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Clinical Trial Results:
A Phase 3 Randomized, Active-Controlled, Open-Label Clinical Study to Evaluate a Switch to Doravirine/Islatravir (DOR/ISL) Once-Daily in Participants With HIV-1 Virologically Suppressed on Antiretroviral Therapy

Summary
EudraCT number	2019-000586-20
Trial protocol	PL ES FR GB IT
Global end of trial date	26 Aug 2024

Results information
Results version number	v1(current)
This version publication date	24 Aug 2025
First version publication date	24 Aug 2025
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

MK-8591A-017

ISRCTN number

US NCT number

NCT04223778

WHO universal trial number (UTN)

Other trial identifiers

JAPIC-CTI: 205165

Sponsor organisation name

Merck Sharp & Dohme LLC

Sponsor organisation address

126 East Lincoln Avenue, P.O. Box 2000, Rahway, NJ, United States, 07065

Public contact

Clinical Trials Disclosure, Merck Sharp & Dohme LLC, ClinicalTrialsDisclosure@msd.com

Scientific contact

Clinical Trials Disclosure, Merck Sharp & Dohme LLC, ClinicalTrialsDisclosure@msd.com

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

26 Aug 2024

Is this the analysis of the primary completion data?

Yes

Primary completion date

08 Sep 2021

Global end of trial reached?

Yes

Global end of trial date

26 Aug 2024

Was the trial ended prematurely?

Main objective of the trial

This study will evaluate the safety and efficacy of a switch to MK-8591A (a fixed dose combination of doravirine and islatravir) in human immunodeficiency virus -1 (HIV-1)-infected participants virologically suppressed on a protocol-specified antiretroviral regimen. The primary hypothesis is that a switch to MK-8591A will be non-inferior to continued treatment with baseline antiretroviral therapy (ART) as assessed by the percentage of participants with HIV-1 ribonucleic acid (RNA) ≥50 copies/mL at Week 48.

Protection of trial subjects

This study was conducted in conformance with Good Clinical Practice standards and applicable country and/or local statutes and regulations regarding ethical committee review, informed consent, and the protection of human subjects participating in biomedical research.

Background therapy

Evidence for comparator

Actual start date of recruitment

18 Feb 2020

Long term follow-up planned

Yes

Long term follow-up rationale

Safety

Long term follow-up duration

33 Months

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Australia: 20

Country: Number of subjects enrolled

Canada: 39

Country: Number of subjects enrolled

Chile: 31

Country: Number of subjects enrolled

Colombia: 31

Country: Number of subjects enrolled

France: 37

Country: Number of subjects enrolled

Italy: 37

Country: Number of subjects enrolled

Japan: 23

Country: Number of subjects enrolled

New Zealand: 7

Country: Number of subjects enrolled

Poland: 29

Country: Number of subjects enrolled

Russian Federation: 46

Country: Number of subjects enrolled

South Africa: 77

Country: Number of subjects enrolled

Spain: 51

Country: Number of subjects enrolled

Switzerland: 65

Country: Number of subjects enrolled

United Kingdom: 36

Country: Number of subjects enrolled

United States: 143

Worldwide total number of subjects

672

EEA total number of subjects

154

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

637

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

Screening details

Adult HIV-1-infected participants receiving baseline ART were enrolled in this study. 672 participants were randomly assigned in a 1:1 ratio to either Group 1: switch baseline ART to doravirine (DOR)/islatravir (ISL) on Day 1 to Week 96; or Group 2: continue baseline ART until Week 48 then switch to DOR/ISL from Week 48 to Week 96.

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Group 1: Doravirine/Islatravir (DOR/ISL)

Arm description

Participants who were previously treated with continuous baseline antiretroviral therapy (ART) received DOR/ISL, a fixed dose combination (FDC) of 100 mg doravirine (DOR)/0.75 mg islatravir (ISL) orally once daily for 96 weeks.

Arm type

Experimental

Investigational medicinal product name

doravirine (DOR)/islatravir (ISL)

Investigational medicinal product code

Other name

MK-8591A

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

A fixed dose combination (FDC) of 100 mg DOR/ 0.75 mg ISL taken in tablet form, orally, once daily

Group 2: Baseline Antiretroviral Therapy (ART)

Arm description

Participants received continuous baseline ART for 48 weeks. Continuing participants delayed switch over from baseline ART to DOR/ISL, fixed dose combination of 100 mg DOR/0.75 mg ISL orally once daily, from Week 48 to Week 96, a total DOR/ISL treatment duration of 48 Weeks.

Arm type

Active comparator

Investigational medicinal product name

Baseline ART Regimen

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Baseline ART regimen will be administered as per approved label. ART medication will not be provided by the Sponsor; participants will provide their own ART medications. Allowed drug classes include nucleoside analog reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), integrase strand transferase inhibitors (InSTIs), fusion inhibitors, chemokine receptor 5 (CCR5) antagonists, post-attachment inhibitor, and pharmacokinetic (PK) boosters.

Investigational medicinal product name

doravirine (DOR)/islatravir (ISL)

Investigational medicinal product code

Other name

MK-8591A

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

A fixed dose combination (FDC) of 100 mg DOR/ 0.75 mg ISL taken in tablet form, orally, once daily

Number of subjects in period 1	Group 1: Doravirine/Islatravir (DOR/ISL)	Group 2: Baseline Antiretroviral Therapy (ART)
Started	336	336
Group 1 DOR/ISL Weeks 0-48	336	0 ^[1]
Group 1 DOR/ISL Weeks 48-96	322	0 ^[2]
Group 2 Baseline ART Weeks 0-48	0 ^[3]	336
Group 2 Switch to DOR/ISL Weeks 48-96	0 ^[4]	326
Completed	279	299
Not completed	57	37
Physician decision	10	6
Consent withdrawn by subject	35	17
Not Reported	7	8
Death	1	1
Lost to follow-up	4	5

Notes
[1] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Per protocol, Group 1 DOR/ISL from Weeks 0-48 is not applicable to Group 2: Baseline ART arm.
[2] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Per protocol, Group 1 DOR/ISL from Weeks 48-96 is not applicable to Group 2: Baseline ART arm.
[3] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Per protocol, Group 2 Baseline ART from Weeks 0-48 is not applicable to Group 1: DOR/ISL arm.
[4] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Per protocol, Group 2 Baseline ART Switch to DOR/ISL is not applicable to Group 1: DOR/ISL arm.

Baseline characteristics

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Reporting group title

Group 1: Doravirine/Islatravir (DOR/ISL)

Reporting group description

Reporting group title

Group 2: Baseline Antiretroviral Therapy (ART)

Reporting group description

Reporting group values	Group 1: Doravirine/Islatravir (DOR/ISL)	Group 2: Baseline Antiretroviral Therapy (ART)	Total
Number of subjects	336	336	672
Age categorical
Units: Subjects
In utero	0	0	0
Preterm newborn infants (gestational age < 37 wks)	0	0	0
Newborns (0-27 days)	0	0	0
Infants and toddlers (28 days-23 months)	0	0	0
Children (2-11 years)	0	0	0
Adolescents (12-17 years)	0	0	0
Adults (18-64 years)	321	316	637
From 65-84 years	15	20	35
85 years and over	0	0	0
Age Continuous
Units: Years
arithmetic mean (standard deviation)	45.5 ( 11.7 )	45.4 ( 11.7 )	-
Sex: Female, Male
Units: Participants
Female	123	126	249
Male	213	210	423
Race (NIH/OMB)
Units: Subjects
American Indian or Alaska Native	4	8	12
Asian	19	19	38
Native Hawaiian or Other Pacific Islander	0	2	2
Black or African American	88	91	179
White	210	198	408
More than one race	13	16	29
Unknown or Not Reported	2	2	4
Ethnicity (NIH/OMB)
Units: Subjects
Hispanic or Latino	67	64	131
Not Hispanic or Latino	266	270	536
Unknown or Not Reported	3	2	5
ART Regimen Stratification
Participants were stratified into the following baseline ART regimen: (1) Protease inhibitor (PI)-containing regimens (including PI- and integrase strand transferase inhibitor [InSTI]-containing regimens); (2) InSTI-based regimens (non-PI containing regimens); (3) All other non-PI- and non-InSTI containing regimens.
Units: Subjects
PI-regimens (both PI- & InSTI-containing regimens)	46	46	92
InSTI-based regimens (non-PI containing regimens)	174	174	348
All other non-PI- & non-InSTI containing regimens	116	116	232

End points

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Reporting group title

Group 1: Doravirine/Islatravir (DOR/ISL)

Reporting group description

Reporting group title

Group 2: Baseline Antiretroviral Therapy (ART)

Reporting group description

Primary: Percentage of Participants with Human Immunodeficiency Virus (HIV)-1 Ribonucleic Acid (RNA) ≥50 copies/mL at Week 48

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End point title

Percentage of Participants with Human Immunodeficiency Virus (HIV)-1 Ribonucleic Acid (RNA) ≥50 copies/mL at Week 48

End point description

HIV-1 RNA levels in blood samples taken at each visit were measured by the Abbott RealTime polymerase chain reaction (PCR) assay with a reliable lower limit of quantification of 40 copies/mL. The percentage of participants with HIV-1 RNA ≥50 copies/mL at Week 48 is presented using the FDA Snapshot missing data approach. The analysis population consisted of all randomized participants who received at least one dose of study intervention.

End point type

Primary

End point timeframe

Week 48

End point values	Group 1: Doravirine/Islatravir (DOR/ISL)	Group 2: Baseline Antiretroviral Therapy (ART)
Number of subjects analysed	336	336
Units: Percentage of Participants
number (not applicable)	0.0	1.5

Treatment Difference (Group 1 – Group 2)

Comparison groups

Group 1: Doravirine/Islatravir (DOR/ISL) v Group 2: Baseline Antiretroviral Therapy (ART)

Number of subjects included in analysis

672

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[1]

P-value

< 0.001

Method

Miettinen and Nurminen

Parameter type

Estimated Difference

Point estimate

-1.49

Confidence interval

level

95%

sides

2-sided

lower limit

-3.44

upper limit

-0.34

Notes
[1] - Doravirine/Islatravir (DOR/ISL)- Baseline Antiretroviral Therapy (ART). Non-inferiority was concluded if the upper bound of the 2-sided multiplicity-adjusted 95% CI was less than 4 percentage points.

Primary: Percentage of Participants with one or more adverse events (AEs) up to Week 48

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End point title

Percentage of Participants with one or more adverse events (AEs) up to Week 48

End point description

End point type

Primary

End point timeframe

Up to ~48 Weeks

End point values	Group 1: Doravirine/Islatravir (DOR/ISL)	Group 2: Baseline Antiretroviral Therapy (ART)
Number of subjects analysed	336	336
Units: Percentage of Participants
number (not applicable)	80.1	70.2

Difference in percentage versus Baseline ART

Comparison groups

Group 1: Doravirine/Islatravir (DOR/ISL) v Group 2: Baseline Antiretroviral Therapy (ART)

Number of subjects included in analysis

672

Analysis specification

Pre-specified

Analysis type

other ^[2]

Method

Parameter type

Estimated Difference

Point estimate

9.8

Confidence interval

level

95%

sides

2-sided

lower limit

3.3

upper limit

16.3

Notes
[2] - Difference in percentage versus Baseline Antiretroviral Therapy (ART). Type of statistical test 'other' denotes no hypothesis testing was conducted.

Primary: Percentage of Participants who discontinued study intervention due to an AE up to Week 48

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End point title

Percentage of Participants who discontinued study intervention due to an AE up to Week 48

End point description

End point type

Primary

End point timeframe

Up to ~48 Weeks

End point values	Group 1: Doravirine/Islatravir (DOR/ISL)	Group 2: Baseline Antiretroviral Therapy (ART)
Number of subjects analysed	336	336
Units: Percentage of Participants
number (not applicable)	2.1	0.3

Difference in percentage versus Baseline ART

Comparison groups

Group 1: Doravirine/Islatravir (DOR/ISL) v Group 2: Baseline Antiretroviral Therapy (ART)

Number of subjects included in analysis

672

Analysis specification

Pre-specified

Analysis type

other ^[3]

Method

Parameter type

Estimated Difference

Point estimate

1.8

Confidence interval

level

95%

sides

2-sided

lower limit

0.2

upper limit

Notes
[3] - Difference in percentage versus Baseline Antiretroviral Therapy (ART). Type of statistical test 'other' denotes no hypothesis testing was conducted.

Secondary: Percentage of Participants with HIV-1 RNA <40 or <50 copies/mL at Week 48

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End point title

Percentage of Participants with HIV-1 RNA <40 or <50 copies/mL at Week 48

End point description

HIV-1 RNA levels in blood samples taken at each visit were measured by the Abbott RealTime PCR assay with a reliable lower limit of quantification of 40 copies/mL. The percentage of participants with HIV-1 RNA <40 copies/mL or <50 copies/mL at Week 48 is presented using the FDA Snapshot missing data approach. The analysis population consisted of all randomized participants who received at least one dose of study intervention.

End point type

Secondary

End point timeframe

Week 48

End point values	Group 1: Doravirine/Islatravir (DOR/ISL)	Group 2: Baseline Antiretroviral Therapy (ART)
Number of subjects analysed	336	336
Units: Percentage of Participants
number (not applicable)
HIV-1 RNA <40 copies/mL	94.6	94.3
HIV-1 RNA <50 copies/mL	95.2	94.3

Treatment Difference (Group 1 – Group 2)

Statistical analysis description

HIV-1 RNA <50 copies/mL

Comparison groups

Group 1: Doravirine/Islatravir (DOR/ISL) v Group 2: Baseline Antiretroviral Therapy (ART)

Number of subjects included in analysis

672

Analysis specification

Pre-specified

Analysis type

other ^[4]

Method

Parameter type

Estimated Difference

Point estimate

0.89

Confidence interval

level

95%

sides

2-sided

lower limit

-2.58

upper limit

4.43

Notes
[4] - Doravirine/Islatravir (DOR/ISL)- Baseline Antiretroviral Therapy (ART). Type of statistical test 'other' denotes no hypothesis testing was conducted.

Treatment Difference (Group 1 – Group 2)

Statistical analysis description

HIV-1 RNA <40 copies/mL

Comparison groups

Group 1: Doravirine/Islatravir (DOR/ISL) v Group 2: Baseline Antiretroviral Therapy (ART)

Number of subjects included in analysis

672

Analysis specification

Pre-specified

Analysis type

other ^[5]

Method

Parameter type

Estimated Difference

Point estimate

0.3

Confidence interval

level

95%

sides

2-sided

lower limit

-3.28

upper limit

3.9

Notes
[5] - Doravirine/Islatravir (DOR/ISL) - Baseline Antiretroviral Therapy (ART). Type of statistical test 'other' denotes no hypothesis testing was conducted.

Secondary: Group 2 (Switch-Over): Percentage of Participants With HIV-1 RNA ≥50 Copies/mL, <40 Copies/mL or <50 Copies/mL at Week 96

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End point title

Group 2 (Switch-Over): Percentage of Participants With HIV-1 RNA ≥50 Copies/mL, <40 Copies/mL or <50 Copies/mL at Week 96

End point description

HIV-1 RNA levels in blood samples taken at each visit was measured by the Abbott RealTime PCR assay with a reliable lower limit of quantification of 40 copies/mL. The percentage of participants with HIV-1 RNA ≥50 copies/mL, <40 copies/mL, or <50 copies/mL at Week 96 is reported for Group 2 participants who delayed switch over from baseline ART to DOR/ISL from Week 48 to Week 96. The analysis population consisted of all randomized participants in Group 2 who delayed switch over from baseline ART to DOR/ISL from Week 48 to Week 96 who received at least one dose of study intervention and had data available for this outcome measure. Per protocol, the percentage of participants with HIV-1 RNA ≥50 copies/mL, <40 copies/mL, or <50 copies/mL at Week 96 for Group 1 participants is a separate outcome measure and is presented later in the record.

End point type

Secondary

End point timeframe

Week 96

End point values	Group 1: Doravirine/Islatravir (DOR/ISL)	Group 2: Baseline Antiretroviral Therapy (ART)
Number of subjects analysed	0 ^[6]	326 ^[7]
Units: Percentage of Participants
number (confidence interval 95%)
HIV-1 RNA ≥50 copies/mL	( to )	0.9 (0.2 to 2.7)
HIV-1 RNA <50 copies/mL	( to )	89.6 (85.7 to 92.7)
HIV-1 RNA <40 copies/mL	( to )	89.6 (85.7 to 92.7)

Notes
[6] - Per protocol, this endpoint is for Group 2 only. Group 1 is presented in a separate endpoint.
[7] - Number of subjects analyzed is participants in Group 2 who delayed switch to DOR/ISL Weeks 48-96

No statistical analyses for this end point

Secondary: Percentage change from baseline in CD4+ T-cell count at Week 48

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End point title

Percentage change from baseline in CD4+ T-cell count at Week 48

End point description

Plasma CD4+ T-Cell Count was measured in cells/mm^3 for baseline and 48 weeks. Baseline measurements were defined as the Day 1 value of each participant. The percentage change from baseline to Week 48 is presented. The analysis population consisted of all randomized participants who received at least one dose of study intervention and who have baseline data.

End point type

Secondary

End point timeframe

Baseline and Week 48

End point values	Group 1: Doravirine/Islatravir (DOR/ISL)	Group 2: Baseline Antiretroviral Therapy (ART)
Number of subjects analysed	313 ^[8]	311 ^[9]
Units: Percentage Change
arithmetic mean (confidence interval 95%)	-0.7 (-4.0 to 2.6)	8.7 (5.4 to 12.0)

Notes
[8] - Number of subjects analyzed is Group 1 treated participants with baseline data available
[9] - Number of subjects analyzed is Group 2 ART treated participants with baseline data available

Difference in percentage versus Baseline ART

Comparison groups

Group 1: Doravirine/Islatravir (DOR/ISL) v Group 2: Baseline Antiretroviral Therapy (ART)

Number of subjects included in analysis

624

Analysis specification

Pre-specified

Analysis type

other ^[10]

Method

Parameter type

Estimated Difference

Point estimate

-8.9

Confidence interval

level

95%

sides

2-sided

lower limit

-13.4

upper limit

-4.5

Notes
[10] - Difference in percentage versus Baseline Antiretroviral Therapy (ART). Type of statistical test 'other' denotes no hypothesis testing was conducted.

Secondary: Group 1: Percentage of Participants with HIV-1 RNA ≥50 copies/mL, <40 copies/mL or <50 copies/mL at Week 96

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End point title

Group 1: Percentage of Participants with HIV-1 RNA ≥50 copies/mL, <40 copies/mL or <50 copies/mL at Week 96

End point description

HIV-1 RNA levels in blood samples taken at each visit was measured by the Abbott RealTime PCR assay with a reliable lower limit of quantification of 40 copies/mL. The percentage of participants with HIV-1 RNA ≥50 copies/mL, <40 copies/mL, or <50 copies/mL at Week 96 is reported for Group 1 participants. The analysis population consisted of all randomized participants in Group 1 who received at least one dose of study intervention and had data available for this outcome measure. Per protocol, the percentage of participants with HIV-1 RNA ≥50 copies/mL, <40 copies/mL, or <50 copies/mL at Week 96 for Group 2 participants who delayed switch over from baseline ART to DOR/ISL from Week 48 to Week 96 is a separate outcome measure and is presented earlier in the record.

End point type

Secondary

End point timeframe

Week 96

End point values	Group 1: Doravirine/Islatravir (DOR/ISL)	Group 2: Baseline Antiretroviral Therapy (ART)
Number of subjects analysed	336	0 ^[11]
Units: Percentage of Participants
number (confidence interval 95%)
HIV-1 RNA ≥50 copies/mL	1.2 (0.3 to 3.0)	( to )
HIV-1 RNA <40 copies/mL	86.0 (81.8 to 89.5)	( to )
HIV-1 RNA <50 copies/mL	85.7 (81.5 to 89.3)	( to )

Notes
[11] - Per protocol, this endpoint is for Group 1 only. Group 2 is presented in a separate endpoint.

No statistical analyses for this end point

Secondary: Percentage of Participants with evidence of viral drug resistance-associated substitutions at Week 96

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End point title

Percentage of Participants with evidence of viral drug resistance-associated substitutions at Week 96

End point description

Viral drug resistance was defined as participants with confirmed HIV-1 RNA ≥400 copies/mL and/or genotypic or phenotypic analysis of data showing evidence of resistance to the study drug administered. The percentage of participants who demonstrate drug resistance at Week 96 is presented for Group 1 and Group 2 participants who switched-over from baseline ART to receive DOR/ISL treatment from Week 48 to Week 96. The analysis population consisted of participants with virologic rebound (2 repeated incidents of HIV-1 RNA ≥200 copies/mL, 2-4 weeks apart) or who discontinued study intervention with HIV-1 RNA ≥200 copies/mL. Participants with available data showing resistance, despite viral load, are included. Per protocol, percentage of participants with evidence of viral drug resistance associated substitutions from week 0 to week 48 for Groups 1 and 2 is a separate outcome measure reported earlier in the record.

End point type

Secondary

End point timeframe

Week 96

End point values	Group 1: Doravirine/Islatravir (DOR/ISL)	Group 2: Baseline Antiretroviral Therapy (ART)
Number of subjects analysed	336	326 ^[12]
Units: Percentage of Participants
number (not applicable)	0.0	0.0

Notes
[12] - Number of subjects analyzed is participants in Group 2 who delayed switch to DOR/ISL Weeks 48-96

No statistical analyses for this end point

Secondary: Percentage of Participants with evidence of viral drug resistance-associated substitutions at Week 48

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End point title

Percentage of Participants with evidence of viral drug resistance-associated substitutions at Week 48

End point description

Viral drug resistance is defined as participants with confirmed HIV-1 RNA ≥400 copies/mL and/or genotypic or phenotypic analysis of data showing evidence of resistance to the study drug administered. The percentage of participants who demonstrated drug resistance at Week 48 is presented. The analysis population consisted of participants who met the definition of confirmed virologic rebound (two consecutive [2 to 4 weeks apart] occurrences of HIV-1 RNA ≥200 copies/mL) at any time during the study or who discontinued study intervention for another reason and have HIV-1 RNA ≥200 copies/mL at the time of discontinuation. Participants for whom available genotypic or phenotypic data showed evidence of resistance, irrespective of viral load, were also included.

End point type

Secondary

End point timeframe

Week 48

End point values	Group 1: Doravirine/Islatravir (DOR/ISL)	Group 2: Baseline Antiretroviral Therapy (ART)
Number of subjects analysed	336	336
Units: Percentage of Participants
number (not applicable)	0.0	0.9

No statistical analyses for this end point

Secondary: Group 1 & Group 2 (Switch-Over): Percentage Change From Week 48 in CD4+ T-cell Count at Week 96

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End point title

Group 1 & Group 2 (Switch-Over): Percentage Change From Week 48 in CD4+ T-cell Count at Week 96

End point description

Plasma CD4+ T-Cell Count was measured in cells/mm^3 for Week 48 and Week 96. The mean percent change from Week 48 to Week 96 is reported for Group 1 and Group 2 participants who delayed switch over from baseline ART to DOR/ISL Week 48 to Week 96. The analysis population consisted of all randomized participants who received at least one dose of study intervention and had data available for this outcome measure for participants in Group 1 and participants in Group 2 who delayed switch over from baseline ART to DOR/ISL from Week 48 to Week 96.

End point type

Secondary

End point timeframe

Week 48 and Week 96

End point values	Group 1: Doravirine/Islatravir (DOR/ISL)	Group 2: Baseline Antiretroviral Therapy (ART)
Number of subjects analysed	289 ^[13]	285 ^[14]
Units: Percentage Change
arithmetic mean (confidence interval 95%)	5.29 (1.99 to 8.58)	0.16 (-2.96 to 3.29)

Notes
[13] - Number of subjects analyzed is Group 1 treated participants with data available
[14] - Number of subjects analyzed Group 2 DOR/ISL treated participants with data available Weeks 48-96

No statistical analyses for this end point

Secondary: Group 1: Percentage Change From Baseline in CD4+ T-cell Count at Week 96

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End point title

Group 1: Percentage Change From Baseline in CD4+ T-cell Count at Week 96

End point description

Plasma CD4+ T-Cell Count was measured in cells/mm^3 for baseline and 96 weeks. Baseline measurements were defined as the Day 1 value of each participant. The mean percent change from baseline to Week 96 in CD4+ T-cell count is reported for Group 1 participants. The analysis population consisted of all randomized participants in Group 1 who received at least one dose of study intervention and had data, including baseline data, available for this outcome measure. Per protocol, the percentage change from baseline in CD4+ T-cell count at Week 96 for Group 2 participants was not planned or conducted.

End point type

Secondary

End point timeframe

Baseline and Week 96

End point values	Group 1: Doravirine/Islatravir (DOR/ISL)	Group 2: Baseline Antiretroviral Therapy (ART)
Number of subjects analysed	284 ^[15]	0 ^[16]
Units: Percentage Change
arithmetic mean (confidence interval 95%)	4.49 (0.56 to 8.43)	( to )

Notes
[15] - Number of subjects analyzed is Group 1 treated participants with data available
[16] - Per protocol, this endpoint is for Group 1 only; Group 2 analysis was not planned or conducted.

No statistical analyses for this end point

Secondary: Change from baseline to Week 24 in fasting lipids in participants on protease inhibitor (PI)-containing regimens (including PI- and integrase strand transferase inhibitor [InSTI]-containing regimens)

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End point title

Change from baseline to Week 24 in fasting lipids in participants on protease inhibitor (PI)-containing regimens (including PI- and integrase strand transferase inhibitor [InSTI]-containing regimens)

End point description

Blood serum samples were taken at baseline and Week 24. Per protocol, this outcome analysis was conducted in participants on PI-containing regimens (including PI- and InSTI-containing regimens), excluding participants who took lipid-lowering therapy during the study. The fasting lipids consisted of fasting cholesterol, fasting high density lipoprotein (HDL) cholesterol, fasting low density lipoprotein (LDL) cholesterol, fasting non-HDL cholesterol, and fasting triglycerides. The mean change from baseline to Week 24 in fasting lipids is presented. The analysis population consisted of all randomized participants on PI-containing regimens (including PI- and InSTI-containing regimens) who received at least one dose of study intervention and had baseline and Week 24 data available for each lipid type, excluding participants who took lipid-lowering therapy during the study, per protocol.

End point type

Secondary

End point timeframe

Baseline and Week 24

End point values	Group 1: Doravirine/Islatravir (DOR/ISL)	Group 2: Baseline Antiretroviral Therapy (ART)
Number of subjects analysed	32 ^[17]	40 ^[18]
Units: mg/dL
arithmetic mean (confidence interval 95%)
Fasting Cholesterol (n=32, 40)	-12.94 (-23.94 to -1.94)	6.20 (-2.16 to 14.56)
Fasting HDL (n=32, 40)	-0.97 (-5.94 to 4.00)	0.76 (-1.80 to 3.32)
Fasting LDL Cholesterol (n=32, 40)	-7.47 (-15.86 to 0.92)	5.93 (-1.08 to 12.93)
Fasting Non-HDL Cholesterol (n=32, 40)	-11.97 (-21.83 to -2.10)	5.44 (-2.29 to 13.16)
Fasting Triglycerides (n=32, 40)	-22.69 (-42.92 to -2.46)	-3.16 (-19.81 to 13.49)

Notes
[17] - Number of subjects analyzed is Group 1 treated participants (PI-containing regimens) with data
[18] - Number of subjects analyzed is Group 2 ART treated participants (PI-containing regimens) with data

Treatment Difference versus Baseline ART

Statistical analysis description

Fasting HDL Cholesterol

Comparison groups

Group 1: Doravirine/Islatravir (DOR/ISL) v Group 2: Baseline Antiretroviral Therapy (ART)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other ^[19]

Method

Parameter type

Estimated Difference

Point estimate

-1.35

Confidence interval

level

95%

sides

2-sided

lower limit

-6.55

upper limit

3.84

Notes
[19] - Treatment Difference vs Baseline ART. Type of statistical test 'other' denotes no hypothesis testing was conducted. Group 1: Doravirine/Islatravir (DOR/ISL) n= 32; Group 2: Baseline Antiretroviral Therapy (ART) n=40).

Treatment Difference versus Baseline ART

Statistical analysis description

Fasting Cholesterol

Comparison groups

Group 1: Doravirine/Islatravir (DOR/ISL) v Group 2: Baseline Antiretroviral Therapy (ART)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other ^[20]

Method

Parameter type

Estimated Difference

Point estimate

-19.75

Confidence interval

level

95%

sides

2-sided

lower limit

-33.07

upper limit

-6.44

Notes
[20] - Treatment Difference vs Baseline ART. Type of statistical test 'other' denotes no hypothesis testing was conducted. Group 1: Doravirine/Islatravir (DOR/ISL) n= 32; Group 2: Baseline Antiretroviral Therapy (ART) n=40).

Treatment Difference versus Baseline ART

Statistical analysis description

Fasting Non-HDL Cholesterol

Comparison groups

Group 1: Doravirine/Islatravir (DOR/ISL) v Group 2: Baseline Antiretroviral Therapy (ART)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other ^[21]

Method

Parameter type

Estimated Difference

Point estimate

-17.74

Confidence interval

level

95%

sides

2-sided

lower limit

-30.02

upper limit

-5.46

Notes
[21] - Treatment Difference vs Baseline ART. Type of statistical test 'other' denotes no hypothesis testing was conducted. Group 1: Doravirine/Islatravir (DOR/ISL) n= 32; Group 2: Baseline Antiretroviral Therapy (ART) n=40).

Treatment Difference versus Baseline ART

Statistical analysis description

Fasting Triglycerides

Comparison groups

Group 1: Doravirine/Islatravir (DOR/ISL) v Group 2: Baseline Antiretroviral Therapy (ART)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other ^[22]

Method

Parameter type

Estimated Difference

Point estimate

-21.28

Confidence interval

level

95%

sides

2-sided

lower limit

-45.51

upper limit

2.96

Notes
[22] - Treatment Difference vs Baseline ART. Type of statistical test 'other' denotes no hypothesis testing was conducted. Group 1: Doravirine/Islatravir (DOR/ISL) n= 32; Group 2: Baseline Antiretroviral Therapy (ART) n=40).

Treatment Difference versus Baseline ART

Statistical analysis description

Fasting LDL Cholesterol

Comparison groups

Group 1: Doravirine/Islatravir (DOR/ISL) v Group 2: Baseline Antiretroviral Therapy (ART)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other ^[23]

Method

Parameter type

Estimated Difference

Point estimate

-13.94

Confidence interval

level

95%

sides

2-sided

lower limit

-24.69

upper limit

-3.2

Notes
[23] - Treatment Difference vs Baseline ART. Type of statistical test 'other' denotes no hypothesis testing was conducted. Group 1: Doravirine/Islatravir (DOR/ISL) n= 32; Group 2: Baseline Antiretroviral Therapy (ART) n=40).

Secondary: Change from baseline to Week 24 in fasting lipids in participants on InSTI-based regimens (non-PI containing regimens)

Top of page

End point title

Change from baseline to Week 24 in fasting lipids in participants on InSTI-based regimens (non-PI containing regimens)

End point description

Blood serum samples were taken at baseline and Week 24. Per protocol, this outcome analysis was conducted in participants on InSTI-based regimens (non-PI containing regimens), excluding participants who took lipid-lowering therapy during the study. The fasting lipids consisted of fasting cholesterol, fasting HDL cholesterol, fasting LDL cholesterol, fasting non-HDL cholesterol, and fasting triglycerides. The mean change from baseline to Week 24 in fasting lipids is presented. The analysis population consisted of all randomized participants on InSTI-based regimens (non-PI containing regimens) who received at least one dose of study intervention and had baseline and Week 24 data available for each lipid type, excluding participants who took lipid-lowering therapy during the study, per protocol.

End point type

Secondary

End point timeframe

Baseline and Week 24

End point values	Group 1: Doravirine/Islatravir (DOR/ISL)	Group 2: Baseline Antiretroviral Therapy (ART)
Number of subjects analysed	130 ^[24]	135 ^[25]
Units: mg/dL
arithmetic mean (confidence interval 95%)
Fasting Cholesterol (n=130, 135)	2.98 (-2.19 to 8.14)	8.74 (4.25 to 13.23)
Fasting HDL Cholesterol (n=130, 135)	0.84 (-1.11 to 2.79)	0.27 (-1.06 to 1.60)
Fasting LDL Cholesterol (n=128, 135)	3.21 (-1.49 to 7.92)	8.50 (4.27 to 12.73)
Fasting Non-HDL Cholesterol (n=130, 135)	2.14 (-3.39 to 7.67)	8.47 (4.05 to 12.90)
Fasting Triglycerides (n=130, 135)	-0.97 (-17.98 to 16.04)	-1.56 (-10.80 to 7.69)

Notes
[24] - Number of subjects analyzed is Group 1 treated participants (InSTI-containing regimens) with data
[25] - Number of subjects analyzed Group 2 ART treated participants (InSTI-containing regimens) with data

Treatment Difference versus Baseline ART

Statistical analysis description

Fasting Cholesterol

Comparison groups

Group 1: Doravirine/Islatravir (DOR/ISL) v Group 2: Baseline Antiretroviral Therapy (ART)

Number of subjects included in analysis

265

Analysis specification

Pre-specified

Analysis type

other ^[26]

Method

Parameter type

Estimated Difference

Point estimate

-4.17

Confidence interval

level

95%

sides

2-sided

lower limit

-10.43

upper limit

2.09

Notes
[26] - Treatment Difference vs Baseline ART. Type of statistical test 'other' denotes no hypothesis testing was conducted. Group 1: Doravirine/Islatravir (DOR/ISL) n= 130; Group 2: Baseline Antiretroviral Therapy (ART) n=135).

Treatment Difference versus Baseline ART

Statistical analysis description

Fasting Triglycerides

Comparison groups

Group 1: Doravirine/Islatravir (DOR/ISL) v Group 2: Baseline Antiretroviral Therapy (ART)

Number of subjects included in analysis

265

Analysis specification

Pre-specified

Analysis type

other ^[27]

Method

Parameter type

Estimated Difference

Point estimate

1.65

Confidence interval

level

95%

sides

2-sided

lower limit

-16.14

upper limit

19.43

Notes
[27] - Treatment Difference vs Baseline ART. Type of statistical test 'other' denotes no hypothesis testing was conducted. Group 1: Doravirine/Islatravir (DOR/ISL) n= 130; Group 2: Baseline Antiretroviral Therapy (ART) n=135).

Treatment Difference versus Baseline ART

Statistical analysis description

Fasting Non-HDL Cholesterol

Comparison groups

Group 1: Doravirine/Islatravir (DOR/ISL) v Group 2: Baseline Antiretroviral Therapy (ART)

Number of subjects included in analysis

265

Analysis specification

Pre-specified

Analysis type

other ^[28]

Method

Parameter type

Estimated Difference

Point estimate

-4.92

Confidence interval

level

95%

sides

2-sided

lower limit

-11.21

upper limit

1.38

Notes
[28] - Treatment Difference vs Baseline ART. Type of statistical test 'other' denotes no hypothesis testing was conducted. Group 1: Doravirine/Islatravir (DOR/ISL) n= 130; Group 2: Baseline Antiretroviral Therapy (ART) n=135).

Treatment Difference versus Baseline ART

Statistical analysis description

Fasting HDL Cholesterol

Comparison groups

Group 1: Doravirine/Islatravir (DOR/ISL) v Group 2: Baseline Antiretroviral Therapy (ART)

Number of subjects included in analysis

265

Analysis specification

Pre-specified

Analysis type

other ^[29]

Method

Parameter type

Estimated Difference

Point estimate

0.81

Confidence interval

level

95%

sides

2-sided

lower limit

-1.46

upper limit

3.09

Notes
[29] - Treatment Difference vs Baseline ART. Type of statistical test 'other' denotes no hypothesis testing was conducted. Group 1: Doravirine/Islatravir (DOR/ISL) n= 130; Group 2: Baseline Antiretroviral Therapy (ART) n=135).

Treatment Difference versus Baseline ART

Statistical analysis description

Fasting LDL Cholesterol

Comparison groups

Group 1: Doravirine/Islatravir (DOR/ISL) v Group 2: Baseline Antiretroviral Therapy (ART)

Number of subjects included in analysis

265

Analysis specification

Pre-specified

Analysis type

other ^[30]

Method

Parameter type

Estimated Difference

Point estimate

-3.87

Confidence interval

level

95%

sides

2-sided

lower limit

-9.47

upper limit

1.74

Notes
[30] - Treatment Difference vs Baseline ART. Type of statistical test 'other' denotes no hypothesis testing was conducted. Group 1: Doravirine/Islatravir (DOR/ISL) n= 128; Group 2: Baseline Antiretroviral Therapy (ART) n=135).

Secondary: Change from baseline to Week 24 in fasting lipids in participants on all other non-PI- and non-InSTI containing regimens

Top of page

End point title

Change from baseline to Week 24 in fasting lipids in participants on all other non-PI- and non-InSTI containing regimens

End point description

Blood serum samples were taken at baseline and Week 24. Per protocol, this outcome analysis was conducted in participants on all other non-PI- and non-InSTI containing regimens, excluding participants who took lipid-lowering therapy during the study. The fasting lipids consisted of fasting cholesterol, fasting HDL cholesterol, fasting LDL cholesterol, fasting non-HDL cholesterol, and fasting triglycerides. The mean change from baseline to Week 24 in fasting lipids is presented. The analysis population consisted of all randomized participants on all other non-PI- and non-InSTI containing regimens, who received at least one dose of study intervention and had baseline and Week 24 data available for each lipid type, excluding participants who took lipid-lowering therapy during the study, per protocol.

End point type

Secondary

End point timeframe

Baseline and Week 24

End point values	Group 1: Doravirine/Islatravir (DOR/ISL)	Group 2: Baseline Antiretroviral Therapy (ART)
Number of subjects analysed	89 ^[31]	95 ^[32]
Units: mg/dL
arithmetic mean (confidence interval 95%)
Fasting Cholesterol (n=89, 95)	7.18 (-0.49 to 14.85)	7.35 (2.44 to 12.25)
Fasting HDL Cholesterol (n=88, 95)	-3.43 (-6.51 to -0.36)	-0.72 (-3.02 to 1.58)
Fasting LDL Cholesterol (n=87, 95)	11.33 (5.75 to 16.92)	7.19 (3.35 to 11.04)
Fasting Non-HDL Cholesterol (n=88, 95)	11.07 (4.40 to 17.74)	8.07 (4.10 to 12.04)
Fasting Triglycerides (n=88, 95)	-1.16 (-14.27 to 11.95)	4.45 (-3.89 to 12.80)

Notes
[31] - Number of subjects analyzed is Group 1 treated participants (non-PI/non-InSTI) with data
[32] - Number of subjects analyzed is Group 2 ART treated participants (non-PI/non-InSTI) with data

Treatment Difference versus Baseline ART

Statistical analysis description

Fasting HDL Cholesterol

Comparison groups

Group 1: Doravirine/Islatravir (DOR/ISL) v Group 2: Baseline Antiretroviral Therapy (ART)

Number of subjects included in analysis

184

Analysis specification

Pre-specified

Analysis type

other ^[33]

Method

Parameter type

Estimated Difference

Point estimate

-3.16

Confidence interval

level

95%

sides

2-sided

lower limit

-6.37

upper limit

0.05

Notes
[33] - Treatment Difference vs Baseline ART. Type of statistical test 'other' denotes no hypothesis testing was conducted. Group 1: Doravirine/Islatravir (DOR/ISL) n=88; Group 2: Baseline Antiretroviral Therapy (ART) n=95).

Treatment Difference versus Baseline ART

Statistical analysis description

Fasting Cholesterol

Comparison groups

Group 1: Doravirine/Islatravir (DOR/ISL) v Group 2: Baseline Antiretroviral Therapy (ART)

Number of subjects included in analysis

184

Analysis specification

Pre-specified

Analysis type

other ^[34]

Method

Parameter type

Estimated Difference

Point estimate

1.05

Confidence interval

level

95%

sides

2-sided

lower limit

-7.6

upper limit

9.7

Notes
[34] - Treatment Difference vs Baseline ART. Type of statistical test 'other' denotes no hypothesis testing was conducted. Group 1: Doravirine/Islatravir (DOR/ISL) n=89; Group 2: Baseline Antiretroviral Therapy (ART) n=95).

Treatment Difference versus Baseline ART

Statistical analysis description

Fasting Non-HDL Cholesterol

Comparison groups

Group 1: Doravirine/Islatravir (DOR/ISL) v Group 2: Baseline Antiretroviral Therapy (ART)

Number of subjects included in analysis

184

Analysis specification

Pre-specified

Analysis type

other ^[35]

Method

Parameter type

Estimated Difference

Point estimate

3.63

Confidence interval

level

95%

sides

2-sided

lower limit

-3.93

upper limit

11.19

Notes
[35] - Treatment Difference vs Baseline ART. Type of statistical test 'other' denotes no hypothesis testing was conducted. Group 1: Doravirine/Islatravir (DOR/ISL) n=88; Group 2: Baseline Antiretroviral Therapy (ART) n=95).

Treatment Difference versus Baseline ART

Statistical analysis description

Fasting Triglycerides

Comparison groups

Group 1: Doravirine/Islatravir (DOR/ISL) v Group 2: Baseline Antiretroviral Therapy (ART)

Number of subjects included in analysis

184

Analysis specification

Pre-specified

Analysis type

other ^[36]

Method

Parameter type

Estimated Difference

Point estimate

-1.79

Confidence interval

level

95%

sides

2-sided

lower limit

-15.89

upper limit

12.31

Notes
[36] - Treatment Difference vs Baseline ART. Type of statistical test 'other' denotes no hypothesis testing was conducted. Group 1: Doravirine/Islatravir (DOR/ISL) n=88; Group 2: Baseline Antiretroviral Therapy (ART) n=95).

Treatment Difference versus Baseline ART

Statistical analysis description

Fasting LDL Cholesterol

Comparison groups

Group 1: Doravirine/Islatravir (DOR/ISL) v Group 2: Baseline Antiretroviral Therapy (ART)

Number of subjects included in analysis

184

Analysis specification

Pre-specified

Analysis type

other ^[37]

Method

Parameter type

Estimated Difference

Point estimate

4.38

Confidence interval

level

95%

sides

2-sided

lower limit

-2.27

upper limit

11.03

Notes
[37] - Treatment Difference vs Baseline ART. Type of statistical test 'other' denotes no hypothesis testing was conducted. Group 1: Doravirine/Islatravir (DOR/ISL) n=87; Group 2: Baseline Antiretroviral Therapy (ART) n=95).

Secondary: Change from baseline to Week 48 in fasting lipids in participants on protease inhibitor (PI)-containing regimens (including PI- and integrase strand transferase inhibitor [InSTI]-containing regimens)

Top of page

End point title

Change from baseline to Week 48 in fasting lipids in participants on protease inhibitor (PI)-containing regimens (including PI- and integrase strand transferase inhibitor [InSTI]-containing regimens)

End point description

Blood serum samples were taken at baseline and Week 48. Per protocol, this outcome analysis was conducted in participants on PI-containing regimens (including PI- and InSTI-containing regimens), excluding participants who took lipid-lowering therapy during the study. The fasting lipids consisted of fasting cholesterol, fasting high density lipoprotein (HDL) cholesterol, fasting low density lipoprotein (LDL) cholesterol, fasting non-HDL cholesterol, and fasting triglycerides. The mean change from baseline to Week 48 in fasting lipids is presented. The analysis population consisted of all randomized participants on PI-containing regimens (including PI- and InSTI-containing regimens) who received at least one dose of study intervention and had baseline and Week 48 data available for each lipid type, excluding participants who took lipid-lowering therapy during the study, per protocol.

End point type

Secondary

End point timeframe

Baseline and Week 48

End point values	Group 1: Doravirine/Islatravir (DOR/ISL)	Group 2: Baseline Antiretroviral Therapy (ART)
Number of subjects analysed	29 ^[38]	37 ^[39]
Units: mg/dL
arithmetic mean (confidence interval 95%)
Fasting Cholesterol (n=29, 37)	-15.31 (-28.99 to -1.64)	1.84 (-5.70 to 9.38)
Fasting HDL Cholesterol (n=29, 36)	-1.45 (-6.01 to 3.11)	-1.08 (-3.91 to 1.75)
Fasting LDL Cholesterol (n=29, 35)	-8.59 (-19.72 to 2.54)	3.37 (-3.30 to 10.04)
Fasting Non-HDL Cholesterol (n=29, 36)	-13.86 (-25.28 to -2.45)	2.81 (-4.40 to 10.01)
Fasting Triglycerides (n=29, 36)	-26.90 (-42.31 to -11.48)	2.28 (-16.39 to 20.95)

Notes
[38] - Number of subjects analyzed is Group 1 treated participants (PI-containing regimens) with data
[39] - Number of subjects analyzed is Group 2 ART treated participants (PI-containing regimens) with data

Treatment Difference versus Baseline ART

Statistical analysis description

Fasting Cholesterol

Comparison groups

Group 1: Doravirine/Islatravir (DOR/ISL) v Group 2: Baseline Antiretroviral Therapy (ART)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other ^[40]

Method

Parameter type

Estimated Difference

Point estimate

-18.41

Confidence interval

level

95%

sides

2-sided

lower limit

-32.05

upper limit

-4.76

Notes
[40] - Treatment Difference vs Baseline ART. Type of statistical test 'other' denotes no hypothesis testing was conducted. Group 1: Doravirine/Islatravir (DOR/ISL) n=29; Group 2: Baseline Antiretroviral Therapy (ART) n=37).

Treatment Difference versus Baseline ART

Statistical analysis description

Fasting LDL Cholesterol

Comparison groups

Group 1: Doravirine/Islatravir (DOR/ISL) v Group 2: Baseline Antiretroviral Therapy (ART)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other ^[41]

Method

Parameter type

Estimated Difference

Point estimate

-14.12

Confidence interval

level

95%

sides

2-sided

lower limit

-25.81

upper limit

-2.43

Notes
[41] - Treatment Difference vs Baseline ART. Type of statistical test 'other' denotes no hypothesis testing was conducted. Group 1: Doravirine/Islatravir (DOR/ISL) n=29; Group 2: Baseline Antiretroviral Therapy (ART) n=35).

Fasting Non-HDL Cholesterol Multiplicity Adjusted

Statistical analysis description

Treatment Difference vs Baseline ART. Superiority will be concluded if the upper bound of the 2-sided multiplicity-adjusted 95% CI is less than 0 percentage points. The multiplicity adjusted 95% CIs for treatment difference were calculated from ANCOVA models with terms for baseline measurement and treatment. Group 1: Doravirine/Islatravir (DOR/ISL) n=29; Group 2: Baseline Antiretroviral Therapy (ART) n=36).

Comparison groups

Group 1: Doravirine/Islatravir (DOR/ISL) v Group 2: Baseline Antiretroviral Therapy (ART)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0021 ^[42]

Method

ANCOVA

Parameter type

Median difference (net)

Point estimate

-18.23

Confidence interval

level

95%

sides

2-sided

lower limit

-32.28

upper limit

-4.17

Notes
[42] - The significance level in model was ANCOVA 0.02497/2=0.012485. The p-value is statistically significant if it is <0.02497/2=0.012485.

Treatment Difference versus Baseline ART

Statistical analysis description

Fasting Triglycerides

Comparison groups

Group 1: Doravirine/Islatravir (DOR/ISL) v Group 2: Baseline Antiretroviral Therapy (ART)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other ^[43]

Method

Parameter type

Estimated Difference

Point estimate

-27.79

Confidence interval

level

95%

sides

2-sided

lower limit

-51.08

upper limit

-4.49

Notes
[43] - Treatment Difference vs Baseline ART. Type of statistical test 'other' denotes no hypothesis testing was conducted. Group 1: Doravirine/Islatravir (DOR/ISL) n=29; Group 2: Baseline Antiretroviral Therapy (ART) n=36).

Treatment Difference vs Baseline ART

Statistical analysis description

Fasting LDL Cholesterol - Multiplicity Adjusted

Comparison groups

Group 1: Doravirine/Islatravir (DOR/ISL) v Group 2: Baseline Antiretroviral Therapy (ART)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[44]

P-value

= 0.0094 ^[45]

Method

ANCOVA

Parameter type

Mean difference (net)

Point estimate

-14.12

Confidence interval

level

95%

sides

2-sided

lower limit

-27.56

upper limit

-0.68

Notes
[44] - Treatment Difference vs Baseline ART. Superiority will be concluded if the upper bound of the 2-sided multiplicity-adjusted 95% CI is less than 0 percentage points. The multiplicity adjusted 95% CIs for treatment difference were calculated from ANCOVA models with terms for baseline measurement and treatment. Group 1: Doravirine/Islatravir (DOR/ISL) n=29; Group 2: Baseline Antiretroviral Therapy (ART) n=35).
[45] - The significance level in ANCOVA model was 0.02497/2=0.012485. The p-value is statistically significant if it is <0.02497/2=0.012485.

Treatment Difference versus Baseline ART

Statistical analysis description

Fasting HDL Cholesterol

Comparison groups

Group 1: Doravirine/Islatravir (DOR/ISL) v Group 2: Baseline Antiretroviral Therapy (ART)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other ^[46]

Method

Parameter type

Estimated Difference

Point estimate

0.01

Confidence interval

level

95%

sides

2-sided

lower limit

-5.06

upper limit

5.08

Notes
[46] - Treatment Difference vs Baseline ART. Type of statistical test 'other' denotes no hypothesis testing was conducted. Group 1: Doravirine/Islatravir (DOR/ISL) n=29; Group 2: Baseline Antiretroviral Therapy (ART) n=36).

Treatment Difference versus Baseline ART

Statistical analysis description

Fasting Non-HDL Cholesterol

Comparison groups

Group 1: Doravirine/Islatravir (DOR/ISL) v Group 2: Baseline Antiretroviral Therapy (ART)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other ^[47]

Method

Parameter type

Estimated Difference

Point estimate

-18.23

Confidence interval

level

95%

sides

2-sided

lower limit

-30.45

upper limit

-6

Notes
[47] - Treatment Difference vs Baseline ART. Type of statistical test 'other' denotes no hypothesis testing was conducted. Group 1: Doravirine/Islatravir (DOR/ISL) n=29; Group 2: Baseline Antiretroviral Therapy (ART) n=36).

Secondary: Change from baseline to Week 48 in fasting lipids in participants on InSTI-based regimens (non-PI containing regimens)

Top of page

End point title

Change from baseline to Week 48 in fasting lipids in participants on InSTI-based regimens (non-PI containing regimens)

End point description

Blood serum samples were taken at baseline and Week 48. Per protocol, this outcome analysis was conducted in participants on InSTI-based regimens (non-PI containing regimens), excluding participants who took lipid-lowering therapy during the study. The fasting lipids consisted of fasting cholesterol, fasting HDL cholesterol, fasting LDL cholesterol, fasting non-HDL cholesterol, and fasting triglycerides. The mean change from baseline to Week 48 in fasting lipids is presented. The analysis population consisted of all randomized participants on InSTI-based regimens (non-PI containing regimens) who received at least one dose of study intervention and had baseline and Week 48 data available for each lipid type, excluding participants who took lipid-lowering therapy during the study, per protocol.

End point type

Secondary

End point timeframe

Baseline and Week 48

End point values	Group 1: Doravirine/Islatravir (DOR/ISL)	Group 2: Baseline Antiretroviral Therapy (ART)
Number of subjects analysed	129 ^[48]	137 ^[49]
Units: mg/dL
arithmetic mean (confidence interval 95%)
Fasting Cholesterol (n=129, 137)	2.23 (-2.70 to 7.17)	4.39 (-0.19 to 8.96)
Fasting HDL Cholesterol (n=129, 136)	0.23 (-1.61 to 2.08)	0.13 (-1.24 to 1.51)
Fasting LDL Cholesterol (n=129, 133)	2.74 (-1.27 to 6.76)	3.44 (-0.88 to 7.76)
Fasting Non-HDL Cholesterol (n=129, 136)	2.00 (-3.16 to 7.16)	4.37 (-0.24 to 8.98)
Fasting Triglycerides (n=129, 136)	-2.29 (-15.02 to 10.44)	4.44 (-5.60 to 14.48)

Notes
[48] - Number of subjects analyzed is Group 1 treated participants (non-PI/-InSTI) with data
[49] - Number of subjects analyzed is Group 2 ART treated participants (non-PI/-InSTI) with data

Treatment Difference versus Baseline ART

Statistical analysis description

Fasting Cholesterol

Comparison groups

Group 1: Doravirine/Islatravir (DOR/ISL) v Group 2: Baseline Antiretroviral Therapy (ART)

Number of subjects included in analysis

266

Analysis specification

Pre-specified

Analysis type

other ^[50]

Method

Parameter type

Estimated Difference

Point estimate

-0.04

Confidence interval

level

95%

sides

2-sided

lower limit

-6.26

upper limit

6.18

Notes
[50] - Treatment Difference vs Baseline ART. Type of statistical test 'other' denotes no hypothesis testing was conducted. Group 1: Doravirine/Islatravir (DOR/ISL) n=129; Group 2: Baseline Antiretroviral Therapy (ART) n=137).

Treatment Difference versus Baseline ART

Statistical analysis description

Fasting HDL Cholesterol

Comparison groups

Group 1: Doravirine/Islatravir (DOR/ISL) v Group 2: Baseline Antiretroviral Therapy (ART)

Number of subjects included in analysis

266

Analysis specification

Pre-specified

Analysis type

other ^[51]

Method

Parameter type

Estimated Difference

Point estimate

0.35

Confidence interval

level

95%

sides

2-sided

lower limit

-1.84

upper limit

2.54

Notes
[51] - Treatment Difference vs Baseline ART. Type of statistical test 'other' denotes no hypothesis testing was conducted. Group 1: Doravirine/Islatravir (DOR/ISL) n=129; Group 2: Baseline Antiretroviral Therapy (ART) n=136).

Treatment Difference versus Baseline ART

Statistical analysis description

Fasting LDL Cholesterol

Comparison groups

Group 1: Doravirine/Islatravir (DOR/ISL) v Group 2: Baseline Antiretroviral Therapy (ART)

Number of subjects included in analysis

266

Analysis specification

Pre-specified

Analysis type

other ^[52]

Method

Parameter type

Estimated Difference

Point estimate

0.64

Confidence interval

level

95%

sides

2-sided

lower limit

-4.83

upper limit

6.11

Notes
[52] - Treatment Difference vs Baseline ART. Type of statistical test 'other' denotes no hypothesis testing was conducted. Group 1: Doravirine/Islatravir (DOR/ISL) n=129; Group 2: Baseline Antiretroviral Therapy (ART) n=133).

Treatment Difference versus Baseline ART

Statistical analysis description

Fasting Non-HDL Cholesterol

Comparison groups

Group 1: Doravirine/Islatravir (DOR/ISL) v Group 2: Baseline Antiretroviral Therapy (ART)

Number of subjects included in analysis

266

Analysis specification

Pre-specified

Analysis type

other ^[53]

Method

Parameter type

Estimated Difference

Point estimate

-0.49

Confidence interval

level

95%

sides

2-sided

lower limit

-6.81

upper limit

5.83

Notes
[53] - Treatment Difference vs Baseline ART. Type of statistical test 'other' denotes no hypothesis testing was conducted. Group 1: Doravirine/Islatravir (DOR/ISL) n=129; Group 2: Baseline Antiretroviral Therapy (ART) n=136).

Treatment Difference versus Baseline ART

Statistical analysis description

Fasting Triglycerides

Comparison groups

Group 1: Doravirine/Islatravir (DOR/ISL) v Group 2: Baseline Antiretroviral Therapy (ART)

Number of subjects included in analysis

266

Analysis specification

Pre-specified

Analysis type

other ^[54]

Method

Parameter type

Estimated Difference

Point estimate

-5.45

Confidence interval

level

95%

sides

2-sided

lower limit

-20.46

upper limit

9.57

Notes
[54] - Treatment Difference vs Baseline ART. Type of statistical test 'other' denotes no hypothesis testing was conducted. Group 1: Doravirine/Islatravir (DOR/ISL) n=129; Group 2: Baseline Antiretroviral Therapy (ART) n=136).

Treatment Difference vs Baseline ART

Statistical analysis description

Fasting LDL Cholesterol - Multiplicity Adjusted

Comparison groups

Group 1: Doravirine/Islatravir (DOR/ISL) v Group 2: Baseline Antiretroviral Therapy (ART)

Number of subjects included in analysis

266

Analysis specification

Pre-specified

Analysis type

superiority ^[55]

P-value

= 0.4093 ^[56]

Method

ANCOVA

Parameter type

Mean difference (net)

Point estimate

0.64

Confidence interval

level

95%

sides

2-sided

lower limit

-5.63

upper limit

6.9

Notes
[55] - Treatment Difference vs Baseline ART. Superiority will be concluded if the upper bound of the 2-sided multiplicity-adjusted 95% CI is less than 0 percentage points. The multiplicity adjusted 95% CIs for treatment difference were calculated from ANCOVA models with terms for baseline measurement and treatment. Group 1: Doravirine/Islatravir (DOR/ISL) n=129; Group 2: Baseline Antiretroviral Therapy (ART) n=133).
[56] - The significance level in ANCOVA model was 0.02497/2=0.012485. The p-value is statistically significant if it is <0.02497/2=0.012485.

Treatment Difference vs Baseline ART

Statistical analysis description

Fasting Non-HDL Cholesterol - Multiplicity Adjusted

Comparison groups

Group 1: Doravirine/Islatravir (DOR/ISL) v Group 2: Baseline Antiretroviral Therapy (ART)

Number of subjects included in analysis

266

Analysis specification

Pre-specified

Analysis type

superiority ^[57]

P-value

= 0.4397 ^[58]

Method

ANCOVA

Parameter type

Mean difference (net)

Point estimate

-0.49

Confidence interval

level

95%

sides

2-sided

lower limit

-7.72

upper limit

6.75

Notes
[57] - Treatment Difference vs Baseline ART. Superiority will be concluded if the upper bound of the 2-sided multiplicity-adjusted 95% CI is less than 0 percentage points. The multiplicity adjusted 95% CIs for treatment difference were calculated from ANCOVA models with terms for baseline measurement and treatment. Group 1: Doravirine/Islatravir (DOR/ISL) n=129; Group 2: Baseline Antiretroviral Therapy (ART) n=136).
[58] - The significance level in ANCOVA model was 0.02497/2=0.012485. The p-value is statistically significant if it is <0.02497/2=0.012485.

Secondary: Change from baseline to Week 48 in fasting lipids in participants on all other non-PI- and non-InSTI containing regimens

Top of page

End point title

Change from baseline to Week 48 in fasting lipids in participants on all other non-PI- and non-InSTI containing regimens

End point description

Blood serum samples were taken at baseline and Week 48. Per protocol, this outcome analysis was conducted in participants on all other non-PI- and non-InSTI containing regimens, excluding participants who took lipid-lowering therapy during the study. The fasting lipids consisted of fasting cholesterol, fasting HDL cholesterol, fasting LDL cholesterol, fasting non-HDL cholesterol, and fasting triglycerides. The mean change from baseline to Week 48 in fasting lipids is presented. The analysis population consisted of all randomized participants on all other non-PI- and non-InSTI containing regimens, who received at least one dose of study intervention and had baseline and Week 48 data available for each lipid type, excluding participants who took lipid-lowering therapy during the study, per protocol.

End point type

Secondary

End point timeframe

Baseline and Week 48

End point values	Group 1: Doravirine/Islatravir (DOR/ISL)	Group 2: Baseline Antiretroviral Therapy (ART)
Number of subjects analysed	91 ^[59]	95 ^[60]
Units: mg/dL
arithmetic mean (confidence interval 95%)
Fasting Cholesterol (n=91, 95)	5.66 (-1.38 to 12.70)	4.62 (0.10 to 9.15)
Fasting HDL Cholesterol (n=90, 95)	-3.84 (-6.72 to -0.97)	-1.98 (-4.60 to 0.63)
Fasting LDL Cholesterol (n=90, 94)	9.27 (4.05 to 14.49)	7.30 (3.97 to 10.63)
Fasting Non-HDL Cholesterol (n=90, 95)	9.94 (4.16 to 15.73)	6.61 (3.13 to 10.08)
Fasting Triglycerides (n=90, 95)	3.33 (-9.54 to 16.21)	-2.97 (-12.37 to 6.43)

Notes
[59] - Number of subjects analyzed is Group 1 treated participants (non-PI/non-InSTI) with data
[60] - Number of subjects analyzed is Group 2 ART treated participants (non-PI/non-InSTI) with data

Treatment Difference versus Baseline ART

Statistical analysis description

Fasting Cholesterol

Comparison groups

Group 1: Doravirine/Islatravir (DOR/ISL) v Group 2: Baseline Antiretroviral Therapy (ART)

Number of subjects included in analysis

186

Analysis specification

Pre-specified

Analysis type

other ^[61]

Method

Parameter type

Estimated Difference

Point estimate

2.31

Confidence interval

level

95%

sides

2-sided

lower limit

-5.54

upper limit

10.17

Notes
[61] - Treatment Difference vs Baseline ART. Type of statistical test 'other' denotes no hypothesis testing was conducted. Group 1: Doravirine/Islatravir (DOR/ISL) n=91; Group 2: Baseline Antiretroviral Therapy (ART) n=95).

Treatment Difference versus Baseline ART

Statistical analysis description

Fasting Triglycerides

Comparison groups

Group 1: Doravirine/Islatravir (DOR/ISL) v Group 2: Baseline Antiretroviral Therapy (ART)

Number of subjects included in analysis

186

Analysis specification

Pre-specified

Analysis type

other ^[62]

Method

Parameter type

Estimated Difference

Point estimate

10.5

Confidence interval

level

95%

sides

2-sided

lower limit

-3.97

upper limit

24.96

Notes
[62] - Treatment Difference vs Baseline ART. Type of statistical test 'other' denotes no hypothesis testing was conducted. Group 1: Doravirine/Islatravir (DOR/ISL) n=90; Group 2: Baseline Antiretroviral Therapy (ART) n=95).

Treatment Difference versus Baseline ART

Statistical analysis description

Fasting Non-HDL Cholesterol

Comparison groups

Group 1: Doravirine/Islatravir (DOR/ISL) v Group 2: Baseline Antiretroviral Therapy (ART)

Number of subjects included in analysis

186

Analysis specification

Pre-specified

Analysis type

other ^[63]

Method

Parameter type

Estimated Difference

Point estimate

3.97

Confidence interval

level

95%

sides

2-sided

lower limit

-2.63

upper limit

10.56

Notes
[63] - Treatment Difference vs Baseline ART. Type of statistical test 'other' denotes no hypothesis testing was conducted. Group 1: Doravirine/Islatravir (DOR/ISL) n=90; Group 2: Baseline Antiretroviral Therapy (ART) n=95).

Treatment Difference versus Baseline ART

Statistical analysis description

Fasting HDL Cholesterol

Comparison groups

Group 1: Doravirine/Islatravir (DOR/ISL) v Group 2: Baseline Antiretroviral Therapy (ART)

Number of subjects included in analysis

186

Analysis specification

Pre-specified

Analysis type

other ^[64]

Method

Parameter type

Estimated Difference

Point estimate

-2.52

Confidence interval

level

95%

sides

2-sided

lower limit

-5.69

upper limit

0.65

Notes
[64] - Treatment Difference vs Baseline ART. Type of statistical test 'other' denotes no hypothesis testing was conducted. Group 1: Doravirine/Islatravir (DOR/ISL) n=90; Group 2: Baseline Antiretroviral Therapy (ART) n=95).

Treatment Difference versus Baseline ART

Statistical analysis description

Fasting LDL Cholesterol

Comparison groups

Group 1: Doravirine/Islatravir (DOR/ISL) v Group 2: Baseline Antiretroviral Therapy (ART)

Number of subjects included in analysis

186

Analysis specification

Pre-specified

Analysis type

other ^[65]

Method

Parameter type

Estimated Difference

Point estimate

2.34

Confidence interval

level

95%

sides

2-sided

lower limit

-3.73

upper limit

8.42

Notes
[65] - Treatment Difference vs Baseline ART. Type of statistical test 'other' denotes no hypothesis testing was conducted. Group 1: Doravirine/Islatravir (DOR/ISL) n=90; Group 2: Baseline Antiretroviral Therapy (ART) n=94).

Secondary: Group 1: Percentage of Participants Who Discontinued Study Intervention Due to an AE up to Week 96

Top of page

End point title

Group 1: Percentage of Participants Who Discontinued Study Intervention Due to an AE up to Week 96

End point description

An AE was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The percentage of participants who discontinued study intervention due to an AE up to Week 96 is reported for Group 1 participants. The analysis population consisted of all randomized participants in Group 1 who received at least one dose of study intervention. Per protocol, the percentage of participants who discontinued study intervention for Group 2 participants is a separate outcome measure and is presented later in the record.

End point type

Secondary

End point timeframe

Up to ~96 Weeks

End point values	Group 1: Doravirine/Islatravir (DOR/ISL)	Group 2: Baseline Antiretroviral Therapy (ART)
Number of subjects analysed	336	0 ^[66]
Units: Percentage of Participants
number (not applicable)	5.7

Notes
[66] - Per protocol, this endpoint is for Group 1 only. Group 2 is presented in a separate endpoint.

No statistical analyses for this end point

Secondary: Group 1: Percentage of Participants With One or More AEs up to Week 96

Top of page

End point title

Group 1: Percentage of Participants With One or More AEs up to Week 96

End point description

An AE was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The percentage of participants who experienced at least one AE up to Week 96 is reported for Group 1 participants. The analysis population consisted of all randomized participants in Group 1 who received at least one dose of study intervention. Per protocol, the percentage of participants with one or more AEs for Group 2 participants is a separate outcome measure and is presented later in the record.

End point type

Secondary

End point timeframe

Up to ~96 Weeks

End point values	Group 1: Doravirine/Islatravir (DOR/ISL)	Group 2: Baseline Antiretroviral Therapy (ART)
Number of subjects analysed	336	0 ^[67]
Units: Percentage of Participants
number (not applicable)	92.3

Notes
[67] - Per protocol, this endpoint is for Group 1 only. Group 2 is presented in a separate endpoint.

No statistical analyses for this end point

Secondary: Change from baseline in body weight at Week 48 for InSTI-based regimens (non-PI-containing regimens)

Top of page

End point title

Change from baseline in body weight at Week 48 for InSTI-based regimens (non-PI-containing regimens)

End point description

Baseline measurements were defined as the Day 1 value of each participant. The change from baseline in body weight to Week 48 is presented for participants who received InSTI- based regimens. The analysis population consisted of all randomized participants who received at least one dose of study intervention, had baseline and Week 48 data available for body weight, and received InSTI-based regimens.

End point type

Secondary

End point timeframe

Baseline and Week 48

End point values	Group 1: Doravirine/Islatravir (DOR/ISL)	Group 2: Baseline Antiretroviral Therapy (ART)
Number of subjects analysed	167 ^[68]	169 ^[69]
Units: kg
arithmetic mean (confidence interval 95%)	0.66 (-0.17 to 1.48)	0.10 (-0.56 to 0.75)

Notes
[68] - Number of subjects analyzed is Group 1 treated participants (InSTI) with data available
[69] - Number of subjects analyzed is Group 2 ART treated participants (InSTI) with data available

Treatment Difference versus Baseline ART

Comparison groups

Group 1: Doravirine/Islatravir (DOR/ISL) v Group 2: Baseline Antiretroviral Therapy (ART)

Number of subjects included in analysis

336

Analysis specification

Pre-specified

Analysis type

other ^[70]

Method

Parameter type

Estimated Difference

Point estimate

0.44

Confidence interval

level

95%

sides

2-sided

lower limit

-0.59

upper limit

1.46

Notes
[70] - Treatment Difference vs Baseline ART. Type of statistical test 'other' denotes no hypothesis testing was conducted.

Secondary: Group 1 & Group 2 (Switch-Over): Percentage of Participants who discontinued study intervention due to an AE from Week 48 to Week 96

Top of page

End point title

Group 1 & Group 2 (Switch-Over): Percentage of Participants who discontinued study intervention due to an AE from Week 48 to Week 96

End point description

An AE was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The percentage of participants who discontinued study intervention due to an AE from Week 48 up to Week 96 is reported for Group 1 participants and Group 2 participants who delayed switch over from baseline ART to DOR/ISL from Week 48 to Week 96. The analysis population consisted of all randomized participants who received at least one dose of study intervention for participants in Group 1 and participants in Group 2 who delayed switch over from baseline ART to DOR/ISL from Week 48 to Week 96.

End point type

Secondary

End point timeframe

Weeks 48-96 (up to ~48 weeks)

End point values	Group 1: Doravirine/Islatravir (DOR/ISL)	Group 2: Baseline Antiretroviral Therapy (ART)
Number of subjects analysed	322 ^[71]	326 ^[72]
Units: Percentage of Participants
number (not applicable)	3.7	2.5

Notes
[71] - Number of Subjects Analyzed is Group 1 participants who received DOR/ISL from 48-96 Weeks
[72] - Number of Subjects Analyzed is Group 2 participants who delayed switch over to DOR/ISL Weeks 48-96

No statistical analyses for this end point

Secondary: Group 1 & Group 2 (Switch-Over): Percentage of Participants With One or More AEs From Week 48 to Week 96

Top of page

End point title

Group 1 & Group 2 (Switch-Over): Percentage of Participants With One or More AEs From Week 48 to Week 96

End point description

An AE was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The percentage of participants who experienced at least one AE from Week 48 up to Week 96 is reported for Group 1 participants and Group 2 participants who delayed switch over from baseline ART to DOR/ISL from Week 48 to Week 96. The analysis population consisted of all randomized participants who received at least one dose of study intervention for participants in Group 1 and participants in Group 2 who delayed switch over from baseline ART to DOR/ISL from Week 48 to Week 96.

End point type

Secondary

End point timeframe

Weeks 48-96 (up to ~48 weeks)

End point values	Group 1: Doravirine/Islatravir (DOR/ISL)	Group 2: Baseline Antiretroviral Therapy (ART)
Number of subjects analysed	322 ^[73]	326 ^[74]
Units: Percentage of Participants
number (not applicable)	73.0	76.4

Notes
[73] - Number of Subjects Analyzed is Group 1 participants who received DOR/ISL from 48-96 Weeks
[74] - Number of Subjects Analyzed is Group 2 participants who delayed switch over to DOR/ISL Weeks 48-96

No statistical analyses for this end point

Adverse events

Top of page

Timeframe for reporting adverse events

Up to approximately 49 months

Adverse event reporting additional description

All cause mortality (ACM): all randomized participants; AEs: all randomized participants who got ≥1 dose of study drug. Reported separately by Weeks 0-48 & 48-End of Trial. Per protocol, pregnancy related AEs & infant serious AEs collected for enrolled pregnant participants; included by participant arm. 1 infant AE death; & not reported for privacy

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

27.0

Reporting group title

Group 1: DOR/ISL Weeks 0-48

Reporting group description

Reporting group title

Group 2: DOR/ISL Weeks 48-End of Trial

Reporting group description

Reporting group title

Group 2: Baseline ART Weeks 0-48

Reporting group description

Reporting group title

Group 1: DOR/ISL Weeks 48-End of Trial

Reporting group description

Serious adverse events	Group 1: DOR/ISL Weeks 0-48	Group 2: DOR/ISL Weeks 48-End of Trial	Group 2: Baseline ART Weeks 0-48	Group 1: DOR/ISL Weeks 48-End of Trial
Total subjects affected by serious adverse events
subjects affected / exposed	16 / 336 (4.76%)	12 / 326 (3.68%)	15 / 336 (4.46%)	13 / 322 (4.04%)
number of deaths (all causes)	0	0	1	1
number of deaths resulting from adverse events	0	0	1	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Hodgkin's disease
subjects affected / exposed	1 / 336 (0.30%)	0 / 326 (0.00%)	0 / 336 (0.00%)	0 / 322 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pancreatic carcinoma
subjects affected / exposed	0 / 336 (0.00%)	0 / 326 (0.00%)	0 / 336 (0.00%)	1 / 322 (0.31%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
Renal cancer
subjects affected / exposed	0 / 336 (0.00%)	1 / 326 (0.31%)	0 / 336 (0.00%)	0 / 322 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Basal cell carcinoma
subjects affected / exposed	0 / 336 (0.00%)	1 / 326 (0.31%)	0 / 336 (0.00%)	0 / 322 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Vascular disorders
Deep vein thrombosis
subjects affected / exposed	1 / 336 (0.30%)	0 / 326 (0.00%)	0 / 336 (0.00%)	0 / 322 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pregnancy, puerperium and perinatal conditions
Premature delivery
subjects affected / exposed	0 / 336 (0.00%)	0 / 326 (0.00%)	0 / 336 (0.00%)	1 / 322 (0.31%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Abortion spontaneous
subjects affected / exposed	0 / 336 (0.00%)	0 / 326 (0.00%)	0 / 336 (0.00%)	1 / 322 (0.31%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Premature baby
subjects affected / exposed	0 / 336 (0.00%)	0 / 326 (0.00%)	0 / 336 (0.00%)	1 / 322 (0.31%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
General disorders and administration site conditions
Non-cardiac chest pain
subjects affected / exposed	0 / 336 (0.00%)	0 / 326 (0.00%)	1 / 336 (0.30%)	0 / 322 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Immune system disorders
Hypersensitivity
subjects affected / exposed	1 / 336 (0.30%)	0 / 326 (0.00%)	0 / 336 (0.00%)	0 / 322 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Lung disorder
subjects affected / exposed	0 / 336 (0.00%)	0 / 326 (0.00%)	1 / 336 (0.30%)	0 / 322 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pulmonary embolism
subjects affected / exposed	1 / 336 (0.30%)	0 / 326 (0.00%)	0 / 336 (0.00%)	0 / 322 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Asthma
subjects affected / exposed	1 / 336 (0.30%)	0 / 326 (0.00%)	0 / 336 (0.00%)	1 / 322 (0.31%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Psychiatric disorders
Paranoia
subjects affected / exposed	1 / 336 (0.30%)	0 / 326 (0.00%)	0 / 336 (0.00%)	0 / 322 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Major depression
subjects affected / exposed	0 / 336 (0.00%)	1 / 326 (0.31%)	0 / 336 (0.00%)	0 / 322 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Investigations
Troponin increased
subjects affected / exposed	0 / 336 (0.00%)	0 / 326 (0.00%)	0 / 336 (0.00%)	1 / 322 (0.31%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Lipase increased
subjects affected / exposed	0 / 336 (0.00%)	1 / 326 (0.31%)	0 / 336 (0.00%)	0 / 322 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Injury, poisoning and procedural complications
Hand fracture
subjects affected / exposed	1 / 336 (0.30%)	0 / 326 (0.00%)	0 / 336 (0.00%)	0 / 322 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Ligament rupture
subjects affected / exposed	0 / 336 (0.00%)	0 / 326 (0.00%)	0 / 336 (0.00%)	1 / 322 (0.31%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Animal bite
subjects affected / exposed	0 / 336 (0.00%)	0 / 326 (0.00%)	1 / 336 (0.30%)	0 / 322 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Foot fracture
subjects affected / exposed	1 / 336 (0.30%)	0 / 326 (0.00%)	0 / 336 (0.00%)	0 / 322 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Post procedural haematoma
subjects affected / exposed	0 / 336 (0.00%)	1 / 326 (0.31%)	0 / 336 (0.00%)	0 / 322 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Tibia fracture
subjects affected / exposed	0 / 336 (0.00%)	0 / 326 (0.00%)	1 / 336 (0.30%)	0 / 322 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Road traffic accident
subjects affected / exposed	0 / 336 (0.00%)	0 / 326 (0.00%)	1 / 336 (0.30%)	0 / 322 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
Cardiac disorders
Supraventricular tachycardia
subjects affected / exposed	0 / 336 (0.00%)	0 / 326 (0.00%)	1 / 336 (0.30%)	0 / 322 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Extrasystoles
subjects affected / exposed	0 / 336 (0.00%)	1 / 326 (0.31%)	0 / 336 (0.00%)	0 / 322 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Nervous system disorders
Epilepsy
subjects affected / exposed	0 / 336 (0.00%)	1 / 326 (0.31%)	0 / 336 (0.00%)	0 / 322 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Encephalopathy neonatal
subjects affected / exposed	0 / 336 (0.00%)	1 / 326 (0.31%)	0 / 336 (0.00%)	0 / 322 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Neuralgic amyotrophy
subjects affected / exposed	0 / 336 (0.00%)	0 / 326 (0.00%)	1 / 336 (0.30%)	0 / 322 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Transient ischaemic attack
subjects affected / exposed	0 / 336 (0.00%)	1 / 326 (0.31%)	0 / 336 (0.00%)	0 / 322 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
VIth nerve paralysis
subjects affected / exposed	0 / 336 (0.00%)	0 / 326 (0.00%)	0 / 336 (0.00%)	1 / 322 (0.31%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Blood and lymphatic system disorders
Lymphadenopathy
subjects affected / exposed	0 / 336 (0.00%)	0 / 326 (0.00%)	1 / 336 (0.30%)	0 / 322 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Lymphadenitis
subjects affected / exposed	0 / 336 (0.00%)	0 / 326 (0.00%)	1 / 336 (0.30%)	0 / 322 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Duodenal perforation
subjects affected / exposed	1 / 336 (0.30%)	0 / 326 (0.00%)	0 / 336 (0.00%)	0 / 322 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Enterocolitis
subjects affected / exposed	0 / 336 (0.00%)	0 / 326 (0.00%)	1 / 336 (0.30%)	0 / 322 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Gastric ulcer
subjects affected / exposed	0 / 336 (0.00%)	1 / 326 (0.31%)	0 / 336 (0.00%)	0 / 322 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Inguinal hernia
subjects affected / exposed	0 / 336 (0.00%)	0 / 326 (0.00%)	1 / 336 (0.30%)	0 / 322 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Renal and urinary disorders
Calculus urinary
subjects affected / exposed	0 / 336 (0.00%)	0 / 326 (0.00%)	1 / 336 (0.30%)	0 / 322 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Renal colic
subjects affected / exposed	0 / 336 (0.00%)	0 / 326 (0.00%)	0 / 336 (0.00%)	1 / 322 (0.31%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Arthritis
subjects affected / exposed	0 / 336 (0.00%)	0 / 326 (0.00%)	0 / 336 (0.00%)	1 / 322 (0.31%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cervical spinal stenosis
subjects affected / exposed	0 / 336 (0.00%)	0 / 326 (0.00%)	0 / 336 (0.00%)	1 / 322 (0.31%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Intervertebral disc protrusion
subjects affected / exposed	1 / 336 (0.30%)	0 / 326 (0.00%)	0 / 336 (0.00%)	1 / 322 (0.31%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Osteoarthritis
subjects affected / exposed	3 / 336 (0.89%)	0 / 326 (0.00%)	0 / 336 (0.00%)	0 / 322 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
COVID-19 pneumonia
subjects affected / exposed	1 / 336 (0.30%)	0 / 326 (0.00%)	0 / 336 (0.00%)	0 / 322 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
COVID-19
subjects affected / exposed	0 / 336 (0.00%)	0 / 326 (0.00%)	1 / 336 (0.30%)	0 / 322 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Appendicitis
subjects affected / exposed	1 / 336 (0.30%)	0 / 326 (0.00%)	1 / 336 (0.30%)	1 / 322 (0.31%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Anal abscess
subjects affected / exposed	0 / 336 (0.00%)	1 / 326 (0.31%)	0 / 336 (0.00%)	0 / 322 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Chronic tonsillitis
subjects affected / exposed	0 / 336 (0.00%)	1 / 326 (0.31%)	1 / 336 (0.30%)	0 / 322 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Plasmodium falciparum infection
subjects affected / exposed	0 / 336 (0.00%)	1 / 326 (0.31%)	0 / 336 (0.00%)	0 / 322 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Peritoneal abscess
subjects affected / exposed	0 / 336 (0.00%)	0 / 326 (0.00%)	1 / 336 (0.30%)	0 / 322 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Omphalitis
subjects affected / exposed	1 / 336 (0.30%)	0 / 326 (0.00%)	0 / 336 (0.00%)	0 / 322 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Malaria
subjects affected / exposed	0 / 336 (0.00%)	0 / 326 (0.00%)	0 / 336 (0.00%)	1 / 322 (0.31%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Infectious pleural effusion
subjects affected / exposed	0 / 336 (0.00%)	1 / 326 (0.31%)	0 / 336 (0.00%)	0 / 322 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia bacterial
subjects affected / exposed	0 / 336 (0.00%)	1 / 326 (0.31%)	0 / 336 (0.00%)	0 / 322 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pyelonephritis acute
subjects affected / exposed	1 / 336 (0.30%)	0 / 326 (0.00%)	0 / 336 (0.00%)	0 / 322 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Staphylococcal bacteraemia
subjects affected / exposed	0 / 336 (0.00%)	1 / 326 (0.31%)	0 / 336 (0.00%)	0 / 322 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Urinary tract infection
subjects affected / exposed	0 / 336 (0.00%)	0 / 326 (0.00%)	1 / 336 (0.30%)	0 / 322 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Tonsillitis
subjects affected / exposed	1 / 336 (0.30%)	0 / 326 (0.00%)	0 / 336 (0.00%)	0 / 322 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Metabolism and nutrition disorders
Hypoglycaemia
subjects affected / exposed	0 / 336 (0.00%)	0 / 326 (0.00%)	1 / 336 (0.30%)	0 / 322 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	Group 1: DOR/ISL Weeks 0-48	Group 2: DOR/ISL Weeks 48-End of Trial	Group 2: Baseline ART Weeks 0-48	Group 1: DOR/ISL Weeks 48-End of Trial
Total subjects affected by non serious adverse events
subjects affected / exposed	85 / 336 (25.30%)	120 / 326 (36.81%)	52 / 336 (15.48%)	115 / 322 (35.71%)
Investigations
Lymphocyte count decreased
subjects affected / exposed	0 / 336 (0.00%)	44 / 326 (13.50%)	0 / 336 (0.00%)	65 / 322 (20.19%)
occurrences all number	0	46	0	70
CD4 lymphocytes decreased
subjects affected / exposed	2 / 336 (0.60%)	39 / 326 (11.96%)	0 / 336 (0.00%)	45 / 322 (13.98%)
occurrences all number	2	41	0	47
Injury, poisoning and procedural complications
Accidental overdose
subjects affected / exposed	24 / 336 (7.14%)	8 / 326 (2.45%)	3 / 336 (0.89%)	4 / 322 (1.24%)
occurrences all number	28	12	4	4
Nervous system disorders
Headache
subjects affected / exposed	36 / 336 (10.71%)	14 / 326 (4.29%)	16 / 336 (4.76%)	12 / 322 (3.73%)
occurrences all number	41	14	17	14
Musculoskeletal and connective tissue disorders
Osteopenia
subjects affected / exposed	10 / 336 (2.98%)	7 / 326 (2.15%)	19 / 336 (5.65%)	2 / 322 (0.62%)
occurrences all number	10	7	19	2
Infections and infestations
COVID-19
subjects affected / exposed	18 / 336 (5.36%)	57 / 326 (17.48%)	15 / 336 (4.46%)	42 / 322 (13.04%)
occurrences all number	19	60	16	42

More information

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Were there any global substantial amendments to the protocol? Yes

16 Jun 2020

Amendment 02: The protocol was amended to: (1) allow participants to rescreen one time following approval from the Sponsor, and (2) add a scheduled study visit at Week 52 so that participants in Group 2 can be monitored 4 weeks after switching to DOR/ISL.

15 Jan 2021

Amendment 03: The main reasons the protocol was amended were to: (1) permit continued administration of study intervention in participants who become pregnant (where allowed by local regulations and as appropriate based on available data/local standard of-care guidelines), (2) add a discontinuation criterion if a participant chooses to breastfeed, and (3) update dose modification instructions.

12 May 2021

Amendment 04: Additional pharmacokinetics (PK) sampling and increased safety monitoring for participants who become pregnant and continue study intervention. Increased safety data collection for infants born to participants who become pregnant.

26 Jan 2022

Amendment 05: To increase frequency of monitoring of CD4+ T-cell counts and lymphocyte counts, and to add discontinuation criteria in response to findings of decreases in CD4+ T-cell counts (in studies of participants with HIV) and lymphocytes (in studies of participants with or without HIV) in ISL clinical studies. Note: The changes made in Amendment 05 were not implemented at clinical sites. Amendment 06 supersedes Amendment 05.

16 Feb 2022

Amendment 06: Given the findings of decreases in CD4+ T-cell and total lymphocyte counts in clinical studies evaluating ISL, the protocol is being amended to increase the frequency of monitoring of CD4+ T-cell and total lymphocyte counts and to specify the management of participants who meet protocol-defined decreases in CD4+ T-cell and/or total lymphocyte counts.

08 Dec 2022

Amendment 08: Merck Sharp & Dohme Corp. underwent an entity name and address change to Merck Sharp & Dohme LLC, Rahway, NJ, USA. This conversion resulted only in an entity name change and update to the address.

24 Apr 2024

Amendment 09: The protocol was amended to revise the post-treatment management of participants with specific decreases in CD4+ T-cell or total lymphocyte counts. The recovery criteria were revised to account for normal physiologic variability in CD4+ T-cell or total lymphocyte counts and the frequency of monitoring was updated to minimize the burden on study participants.

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

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Clinical trials

Clinical Trial Results: A Phase 3 Randomized, Active-Controlled, Open-Label Clinical Study to Evaluate a Switch to Doravirine/Islatravir (DOR/ISL) Once-Daily in Participants With HIV-1 Virologically Suppressed on Antiretroviral Therapy

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Percentage of Participants with Human Immunodeficiency Virus (HIV)-1 Ribonucleic Acid (RNA) ≥50 copies/mL at Week 48

Primary: Percentage of Participants with Human Immunodeficiency Virus (HIV)-1 Ribonucleic Acid (RNA) ≥50 copies/mL at Week 48

Primary: Percentage of Participants with one or more adverse events (AEs) up to Week 48

Primary: Percentage of Participants with one or more adverse events (AEs) up to Week 48

Primary: Percentage of Participants who discontinued study intervention due to an AE up to Week 48

Primary: Percentage of Participants who discontinued study intervention due to an AE up to Week 48

Secondary: Percentage of Participants with HIV-1 RNA <40 or <50 copies/mL at Week 48

Secondary: Percentage of Participants with HIV-1 RNA <40 or <50 copies/mL at Week 48

Secondary: Group 2 (Switch-Over): Percentage of Participants With HIV-1 RNA ≥50 Copies/mL, <40 Copies/mL or <50 Copies/mL at Week 96

Secondary: Group 2 (Switch-Over): Percentage of Participants With HIV-1 RNA ≥50 Copies/mL, <40 Copies/mL or <50 Copies/mL at Week 96

Secondary: Percentage change from baseline in CD4+ T-cell count at Week 48

Secondary: Percentage change from baseline in CD4+ T-cell count at Week 48

Secondary: Group 1: Percentage of Participants with HIV-1 RNA ≥50 copies/mL, <40 copies/mL or <50 copies/mL at Week 96

Secondary: Group 1: Percentage of Participants with HIV-1 RNA ≥50 copies/mL, <40 copies/mL or <50 copies/mL at Week 96

Secondary: Percentage of Participants with evidence of viral drug resistance-associated substitutions at Week 96

Secondary: Percentage of Participants with evidence of viral drug resistance-associated substitutions at Week 96

Secondary: Percentage of Participants with evidence of viral drug resistance-associated substitutions at Week 48

Secondary: Percentage of Participants with evidence of viral drug resistance-associated substitutions at Week 48

Secondary: Group 1 & Group 2 (Switch-Over): Percentage Change From Week 48 in CD4+ T-cell Count at Week 96

Secondary: Group 1 & Group 2 (Switch-Over): Percentage Change From Week 48 in CD4+ T-cell Count at Week 96

Secondary: Group 1: Percentage Change From Baseline in CD4+ T-cell Count at Week 96

Secondary: Group 1: Percentage Change From Baseline in CD4+ T-cell Count at Week 96

Secondary: Change from baseline to Week 24 in fasting lipids in participants on protease inhibitor (PI)-containing regimens (including PI- and integrase strand transferase inhibitor [InSTI]-containing regimens)

Secondary: Change from baseline to Week 24 in fasting lipids in participants on protease inhibitor (PI)-containing regimens (including PI- and integrase strand transferase inhibitor [InSTI]-containing regimens)

Secondary: Change from baseline to Week 24 in fasting lipids in participants on InSTI-based regimens (non-PI containing regimens)

Secondary: Change from baseline to Week 24 in fasting lipids in participants on InSTI-based regimens (non-PI containing regimens)

Secondary: Change from baseline to Week 24 in fasting lipids in participants on all other non-PI- and non-InSTI containing regimens

Secondary: Change from baseline to Week 24 in fasting lipids in participants on all other non-PI- and non-InSTI containing regimens

Secondary: Change from baseline to Week 48 in fasting lipids in participants on protease inhibitor (PI)-containing regimens (including PI- and integrase strand transferase inhibitor [InSTI]-containing regimens)

Secondary: Change from baseline to Week 48 in fasting lipids in participants on protease inhibitor (PI)-containing regimens (including PI- and integrase strand transferase inhibitor [InSTI]-containing regimens)

Secondary: Change from baseline to Week 48 in fasting lipids in participants on InSTI-based regimens (non-PI containing regimens)

Secondary: Change from baseline to Week 48 in fasting lipids in participants on InSTI-based regimens (non-PI containing regimens)

Secondary: Change from baseline to Week 48 in fasting lipids in participants on all other non-PI- and non-InSTI containing regimens

Secondary: Change from baseline to Week 48 in fasting lipids in participants on all other non-PI- and non-InSTI containing regimens

Secondary: Group 1: Percentage of Participants Who Discontinued Study Intervention Due to an AE up to Week 96

Secondary: Group 1: Percentage of Participants Who Discontinued Study Intervention Due to an AE up to Week 96

Secondary: Group 1: Percentage of Participants With One or More AEs up to Week 96

Secondary: Group 1: Percentage of Participants With One or More AEs up to Week 96

Secondary: Change from baseline in body weight at Week 48 for InSTI-based regimens (non-PI-containing regimens)

Secondary: Change from baseline in body weight at Week 48 for InSTI-based regimens (non-PI-containing regimens)

Secondary: Group 1 & Group 2 (Switch-Over): Percentage of Participants who discontinued study intervention due to an AE from Week 48 to Week 96

Secondary: Group 1 & Group 2 (Switch-Over): Percentage of Participants who discontinued study intervention due to an AE from Week 48 to Week 96

Secondary: Group 1 & Group 2 (Switch-Over): Percentage of Participants With One or More AEs From Week 48 to Week 96

Secondary: Group 1 & Group 2 (Switch-Over): Percentage of Participants With One or More AEs From Week 48 to Week 96

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
A Phase 3 Randomized, Active-Controlled, Open-Label Clinical Study to Evaluate a Switch to Doravirine/Islatravir (DOR/ISL) Once-Daily in Participants With HIV-1 Virologically Suppressed on Antiretroviral Therapy