseline data were collected after the first dose of study medication through 14 days after the last dose of study medication.
Baseline and Week 96
Change From Baseline in CD4+ T-cell Count at Week 144
Blood samples were collected and CD4+ T-cell counts were performed, where baseline measurements are defined as the Day 1 value, and baseline values were carried forward for participants who discontinue due to lack of efficacy. Post-baseline data were collected after the first dose of study medication through 14 days after the last dose of study medication.
Baseline and Week 144
Change From Baseline in CD4+ T-cell Count at Week 192 (Part 4)
Blood samples were collected and CD4+ T-cell counts were performed, where baseline measurements are defined as the Week 144 value. The change from baseline in CD4+ T-cell count at Week 192 (Part 4) are reported.
Baseline and Week 192
Number of Participants Experiencing AEs Through 24 Weeks After 3TC and Placebo Are Discontinued From the Regimen
An AE is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study treatment. 3TC and placebo are discontinued from the regimen from Week 24 up to Week 52.
Up to 24 weeks
Number of Participants Discontinuing Study Drug Due to AEs Through 24 Weeks After 3TC and Placebo Are Discontinued From the Regimen
An AE is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study treatment. 3TC and placebo are discontinued from the regimen from Week 24 up to Week 52.
Up to 24 weeks
Number of Participants Experiencing AEs From Week 96 Through Study Duration
An AE is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study treatment.
Week 96 up to Week 192
Number of Participants Discontinuing Study Drug Due to AEs From Week 96 Through Study Duration
An AE is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study treatment.
Week 96 up to Week 192
Number of Participants Experiencing AEs During Open Label Doravirine/Islatravir Treatment After Week 144 up to Week 192 (Part 4)
An AE is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study treatment. The number of participants who experienced AEs during Part 4 are reported.
Week 144 up to Week 192
Number of Participants Discontinuing Study Drug Due to AEs During Open Label Doravirine/Islatravir Treatment After Week 144 up to Week 192 (Part 4)
An AE is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study treatment. The number of participants who discontinued the study drug due to AEs in Part 4 are reported.
Week 144 up to Week 192
Sacramento
California
95817
United States
Whitman Walker Clinic ( Site 0108)
Washington D.C.
District of Columbia
20005
United States
Orlando Immunology Center (OIC) ( Site 0105)
Orlando
Florida
32803
United States
Northstar Medical Center ( Site 0102)
Chicago
Illinois
60657
United States
Kansas City CARE Clinic ( Site 0106)
Kansas City
Missouri
64111
United States
Saint Hope Foundation, Inc. ( Site 0116)
Bellaire
Texas
77401
United States
North Texas Infectious Diseases Consultants, PA ( Site 0103)
Dallas
Texas
75246
United States
Tarrant County Infectious Disease Associates ( Site 0112)
Fort Worth
Texas
76104
United States
The Crofoot Research Center, Inc. ( Site 0118)
Houston
Texas
77098
United States
Clinica Arauco Salud ( Site 0200)
Santiago
RM
Chile
Biomedica Research Group ( Site 0202)
Santiago
Chile
Hospital Dr. Hernan Henriquez Aravena ( Site 0203)
Temuco
Chile
Hopital Avicenne ( Site 2302)
Bobigny
France
Hopital Saint-Andre ( Site 2307)
Bordeaux
France
CHU Hotel Dieu ( Site 2308)
Nantes
France
CHU de Nice Hopital Archet 1 ( Site 2303)
Nice
France
Hopital Bichat - Claude Bernard ( Site 2309)
Paris
France
Hopital Pitie Salpetriere ( Site 2305)
Paris
France
Hopital Saint Louis ( Site 2306)
Paris
France
Centre Hospitalier de Tourcoing ( Site 2301)
Tourcoing
France
Brighton and Sussex University Hospitals NHS Trust ( Site 2105)
Brighton
East Sussex
United Kingdom
Chelsea and Westminster Hospital ( Site 2101)
London
United Kingdom
Royal London Hospital ( Site 2103)
London
United Kingdom
The Royal Free London NHS Foundation Trust ( Site 2102)
London
United Kingdom
North Manchester General Hospital ( Site 2104)
Manchester
United Kingdom
Derived
Molina JM, Yazdanpanah Y, Afani Saud A, Bettacchi C, Chahin Anania C, DeJesus E, Olsen Klopfer S, Grandhi A, Eves K, Robertson MN, Correll T, Hwang C, Hanna GJ, Sklar P. Islatravir in combination with doravirine for treatment-naive adults with HIV-1 infection receiving initial treatment with islatravir, doravirine, and lamivudine: a phase 2b, randomised, double-blind, dose-ranging trial. Lancet HIV. 2021 Jun;8(6):e324-e333. doi: 10.1016/S2352-3018(21)00021-7. Epub 2021 May 14.
FG001
Islatravir 0.75 mg
In Part 1, participants were treated QD with 0.75 mg islatravir, 100 mg DOR, 300 mg 3TC, and placebo to DOR/3TC/TDF for a minimum of 24 weeks. In part 2, after receiving at least 24 weeks of study intervention, participants with HIV-1 RNA <50 copies/mL and no PDVF discontinued treatment of 3TC and placebo to DOR/3TC/TDF. Part 2 assessed ISL 0.75 mg (blind maintained) + DOR QD. After all participants had received at least 48 weeks of study intervention and the islatravir dose was selected, all participants in the islatravir group were switched to the selected dose 0.75 mg (between week 60 and week 84). Part 3 assessed Islatravir 0.75 mg + DOR QD open label through Week 144. In Part 4, beginning with Week 144, participants received the fixed dose combination of doravirine (100 mg)/islatravir (0.75 mg) QD open label and continued treatment until Week 192.
FG002
Islatravir 2.25 mg
In Part 1, participants were treated QD with 2.25 mg islatravir, 100 mg DOR, 300 mg 3TC, and placebo to DOR/3TC/TDF for a minimum of 24 weeks. In part 2, after receiving at least 24 weeks of study intervention, participants with HIV-1 RNA <50 copies/mL and no PDVF discontinued treatment of 3TC and placebo to DOR/3TC/TDF. Part 2 assessed ISL 2.25 mg (blind maintained) + DOR QD. After all participants had received at least 48 weeks of study intervention and the islatravir dose was selected, all participants in the islatravir group were switched to the selected dose 0.75 mg (between week 60 and week 84). Part 3 assessed Islatravir 0.75 mg + DOR QD open label through Week 144. In Part 4, beginning with Week 144, participants received the fixed dose combination of doravirine (100 mg)/islatravir (0.75 mg) QD open label and continued treatment until Week 192.
FG003
DOR/3TC/TDF
In Part 1, participants were treated QD with placebo to islatravir, placebo to DOR, placebo to 3TC, and a fixed dose combination of DOR/3TC/TDF consisting of 100 mg DOR + 300 mg 3TC + 300 mg TDF for a minimum of 24 weeks. In Parts 2 and 3, after a minimum of 24 weeks of treatment, placebo treatments were discontinued and participants received only DOR/3TC/TDF QD open label up to Week 144. In Part 4, beginning with Week 144, participants received the fixed dose combination of doravirine (100 mg)/islatravir (0.75 mg) QD open label and continued treatment until Week 192.
FG00031 subjects
FG00130 subjects
FG00231 subjects
FG00331 subjects
Treated
FG00029 subjects
FG00130 subjects
FG00231 subjects
FG00331 subjects
COMPLETED
FG00020 subjects
FG00124 subjects
FG00219 subjects
FG00324 subjects
NOT COMPLETED
FG00011 subjects
FG0016 subjects
FG00212 subjects
FG0037 subjects
Type
Comment
Reasons
Death
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0031 subjects
Lost to Follow-up
FG0001 subjects
FG0013 subjects
FG0025 subjects
FG0031 subjects
Physician Decision
FG0004 subjects
FG0012 subjects
FG0025 subjects
FG0034 subjects
Screen Failure
FG0001 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
Withdrawal by Subject
FG0005 subjects
FG0011 subjects
FG0022 subjects
FG0031 subjects
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
BG000
Islatravir 0.25 mg
In Part 1, participants were treated QD with 0.75 mg islatravir, 100 mg DOR, 300 mg 3TC, and placebo to DOR/3TC/TDF for a minimum of 24 weeks. In part 2, after receiving at least 24 weeks of study intervention, participants with HIV-1 RNA <50 copies/mL and no PDVF discontinued treatment of 3TC and placebo to DOR/3TC/TDF. Part 2 assessed ISL 0.75 mg (blind maintained) + DOR QD. After all participants had received at least 48 weeks of study intervention and the islatravir dose was selected, all participants in the islatravir group were switched to the selected dose 0.75 mg (between week 60 and week 84). Part 3 assessed Islatravir 0.75 mg + DOR QD open label through Week 144. In Part 4, beginning with Week 144, participants received the fixed dose combination of doravirine (100 mg)/islatravir (0.75 mg) QD open label and continued treatment until Week 192.
BG001
Islatravir 0.75 mg
In Part 1, participants were treated QD with 0.75 mg islatravir, 100 mg DOR, 300 mg 3TC, and placebo to DOR/3TC/TDF for a minimum of 24 weeks. In part 2, after receiving at least 24 weeks of study intervention, participants with HIV-1 RNA <50 copies/mL and no PDVF discontinued treatment of 3TC and placebo to DOR/3TC/TDF. Part 2 assessed ISL 0.75 mg (blind maintained) + DOR QD. After all participants had received at least 48 weeks of study intervention and the islatravir dose was selected, all participants in the islatravir group were switched to the selected dose 0.75 mg (between week 60 and week 84). Part 3 assessed Islatravir 0.75 mg + DOR QD open label through Week 144. In Part 4, beginning with Week 144, participants received the fixed dose combination of doravirine (100 mg)/islatravir (0.75 mg) QD open label and continued treatment until Week 192.
BG002
Islatravir 2.25 mg
In Part 1, participants were treated QD with 2.25 mg islatravir, 100 mg DOR, 300 mg 3TC, and placebo to DOR/3TC/TDF for a minimum of 24 weeks. In part 2, after receiving at least 24 weeks of study intervention, participants with HIV-1 RNA <50 copies/mL and no PDVF discontinued treatment of 3TC and placebo to DOR/3TC/TDF. Part 2 assessed ISL 2.25 mg (blind maintained) + DOR QD. After all participants had received at least 48 weeks of study intervention and the islatravir dose was selected, all participants in the islatravir group were switched to the selected dose 0.75 mg (between week 60 and week 84). Part 3 assessed Islatravir 0.75 mg + DOR QD open label through Week 144. In Part 4, beginning with Week 144, participants received the fixed dose combination of doravirine (100 mg)/islatravir (0.75 mg) QD open label and continued treatment until Week 192.
BG003
DOR/3TC/TDF
In Part 1, participants were treated QD with placebo to islatravir, placebo to DOR, placebo to 3TC, and a fixed dose combination of DOR/3TC/TDF consisting of 100 mg DOR + 300 mg 3TC + 300 mg TDF for a minimum of 24 weeks. In Parts 2 and 3, after a minimum of 24 weeks of treatment, placebo treatments were discontinued and participants received only DOR/3TC/TDF QD open label up to Week 144. In Part 4, beginning with Week 144, participants received the fixed dose combination of doravirine (100 mg)/islatravir (0.75 mg) QD open label and continued treatment until Week 192.
BG004
Total
Total of all reporting groups
Denominators
Units
Counts
Participants
BG00031
BG00130
BG00231
BG00331
BG004123
Baseline Measures
Title
Description
Population Description
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Denominator Units Selected
Denominators
Classes
Age, Continuous
Mean
Standard Deviation
Years
Title
Denominators
Categories
ParticipantsBG00031
ParticipantsBG00130
ParticipantsBG00231
ParticipantsBG003
Sex: Female, Male
Count of Participants
Participants
Title
Denominators
Categories
ParticipantsBG00031
ParticipantsBG00130
ParticipantsBG002
Ethnicity (NIH/OMB)
Count of Participants
Participants
Title
Denominators
Categories
ParticipantsBG00031
ParticipantsBG00130
ParticipantsBG002
Race (NIH/OMB)
Count of Participants
Participants
Title
Denominators
Categories
ParticipantsBG00031
ParticipantsBG00130
ParticipantsBG002
CD4+ T-Cell Count
Two untreated participants from the Islatravir 0.25 mg treatment group were not analyzed.
Mean
Standard Deviation
cells/mm^3
Title
Denominators
Categories
ParticipantsBG00029
ParticipantsBG00130
ParticipantsBG002
Participants with <=100,000 copies/mL of HIV-1 RNA
Number of participants at screening with <=100,000 copies/mL of HIV-1 RNA
Count of Participants
Participants
Title
Denominators
Categories
ParticipantsBG00031
ParticipantsBG00130
ParticipantsBG002
Participants with >100,000 copies/mL of HIV-1 RNA
Number of participants at screening with >100,000 copies/mL of HIV-1 RNA
Count of Participants
Participants
Title
Denominators
Categories
ParticipantsBG00031
ParticipantsBG00130
ParticipantsBG002
Type
Title
Description
Population Description
Reporting Status
Anticipated Posting Date
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Time Frame
Units Analyzed
Denominator Units Selected
Arm/Group Information
Denominators
Classes
Analyses
Primary
Percentage of Participants With HIV-1 RNA <50 Copies/mL at Week 24
Blood samples were collected and plasma human immunodeficiency virus 1 (HIV-1) ribonucleic acid (RNA) were quantified using a real time polymerase chain reaction (PCR) assay with a lower limit of detection of 40 copies/mL. Missing values were counted as failure.
All randomized participants who received at least 1 dose of study treatment and have baseline data for those analyses that require baseline data.
Posted
Number
Percentage of participants
Week 24
ID
Title
Description
OG000
Islatravir 0.25 mg
In Part 1, participants were treated QD with 0.75 mg islatravir, 100 mg DOR, 300 mg 3TC, and placebo to DOR/3TC/TDF for a minimum of 24 weeks. In part 2, after receiving at least 24 weeks of study intervention, participants with HIV-1 RNA <50 copies/mL and no PDVF discontinued treatment of 3TC and placebo to DOR/3TC/TDF. Part 2 assessed ISL 0.75 mg (blind maintained) + DOR QD. After all participants had received at least 48 weeks of study intervention and the islatravir dose was selected, all participants in the islatravir group were switched to the selected dose 0.75 mg (between week 60 and week 84). Part 3 assessed Islatravir 0.75 mg + DOR QD open label through Week 144. In Part 4, beginning with Week 144, participants received the fixed dose combination of doravirine (100 mg)/islatravir (0.75 mg) QD open label and continued treatment until Week 192.
OG001
Islatravir 0.75 mg
In Part 1, participants were treated QD with 0.75 mg islatravir, 100 mg DOR, 300 mg 3TC, and placebo to DOR/3TC/TDF for a minimum of 24 weeks. In part 2, after receiving at least 24 weeks of study intervention, participants with HIV-1 RNA <50 copies/mL and no PDVF discontinued treatment of 3TC and placebo to DOR/3TC/TDF. Part 2 assessed ISL 0.75 mg (blind maintained) + DOR QD. After all participants had received at least 48 weeks of study intervention and the islatravir dose was selected, all participants in the islatravir group were switched to the selected dose 0.75 mg (between week 60 and week 84). Part 3 assessed Islatravir 0.75 mg + DOR QD open label through Week 144. In Part 4, beginning with Week 144, participants received the fixed dose combination of doravirine (100 mg)/islatravir (0.75 mg) QD open label and continued treatment until Week 192.
OG002
Islatravir 2.25 mg
In Part 1, participants were treated QD with 2.25 mg islatravir, 100 mg DOR, 300 mg 3TC, and placebo to DOR/3TC/TDF for a minimum of 24 weeks. In part 2, after receiving at least 24 weeks of study intervention, participants with HIV-1 RNA <50 copies/mL and no PDVF discontinued treatment of 3TC and placebo to DOR/3TC/TDF. Part 2 assessed ISL 2.25 mg (blind maintained) + DOR QD. After all participants had received at least 48 weeks of study intervention and the islatravir dose was selected, all participants in the islatravir group were switched to the selected dose 0.75 mg (between week 60 and week 84). Part 3 assessed Islatravir 0.75 mg + DOR QD open label through Week 144. In Part 4, beginning with Week 144, participants received the fixed dose combination of doravirine (100 mg)/islatravir (0.75 mg) QD open label and continued treatment until Week 192.
OG003
DOR/3TC/TDF
In Part 1, participants were treated QD with placebo to islatravir, placebo to DOR, placebo to 3TC, and a fixed dose combination of DOR/3TC/TDF consisting of 100 mg DOR + 300 mg 3TC + 300 mg TDF for a minimum of 24 weeks. In Parts 2 and 3, after a minimum of 24 weeks of treatment, placebo treatments were discontinued and participants received only DOR/3TC/TDF QD open label up to Week 144. In Part 4, beginning with Week 144, participants received the fixed dose combination of doravirine (100 mg)/islatravir (0.75 mg) QD open label and continued treatment until Week 192.
Units
Counts
Participants
OG00029
OG00130
OG00231
OG003
Title
Denominators
Categories
Title
Measurements
OG00093.1
OG001100.0
OG00290.3
OG003
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG003
Treatment difference in percent response
Treatment Difference
2.9
2-Sided
95
-12.5
18.3
Islatravir minus DOR/3TC/TDF
Other
The 95% confidence intervals (CIs) were calculated using stratum-adjusted Mantel-Haenszel method with the difference weighted by the harmonic mean of sample size per arm for each stratum (screening HIV-1 RNA ≤100,000 or >100,000 copies/mL).
Primary
Percentage of Participants With HIV-1 RNA <50 Copies/mL at Week 48
Blood samples were collected and plasma HIV-1 RNA were quantified using a real time PCR assay with a lower limit of detection of 40 copies/mL. Missing values were counted as failure.
All randomized participants who received at least 1 dose of study treatment and have baseline data for those analyses that require baseline data.
Posted
Number
Percentage of participants
Week 48
ID
Title
Description
OG000
Islatravir 0.25 mg
In Part 1, participants were treated QD with 0.75 mg islatravir, 100 mg DOR, 300 mg 3TC, and placebo to DOR/3TC/TDF for a minimum of 24 weeks. In part 2, after receiving at least 24 weeks of study intervention, participants with HIV-1 RNA <50 copies/mL and no PDVF discontinued treatment of 3TC and placebo to DOR/3TC/TDF. Part 2 assessed ISL 0.75 mg (blind maintained) + DOR QD. After all participants had received at least 48 weeks of study intervention and the islatravir dose was selected, all participants in the islatravir group were switched to the selected dose 0.75 mg (between week 60 and week 84). Part 3 assessed Islatravir 0.75 mg + DOR QD open label through Week 144. In Part 4, beginning with Week 144, participants received the fixed dose combination of doravirine (100 mg)/islatravir (0.75 mg) QD open label and continued treatment until Week 192.
OG001
Islatravir 0.75 mg
In Part 1, participants were treated QD with 0.75 mg islatravir, 100 mg DOR, 300 mg 3TC, and placebo to DOR/3TC/TDF for a minimum of 24 weeks. In part 2, after receiving at least 24 weeks of study intervention, participants with HIV-1 RNA <50 copies/mL and no PDVF discontinued treatment of 3TC and placebo to DOR/3TC/TDF. Part 2 assessed ISL 0.75 mg (blind maintained) + DOR QD. After all participants had received at least 48 weeks of study intervention and the islatravir dose was selected, all participants in the islatravir group were switched to the selected dose 0.75 mg (between week 60 and week 84). Part 3 assessed Islatravir 0.75 mg + DOR QD open label through Week 144. In Part 4, beginning with Week 144, participants received the fixed dose combination of doravirine (100 mg)/islatravir (0.75 mg) QD open label and continued treatment until Week 192.
Primary
Number of Participants Experiencing Adverse Events (AEs) up to Week 144
An adverse event (AE) is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study treatment.
All randomized participants who received at least 1 dose of study treatment, corresponding to the study treatment they actually received.
Posted
Count of Participants
Participants
Up to 144 weeks
ID
Title
Description
OG000
Islatravir 0.25 mg
In Part 1, participants were treated QD with 0.75 mg islatravir, 100 mg DOR, 300 mg 3TC, and placebo to DOR/3TC/TDF for a minimum of 24 weeks. In part 2, after receiving at least 24 weeks of study intervention, participants with HIV-1 RNA <50 copies/mL and no PDVF discontinued treatment of 3TC and placebo to DOR/3TC/TDF. Part 2 assessed ISL 0.75 mg (blind maintained) + DOR QD. After all participants had received at least 48 weeks of study intervention and the islatravir dose was selected, all participants in the islatravir group were switched to the selected dose 0.75 mg (between week 60 and week 84). Part 3 assessed Islatravir 0.75 mg + DOR QD open label through Week 144. In Part 4, beginning with Week 144, participants received the fixed dose combination of doravirine (100 mg)/islatravir (0.75 mg) QD open label and continued treatment until Week 192.
OG001
Primary
Number of Participants Discontinuing Study Drug Due to AEs up to Week 144
An AE is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study treatment.
All randomized participants who received at least 1 dose of study treatment, corresponding to the study treatment they actually received.
Posted
Count of Participants
Participants
Up to 144 weeks
ID
Title
Description
OG000
Islatravir 0.25 mg
In Part 1, participants were treated QD with 0.75 mg islatravir, 100 mg DOR, 300 mg 3TC, and placebo to DOR/3TC/TDF for a minimum of 24 weeks. In part 2, after receiving at least 24 weeks of study intervention, participants with HIV-1 RNA <50 copies/mL and no PDVF discontinued treatment of 3TC and placebo to DOR/3TC/TDF. Part 2 assessed ISL 0.75 mg (blind maintained) + DOR QD. After all participants had received at least 48 weeks of study intervention and the islatravir dose was selected, all participants in the islatravir group were switched to the selected dose 0.75 mg (between week 60 and week 84). Part 3 assessed Islatravir 0.75 mg + DOR QD open label through Week 144. In Part 4, beginning with Week 144, participants received the fixed dose combination of doravirine (100 mg)/islatravir (0.75 mg) QD open label and continued treatment until Week 192.
OG001
Secondary
Percentage of Participants With HIV-1 RNA <50 Copies/mL up to 24 Weeks After 3TC and Placebo Are Discontinued From the Regimen
Blood samples were collected and plasma HIV-1 RNA were quantified using a real time PCR assay with a lower limit of detection of 40 copies/mL, and missing values were counted as failure. 3TC and placebo are discontinued from the regimen from Week 24 up to Week 52.
All randomized participants who received at least 1 dose of study treatment and have baseline data for those analyses that require baseline data.
Posted
Number
Percentage of participants
Up to 24 weeks after 3TC and Placebo are discontinued from the regimen (up to approximately 60 weeks after initiating treatment)
ID
Title
Description
OG000
Islatravir 0.25 mg
In Part 1, participants were treated QD with 0.75 mg islatravir, 100 mg DOR, 300 mg 3TC, and placebo to DOR/3TC/TDF for a minimum of 24 weeks. In part 2, after receiving at least 24 weeks of study intervention, participants with HIV-1 RNA <50 copies/mL and no PDVF discontinued treatment of 3TC and placebo to DOR/3TC/TDF. Part 2 assessed ISL 0.75 mg (blind maintained) + DOR QD. After all participants had received at least 48 weeks of study intervention and the islatravir dose was selected, all participants in the islatravir group were switched to the selected dose 0.75 mg (between week 60 and week 84). Part 3 assessed Islatravir 0.75 mg + DOR QD open label through Week 144. In Part 4, beginning with Week 144, participants received the fixed dose combination of doravirine (100 mg)/islatravir (0.75 mg) QD open label and continued treatment until Week 192.
Secondary
Percentage of Participants With HIV-1 RNA <50 Copies/mL up to 48 Weeks After 3TC and Placebo Are Discontinued From the Regimen
Blood samples were collected and plasma HIV-1 RNA were quantified using a real time PCR assay with a lower limit of detection of 40 copies/mL, and missing values were counted as failure. 3TC and placebo are discontinued from the regimen from Week 24 up to Week 52.
All randomized participants who received at least 1 dose of study treatment and have baseline data for those analyses that require baseline data.
Posted
Number
Percentage of participants
Up to 48 weeks
ID
Title
Description
OG000
Islatravir 0.25 mg
In Part 1, participants were treated QD with 0.75 mg islatravir, 100 mg DOR, 300 mg 3TC, and placebo to DOR/3TC/TDF for a minimum of 24 weeks. In part 2, after receiving at least 24 weeks of study intervention, participants with HIV-1 RNA <50 copies/mL and no PDVF discontinued treatment of 3TC and placebo to DOR/3TC/TDF. Part 2 assessed ISL 0.75 mg (blind maintained) + DOR QD. After all participants had received at least 48 weeks of study intervention and the islatravir dose was selected, all participants in the islatravir group were switched to the selected dose 0.75 mg (between week 60 and week 84). Part 3 assessed Islatravir 0.75 mg + DOR QD open label through Week 144. In Part 4, beginning with Week 144, participants received the fixed dose combination of doravirine (100 mg)/islatravir (0.75 mg) QD open label and continued treatment until Week 192.
OG001
Islatravir 0.75 mg
Secondary
Percentage of Participants With HIV-1 RNA <50 Copies/mL up to 48 Weeks After Starting Open-label Doravirine/Islatravir Regimen (Part 4)
Blood samples were collected and plasma HIV-1 RNA were quantified using a real time PCR assay with a lower limit of detection of 40 copies/mL. Missing values were counted as failure. The percentage of participants with HIV-1 RNA <50 copies in Part 4 are reported.
Per protocol, all randomized participants who entered Part 4 and either continued treatment with DOR/ISL from Part 3 or switched from DOR/3TC/TDF in Part 3 to DOR/ISL in Part 4; and received at least 1 dose of study treatment and have baseline data for those analyses that require baseline data were analyzed.
Posted
Number
Percentage of participants
Up to Week 192
ID
Title
Description
OG000
DOR/ISL Continued (Part 4)
In Part 4, beginning with week 144, participants who received the fixed dose combination of doravirine (100 mg)/islatravir (0.75 mg) QD open label in Part 3 and continued treatment through Week 192.
OG001
DOR/ISL Switch (Part 4)
In Part 4, beginning with week 144, participants who received DOR/3TC/TDF QD open label up to Week 144 were switched to the fixed dose combination of doravirine (100 mg)/islatravir (0.75 mg) QD open label and continued treatment until Week 192.
Secondary
Change From Baseline in Mature T-helper (CD4+ T)-Cell Count at Week 24
Blood samples were collected and cluster of differentiation (CD4)+ T-cell counts were performed, where baseline measurements are defined as the Day 1 value, and baseline values were carried forward for participants who discontinue due to lack of efficacy. Post-baseline data were collected after the first dose of study medication through 14 days after the last dose of study medication.
All randomized participants who received at least 1 dose of study treatment and have baseline data for those analyses that require baseline data.
Posted
Mean
95% Confidence Interval
cells/mm^3
Baseline and Week 24
ID
Title
Description
OG000
Islatravir 0.25 mg
In Part 1, participants were treated QD with 0.75 mg islatravir, 100 mg DOR, 300 mg 3TC, and placebo to DOR/3TC/TDF for a minimum of 24 weeks. In part 2, after receiving at least 24 weeks of study intervention, participants with HIV-1 RNA <50 copies/mL and no PDVF discontinued treatment of 3TC and placebo to DOR/3TC/TDF. Part 2 assessed ISL 0.75 mg (blind maintained) + DOR QD. After all participants had received at least 48 weeks of study intervention and the islatravir dose was selected, all participants in the islatravir group were switched to the selected dose 0.75 mg (between week 60 and week 84). Part 3 assessed Islatravir 0.75 mg + DOR QD open label through Week 144. In Part 4, beginning with Week 144, participants received the fixed dose combination of doravirine (100 mg)/islatravir (0.75 mg) QD open label and continued treatment until Week 192.
OG001
Secondary
Change From Baseline in CD4+ T-cell Count at Week 48
Blood samples were collected and CD4+ T-cell counts were performed, where baseline measurements are defined as the Day 1 value, and baseline values were carried forward for participants who discontinue due to lack of efficacy. Post-baseline data were collected after the first dose of study medication through 14 days after the last dose of study medication.
All randomized participants who received at least 1 dose of study treatment and have baseline data for those analyses that require baseline data.
Posted
Mean
95% Confidence Interval
cells/mm^3
Baseline and Week 48
ID
Title
Description
OG000
Islatravir 0.25 mg
In Part 1, participants were treated QD with 0.75 mg islatravir, 100 mg DOR, 300 mg 3TC, and placebo to DOR/3TC/TDF for a minimum of 24 weeks. In part 2, after receiving at least 24 weeks of study intervention, participants with HIV-1 RNA <50 copies/mL and no PDVF discontinued treatment of 3TC and placebo to DOR/3TC/TDF. Part 2 assessed ISL 0.75 mg (blind maintained) + DOR QD. After all participants had received at least 48 weeks of study intervention and the islatravir dose was selected, all participants in the islatravir group were switched to the selected dose 0.75 mg (between week 60 and week 84). Part 3 assessed Islatravir 0.75 mg + DOR QD open label through Week 144. In Part 4, beginning with Week 144, participants received the fixed dose combination of doravirine (100 mg)/islatravir (0.75 mg) QD open label and continued treatment until Week 192.
OG001
Islatravir 0.75 mg
Secondary
Change From Baseline in CD4+ T-cell Count at Week 96
Blood samples were collected and CD4+ T-cell counts were performed, where baseline measurements are defined as the Day 1 value, and baseline values were carried forward for participants who discontinue due to lack of efficacy. Post-baseline data were collected after the first dose of study medication through 14 days after the last dose of study medication.
All randomized participants who received at least 1 dose of study treatment and have baseline data for those analyses that require baseline data.
Posted
Mean
95% Confidence Interval
cells/mm^3
Baseline and Week 96
ID
Title
Description
OG000
Islatravir 0.25 mg
In Part 1, participants were treated QD with 0.75 mg islatravir, 100 mg DOR, 300 mg 3TC, and placebo to DOR/3TC/TDF for a minimum of 24 weeks. In part 2, after receiving at least 24 weeks of study intervention, participants with HIV-1 RNA <50 copies/mL and no PDVF discontinued treatment of 3TC and placebo to DOR/3TC/TDF. Part 2 assessed ISL 0.75 mg (blind maintained) + DOR QD. After all participants had received at least 48 weeks of study intervention and the islatravir dose was selected, all participants in the islatravir group were switched to the selected dose 0.75 mg (between week 60 and week 84). Part 3 assessed Islatravir 0.75 mg + DOR QD open label through Week 144. In Part 4, beginning with Week 144, participants received the fixed dose combination of doravirine (100 mg)/islatravir (0.75 mg) QD open label and continued treatment until Week 192.
OG001
Islatravir 0.75 mg
Secondary
Change From Baseline in CD4+ T-cell Count at Week 144
Blood samples were collected and CD4+ T-cell counts were performed, where baseline measurements are defined as the Day 1 value, and baseline values were carried forward for participants who discontinue due to lack of efficacy. Post-baseline data were collected after the first dose of study medication through 14 days after the last dose of study medication.
All randomized participants who received at least 1 dose of study treatment and have baseline data for those analyses that require baseline data.
Posted
Mean
95% Confidence Interval
cells/mm^3
Baseline and Week 144
ID
Title
Description
OG000
Islatravir 0.25 mg
In Part 1, participants were treated QD with 0.75 mg islatravir, 100 mg DOR, 300 mg 3TC, and placebo to DOR/3TC/TDF for a minimum of 24 weeks. In part 2, after receiving at least 24 weeks of study intervention, participants with HIV-1 RNA <50 copies/mL and no PDVF discontinued treatment of 3TC and placebo to DOR/3TC/TDF. Part 2 assessed ISL 0.75 mg (blind maintained) + DOR QD. After all participants had received at least 48 weeks of study intervention and the islatravir dose was selected, all participants in the islatravir group were switched to the selected dose 0.75 mg (between week 60 and week 84). Part 3 assessed Islatravir 0.75 mg + DOR QD open label through Week 144. In Part 4, beginning with Week 144, participants received the fixed dose combination of doravirine (100 mg)/islatravir (0.75 mg) QD open label and continued treatment until Week 192.
OG001
Islatravir 0.75 mg
Secondary
Change From Baseline in CD4+ T-cell Count at Week 192 (Part 4)
Blood samples were collected and CD4+ T-cell counts were performed, where baseline measurements are defined as the Week 144 value. The change from baseline in CD4+ T-cell count at Week 192 (Part 4) are reported.
Per protocol, all randomized participants who entered Part 4 and either continued treatment with DOR/ISL from Part 3 or switched from DOR/3TC/TDF in Part 3 to DOR/ISL in Part 4; and received at least 1 dose of study treatment and have baseline data for those analyses that require baseline data were analyzed.
Posted
Mean
95% Confidence Interval
cells/mm^3
Baseline and Week 192
ID
Title
Description
OG000
DOR/ISL Continued (Part 4)
In Part 4, beginning with week 144, participants who received the fixed dose combination of doravirine (100 mg)/islatravir (0.75 mg) QD open label in Part 3 and continued treatment through Week 192.
OG001
DOR/ISL Switch (Part 4)
In Part 4, beginning with week 144, participants who received DOR/3TC/TDF QD open label up to Week 144 were switched to the fixed dose combination of doravirine (100 mg)/islatravir (0.75 mg) QD open label and continued treatment until Week 192.
Units
Secondary
Number of Participants Experiencing AEs Through 24 Weeks After 3TC and Placebo Are Discontinued From the Regimen
An AE is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study treatment. 3TC and placebo are discontinued from the regimen from Week 24 up to Week 52.
All randomized participants who received at least 1 dose of study treatment, corresponding to the study treatment they actually received.
Posted
Count of Participants
Participants
Up to 24 weeks
ID
Title
Description
OG000
Islatravir 0.25 mg
In Part 1, participants were treated QD with 0.75 mg islatravir, 100 mg DOR, 300 mg 3TC, and placebo to DOR/3TC/TDF for a minimum of 24 weeks. In part 2, after receiving at least 24 weeks of study intervention, participants with HIV-1 RNA <50 copies/mL and no PDVF discontinued treatment of 3TC and placebo to DOR/3TC/TDF. Part 2 assessed ISL 0.75 mg (blind maintained) + DOR QD. After all participants had received at least 48 weeks of study intervention and the islatravir dose was selected, all participants in the islatravir group were switched to the selected dose 0.75 mg (between week 60 and week 84). Part 3 assessed Islatravir 0.75 mg + DOR QD open label through Week 144. In Part 4, beginning with Week 144, participants received the fixed dose combination of doravirine (100 mg)/islatravir (0.75 mg) QD open label and continued treatment until Week 192.
Secondary
Number of Participants Discontinuing Study Drug Due to AEs Through 24 Weeks After 3TC and Placebo Are Discontinued From the Regimen
An AE is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study treatment. 3TC and placebo are discontinued from the regimen from Week 24 up to Week 52.
All randomized participants who received at least 1 dose of study treatment, corresponding to the study treatment they actually received.
Posted
Count of Participants
Participants
Up to 24 weeks
ID
Title
Description
OG000
Islatravir 0.25 mg
In Part 1, participants were treated QD with 0.75 mg islatravir, 100 mg DOR, 300 mg 3TC, and placebo to DOR/3TC/TDF for a minimum of 24 weeks. In part 2, after receiving at least 24 weeks of study intervention, participants with HIV-1 RNA <50 copies/mL and no PDVF discontinued treatment of 3TC and placebo to DOR/3TC/TDF. Part 2 assessed ISL 0.75 mg (blind maintained) + DOR QD. After all participants had received at least 48 weeks of study intervention and the islatravir dose was selected, all participants in the islatravir group were switched to the selected dose 0.75 mg (between week 60 and week 84). Part 3 assessed Islatravir 0.75 mg + DOR QD open label through Week 144. In Part 4, beginning with Week 144, participants received the fixed dose combination of doravirine (100 mg)/islatravir (0.75 mg) QD open label and continued treatment until Week 192.
Secondary
Number of Participants Experiencing AEs From Week 96 Through Study Duration
An AE is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study treatment.
Per protocol, all randomized participants who received at least 1 dose of open label study treatment in Part 3 or Part 4, corresponding to the study treatment they actually received were analyzed.
Posted
Count of Participants
Participants
Week 96 up to Week 192
ID
Title
Description
OG000
Islatravir 0.25 mg
In Part 1, participants were treated QD with 0.75 mg islatravir, 100 mg DOR, 300 mg 3TC, and placebo to DOR/3TC/TDF for a minimum of 24 weeks. In part 2, after receiving at least 24 weeks of study intervention, participants with HIV-1 RNA <50 copies/mL and no PDVF discontinued treatment of 3TC and placebo to DOR/3TC/TDF. Part 2 assessed ISL 0.75 mg (blind maintained) + DOR QD. After all participants had received at least 48 weeks of study intervention and the islatravir dose was selected, all participants in the islatravir group were switched to the selected dose 0.75 mg (between week 60 and week 84). Part 3 assessed Islatravir 0.75 mg + DOR QD open label through Week 144.
OG001
Islatravir 0.75 mg
Secondary
Number of Participants Discontinuing Study Drug Due to AEs From Week 96 Through Study Duration
An AE is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study treatment.
Per protocol, all randomized participants who received at least 1 dose of open label study treatment in Part 3 or Part 4, corresponding to the study treatment they actually received.
Posted
Count of Participants
Participants
Week 96 up to Week 192
ID
Title
Description
OG000
Islatravir 0.25 mg
In Part 1, participants were treated QD with 0.75 mg islatravir, 100 mg DOR, 300 mg 3TC, and placebo to DOR/3TC/TDF for a minimum of 24 weeks. In part 2, after receiving at least 24 weeks of study intervention, participants with HIV-1 RNA <50 copies/mL and no PDVF discontinued treatment of 3TC and placebo to DOR/3TC/TDF. Part 2 assessed ISL 0.75 mg (blind maintained) + DOR QD. After all participants had received at least 48 weeks of study intervention and the islatravir dose was selected, all participants in the islatravir group were switched to the selected dose 0.75 mg (between week 60 and week 84). Part 3 assessed Islatravir 0.75 mg + DOR QD open label through Week 144.
OG001
Islatravir 0.75 mg
Secondary
Number of Participants Experiencing AEs During Open Label Doravirine/Islatravir Treatment After Week 144 up to Week 192 (Part 4)
An AE is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study treatment. The number of participants who experienced AEs during Part 4 are reported.
Per protocol, all randomized participants who entered Part 4 and either continued treatment with DOR/ISL from Part 3 or switched from DOR/3TC/TDF in Part 3 to DOR/ISL in Part 4; and received at least 1 dose of study treatment, corresponding to the study treatment they actually received were analyzed.
Posted
Count of Participants
Participants
Week 144 up to Week 192
ID
Title
Description
OG000
DOR/ISL Continued (Part 4)
In Part 4, beginning with week 144, participants who received the fixed dose combination of doravirine (100mg)/islatravir (0.75mg) QD open label in Part 3 and continued treatment through Week 192.
OG001
DOR/ISL Switch (Part 4)
In Part 4, beginning with week 144, participants who received DOR/3TC/TDF QD open label up to Week 144 were switched to the fixed dose combination of doravirine (100mg)/islatravir (0.75mg) QD open label and continued treatment until Week 192.
Secondary
Number of Participants Discontinuing Study Drug Due to AEs During Open Label Doravirine/Islatravir Treatment After Week 144 up to Week 192 (Part 4)
An AE is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study treatment. The number of participants who discontinued the study drug due to AEs in Part 4 are reported.
Per protocol, all randomized participants who entered Part 4 and either continued treatment with DOR/ISL from Part 3 or switched from DOR/3TC/TDF in Part 3 to DOR/ISL in Part 4; and received at least 1 dose of study treatment, corresponding to the study treatment they actually received were analyzed.
Posted
Count of Participants
Participants
Week 144 up to Week 192
ID
Title
Description
OG000
DOR/ISL Continued (Part 4)
In Part 4, beginning with week 144, participants who received the fixed dose combination of doravirine (100mg)/islatravir (0.75mg) QD open label in Part 3 and continued treatment through Week 192.
OG001
DOR/ISL Switch (Part 4)
In Part 4, beginning with week 144, participants who received DOR/3TC/TDF QD open label up to Week 144 were switched to the fixed dose combination of doravirine (100mg)/islatravir (0.75mg) QD open label and continued treatment until Week 192.
Time Frame
For All-Cause Mortality: from randomization up to 198 weeks. For AEs: from first treatment up to 198 weeks.
Description
The population analyzed for All-Cause Mortality was all randomized participants. The population analyzed for AEs was all randomized participants who received at least 1 dose of study treatment, corresponding to the study treatment they actually received.
All-Cause Mortality Comment
Not provided
Arm/Groups
ID
Title
Description
Deaths (Affected)
Deaths (At Risk)
Serious Events (Affected)
Serious Events (At Risk)
Other Events (Affected)
Other Events (At Risk)
EG000
Islatravir 0.25mg
In Part 1, participants were treated QD with 0.75 mg islatravir, 100 mg DOR, 300 mg 3TC, and placebo to DOR/3TC/TDF for a minimum of 24 weeks. In part 2, after receiving at least 24 weeks of study intervention, participants with HIV-1 RNA <50 copies/mL and no PDVF discontinued treatment of 3TC and placebo to DOR/3TC/TDF. Part 2 assessed ISL 0.75 mg (blind maintained) + DOR QD. After all participants had received at least 48 weeks of study intervention and the islatravir dose was selected, all participants in the islatravir group were switched to the selected dose 0.75 mg (between week 60 and week 84). Part 3 assessed Islatravir 0.75 mg + DOR QD open label through Week 144.
0
31
2
29
22
29
EG001
Islatravir 0.75mg
In Part 1, participants were treated QD with 0.75 mg islatravir, 100 mg DOR, 300 mg 3TC, and placebo to DOR/3TC/TDF for a minimum of 24 weeks. In part 2, after receiving at least 24 weeks of study intervention, participants with HIV-1 RNA <50 copies/mL and no PDVF discontinued treatment of 3TC and placebo to DOR/3TC/TDF. Part 2 assessed ISL 0.75 mg (blind maintained) + DOR QD. After all participants had received at least 48 weeks of study intervention and the islatravir dose was selected, all participants in the islatravir group were switched to the selected dose 0.75 mg (between week 60 and week 84). Part 3 assessed Islatravir 0.75 mg + DOR QD open label through Week 144.
0
30
6
30
26
30
EG002
Islatravir 2.25mg
In Part 1, participants were treated QD with 2.25 mg islatravir, 100 mg DOR, 300 mg 3TC, and placebo to DOR/3TC/TDF for a minimum of 24 weeks. In part 2, after receiving at least 24 weeks of study intervention, participants with HIV-1 RNA <50 copies/mL and no PDVF discontinued treatment of 3TC and placebo to DOR/3TC/TDF. Part 2 assessed ISL 2.25 mg (blind maintained) + DOR QD. After all participants had received at least 48 weeks of study intervention and the islatravir dose was selected, all participants in the islatravir group were switched to the selected dose 0.75 mg (between week 60 and week 84). Part 3 assessed Islatravir 0.75 mg + DOR QD open label through Week 144.
0
31
2
31
23
31
EG003
DOR/3TC/TDF
In Part 1, participants were treated QD with placebo to islatravir, placebo to DOR, placebo to 3TC, and a fixed dose combination of DOR/3TC/TDF consisting of 100 mg DOR + 300 mg 3TC + 300 mg TDF for a minimum of 24 weeks. In Parts 2 and 3, after a minimum of 24 weeks of treatment, placebo treatments were discontinued and participants received only DOR/3TC/TDF QD open label up to Week 144.
1
31
4
31
22
31
EG004
DOR/ISL Continued
In Part 4, beginning with week 144, participants who received the fixed dose combination of doravirine (100mg)/islatravir (0.75mg) QD open label in Part 3 and continued treatment through Week 192.
0
67
2
67
21
67
EG005
DOR/ISL Switch
In Part 4, beginning with week 144, participants who received DOR/3TC/TDF QD open label up to Week 144 were switched to the fixed dose combination of doravirine (100mg)/islatravir (0.75mg) QD open label and continued treatment until Week 192.
0
22
1
22
11
22
Serious Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Lymphadenopathy
Blood and lymphatic system disorders
MedDRA 25.0
Systematic Assessment
EG0000 events0 affected29 at risk
EG0011 events1 affected30 at risk
EG0020 events0 affected31 at risk
EG0030 events0 affected31 at risk
EG0040 events0 affected67 at risk
EG0050 events0 affected22 at risk
Atrial fibrillation
Cardiac disorders
MedDRA 25.0
Systematic Assessment
EG0001 events1 affected29 at risk
EG0010 events0 affected30 at risk
EG0020 events0 affected31 at risk
EG003
Long QT syndrome congenital
Congenital, familial and genetic disorders
MedDRA 25.0
Systematic Assessment
EG0000 events0 affected29 at risk
EG0010 events0 affected30 at risk
EG0020 events0 affected31 at risk
EG003
Death
General disorders
MedDRA 25.0
Systematic Assessment
EG0000 events0 affected29 at risk
EG0010 events0 affected30 at risk
EG0020 events0 affected31 at risk
EG003
Appendicitis
Infections and infestations
MedDRA 25.0
Systematic Assessment
EG0000 events0 affected29 at risk
EG0011 events1 affected30 at risk
EG0020 events0 affected31 at risk
EG003
COVID-19
Infections and infestations
MedDRA 25.0
Systematic Assessment
EG0000 events0 affected29 at risk
EG0010 events0 affected30 at risk
EG0020 events0 affected31 at risk
EG003
Dysentery
Infections and infestations
MedDRA 25.0
Systematic Assessment
EG0000 events0 affected29 at risk
EG0010 events0 affected30 at risk
EG0020 events0 affected31 at risk
EG003
Epididymitis
Infections and infestations
MedDRA 25.0
Systematic Assessment
EG0000 events0 affected29 at risk
EG0010 events0 affected30 at risk
EG0020 events0 affected31 at risk
EG003
Large intestine infection
Infections and infestations
MedDRA 25.0
Systematic Assessment
EG0000 events0 affected29 at risk
EG0011 events1 affected30 at risk
EG0021 events1 affected31 at risk
EG003
Pneumonia chlamydial
Infections and infestations
MedDRA 25.0
Systematic Assessment
EG0000 events0 affected29 at risk
EG0010 events0 affected30 at risk
EG0020 events0 affected31 at risk
EG003
Pulmonary tuberculosis
Infections and infestations
MedDRA 25.0
Systematic Assessment
EG0000 events0 affected29 at risk
EG0010 events0 affected30 at risk
EG0021 events1 affected31 at risk
EG003
Ankle fracture
Injury, poisoning and procedural complications
MedDRA 25.0
Systematic Assessment
EG0000 events0 affected29 at risk
EG0011 events1 affected30 at risk
EG0020 events0 affected31 at risk
EG003
Burkitt's lymphoma
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA 25.0
Systematic Assessment
EG0001 events1 affected29 at risk
EG0010 events0 affected30 at risk
EG0020 events0 affected31 at risk
EG003
Facial paralysis
Nervous system disorders
MedDRA 25.0
Systematic Assessment
EG0000 events0 affected29 at risk
EG0011 events1 affected30 at risk
EG0020 events0 affected31 at risk
EG003
Alcohol withdrawal syndrome
Psychiatric disorders
MedDRA 25.0
Systematic Assessment
EG0000 events0 affected29 at risk
EG0011 events1 affected30 at risk
EG0020 events0 affected31 at risk
EG003
Psychotic disorder
Psychiatric disorders
MedDRA 25.0
Systematic Assessment
EG0000 events0 affected29 at risk
EG0010 events0 affected30 at risk
EG0020 events0 affected31 at risk
EG003
Suicidal ideation
Psychiatric disorders
MedDRA 25.0
Systematic Assessment
EG0000 events0 affected29 at risk
EG0011 events1 affected30 at risk
EG0020 events0 affected31 at risk
EG003
Suicide attempt
Psychiatric disorders
MedDRA 25.0
Systematic Assessment
EG0000 events0 affected29 at risk
EG0013 events2 affected30 at risk
EG0020 events0 affected31 at risk
EG003
Other Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Lymphadenopathy
Blood and lymphatic system disorders
MedDRA 25.0
Systematic Assessment
EG0000 events0 affected29 at risk
EG0010 events0 affected30 at risk
EG0023 events1 affected31 at risk
EG0032 events2 affected31 at risk
EG0041 events1 affected67 at risk
EG0050 events0 affected22 at risk
Vertigo
Ear and labyrinth disorders
MedDRA 25.0
Systematic Assessment
EG0000 events0 affected29 at risk
EG0010 events0 affected30 at risk
EG0022 events2 affected31 at risk
EG003
Abdominal distension
Gastrointestinal disorders
MedDRA 25.0
Systematic Assessment
EG0000 events0 affected29 at risk
EG0012 events2 affected30 at risk
EG0020 events0 affected31 at risk
EG003
Abdominal pain
Gastrointestinal disorders
MedDRA 25.0
Systematic Assessment
EG0002 events1 affected29 at risk
EG0012 events1 affected30 at risk
EG0022 events2 affected31 at risk
EG003
Abdominal pain upper
Gastrointestinal disorders
MedDRA 25.0
Systematic Assessment
EG0002 events2 affected29 at risk
EG0012 events2 affected30 at risk
EG0021 events1 affected31 at risk
EG003
Aphthous ulcer
Gastrointestinal disorders
MedDRA 25.0
Systematic Assessment
EG0000 events0 affected29 at risk
EG0010 events0 affected30 at risk
EG0022 events2 affected31 at risk
EG003
Diarrhoea
Gastrointestinal disorders
MedDRA 25.0
Systematic Assessment
EG0001 events1 affected29 at risk
EG0018 events6 affected30 at risk
EG0023 events3 affected31 at risk
EG003
Nausea
Gastrointestinal disorders
MedDRA 25.0
Systematic Assessment
EG0001 events1 affected29 at risk
EG0016 events5 affected30 at risk
EG0023 events3 affected31 at risk
EG003
Proctitis
Gastrointestinal disorders
MedDRA 25.0
Systematic Assessment
EG0002 events2 affected29 at risk
EG0010 events0 affected30 at risk
EG0020 events0 affected31 at risk
EG003
Vomiting
Gastrointestinal disorders
MedDRA 25.0
Systematic Assessment
EG0003 events3 affected29 at risk
EG0013 events3 affected30 at risk
EG0022 events2 affected31 at risk
EG003
Asthenia
General disorders
MedDRA 25.0
Systematic Assessment
EG0000 events0 affected29 at risk
EG0011 events1 affected30 at risk
EG0020 events0 affected31 at risk
EG003
Fatigue
General disorders
MedDRA 25.0
Systematic Assessment
EG0001 events1 affected29 at risk
EG0014 events4 affected30 at risk
EG0022 events2 affected31 at risk
EG003
Influenza like illness
General disorders
MedDRA 25.0
Systematic Assessment
EG0001 events1 affected29 at risk
EG0010 events0 affected30 at risk
EG0021 events1 affected31 at risk
EG003
Pyrexia
General disorders
MedDRA 25.0
Systematic Assessment
EG0001 events1 affected29 at risk
EG0014 events2 affected30 at risk
EG0020 events0 affected31 at risk
EG003
Seasonal allergy
Immune system disorders
MedDRA 25.0
Systematic Assessment
EG0002 events2 affected29 at risk
EG0010 events0 affected30 at risk
EG0020 events0 affected31 at risk
EG003
Anal chlamydia infection
Infections and infestations
MedDRA 25.0
Systematic Assessment
EG0002 events2 affected29 at risk
EG0013 events2 affected30 at risk
EG0021 events1 affected31 at risk
EG003
Bronchitis
Infections and infestations
MedDRA 25.0
Systematic Assessment
EG0003 events2 affected29 at risk
EG0017 events7 affected30 at risk
EG0021 events1 affected31 at risk
EG003
COVID-19
Infections and infestations
MedDRA 25.0
Systematic Assessment
EG0000 events0 affected29 at risk
EG0013 events3 affected30 at risk
EG0021 events1 affected31 at risk
EG003
Cellulitis
Infections and infestations
MedDRA 25.0
Systematic Assessment
EG0002 events2 affected29 at risk
EG0010 events0 affected30 at risk
EG0022 events1 affected31 at risk
EG003
Conjunctivitis
Infections and infestations
MedDRA 25.0
Systematic Assessment
EG0000 events0 affected29 at risk
EG0012 events2 affected30 at risk
EG0021 events1 affected31 at risk
EG003
Escherichia urinary tract infection
Infections and infestations
MedDRA 25.0
Systematic Assessment
EG0002 events2 affected29 at risk
EG0011 events1 affected30 at risk
EG0020 events0 affected31 at risk
EG003
Folliculitis
Infections and infestations
MedDRA 25.0
Systematic Assessment
EG0001 events1 affected29 at risk
EG0010 events0 affected30 at risk
EG0022 events2 affected31 at risk
EG003
Fungal skin infection
Infections and infestations
MedDRA 25.0
Systematic Assessment
EG0002 events2 affected29 at risk
EG0010 events0 affected30 at risk
EG0020 events0 affected31 at risk
EG003
Gastroenteritis
Infections and infestations
MedDRA 25.0
Systematic Assessment
EG0001 events1 affected29 at risk
EG0011 events1 affected30 at risk
EG0021 events1 affected31 at risk
EG003
Influenza
Infections and infestations
MedDRA 25.0
Systematic Assessment
EG0003 events3 affected29 at risk
EG0011 events1 affected30 at risk
EG0021 events1 affected31 at risk
EG003
Lower respiratory tract infection
Infections and infestations
MedDRA 25.0
Systematic Assessment
EG0001 events1 affected29 at risk
EG0012 events2 affected30 at risk
EG0020 events0 affected31 at risk
EG003
Nasopharyngitis
Infections and infestations
MedDRA 25.0
Systematic Assessment
EG0004 events2 affected29 at risk
EG00110 events9 affected30 at risk
EG0022 events2 affected31 at risk
EG003
Oral herpes
Infections and infestations
MedDRA 25.0
Systematic Assessment
EG0003 events2 affected29 at risk
EG0012 events2 affected30 at risk
EG0021 events1 affected31 at risk
EG003
Oropharyngeal gonococcal infection
Infections and infestations
MedDRA 25.0
Systematic Assessment
EG0001 events1 affected29 at risk
EG0012 events2 affected30 at risk
EG0021 events1 affected31 at risk
EG003
Otitis media
Infections and infestations
MedDRA 25.0
Systematic Assessment
EG0001 events1 affected29 at risk
EG0010 events0 affected30 at risk
EG0020 events0 affected31 at risk
EG003
Paronychia
Infections and infestations
MedDRA 25.0
Systematic Assessment
EG0000 events0 affected29 at risk
EG0010 events0 affected30 at risk
EG0022 events2 affected31 at risk
EG003
Pharyngitis
Infections and infestations
MedDRA 25.0
Systematic Assessment
EG0001 events1 affected29 at risk
EG0013 events3 affected30 at risk
EG0020 events0 affected31 at risk
EG003
Proctitis chlamydial
Infections and infestations
MedDRA 25.0
Systematic Assessment
EG0000 events0 affected29 at risk
EG0012 events2 affected30 at risk
EG0021 events1 affected31 at risk
EG003
Proctitis gonococcal
Infections and infestations
MedDRA 25.0
Systematic Assessment
EG0002 events2 affected29 at risk
EG0012 events2 affected30 at risk
EG0021 events1 affected31 at risk
EG003
Sinusitis
Infections and infestations
MedDRA 25.0
Systematic Assessment
EG0004 events4 affected29 at risk
EG0010 events0 affected30 at risk
EG0020 events0 affected31 at risk
EG003
Syphilis
Infections and infestations
MedDRA 25.0
Systematic Assessment
EG0006 events6 affected29 at risk
EG0018 events8 affected30 at risk
EG0022 events2 affected31 at risk
EG003
Tonsillitis
Infections and infestations
MedDRA 25.0
Systematic Assessment
EG0004 events2 affected29 at risk
EG0018 events3 affected30 at risk
EG0021 events1 affected31 at risk
EG003
Tooth abscess
Infections and infestations
MedDRA 25.0
Systematic Assessment
EG0000 events0 affected29 at risk
EG0010 events0 affected30 at risk
EG0022 events2 affected31 at risk
EG003
Upper respiratory tract infection
Infections and infestations
MedDRA 25.0
Systematic Assessment
EG0002 events2 affected29 at risk
EG0013 events3 affected30 at risk
EG0024 events3 affected31 at risk
EG003
Urethritis
Infections and infestations
MedDRA 25.0
Systematic Assessment
EG0001 events1 affected29 at risk
EG0012 events2 affected30 at risk
EG0020 events0 affected31 at risk
EG003
Viral pharyngitis
Infections and infestations
MedDRA 25.0
Systematic Assessment
EG0001 events1 affected29 at risk
EG0012 events2 affected30 at risk
EG0020 events0 affected31 at risk
EG003
Procedural pain
Injury, poisoning and procedural complications
MedDRA 25.0
Systematic Assessment
EG0000 events0 affected29 at risk
EG0012 events2 affected30 at risk
EG0021 events1 affected31 at risk
EG003
Alanine aminotransferase increased
Investigations
MedDRA 25.0
Systematic Assessment
EG0002 events2 affected29 at risk
EG0012 events2 affected30 at risk
EG0021 events1 affected31 at risk
EG003
Aspartate aminotransferase increased
Investigations
MedDRA 25.0
Systematic Assessment
EG0002 events2 affected29 at risk
EG0011 events1 affected30 at risk
EG0021 events1 affected31 at risk
EG003
Weight increased
Investigations
MedDRA 25.0
Systematic Assessment
EG0000 events0 affected29 at risk
EG0012 events2 affected30 at risk
EG0020 events0 affected31 at risk
EG003
Decreased appetite
Metabolism and nutrition disorders
MedDRA 25.0
Systematic Assessment
EG0000 events0 affected29 at risk
EG0010 events0 affected30 at risk
EG0021 events1 affected31 at risk
EG003
Vitamin D deficiency
Metabolism and nutrition disorders
MedDRA 25.0
Systematic Assessment
EG0001 events1 affected29 at risk
EG0016 events6 affected30 at risk
EG0024 events4 affected31 at risk
EG003
Arthralgia
Musculoskeletal and connective tissue disorders
MedDRA 25.0
Systematic Assessment
EG0001 events1 affected29 at risk
EG0012 events2 affected30 at risk
EG0024 events4 affected31 at risk
EG003
Back pain
Musculoskeletal and connective tissue disorders
MedDRA 25.0
Systematic Assessment
EG0002 events2 affected29 at risk
EG0012 events2 affected30 at risk
EG0024 events3 affected31 at risk
EG003
Musculoskeletal chest pain
Musculoskeletal and connective tissue disorders
MedDRA 25.0
Systematic Assessment
EG0000 events0 affected29 at risk
EG0010 events0 affected30 at risk
EG0021 events1 affected31 at risk
EG003
Neck pain
Musculoskeletal and connective tissue disorders
MedDRA 25.0
Systematic Assessment
EG0002 events2 affected29 at risk
EG0010 events0 affected30 at risk
EG0021 events1 affected31 at risk
EG003
Osteopenia
Musculoskeletal and connective tissue disorders
MedDRA 25.0
Systematic Assessment
EG0000 events0 affected29 at risk
EG0012 events2 affected30 at risk
EG0020 events0 affected31 at risk
EG003
Pain in extremity
Musculoskeletal and connective tissue disorders
MedDRA 25.0
Systematic Assessment
EG0005 events3 affected29 at risk
EG0011 events1 affected30 at risk
EG0020 events0 affected31 at risk
EG003
Anogenital warts
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA 25.0
Systematic Assessment
EG0002 events1 affected29 at risk
EG0012 events2 affected30 at risk
EG0022 events2 affected31 at risk
EG003
Dizziness
Nervous system disorders
MedDRA 25.0
Systematic Assessment
EG0001 events1 affected29 at risk
EG0011 events1 affected30 at risk
EG0024 events3 affected31 at risk
EG003
Headache
Nervous system disorders
MedDRA 25.0
Systematic Assessment
EG0005 events5 affected29 at risk
EG0015 events2 affected30 at risk
EG0026 events5 affected31 at risk
EG003
Sciatica
Nervous system disorders
MedDRA 25.0
Systematic Assessment
EG0000 events0 affected29 at risk
EG0010 events0 affected30 at risk
EG0020 events0 affected31 at risk
EG003
Syncope
Nervous system disorders
MedDRA 25.0
Systematic Assessment
EG0001 events1 affected29 at risk
EG0010 events0 affected30 at risk
EG0020 events0 affected31 at risk
EG003
Adjustment disorder with depressed mood
Psychiatric disorders
MedDRA 25.0
Systematic Assessment
EG0000 events0 affected29 at risk
EG0012 events2 affected30 at risk
EG0020 events0 affected31 at risk
EG003
Anxiety
Psychiatric disorders
MedDRA 25.0
Systematic Assessment
EG0003 events3 affected29 at risk
EG0017 events6 affected30 at risk
EG0020 events0 affected31 at risk
EG003
Depression
Psychiatric disorders
MedDRA 25.0
Systematic Assessment
EG0001 events1 affected29 at risk
EG0014 events3 affected30 at risk
EG0022 events2 affected31 at risk
EG003
Insomnia
Psychiatric disorders
MedDRA 25.0
Systematic Assessment
EG0001 events1 affected29 at risk
EG0010 events0 affected30 at risk
EG0020 events0 affected31 at risk
EG003
Nephrolithiasis
Renal and urinary disorders
MedDRA 25.0
Systematic Assessment
EG0000 events0 affected29 at risk
EG0012 events2 affected30 at risk
EG0020 events0 affected31 at risk
EG003
Cough
Respiratory, thoracic and mediastinal disorders
MedDRA 25.0
Systematic Assessment
EG0001 events1 affected29 at risk
EG0012 events2 affected30 at risk
EG0020 events0 affected31 at risk
EG003
Oropharyngeal pain
Respiratory, thoracic and mediastinal disorders
MedDRA 25.0
Systematic Assessment
EG0003 events3 affected29 at risk
EG0013 events3 affected30 at risk
EG0023 events1 affected31 at risk
EG003
Respiratory disorder
Respiratory, thoracic and mediastinal disorders
MedDRA 25.0
Systematic Assessment
EG0001 events1 affected29 at risk
EG0013 events2 affected30 at risk
EG0021 events1 affected31 at risk
EG003
Rhinitis allergic
Respiratory, thoracic and mediastinal disorders
MedDRA 25.0
Systematic Assessment
EG0002 events2 affected29 at risk
EG0010 events0 affected30 at risk
EG0020 events0 affected31 at risk
EG003
Rhinorrhoea
Respiratory, thoracic and mediastinal disorders
MedDRA 25.0
Systematic Assessment
EG0000 events0 affected29 at risk
EG0012 events2 affected30 at risk
EG0020 events0 affected31 at risk
EG003
Sinus congestion
Respiratory, thoracic and mediastinal disorders
MedDRA 25.0
Systematic Assessment
EG0000 events0 affected29 at risk
EG0013 events2 affected30 at risk
EG0020 events0 affected31 at risk
EG003
Sneezing
Respiratory, thoracic and mediastinal disorders
MedDRA 25.0
Systematic Assessment
EG0000 events0 affected29 at risk
EG0010 events0 affected30 at risk
EG0020 events0 affected31 at risk
EG003
Eczema
Skin and subcutaneous tissue disorders
MedDRA 25.0
Systematic Assessment
EG0000 events0 affected29 at risk
EG0010 events0 affected30 at risk
EG0020 events0 affected31 at risk
EG003
Penile ulceration
Skin and subcutaneous tissue disorders
MedDRA 25.0
Systematic Assessment
EG0000 events0 affected29 at risk
EG0010 events0 affected30 at risk
EG0022 events2 affected31 at risk
EG003
Rash
Skin and subcutaneous tissue disorders
MedDRA 25.0
Systematic Assessment
EG0004 events3 affected29 at risk
EG0013 events2 affected30 at risk
EG0022 events1 affected31 at risk
EG003
Certain Agreements
Are all PI(s) employees of the sponsor?
No
Restriction Type
OTHER
Results Disclosure Restriction on PI(s)?
Yes
Other Details
If publication activity is not directed by the sponsor, the investigator agrees to submit all manuscripts or abstracts to the sponsor before submission.
Point of Contact
Title
Organization
Phone
Extension
Email
Senior Vice President, Global Clinical Development
The 95% CIs were calculated using stratum-adjusted Mantel-Haenszel method with the difference weighted by the harmonic mean of sample size per arm for each stratum (screening HIV-1 RNA ≤100,000 or >100,000 copies/mL).
OG002
OG003
Treatment difference in percent response
Treatment Difference
0.2
2-Sided
95
-16.0
16.3
Islatravir minus DOR/3TC/TDF
Other
The 95% CIs were calculated using stratum-adjusted Mantel-Haenszel method with the difference weighted by the harmonic mean of sample size per arm for each stratum (screening HIV-1 RNA ≤100,000 or >100,000 copies/mL).
OG002
Islatravir 2.25 mg
In Part 1, participants were treated QD with 2.25 mg islatravir, 100 mg DOR, 300 mg 3TC, and placebo to DOR/3TC/TDF for a minimum of 24 weeks. In part 2, after receiving at least 24 weeks of study intervention, participants with HIV-1 RNA <50 copies/mL and no PDVF discontinued treatment of 3TC and placebo to DOR/3TC/TDF. Part 2 assessed ISL 2.25 mg (blind maintained) + DOR QD. After all participants had received at least 48 weeks of study intervention and the islatravir dose was selected, all participants in the islatravir group were switched to the selected dose 0.75 mg (between week 60 and week 84). Part 3 assessed Islatravir 0.75 mg + DOR QD open label through Week 144. In Part 4, beginning with Week 144, participants received the fixed dose combination of doravirine (100 mg)/islatravir (0.75 mg) QD open label and continued treatment until Week 192.
OG003
DOR/3TC/TDF
In Part 1, participants were treated QD with placebo to islatravir, placebo to DOR, placebo to 3TC, and a fixed dose combination of DOR/3TC/TDF consisting of 100 mg DOR + 300 mg 3TC + 300 mg TDF for a minimum of 24 weeks. In Parts 2 and 3, after a minimum of 24 weeks of treatment, placebo treatments were discontinued and participants received only DOR/3TC/TDF QD open label up to Week 144. In Part 4, beginning with Week 144, participants received the fixed dose combination of doravirine (100 mg)/islatravir (0.75 mg) QD open label and continued treatment until Week 192.
Units
Counts
Participants
OG00029
OG00130
OG00231
OG00331
Title
Denominators
Categories
Title
Measurements
OG00089.7
OG00190.0
OG00277.4
OG00383.9
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG003
Treatment difference in percent response
Treatment Difference
6.1
2-Sided
95
-12.2
24.4
Islatravir minus DOR/3TC/TDF
Other
The 95% CIs were calculated using stratum-adjusted Mantel-Haenszel method with the difference weighted by the harmonic mean of sample size per arm for each stratum (screening HIV-1 RNA ≤100,000 or >100,000 copies/mL).
OG001
OG003
Treatment difference in percent response
Treatment Difference
6.2
2-Sided
95
-12.2
24.6
Islatravir minus DOR/3TC/TDF
Other
The 95% CIs were calculated using stratum-adjusted Mantel-Haenszel method with the difference weighted by the harmonic mean of sample size per arm for each stratum (screening HIV-1 RNA ≤100,000 or >100,000 copies/mL).
OG002
OG003
Treatment difference in percent response
Treatment Difference
-6.1
2-Sided
95
-27.1
14.8
Islatravir minus DOR/3TC/TDF
Other
The 95% CIs were calculated using stratum-adjusted Mantel-Haenszel method with the difference weighted by the harmonic mean of sample size per arm for each stratum (screening HIV-1 RNA ≤100,000 or >100,000 copies/mL).
Islatravir 0.75 mg
In Part 1, participants were treated QD with 0.75 mg islatravir, 100 mg DOR, 300 mg 3TC, and placebo to DOR/3TC/TDF for a minimum of 24 weeks. In part 2, after receiving at least 24 weeks of study intervention, participants with HIV-1 RNA <50 copies/mL and no PDVF discontinued treatment of 3TC and placebo to DOR/3TC/TDF. Part 2 assessed ISL 0.75 mg (blind maintained) + DOR QD. After all participants had received at least 48 weeks of study intervention and the islatravir dose was selected, all participants in the islatravir group were switched to the selected dose 0.75 mg (between week 60 and week 84). Part 3 assessed Islatravir 0.75 mg + DOR QD open label through Week 144. In Part 4, beginning with Week 144, participants received the fixed dose combination of doravirine (100 mg)/islatravir (0.75 mg) QD open label and continued treatment until Week 192.
OG002
Islatravir 2.25 mg
In Part 1, participants were treated QD with 2.25 mg islatravir, 100 mg DOR, 300 mg 3TC, and placebo to DOR/3TC/TDF for a minimum of 24 weeks. In part 2, after receiving at least 24 weeks of study intervention, participants with HIV-1 RNA <50 copies/mL and no PDVF discontinued treatment of 3TC and placebo to DOR/3TC/TDF. Part 2 assessed ISL 2.25 mg (blind maintained) + DOR QD. After all participants had received at least 48 weeks of study intervention and the islatravir dose was selected, all participants in the islatravir group were switched to the selected dose 0.75 mg (between week 60 and week 84). Part 3 assessed Islatravir 0.75 mg + DOR QD open label through Week 144. In Part 4, beginning with Week 144, participants received the fixed dose combination of doravirine (100 mg)/islatravir (0.75 mg) QD open label and continued treatment until Week 192.
OG003
DOR/3TC/TDF
In Part 1, participants were treated QD with placebo to islatravir, placebo to DOR, placebo to 3TC, and a fixed dose combination of DOR/3TC/TDF consisting of 100 mg DOR + 300 mg 3TC + 300 mg TDF for a minimum of 24 weeks. In Parts 2 and 3, after a minimum of 24 weeks of treatment, placebo treatments were discontinued and participants received only DOR/3TC/TDF QD open label up to Week 144. In Part 4, beginning with Week 144, participants received the fixed dose combination of doravirine (100 mg)/islatravir (0.75 mg) QD open label and continued treatment until Week 192.
Units
Counts
Participants
OG00029
OG00130
OG00231
OG00331
Title
Denominators
Categories
Title
Measurements
OG00026
OG00127
OG00224
OG00327
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG003
Difference in % Islatravir vs DOR/3TC/TDF
Difference in %
2.6
2-Sided
95
-15.7
20.5
Islatravir minus DOR/3TC/TDF
Other
Based on Miettinen & Nurminen method.
OG001
OG003
Difference in % Islatravir vs DOR/3TC/TDF
Difference in %
2.9
2-Sided
95
-15.0
20.8
Islatravir minus DOR/3TC/TDF
Other
Based on Miettinen & Nurminen method.
OG002
OG003
Difference in % Islatravir vs DOR/3TC/TDF
Difference in %
-9.7
2-Sided
95
-29.4
10.1
Islatravir minus DOR/3TC/TDF
Other
Based on Miettinen & Nurminen method.
Islatravir 0.75 mg
In Part 1, participants were treated QD with 0.75 mg islatravir, 100 mg DOR, 300 mg 3TC, and placebo to DOR/3TC/TDF for a minimum of 24 weeks. In part 2, after receiving at least 24 weeks of study intervention, participants with HIV-1 RNA <50 copies/mL and no PDVF discontinued treatment of 3TC and placebo to DOR/3TC/TDF. Part 2 assessed ISL 0.75 mg (blind maintained) + DOR QD. After all participants had received at least 48 weeks of study intervention and the islatravir dose was selected, all participants in the islatravir group were switched to the selected dose 0.75 mg (between week 60 and week 84). Part 3 assessed Islatravir 0.75 mg + DOR QD open label through Week 144. In Part 4, beginning with Week 144, participants received the fixed dose combination of doravirine (100 mg)/islatravir (0.75 mg) QD open label and continued treatment until Week 192.
OG002
Islatravir 2.25 mg
In Part 1, participants were treated QD with 2.25 mg islatravir, 100 mg DOR, 300 mg 3TC, and placebo to DOR/3TC/TDF for a minimum of 24 weeks. In part 2, after receiving at least 24 weeks of study intervention, participants with HIV-1 RNA <50 copies/mL and no PDVF discontinued treatment of 3TC and placebo to DOR/3TC/TDF. Part 2 assessed ISL 2.25 mg (blind maintained) + DOR QD. After all participants had received at least 48 weeks of study intervention and the islatravir dose was selected, all participants in the islatravir group were switched to the selected dose 0.75 mg (between week 60 and week 84). Part 3 assessed Islatravir 0.75 mg + DOR QD open label through Week 144. In Part 4, beginning with Week 144, participants received the fixed dose combination of doravirine (100 mg)/islatravir (0.75 mg) QD open label and continued treatment until Week 192.
OG003
DOR/3TC/TDF
In Part 1, participants were treated QD with placebo to islatravir, placebo to DOR, placebo to 3TC, and a fixed dose combination of DOR/3TC/TDF consisting of 100 mg DOR + 300 mg 3TC + 300 mg TDF for a minimum of 24 weeks. In Parts 2 and 3, after a minimum of 24 weeks of treatment, placebo treatments were discontinued and participants received only DOR/3TC/TDF QD open label up to Week 144. In Part 4, beginning with Week 144, participants received the fixed dose combination of doravirine (100 mg)/islatravir (0.75 mg) QD open label and continued treatment until Week 192.
Units
Counts
Participants
OG00029
OG00130
OG00231
OG00331
Title
Denominators
Categories
Title
Measurements
OG0001
OG0010
OG0022
OG0031
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG003
Difference in % Islatravir vs DOR/3TC/TDF
Difference in %
0.2
2-Sided
95
-13.4
14.5
Islatravir minus DOR/3TC/TDF
Other
Based on Miettinen & Nurminen method
OG001
OG003
Difference in % Islatravir vs DOR/3TC/TDF
Difference in %
-3.2
2-Sided
95
-16.4
8.5
Islatravir minus DOR/3TC/TDF
Other
Based on Miettinen & Nurminen method
OG002
OG003
Difference in % Islatravir vs DOR/3TC/TDF
Difference in %
3.2
2-Sided
95
-10.8
18.1
Islatravir minus DOR/3TC/TDF
Other
Based on Miettinen & Nurminen method
OG001
Islatravir 0.75 mg
In Part 1, participants were treated QD with 0.75 mg islatravir, 100 mg DOR, 300 mg 3TC, and placebo to DOR/3TC/TDF for a minimum of 24 weeks. In part 2, after receiving at least 24 weeks of study intervention, participants with HIV-1 RNA <50 copies/mL and no PDVF discontinued treatment of 3TC and placebo to DOR/3TC/TDF. Part 2 assessed ISL 0.75 mg (blind maintained) + DOR QD. After all participants had received at least 48 weeks of study intervention and the islatravir dose was selected, all participants in the islatravir group were switched to the selected dose 0.75 mg (between week 60 and week 84). Part 3 assessed Islatravir 0.75 mg + DOR QD open label through Week 144. In Part 4, beginning with Week 144, participants received the fixed dose combination of doravirine (100 mg)/islatravir (0.75 mg) QD open label and continued treatment until Week 192.
OG002
Islatravir 2.25 mg
In Part 1, participants were treated QD with 2.25 mg islatravir, 100 mg DOR, 300 mg 3TC, and placebo to DOR/3TC/TDF for a minimum of 24 weeks. In part 2, after receiving at least 24 weeks of study intervention, participants with HIV-1 RNA <50 copies/mL and no PDVF discontinued treatment of 3TC and placebo to DOR/3TC/TDF. Part 2 assessed ISL 2.25 mg (blind maintained) + DOR QD. After all participants had received at least 48 weeks of study intervention and the islatravir dose was selected, all participants in the islatravir group were switched to the selected dose 0.75 mg (between week 60 and week 84). Part 3 assessed Islatravir 0.75 mg + DOR QD open label through Week 144. In Part 4, beginning with Week 144, participants received the fixed dose combination of doravirine (100 mg)/islatravir (0.75 mg) QD open label and continued treatment until Week 192.
OG003
DOR/3TC/TDF
In Part 1, participants were treated QD with placebo to islatravir, placebo to DOR, placebo to 3TC, and a fixed dose combination of DOR/3TC/TDF consisting of 100 mg DOR + 300 mg 3TC + 300 mg TDF for a minimum of 24 weeks. In Parts 2 and 3, after a minimum of 24 weeks of treatment, placebo treatments were discontinued and participants received only DOR/3TC/TDF QD open label up to Week 144. In Part 4, beginning with Week 144, participants received the fixed dose combination of doravirine (100 mg)/islatravir (0.75 mg) QD open label and continued treatment until Week 192.
Units
Counts
Participants
OG00029
OG00130
OG00227
OG00328
Title
Denominators
Categories
Title
Measurements
OG00086.2
OG00190.0
OG00288.9
OG00396.4
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG003
Treatment difference in percent response
Treatment Difference
-9.7
2-Sided
95
-26.1
6.6
Islatravir minus DOR/3TC/TDF
Other
The 95% CIs were calculated using stratum-adjusted Mantel-Haenszel method with the difference weighted by the harmonic mean of sample size per arm for each stratum (screening HIV-1 RNA ≤100,000 or >100,000 copies/mL).
OG001
OG003
Treatment difference in percent response
Treatment Difference
-6.2
2-Sided
95
-21.5
9.1
Islatravir minus DOR/3TC/TDF
Other
The 95% CIs were calculated using stratum-adjusted Mantel-Haenszel method with the difference weighted by the harmonic mean of sample size per arm for each stratum (screening HIV-1 RNA ≤100,000 or >100,000 copies/mL).
OG002
OG003
Treatment difference in percent response
Treatment Difference
-7.5
2-Sided
95
-23.9
8.8
Islatravir minus DOR/3TC/TDF
Other
The 95% CIs were calculated using stratum-adjusted Mantel-Haenszel method with the difference weighted by the harmonic mean of sample size per arm for each stratum (screening HIV-1 RNA ≤100,000 or >100,000 copies/mL).
In Part 1, participants were treated QD with 0.75 mg islatravir, 100 mg DOR, 300 mg 3TC, and placebo to DOR/3TC/TDF for a minimum of 24 weeks. In part 2, after receiving at least 24 weeks of study intervention, participants with HIV-1 RNA <50 copies/mL and no PDVF discontinued treatment of 3TC and placebo to DOR/3TC/TDF. Part 2 assessed ISL 0.75 mg (blind maintained) + DOR QD. After all participants had received at least 48 weeks of study intervention and the islatravir dose was selected, all participants in the islatravir group were switched to the selected dose 0.75 mg (between week 60 and week 84). Part 3 assessed Islatravir 0.75 mg + DOR QD open label through Week 144. In Part 4, beginning with Week 144, participants received the fixed dose combination of doravirine (100 mg)/islatravir (0.75 mg) QD open label and continued treatment until Week 192.
OG002
Islatravir 2.25 mg
In Part 1, participants were treated QD with 2.25 mg islatravir, 100 mg DOR, 300 mg 3TC, and placebo to DOR/3TC/TDF for a minimum of 24 weeks. In part 2, after receiving at least 24 weeks of study intervention, participants with HIV-1 RNA <50 copies/mL and no PDVF discontinued treatment of 3TC and placebo to DOR/3TC/TDF. Part 2 assessed ISL 2.25 mg (blind maintained) + DOR QD. After all participants had received at least 48 weeks of study intervention and the islatravir dose was selected, all participants in the islatravir group were switched to the selected dose 0.75 mg (between week 60 and week 84). Part 3 assessed Islatravir 0.75 mg + DOR QD open label through Week 144. In Part 4, beginning with Week 144, participants received the fixed dose combination of doravirine (100 mg)/islatravir (0.75 mg) QD open label and continued treatment until Week 192.
OG003
DOR/3TC/TDF
In Part 1, participants were treated QD with placebo to islatravir, placebo to DOR, placebo to 3TC, and a fixed dose combination of DOR/3TC/TDF consisting of 100 mg DOR + 300 mg 3TC + 300 mg TDF for a minimum of 24 weeks. In Parts 2 and 3, after a minimum of 24 weeks of treatment, placebo treatments were discontinued and participants received only DOR/3TC/TDF QD open label up to Week 144. In Part 4, beginning with Week 144, participants received the fixed dose combination of doravirine (100 mg)/islatravir (0.75 mg) QD open label and continued treatment until Week 192.
Units
Counts
Participants
OG00029
OG00130
OG00227
OG00328
Title
Denominators
Categories
Title
Measurements
OG00062.1
OG00156.7
OG00259.3
OG00360.7
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG003
Treatment difference in percent response
Treatment Difference
2.2
2-Sided
95
-23.4
27.7
Islatravir minus DOR/3TC/TDF
Other
The 95% CIs were calculated using stratum-adjusted Mantel-Haenszel method with the difference weighted by the harmonic mean of sample size per arm for each stratum (screening HIV-1 RNA ≤100,000 or >100,000 copies/mL).
OG001
OG003
Treatment difference in percent response
Treatment Difference
-3.7
2-Sided
95
-29.6
22.1
Islatravir minus DOR/3TC/TDF
Other
The 95% CIs were calculated using stratum-adjusted Mantel-Haenszel method with the difference weighted by the harmonic mean of sample size per arm for each stratum (screening HIV-1 RNA ≤100,000 or >100,000 copies/mL).
OG002
OG003
Treatment difference in percent response
Treatment Difference
-1.3
2-Sided
95
-27.7
25.2
Islatravir minus DOR/3TC/TDF
Other
The 95% CIs were calculated using stratum-adjusted Mantel-Haenszel method with the difference weighted by the harmonic mean of sample size per arm for each stratum (screening HIV-1 RNA ≤100,000 or >100,000 copies/mL).
Units
Counts
Participants
OG00067
OG00122
Title
Denominators
Categories
Title
Measurements
OG00085.1
OG00195.5
Islatravir 0.75 mg
In Part 1, participants were treated QD with 0.75 mg islatravir, 100 mg DOR, 300 mg 3TC, and placebo to DOR/3TC/TDF for a minimum of 24 weeks. In part 2, after receiving at least 24 weeks of study intervention, participants with HIV-1 RNA <50 copies/mL and no PDVF discontinued treatment of 3TC and placebo to DOR/3TC/TDF. Part 2 assessed ISL 0.75 mg (blind maintained) + DOR QD. After all participants had received at least 48 weeks of study intervention and the islatravir dose was selected, all participants in the islatravir group were switched to the selected dose 0.75 mg (between week 60 and week 84). Part 3 assessed Islatravir 0.75 mg + DOR QD open label through Week 144. In Part 4, beginning with Week 144, participants received the fixed dose combination of doravirine (100 mg)/islatravir (0.75 mg) QD open label and continued treatment until Week 192.
OG002
Islatravir 2.25 mg
In Part 1, participants were treated QD with 2.25 mg islatravir, 100 mg DOR, 300 mg 3TC, and placebo to DOR/3TC/TDF for a minimum of 24 weeks. In part 2, after receiving at least 24 weeks of study intervention, participants with HIV-1 RNA <50 copies/mL and no PDVF discontinued treatment of 3TC and placebo to DOR/3TC/TDF. Part 2 assessed ISL 2.25 mg (blind maintained) + DOR QD. After all participants had received at least 48 weeks of study intervention and the islatravir dose was selected, all participants in the islatravir group were switched to the selected dose 0.75 mg (between week 60 and week 84). Part 3 assessed Islatravir 0.75 mg + DOR QD open label through Week 144. In Part 4, beginning with Week 144, participants received the fixed dose combination of doravirine (100 mg)/islatravir (0.75 mg) QD open label and continued treatment until Week 192.
OG003
DOR/3TC/TDF
In Part 1, participants were treated QD with placebo to islatravir, placebo to DOR, placebo to 3TC, and a fixed dose combination of DOR/3TC/TDF consisting of 100 mg DOR + 300 mg 3TC + 300 mg TDF for a minimum of 24 weeks. In Parts 2 and 3, after a minimum of 24 weeks of treatment, placebo treatments were discontinued and participants received only DOR/3TC/TDF QD open label up to Week 144. In Part 4, beginning with Week 144, participants received the fixed dose combination of doravirine (100 mg)/islatravir (0.75 mg) QD open label and continued treatment until Week 192.
Units
Counts
Participants
OG00029
OG00130
OG00231
OG00331
Title
Denominators
Categories
Title
Measurements
OG000220.5(170.3 to 270.8)
OG001192.8(117.9 to 267.7)
OG002142.9(89.9 to 196.0)
OG003142.1(105.7 to 178.5)
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG003
Treatment difference in T-cell count
Treatment Difference
78.4
2-Sided
95
18.8
138.1
Islatravir minus DOR/3TC/TDF
Other
The 95% CI for mean difference in CD4 change was based on t-distribution.
OG001
OG003
Treatment difference in T-cell count
Treatment Difference
50.7
2-Sided
95
-31.7
133.1
Islatravir minus DOR/3TC/TDF
Other
The 95% CI for mean difference in CD4 change was based on t-distribution.
OG002
OG003
Treatment difference in T-cell count
Treatment Difference
0.8
2-Sided
95
-63.0
64.7
Islatravir minus DOR/3TC/TDF
Other
The 95% CI for mean difference in CD4 change was based on t-distribution.
In Part 1, participants were treated QD with 0.75 mg islatravir, 100 mg DOR, 300 mg 3TC, and placebo to DOR/3TC/TDF for a minimum of 24 weeks. In part 2, after receiving at least 24 weeks of study intervention, participants with HIV-1 RNA <50 copies/mL and no PDVF discontinued treatment of 3TC and placebo to DOR/3TC/TDF. Part 2 assessed ISL 0.75 mg (blind maintained) + DOR QD. After all participants had received at least 48 weeks of study intervention and the islatravir dose was selected, all participants in the islatravir group were switched to the selected dose 0.75 mg (between week 60 and week 84). Part 3 assessed Islatravir 0.75 mg + DOR QD open label through Week 144. In Part 4, beginning with Week 144, participants received the fixed dose combination of doravirine (100 mg)/islatravir (0.75 mg) QD open label and continued treatment until Week 192.
OG002
Islatravir 2.25 mg
In Part 1, participants were treated QD with 2.25 mg islatravir, 100 mg DOR, 300 mg 3TC, and placebo to DOR/3TC/TDF for a minimum of 24 weeks. In part 2, after receiving at least 24 weeks of study intervention, participants with HIV-1 RNA <50 copies/mL and no PDVF discontinued treatment of 3TC and placebo to DOR/3TC/TDF. Part 2 assessed ISL 2.25 mg (blind maintained) + DOR QD. After all participants had received at least 48 weeks of study intervention and the islatravir dose was selected, all participants in the islatravir group were switched to the selected dose 0.75 mg (between week 60 and week 84). Part 3 assessed Islatravir 0.75 mg + DOR QD open label through Week 144. In Part 4, beginning with Week 144, participants received the fixed dose combination of doravirine (100 mg)/islatravir (0.75 mg) QD open label and continued treatment until Week 192.
OG003
DOR/3TC/TDF
In Part 1, participants were treated QD with placebo to islatravir, placebo to DOR, placebo to 3TC, and a fixed dose combination of DOR/3TC/TDF consisting of 100 mg DOR + 300 mg 3TC + 300 mg TDF for a minimum of 24 weeks. In Parts 2 and 3, after a minimum of 24 weeks of treatment, placebo treatments were discontinued and participants received only DOR/3TC/TDF QD open label up to Week 144. In Part 4, beginning with Week 144, participants received the fixed dose combination of doravirine (100 mg)/islatravir (0.75 mg) QD open label and continued treatment until Week 192.
Units
Counts
Participants
OG00029
OG00130
OG00231
OG00331
Title
Denominators
Categories
Title
Measurements
OG000182.0(119.6 to 244.5)
OG001183.0(124.7 to 241.2)
OG002100.7(25.0 to 176.3)
OG003181.4(137.2 to 225.6)
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG003
Treatment difference in T-cell count
Treatment Difference
0.6
2-Sided
95
-74.1
75.3
Islatravir minus DOR/3TC/TDF
Other
The 95% CI for mean difference in CD4 change was based on t-distribution.
OG001
OG003
Treatment difference in T-cell count
Treatment Difference
1.5
2-Sided
95
-70.7
73.8
Islatravir minus DOR/3TC/TDF
Other
The 95% CI for mean difference in CD4 change was based on t-distribution.
OG002
OG003
Treatment difference in T-cell count
Treatment Difference
-80.8
2-Sided
95
-165.6
4.0
Islatravir minus DOR/3TC/TDF
Other
The 95% CI for mean difference in CD4 change was based on t-distribution.
In Part 1, participants were treated QD with 0.75 mg islatravir, 100 mg DOR, 300 mg 3TC, and placebo to DOR/3TC/TDF for a minimum of 24 weeks. In part 2, after receiving at least 24 weeks of study intervention, participants with HIV-1 RNA <50 copies/mL and no PDVF discontinued treatment of 3TC and placebo to DOR/3TC/TDF. Part 2 assessed ISL 0.75 mg (blind maintained) + DOR QD. After all participants had received at least 48 weeks of study intervention and the islatravir dose was selected, all participants in the islatravir group were switched to the selected dose 0.75 mg (between week 60 and week 84). Part 3 assessed Islatravir 0.75 mg + DOR QD open label through Week 144. In Part 4, beginning with Week 144, participants received the fixed dose combination of doravirine (100 mg)/islatravir (0.75 mg) QD open label and continued treatment until Week 192.
OG002
Islatravir 2.25 mg
In Part 1, participants were treated QD with 2.25 mg islatravir, 100 mg DOR, 300 mg 3TC, and placebo to DOR/3TC/TDF for a minimum of 24 weeks. In part 2, after receiving at least 24 weeks of study intervention, participants with HIV-1 RNA <50 copies/mL and no PDVF discontinued treatment of 3TC and placebo to DOR/3TC/TDF. Part 2 assessed ISL 2.25 mg (blind maintained) + DOR QD. After all participants had received at least 48 weeks of study intervention and the islatravir dose was selected, all participants in the islatravir group were switched to the selected dose 0.75 mg (between week 60 and week 84). Part 3 assessed Islatravir 0.75 mg + DOR QD open label through Week 144. In Part 4, beginning with Week 144, participants received the fixed dose combination of doravirine (100 mg)/islatravir (0.75 mg) QD open label and continued treatment until Week 192.
OG003
DOR/3TC/TDF
In Part 1, participants were treated QD with placebo to islatravir, placebo to DOR, placebo to 3TC, and a fixed dose combination of DOR/3TC/TDF consisting of 100 mg DOR + 300 mg 3TC + 300 mg TDF for a minimum of 24 weeks. In Parts 2 and 3, after a minimum of 24 weeks of treatment, placebo treatments were discontinued and participants received only DOR/3TC/TDF QD open label up to Week 144. In Part 4, beginning with Week 144, participants received the fixed dose combination of doravirine (100 mg)/islatravir (0.75 mg) QD open label and continued treatment until Week 192.
Units
Counts
Participants
OG00029
OG00130
OG00231
OG00331
Title
Denominators
Categories
Title
Measurements
OG000243.4(165.5 to 321.3)
OG001161.3(90.2 to 232.4)
OG002136.5(57.0 to 216.0)
OG003268.9(188.5 to 349.3)
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG003
Treatment difference in T-cell count
Treatment Difference
-25.5
2-Sided
95
-134.8
83.8
Islatravir minus DOR/3TC/TDF
Other
The 95% CI for mean difference in CD4 change was based on t-distribution.
OG001
OG003
Treatment difference in T-cell count
Treatment Difference
-107.6
2-Sided
95
-212.1
-3.1
Islatravir minus DOR/3TC/TDF
Other
The 95% CI for mean difference in CD4 change was based on t-distribution.
OG002
OG003
Treatment difference in T-cell count
Treatment Difference
-132.4
2-Sided
95
-242.9
-21.9
Islatravir minus DOR/3TC/TDF
Other
The 95% CI for mean difference in CD4 change was based on t-distribution.
In Part 1, participants were treated QD with 0.75 mg islatravir, 100 mg DOR, 300 mg 3TC, and placebo to DOR/3TC/TDF for a minimum of 24 weeks. In part 2, after receiving at least 24 weeks of study intervention, participants with HIV-1 RNA <50 copies/mL and no PDVF discontinued treatment of 3TC and placebo to DOR/3TC/TDF. Part 2 assessed ISL 0.75 mg (blind maintained) + DOR QD. After all participants had received at least 48 weeks of study intervention and the islatravir dose was selected, all participants in the islatravir group were switched to the selected dose 0.75 mg (between week 60 and week 84). Part 3 assessed Islatravir 0.75 mg + DOR QD open label through Week 144. In Part 4, beginning with Week 144, participants received the fixed dose combination of doravirine (100 mg)/islatravir (0.75 mg) QD open label and continued treatment until Week 192.
OG002
Islatravir 2.25 mg
In Part 1, participants were treated QD with 2.25 mg islatravir, 100 mg DOR, 300 mg 3TC, and placebo to DOR/3TC/TDF for a minimum of 24 weeks. In part 2, after receiving at least 24 weeks of study intervention, participants with HIV-1 RNA <50 copies/mL and no PDVF discontinued treatment of 3TC and placebo to DOR/3TC/TDF. Part 2 assessed ISL 2.25 mg (blind maintained) + DOR QD. After all participants had received at least 48 weeks of study intervention and the islatravir dose was selected, all participants in the islatravir group were switched to the selected dose 0.75 mg (between week 60 and week 84). Part 3 assessed Islatravir 0.75 mg + DOR QD open label through Week 144. In Part 4, beginning with Week 144, participants received the fixed dose combination of doravirine (100 mg)/islatravir (0.75 mg) QD open label and continued treatment until Week 192.
OG003
DOR/3TC/TDF
In Part 1, participants were treated QD with placebo to islatravir, placebo to DOR, placebo to 3TC, and a fixed dose combination of DOR/3TC/TDF consisting of 100 mg DOR + 300 mg 3TC + 300 mg TDF for a minimum of 24 weeks. In Parts 2 and 3, after a minimum of 24 weeks of treatment, placebo treatments were discontinued and participants received only DOR/3TC/TDF QD open label up to Week 144. In Part 4, beginning with Week 144, participants received the fixed dose combination of doravirine (100 mg)/islatravir (0.75 mg) QD open label and continued treatment until Week 192.
Units
Counts
Participants
OG00029
OG00130
OG00231
OG00331
Title
Denominators
Categories
Title
Measurements
OG000204.4(102.0 to 306.7)
OG001209.0(111.5 to 306.6)
OG002162.9(70.2 to 255.5)
OG003270.0(183.2 to 356.8)
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG003
Treatment difference in T-cell count
Treatment Difference
-65.6
2-Sided
95
-195.3
64.0
Islatravir minus DOR/3TC/TDF
Other
The 95% CI for mean difference in CD4 change was based on t-distribution.
OG001
OG003
Treatment difference in T-cell count
Treatment Difference
-61.0
2-Sided
95
-188.7
66.8
Islatravir minus DOR/3TC/TDF
Other
The 95% CI for mean difference in CD4 change was based on t-distribution.
OG002
OG003
Treatment difference in T-cell count
Treatment Difference
-107.1
2-Sided
95
-231.2
16.9
Islatravir minus DOR/3TC/TDF
Other
The 95% CI for mean difference in CD4 change was based on t-distribution.
Counts
Participants
OG00057
OG00121
Title
Denominators
Categories
Title
Measurements
OG0003.8(-1.9 to 9.5)
OG001-3.4(-12.0 to 5.2)
OG001
Islatravir 0.75 mg
In Part 1, participants were treated QD with 0.75 mg islatravir, 100 mg DOR, 300 mg 3TC, and placebo to DOR/3TC/TDF for a minimum of 24 weeks. In part 2, after receiving at least 24 weeks of study intervention, participants with HIV-1 RNA <50 copies/mL and no PDVF discontinued treatment of 3TC and placebo to DOR/3TC/TDF. Part 2 assessed ISL 0.75 mg (blind maintained) + DOR QD. After all participants had received at least 48 weeks of study intervention and the islatravir dose was selected, all participants in the islatravir group were switched to the selected dose 0.75 mg (between week 60 and week 84). Part 3 assessed Islatravir 0.75 mg + DOR QD open label through Week 144. In Part 4, beginning with Week 144, participants received the fixed dose combination of doravirine (100 mg)/islatravir (0.75 mg) QD open label and continued treatment until Week 192.
OG002
Islatravir 2.25 mg
In Part 1, participants were treated QD with 2.25 mg islatravir, 100 mg DOR, 300 mg 3TC, and placebo to DOR/3TC/TDF for a minimum of 24 weeks. In part 2, after receiving at least 24 weeks of study intervention, participants with HIV-1 RNA <50 copies/mL and no PDVF discontinued treatment of 3TC and placebo to DOR/3TC/TDF. Part 2 assessed ISL 2.25 mg (blind maintained) + DOR QD. After all participants had received at least 48 weeks of study intervention and the islatravir dose was selected, all participants in the islatravir group were switched to the selected dose 0.75 mg (between week 60 and week 84). Part 3 assessed Islatravir 0.75 mg + DOR QD open label through Week 144. In Part 4, beginning with Week 144, participants received the fixed dose combination of doravirine (100 mg)/islatravir (0.75 mg) QD open label and continued treatment until Week 192.
OG003
DOR/3TC/TDF
In Part 1, participants were treated QD with placebo to islatravir, placebo to DOR, placebo to 3TC, and a fixed dose combination of DOR/3TC/TDF consisting of 100 mg DOR + 300 mg 3TC + 300 mg TDF for a minimum of 24 weeks. In Parts 2 and 3, after a minimum of 24 weeks of treatment, placebo treatments were discontinued and participants received only DOR/3TC/TDF QD open label up to Week 144. In Part 4, beginning with Week 144, participants received the fixed dose combination of doravirine (100 mg)/islatravir (0.75 mg) QD open label and continued treatment until Week 192.
Units
Counts
Participants
OG00029
OG00130
OG00227
OG00328
Title
Denominators
Categories
Title
Measurements
OG00018
OG00120
OG00214
OG00316
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG003
Difference in % Islatravir vs DOR/3TC/TDF
Difference in %
4.9
2-Sided
95
-20.3
29.6
Islatravir minus DOR/3TC/TDF
Other
Based on Miettinen & Nurminen method.
OG001
OG003
Difference in % Islatravir vs DOR/3TC/TDF
Difference in %
9.5
2-Sided
95
-15.4
33.5
Islatravir minus DOR/3TC/TDF
Other
Based on Miettinen & Nurminen method.
OG002
OG003
Difference in % Islatravir vs DOR/3TC/TDF
Difference in %
-5.3
2-Sided
95
-30.6
20.7
Islatravir minus DOR/3TC/TDF
Other
Based on Miettinen & Nurminen method.
OG001
Islatravir 0.75 mg
In Part 1, participants were treated QD with 0.75 mg islatravir, 100 mg DOR, 300 mg 3TC, and placebo to DOR/3TC/TDF for a minimum of 24 weeks. In part 2, after receiving at least 24 weeks of study intervention, participants with HIV-1 RNA <50 copies/mL and no PDVF discontinued treatment of 3TC and placebo to DOR/3TC/TDF. Part 2 assessed ISL 0.75 mg (blind maintained) + DOR QD. After all participants had received at least 48 weeks of study intervention and the islatravir dose was selected, all participants in the islatravir group were switched to the selected dose 0.75 mg (between week 60 and week 84). Part 3 assessed Islatravir 0.75 mg + DOR QD open label through Week 144. In Part 4, beginning with Week 144, participants received the fixed dose combination of doravirine (100 mg)/islatravir (0.75 mg) QD open label and continued treatment until Week 192.
OG002
Islatravir 2.25 mg
In Part 1, participants were treated QD with 2.25 mg islatravir, 100 mg DOR, 300 mg 3TC, and placebo to DOR/3TC/TDF for a minimum of 24 weeks. In part 2, after receiving at least 24 weeks of study intervention, participants with HIV-1 RNA <50 copies/mL and no PDVF discontinued treatment of 3TC and placebo to DOR/3TC/TDF. Part 2 assessed ISL 2.25 mg (blind maintained) + DOR QD. After all participants had received at least 48 weeks of study intervention and the islatravir dose was selected, all participants in the islatravir group were switched to the selected dose 0.75 mg (between week 60 and week 84). Part 3 assessed Islatravir 0.75 mg + DOR QD open label through Week 144. In Part 4, beginning with Week 144, participants received the fixed dose combination of doravirine (100 mg)/islatravir (0.75 mg) QD open label and continued treatment until Week 192.
OG003
DOR/3TC/TDF
In Part 1, participants were treated QD with placebo to islatravir, placebo to DOR, placebo to 3TC, and a fixed dose combination of DOR/3TC/TDF consisting of 100 mg DOR + 300 mg 3TC + 300 mg TDF for a minimum of 24 weeks. In Parts 2 and 3, after a minimum of 24 weeks of treatment, placebo treatments were discontinued and participants received only DOR/3TC/TDF QD open label up to Week 144. In Part 4, beginning with Week 144, participants received the fixed dose combination of doravirine (100 mg)/islatravir (0.75 mg) QD open label and continued treatment until Week 192.
Units
Counts
Participants
OG00029
OG00130
OG00227
OG00328
Title
Denominators
Categories
Title
Measurements
OG0000
OG0010
OG0022
OG0031
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG003
Difference in % Islatravir vs DOR/3TC/TDF
Difference in %
-3.6
2-Sided
95
-17.9
8.5
Islatravir minus DOR/3TC/TDF
Other
Based on Miettinen & Nurminen method.
OG001
OG003
Difference in % Islatravir vs DOR/3TC/TDF
Difference in %
-3.6
2-Sided
95
-17.9
8.2
Islatravir minus DOR/3TC/TDF
Other
Based on Miettinen & Nurminen method.
OG002
OG003
Difference in % Islatravir vs DOR/3TC/TDF
Difference in %
3.8
2-Sided
95
-11.5
20.6
Islatravir minus DOR/3TC/TDF
Other
Based on Miettinen & Nurminen method.
In Part 1, participants were treated QD with 0.75 mg islatravir, 100 mg DOR, 300 mg 3TC, and placebo to DOR/3TC/TDF for a minimum of 24 weeks. In part 2, after receiving at least 24 weeks of study intervention, participants with HIV-1 RNA <50 copies/mL and no PDVF discontinued treatment of 3TC and placebo to DOR/3TC/TDF. Part 2 assessed ISL 0.75 mg (blind maintained) + DOR QD. After all participants had received at least 48 weeks of study intervention and the islatravir dose was selected, all participants in the islatravir group were switched to the selected dose 0.75 mg (between week 60 and week 84). Part 3 assessed Islatravir 0.75 mg + DOR QD open label through Week 144.
OG002
Islatravir 2.25 mg
In Part 1, participants were treated QD with 2.25 mg islatravir, 100 mg DOR, 300 mg 3TC, and placebo to DOR/3TC/TDF for a minimum of 24 weeks. In part 2, after receiving at least 24 weeks of study intervention, participants with HIV-1 RNA <50 copies/mL and no PDVF discontinued treatment of 3TC and placebo to DOR/3TC/TDF. Part 2 assessed ISL 2.25 mg (blind maintained) + DOR QD. After all participants had received at least 48 weeks of study intervention and the islatravir dose was selected, all participants in the islatravir group were switched to the selected dose 0.75 mg (between week 60 and week 84). Part 3 assessed Islatravir 0.75 mg + DOR QD open label through Week 144.
OG003
DOR/3TC/TDF
In Part 1, participants were treated QD with placebo to islatravir, placebo to DOR, placebo to 3TC, and a fixed dose combination of DOR/3TC/TDF consisting of 100 mg DOR + 300 mg 3TC + 300 mg TDF for a minimum of 24 weeks. In Parts 2 and 3, after a minimum of 24 weeks of treatment, placebo treatments were discontinued and participants received only DOR/3TC/TDF QD open label up to Week 144.
OG004
DOR/ISL Continued
In Part 4, beginning with week 144, participants who received the fixed dose combination of doravirine (100mg)/islatravir (0.75mg) QD open label in Part 3 and continued treatment through Week 192.
OG005
DOR/ISL Switch
In Part 4, beginning with week 144, participants who received DOR/3TC/TDF QD open label up to Week 144 were switched to the fixed dose combination of doravirine (100mg)/islatravir (0.75mg) QD open label and continued treatment until Week 192.
Units
Counts
Participants
OG00029
OG00130
OG00231
OG00331
OG00467
OG00522
Title
Denominators
Categories
Title
Measurements
OG00012
OG00119
OG00211
OG00312
OG00436
OG00514
In Part 1, participants were treated QD with 0.75 mg islatravir, 100 mg DOR, 300 mg 3TC, and placebo to DOR/3TC/TDF for a minimum of 24 weeks. In part 2, after receiving at least 24 weeks of study intervention, participants with HIV-1 RNA <50 copies/mL and no PDVF discontinued treatment of 3TC and placebo to DOR/3TC/TDF. Part 2 assessed ISL 0.75 mg (blind maintained) + DOR QD. After all participants had received at least 48 weeks of study intervention and the islatravir dose was selected, all participants in the islatravir group were switched to the selected dose 0.75 mg (between week 60 and week 84). Part 3 assessed Islatravir 0.75 mg + DOR QD open label through Week 144.
OG002
Islatravir 2.25 mg
In Part 1, participants were treated QD with 2.25 mg islatravir, 100 mg DOR, 300 mg 3TC, and placebo to DOR/3TC/TDF for a minimum of 24 weeks. In part 2, after receiving at least 24 weeks of study intervention, participants with HIV-1 RNA <50 copies/mL and no PDVF discontinued treatment of 3TC and placebo to DOR/3TC/TDF. Part 2 assessed ISL 2.25 mg (blind maintained) + DOR QD. After all participants had received at least 48 weeks of study intervention and the islatravir dose was selected, all participants in the islatravir group were switched to the selected dose 0.75 mg (between week 60 and week 84). Part 3 assessed Islatravir 0.75 mg + DOR QD open label through Week 144.
OG003
DOR/3TC/TDF
In Part 1, participants were treated QD with placebo to islatravir, placebo to DOR, placebo to 3TC, and a fixed dose combination of DOR/3TC/TDF consisting of 100 mg DOR + 300 mg 3TC + 300 mg TDF for a minimum of 24 weeks. In Parts 2 and 3, after a minimum of 24 weeks of treatment, placebo treatments were discontinued and participants received only DOR/3TC/TDF QD open label up to Week 144.
OG004
DOR/ISL Continued
In Part 4, beginning with week 144, participants who received the fixed dose combination of doravirine (100mg)/islatravir (0.75mg) QD open label in Part 3 and continued treatment through Week 192.
OG005
DOR/ISL Switch
In Part 4, beginning with week 144, participants who received DOR/3TC/TDF QD open label up to Week 144 were switched to the fixed dose combination of doravirine (100mg)/islatravir (0.75mg) QD open label and continued treatment until Week 192.