Trial Outcomes & Findings for A Switch to Doravirine/Islatravir (DOR/ISL) in Participants With Human Immunodeficiency Virus Type 1 (HIV-1) Who Are Virologically Suppressed on Antiretroviral Therapy (ART) (MK-8591A-051) (NCT NCT05631093)

Last Updated: 2025-11-21

Results Overview

HIV-1 RNA levels in plasma were measured by polymerase chain reaction (PCR) assay with a reliable lower limit of quantification of \<50 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.

Recruitment status

ACTIVE_NOT_RECRUITING

Study phase

PHASE3

Target enrollment

553 participants

Primary outcome timeframe

Week 48

Results posted on

2025-11-21

Participant Flow

Adults living with human immunodeficiency virus-1 (HIV-1) receiving baseline antiretroviral therapy (ART) were enrolled.

Of the 553 participants randomly assigned in a 2:1 ratio to either Group 1: participants switched from baseline ART to doravirine (DOR)/islatravir (ISL) on Day 1 to Week 144; or Group 2: participants continued baseline ART until Week 48 then switch to DOR/ISL from Week 48 to Week 144, 551 participants received treatment.

Participant milestones

Participant milestones
Measure	Doravirine/Islatravir (DOR/ISL) Participants with Human Immunodeficiency Virus-1 (HIV-1) that have been virologically suppressed for ≥3 consecutive months who were previously treated with continuous baseline antiretroviral therapy (ART) received doravine/islatravir (DOR/ISL), a fixed dose combination (FDC) of 100 mg DOR/0.25 mg ISL orally once daily (qd) for 144 weeks. At Week 144, participants who consent to enter the optional study extension will continue to receive DOR/ISL qd (100 mg/0.25 mg) for an additional 96 weeks or until it is commercially accessible (whichever comes first).	Baseline ART + DOR/ISL Participants with HIV-1 that has been virologically suppressed for ≥3 consecutive months who were previously treated with continuous baseline ART received standard of care (SOC) ART for 48 weeks, followed by treatment with DOR/ISL as a FDC of 100 mg DOR/0.25 mg ISL orally qd until Week 144. At Week 144, participants who consent to enter the optional study extension will continue to receive DOR/ISL qd (100 mg/0.25 mg) for an additional 96 weeks or until it is commercially accessible (whichever comes first).
Overall Study STARTED	368	185
Overall Study Treated	366	185
Overall Study COMPLETED	9	3
Overall Study NOT COMPLETED	359	182

Reasons for withdrawal

Reasons for withdrawal
Measure	Doravirine/Islatravir (DOR/ISL) Participants with Human Immunodeficiency Virus-1 (HIV-1) that have been virologically suppressed for ≥3 consecutive months who were previously treated with continuous baseline antiretroviral therapy (ART) received doravine/islatravir (DOR/ISL), a fixed dose combination (FDC) of 100 mg DOR/0.25 mg ISL orally once daily (qd) for 144 weeks. At Week 144, participants who consent to enter the optional study extension will continue to receive DOR/ISL qd (100 mg/0.25 mg) for an additional 96 weeks or until it is commercially accessible (whichever comes first).	Baseline ART + DOR/ISL Participants with HIV-1 that has been virologically suppressed for ≥3 consecutive months who were previously treated with continuous baseline ART received standard of care (SOC) ART for 48 weeks, followed by treatment with DOR/ISL as a FDC of 100 mg DOR/0.25 mg ISL orally qd until Week 144. At Week 144, participants who consent to enter the optional study extension will continue to receive DOR/ISL qd (100 mg/0.25 mg) for an additional 96 weeks or until it is commercially accessible (whichever comes first).
Overall Study Death	0	1
Overall Study Lost to Follow-up	1	2
Overall Study Physician Decision	1	0
Overall Study Withdrawal by Subject	4	1
Overall Study Ongoing	353	177
Overall Study Adverse Event	0	1

Baseline Characteristics

All randomized participants who received study intervention.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Doravirine/Islatravir (DOR/ISL) n=368 Participants Participants with Human Immunodeficiency Virus-1 (HIV-1) that have been virologically suppressed for ≥3 consecutive months who were previously treated with continuous baseline antiretroviral therapy (ART) received doravine/islatravir (DOR/ISL), a fixed dose combination (FDC) of 100 mg DOR/0.25 mg ISL orally once daily (qd) for 144 weeks. At Week 144, participants who consent to enter the optional study extension will continue to receive DOR/ISL qd (100 mg/0.25 mg) for an additional 96 weeks or until it is commercially accessible (whichever comes first).	Baseline ART + DOR/ISL n=185 Participants Participants with HIV-1 that has been virologically suppressed for ≥3 consecutive months who were previously treated with continuous baseline ART received standard of care (SOC) ART for 48 weeks, followed by treatment with DOR/ISL as a FDC of 100 mg DOR/0.25 mg ISL orally qd until Week 144. At Week 144, participants who consent to enter the optional study extension will continue to receive DOR/ISL qd (100 mg/0.25 mg) for an additional 96 weeks or until it is commercially accessible (whichever comes first).	Total n=553 Participants Total of all reporting groups
Age, Continuous	49.9 Years STANDARD_DEVIATION 12.6 • n=368 Participants	49.5 Years STANDARD_DEVIATION 11.8 • n=185 Participants	49.8 Years STANDARD_DEVIATION 12.3 • n=553 Participants
Sex: Female, Male Female	152 Participants n=368 Participants	67 Participants n=185 Participants	219 Participants n=553 Participants
Sex: Female, Male Male	216 Participants n=368 Participants	118 Participants n=185 Participants	334 Participants n=553 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	54 Participants n=368 Participants	26 Participants n=185 Participants	80 Participants n=553 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	310 Participants n=368 Participants	157 Participants n=185 Participants	467 Participants n=553 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	4 Participants n=368 Participants	2 Participants n=185 Participants	6 Participants n=553 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=368 Participants	0 Participants n=185 Participants	1 Participants n=553 Participants
Race (NIH/OMB) Asian	18 Participants n=368 Participants	10 Participants n=185 Participants	28 Participants n=553 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=368 Participants	1 Participants n=185 Participants	2 Participants n=553 Participants
Race (NIH/OMB) Black or African American	166 Participants n=368 Participants	84 Participants n=185 Participants	250 Participants n=553 Participants
Race (NIH/OMB) White	143 Participants n=368 Participants	74 Participants n=185 Participants	217 Participants n=553 Participants
Race (NIH/OMB) More than one race	38 Participants n=368 Participants	16 Participants n=185 Participants	54 Participants n=553 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=368 Participants	0 Participants n=185 Participants	1 Participants n=553 Participants
Baseline Antiretroviral (ART) Stratification at Randomization PI-containing regimens (including PI- and InSTI-containing regimens)	22 Count of Participants n=366 Participants • All randomized participants who received study intervention.	8 Count of Participants n=185 Participants • All randomized participants who received study intervention.	30 Count of Participants n=551 Participants • All randomized participants who received study intervention.
Baseline Antiretroviral (ART) Stratification at Randomization InSTI-based regimens (non-PI containing regimens)	233 Count of Participants n=366 Participants • All randomized participants who received study intervention.	121 Count of Participants n=185 Participants • All randomized participants who received study intervention.	354 Count of Participants n=551 Participants • All randomized participants who received study intervention.
Baseline Antiretroviral (ART) Stratification at Randomization All other non-PI- and non-InSTI containing regimens	111 Count of Participants n=366 Participants • All randomized participants who received study intervention.	56 Count of Participants n=185 Participants • All randomized participants who received study intervention.	167 Count of Participants n=551 Participants • All randomized participants who received study intervention.

PRIMARY outcome

Timeframe: Week 48

Population: All randomized participants who received at least one dose of study intervention and had data for analysis.

Outcome measures

Outcome measures
Measure	Doravirine/Islatravir (DOR/ISL) n=366 Participants Participants with Human Immunodeficiency Virus-1 (HIV-1) that have been virologically suppressed for ≥3 consecutive months who were previously treated with continuous baseline antiretroviral therapy (ART) received doravine/islatravir (DOR/ISL), a fixed dose combination (FDC) of 100 mg DOR/0.25 mg ISL orally once daily (qd) for 144 weeks. At Week 144, participants who consent to enter the optional study extension will continue to receive DOR/ISL qd (100 mg/0.25 mg) for an additional 96 weeks or until it is commercially accessible (whichever comes first).	Baseline ART + DOR/ISL n=185 Participants Participants with HIV-1 that has been virologically suppressed for ≥3 consecutive months who were previously treated with continuous baseline ART received standard of care (SOC) ART for 48 weeks, followed by treatment with DOR/ISL as a FDC of 100 mg DOR/0.25 mg ISL orally qd until Week 144. At Week 144, participants who consent to enter the optional study extension will continue to receive DOR/ISL qd (100 mg/0.25 mg) for an additional 96 weeks or until it is commercially accessible (whichever comes first).
Percentage of Participants With HIV-1 RNA ≥50 Copies/mL at Week 48	1.4 Percentage of Participants	4.9 Percentage of Participants

PRIMARY outcome

Timeframe: Up to Week 48

Population: All randomized participants who received at least one dose of study intervention.

An AE is 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 Day 1 up to Week 48 are reported.

Outcome measures

Outcome measures
Measure	Doravirine/Islatravir (DOR/ISL) n=366 Participants Participants with Human Immunodeficiency Virus-1 (HIV-1) that have been virologically suppressed for ≥3 consecutive months who were previously treated with continuous baseline antiretroviral therapy (ART) received doravine/islatravir (DOR/ISL), a fixed dose combination (FDC) of 100 mg DOR/0.25 mg ISL orally once daily (qd) for 144 weeks. At Week 144, participants who consent to enter the optional study extension will continue to receive DOR/ISL qd (100 mg/0.25 mg) for an additional 96 weeks or until it is commercially accessible (whichever comes first).	Baseline ART + DOR/ISL n=185 Participants Participants with HIV-1 that has been virologically suppressed for ≥3 consecutive months who were previously treated with continuous baseline ART received standard of care (SOC) ART for 48 weeks, followed by treatment with DOR/ISL as a FDC of 100 mg DOR/0.25 mg ISL orally qd until Week 144. At Week 144, participants who consent to enter the optional study extension will continue to receive DOR/ISL qd (100 mg/0.25 mg) for an additional 96 weeks or until it is commercially accessible (whichever comes first).
Percentage of Participants With One or More Adverse Events (AEs) at Week 48	79.5 Percentage of Participants	83.8 Percentage of Participants

PRIMARY outcome

Timeframe: Up to Week 48

Population: All randomized participants who received at least one dose of study intervention.

Outcome measures

Outcome measures
Measure	Doravirine/Islatravir (DOR/ISL) n=366 Participants Participants with Human Immunodeficiency Virus-1 (HIV-1) that have been virologically suppressed for ≥3 consecutive months who were previously treated with continuous baseline antiretroviral therapy (ART) received doravine/islatravir (DOR/ISL), a fixed dose combination (FDC) of 100 mg DOR/0.25 mg ISL orally once daily (qd) for 144 weeks. At Week 144, participants who consent to enter the optional study extension will continue to receive DOR/ISL qd (100 mg/0.25 mg) for an additional 96 weeks or until it is commercially accessible (whichever comes first).	Baseline ART + DOR/ISL n=185 Participants Participants with HIV-1 that has been virologically suppressed for ≥3 consecutive months who were previously treated with continuous baseline ART received standard of care (SOC) ART for 48 weeks, followed by treatment with DOR/ISL as a FDC of 100 mg DOR/0.25 mg ISL orally qd until Week 144. At Week 144, participants who consent to enter the optional study extension will continue to receive DOR/ISL qd (100 mg/0.25 mg) for an additional 96 weeks or until it is commercially accessible (whichever comes first).
Percentage of Participants With an AE Leading to Discontinuation of Study Intervention at Week 48	0.5 Percentage of Participants	2.2 Percentage of Participants

SECONDARY outcome

Timeframe: Week 48

Population: All randomized participants who received at least one dose of study intervention and had data for analysis excluding participants who had at least one major deviation that may substantially affect the results of the outcome measure.

HIV-1 RNA levels in plasma were measured by a polymerase chain reaction (PCR) assay with a reliable lower limit of quantification of \<50 copies/mL. The percentage of participants with HIV-1 RNA \<200 copies/mL at Week 48 is presented using the FDA Snapshot missing data approach.

Outcome measures

Outcome measures
Measure	Doravirine/Islatravir (DOR/ISL) n=366 Participants Participants with Human Immunodeficiency Virus-1 (HIV-1) that have been virologically suppressed for ≥3 consecutive months who were previously treated with continuous baseline antiretroviral therapy (ART) received doravine/islatravir (DOR/ISL), a fixed dose combination (FDC) of 100 mg DOR/0.25 mg ISL orally once daily (qd) for 144 weeks. At Week 144, participants who consent to enter the optional study extension will continue to receive DOR/ISL qd (100 mg/0.25 mg) for an additional 96 weeks or until it is commercially accessible (whichever comes first).	Baseline ART + DOR/ISL n=185 Participants Participants with HIV-1 that has been virologically suppressed for ≥3 consecutive months who were previously treated with continuous baseline ART received standard of care (SOC) ART for 48 weeks, followed by treatment with DOR/ISL as a FDC of 100 mg DOR/0.25 mg ISL orally qd until Week 144. At Week 144, participants who consent to enter the optional study extension will continue to receive DOR/ISL qd (100 mg/0.25 mg) for an additional 96 weeks or until it is commercially accessible (whichever comes first).
Percentage of Participants With HIV-1 RNA <200 Copies/mL at Week 48	95.6 Percentage of Participants	95.7 Percentage of Participants

SECONDARY outcome

Timeframe: Week 48

HIV-1 RNA levels in plasma were measured by a polymerase chain reaction (PCR) assay with a reliable lower limit of quantification of \<50 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.

Outcome measures

Outcome measures
Measure	Doravirine/Islatravir (DOR/ISL) n=366 Participants Participants with Human Immunodeficiency Virus-1 (HIV-1) that have been virologically suppressed for ≥3 consecutive months who were previously treated with continuous baseline antiretroviral therapy (ART) received doravine/islatravir (DOR/ISL), a fixed dose combination (FDC) of 100 mg DOR/0.25 mg ISL orally once daily (qd) for 144 weeks. At Week 144, participants who consent to enter the optional study extension will continue to receive DOR/ISL qd (100 mg/0.25 mg) for an additional 96 weeks or until it is commercially accessible (whichever comes first).	Baseline ART + DOR/ISL n=185 Participants Participants with HIV-1 that has been virologically suppressed for ≥3 consecutive months who were previously treated with continuous baseline ART received standard of care (SOC) ART for 48 weeks, followed by treatment with DOR/ISL as a FDC of 100 mg DOR/0.25 mg ISL orally qd until Week 144. At Week 144, participants who consent to enter the optional study extension will continue to receive DOR/ISL qd (100 mg/0.25 mg) for an additional 96 weeks or until it is commercially accessible (whichever comes first).
Percentage of Participants With HIV-1 RNA <50 Copies/mL at Week 48	95.6 Percentage of Participants	91.9 Percentage of Participants

SECONDARY outcome

Timeframe: Week 96

HIV-1 RNA levels in plasma were measured by a polymerase chain reaction (PCR) assay with a reliable lower limit of quantification of \<50 copies/mL. The percentage of participants with HIV-1 RNA \<200 copies/mL at Week 96 is presented using the FDA Snapshot missing data approach.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Week 144

HIV-1 RNA levels in plasma were measured by a polymerase chain reaction (PCR) assay with a reliable lower limit of quantification of \<50 copies/mL. The percentage of participants with HIV-1 RNA \<200 copies/mL at Week 144 is presented using the FDA Snapshot missing data approach.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Week 96

HIV-1 RNA levels in plasma were measured by a polymerase chain reaction (PCR) assay with a reliable lower limit of quantification of \<50 copies/mL. The percentage of participants with HIV-1 RNA ≥50 copies/mL at Week 96 is presented using the FDA Snapshot missing data approach.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Week 144

HIV-1 RNA levels in plasma were measured by a polymerase chain reaction (PCR) assay with a reliable lower limit of quantification of \<50 copies/mL. The percentage of participants with HIV-1 RNA ≥50 copies/mL at Week 144 is presented using the FDA Snapshot missing data approach.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Week 96

HIV-1 RNA levels in plasma were measured by a polymerase chain reaction (PCR) assay with a reliable lower limit of quantification of \<50 copies/mL. The percentage of participants with HIV-1 RNA \<50 copies/mL at Week 96 is presented using the FDA Snapshot missing data approach.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Week 144

HIV-1 RNA levels in plasma were measured by a polymerase chain reaction (PCR) assay with a reliable lower limit of quantification of \<50 copies/mL. The percentage of participants with HIV-1 RNA \<50 copies/mL at Week 144 is presented using the FDA Snapshot missing data approach.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline at Day 1 and Week 48

Population: All randomized participants who received at least one dose of study intervention and who have baseline data.

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 mean change of plasma CD4+ T-Cell count from baseline to Week 48 is presented.

Outcome measures

Outcome measures
Measure	Doravirine/Islatravir (DOR/ISL) n=352 Participants Participants with Human Immunodeficiency Virus-1 (HIV-1) that have been virologically suppressed for ≥3 consecutive months who were previously treated with continuous baseline antiretroviral therapy (ART) received doravine/islatravir (DOR/ISL), a fixed dose combination (FDC) of 100 mg DOR/0.25 mg ISL orally once daily (qd) for 144 weeks. At Week 144, participants who consent to enter the optional study extension will continue to receive DOR/ISL qd (100 mg/0.25 mg) for an additional 96 weeks or until it is commercially accessible (whichever comes first).	Baseline ART + DOR/ISL n=178 Participants Participants with HIV-1 that has been virologically suppressed for ≥3 consecutive months who were previously treated with continuous baseline ART received standard of care (SOC) ART for 48 weeks, followed by treatment with DOR/ISL as a FDC of 100 mg DOR/0.25 mg ISL orally qd until Week 144. At Week 144, participants who consent to enter the optional study extension will continue to receive DOR/ISL qd (100 mg/0.25 mg) for an additional 96 weeks or until it is commercially accessible (whichever comes first).
Mean Change of Plasma Cluster of Differentiation 4 (CD4+) T-Cell Count From Baseline Day 1 to Week 48	5.41 cells/mm^3 Interval -12.11 to 22.94	18.22 cells/mm^3 Interval -11.84 to 48.28

SECONDARY outcome

Timeframe: Baseline at Week 48 and Week 96

Mean change from baseline at Week 48 in CD4+ T-cell count at Week 96. This outcome measure is applicable to participants who were randomized to switch to DOR/ISL at Week 48.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline at Week 48 and Week 144

Mean change from baseline at Week 48 in CD4+ T-cell count at Week 144. This outcome measure is applicable to participants who were randomized to switch to DOR/ISL at Week 48.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline at Day 1 and Week 96

Mean change from baseline at Day 1 in CD4+ T-cell count at Week 96. This outcome measure is applicable to those randomized to start DOR/ISL on Day 1.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline at Day 1 and Week 144

Mean change from baseline at Day 1 in CD4+ T-cell count at Week 144. This outcome measure is applicable to those randomized to start DOR/ISL on Day 1.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to Week 48

Population: Participants with HIV-1 RNA \>=400 copies/mL or any participant for whom available genotypic or phenotypic data show evidence of resistance, irrespective of viral load were included in the resistance analysis subset.

Participants with clinically significant confirmed viremia \[2 consecutive occurences 4 weeks (+-1 week) apart of HIV-1 RNA \>=200 copies/mL at any time during the study\] or who discontinue study intervention for another reason with HIV-1 RNA \>=200 copies/mL at the time of discontinuation met the criteria for post-baseline resistance testing. Participants with HIV-1 RNA \>=400 copies/mL or any participant for whom available genotypic or phenotypic data show evidence of resistance, irrespective of viral load were included in the resistance analysis subset. Plasma samples were collected for genotypic and phenotypic HIV-1 viral drug resistance testing and used to assess resistance-associated substitutions and virus susceptibility to study intervention. The percentage of participants in the resistance analysis subset with treatment-emergent resistance-associated substitutions to the study intervention is presented.

Outcome measures

Outcome measures
Measure	Doravirine/Islatravir (DOR/ISL) n=3 Participants Participants with Human Immunodeficiency Virus-1 (HIV-1) that have been virologically suppressed for ≥3 consecutive months who were previously treated with continuous baseline antiretroviral therapy (ART) received doravine/islatravir (DOR/ISL), a fixed dose combination (FDC) of 100 mg DOR/0.25 mg ISL orally once daily (qd) for 144 weeks. At Week 144, participants who consent to enter the optional study extension will continue to receive DOR/ISL qd (100 mg/0.25 mg) for an additional 96 weeks or until it is commercially accessible (whichever comes first).	Baseline ART + DOR/ISL Participants with HIV-1 that has been virologically suppressed for ≥3 consecutive months who were previously treated with continuous baseline ART received standard of care (SOC) ART for 48 weeks, followed by treatment with DOR/ISL as a FDC of 100 mg DOR/0.25 mg ISL orally qd until Week 144. At Week 144, participants who consent to enter the optional study extension will continue to receive DOR/ISL qd (100 mg/0.25 mg) for an additional 96 weeks or until it is commercially accessible (whichever comes first).
Percentage of Participants With Treatment-Emergent, Resistance-associated Substitutions at Week 48	0 Percentage of participants	—

SECONDARY outcome

Timeframe: Baseline and Week 48

Population: All randomized participants who received at least one dose of study intervention and had baseline data and at least one post-baseline test result in the specified analysis window.

Blood serum samples were taken at baseline and Week 48. The mean change from baseline in fasting Low density lipoprotein cholesterol (LDL-C) at Week 48 is presented for PI-containing regimens (including PI- + InSTI-containing regimens), non-PI- and non-InSTI-containing regimens, and InSTI-containing regimens (non-PI-containing regimens) are presented.

Outcome measures

Outcome measures
Measure	Doravirine/Islatravir (DOR/ISL) n=235 Participants Participants with Human Immunodeficiency Virus-1 (HIV-1) that have been virologically suppressed for ≥3 consecutive months who were previously treated with continuous baseline antiretroviral therapy (ART) received doravine/islatravir (DOR/ISL), a fixed dose combination (FDC) of 100 mg DOR/0.25 mg ISL orally once daily (qd) for 144 weeks. At Week 144, participants who consent to enter the optional study extension will continue to receive DOR/ISL qd (100 mg/0.25 mg) for an additional 96 weeks or until it is commercially accessible (whichever comes first).	Baseline ART + DOR/ISL n=129 Participants Participants with HIV-1 that has been virologically suppressed for ≥3 consecutive months who were previously treated with continuous baseline ART received standard of care (SOC) ART for 48 weeks, followed by treatment with DOR/ISL as a FDC of 100 mg DOR/0.25 mg ISL orally qd until Week 144. At Week 144, participants who consent to enter the optional study extension will continue to receive DOR/ISL qd (100 mg/0.25 mg) for an additional 96 weeks or until it is commercially accessible (whichever comes first).
Mean Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) at Week 48 PI-containing regimens (including PI- + InSTI-containing regimens)	-7.10 mg/dL Interval -27.06 to 12.86	-2.75 mg/dL Interval -9.91 to 4.41
Mean Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) at Week 48 non-PI- and non-InSTI-containing regimens	5.07 mg/dL Interval -0.77 to 10.91	0.29 mg/dL Interval -5.92 to 6.5
Mean Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) at Week 48 InSTI-containing regimens (non-PI-containing regimens)	2.45 mg/dL Interval -0.73 to 5.63	-0.37 mg/dL Interval -5.02 to 4.28

SECONDARY outcome

Timeframe: Baseline and Week 48

Population: All randomized participants who received at least one dose of study intervention and had baseline data and at least one post-baseline test result in the specified analysis window.

Blood serum samples were taken at baseline and Week 48. The mean change from baseline in fasting Non-HDL-C at Week 48 is presented for PI-containing regimens (including PI- + InSTI-containing regimens), non-PI- and non-InSTI-containing regimens, and InSTI-containing regimens (non-PI-containing regimens) are presented.

Outcome measures

Outcome measures
Measure	Doravirine/Islatravir (DOR/ISL) n=235 Participants Participants with Human Immunodeficiency Virus-1 (HIV-1) that have been virologically suppressed for ≥3 consecutive months who were previously treated with continuous baseline antiretroviral therapy (ART) received doravine/islatravir (DOR/ISL), a fixed dose combination (FDC) of 100 mg DOR/0.25 mg ISL orally once daily (qd) for 144 weeks. At Week 144, participants who consent to enter the optional study extension will continue to receive DOR/ISL qd (100 mg/0.25 mg) for an additional 96 weeks or until it is commercially accessible (whichever comes first).	Baseline ART + DOR/ISL n=129 Participants Participants with HIV-1 that has been virologically suppressed for ≥3 consecutive months who were previously treated with continuous baseline ART received standard of care (SOC) ART for 48 weeks, followed by treatment with DOR/ISL as a FDC of 100 mg DOR/0.25 mg ISL orally qd until Week 144. At Week 144, participants who consent to enter the optional study extension will continue to receive DOR/ISL qd (100 mg/0.25 mg) for an additional 96 weeks or until it is commercially accessible (whichever comes first).
Mean Change From Baseline in Fasting Non-High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 48 PI-containing regimens (including PI- + InSTI-containing regimens)	-11.80 mg/dL Interval -32.04 to 8.44	-2.75 mg/dL Interval -10.9 to 5.4
Mean Change From Baseline in Fasting Non-High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 48 non-PI- and non-InSTI-containing regimens	5.78 mg/dL Interval -0.4 to 11.97	0.44 mg/dL Interval -6.47 to 7.35
Mean Change From Baseline in Fasting Non-High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 48 InSTI-containing regimens (non-PI-containing regimens)	3.60 mg/dL Interval 0.06 to 7.14	3.29 mg/dL Interval -5.87 to 12.44

SECONDARY outcome

Timeframe: Up to Week 96

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to Week 144

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to Week 96

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to Week 144

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Week 48 up to Week 96

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Week 48 up to Week 144

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Week 48 up to Week 96

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Week 48 up to Week 144

Outcome measures

Outcome data not reported

Adverse Events

Doravirine/Islatravir (DOR/ISL)

Serious events: 23 serious events

Other events: 123 other events

Deaths: 0 deaths

Baseline ART + DOR/ISL

Serious events: 9 serious events

Other events: 73 other events

Deaths: 1 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Doravirine/Islatravir (DOR/ISL) n=366 participants at risk Participants with Human Immunodeficiency Virus-1 (HIV-1) that have been virologically suppressed for ≥3 consecutive months who were previously treated with continuous baseline antiretroviral therapy (ART) received doravine/islatravir (DOR/ISL), a fixed dose combination (FDC) of 100 mg DOR/0.25 mg ISL orally once daily (qd) for 144 weeks. At Week 144, participants who consent to enter the optional study extension will continue to receive DOR/ISL qd (100 mg/0.25 mg) for an additional 96 weeks or until it is commercially accessible (whichever comes first).	Baseline ART + DOR/ISL n=185 participants at risk Participants with HIV-1 that has been virologically suppressed for ≥3 consecutive months who were previously treated with continuous baseline ART received standard of care (SOC) ART for 48 weeks, followed by treatment with DOR/ISL as a FDC of 100 mg DOR/0.25 mg ISL orally qd until Week 144. At Week 144, participants who consent to enter the optional study extension will continue to receive DOR/ISL qd (100 mg/0.25 mg) for an additional 96 weeks or until it is commercially accessible (whichever comes first).
Nervous system disorders Headache	5.2% 19/366 • Number of events 21 • All-cause mortality and adverse events up to 48 weeks. All-cause mortality (ACM): all randomized participants; AEs: all randomized participants who received at least one dose of study treatment.	7.6% 14/185 • Number of events 17 • All-cause mortality and adverse events up to 48 weeks. All-cause mortality (ACM): all randomized participants; AEs: all randomized participants who received at least one dose of study treatment.
Gastrointestinal disorders Diarrhoea	7.9% 29/366 • Number of events 30 • All-cause mortality and adverse events up to 48 weeks. All-cause mortality (ACM): all randomized participants; AEs: all randomized participants who received at least one dose of study treatment.	1.6% 3/185 • Number of events 3 • All-cause mortality and adverse events up to 48 weeks. All-cause mortality (ACM): all randomized participants; AEs: all randomized participants who received at least one dose of study treatment.
Infections and infestations COVID-19	3.8% 14/366 • Number of events 15 • All-cause mortality and adverse events up to 48 weeks. All-cause mortality (ACM): all randomized participants; AEs: all randomized participants who received at least one dose of study treatment.	5.4% 10/185 • Number of events 10 • All-cause mortality and adverse events up to 48 weeks. All-cause mortality (ACM): all randomized participants; AEs: all randomized participants who received at least one dose of study treatment.
Infections and infestations Nasopharyngitis	5.5% 20/366 • Number of events 24 • All-cause mortality and adverse events up to 48 weeks. All-cause mortality (ACM): all randomized participants; AEs: all randomized participants who received at least one dose of study treatment.	6.5% 12/185 • Number of events 14 • All-cause mortality and adverse events up to 48 weeks. All-cause mortality (ACM): all randomized participants; AEs: all randomized participants who received at least one dose of study treatment.
Infections and infestations Upper respiratory tract infection	10.4% 38/366 • Number of events 45 • All-cause mortality and adverse events up to 48 weeks. All-cause mortality (ACM): all randomized participants; AEs: all randomized participants who received at least one dose of study treatment.	13.5% 25/185 • Number of events 29 • All-cause mortality and adverse events up to 48 weeks. All-cause mortality (ACM): all randomized participants; AEs: all randomized participants who received at least one dose of study treatment.
Musculoskeletal and connective tissue disorders Arthralgia	4.4% 16/366 • Number of events 19 • All-cause mortality and adverse events up to 48 weeks. All-cause mortality (ACM): all randomized participants; AEs: all randomized participants who received at least one dose of study treatment.	7.6% 14/185 • Number of events 15 • All-cause mortality and adverse events up to 48 weeks. All-cause mortality (ACM): all randomized participants; AEs: all randomized participants who received at least one dose of study treatment.
Musculoskeletal and connective tissue disorders Back pain	4.9% 18/366 • Number of events 19 • All-cause mortality and adverse events up to 48 weeks. All-cause mortality (ACM): all randomized participants; AEs: all randomized participants who received at least one dose of study treatment.	5.4% 10/185 • Number of events 10 • All-cause mortality and adverse events up to 48 weeks. All-cause mortality (ACM): all randomized participants; AEs: all randomized participants who received at least one dose of study treatment.

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme LLC

Phone: 1-800-672-6372

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee If publication activity is not directed by the Sponsor, the investigator agrees to submit all manuscripts or abstracts to the Sponsor before submission. This allows the Sponsor to protect proprietary information and to provide comments. Authorship will be determined by mutual agreement and in line with International Committee of Medical Journal Editors (ICMJE) authorship requirements.
Publication restrictions are in place

Restriction type: OTHER

Measure	Doravirine/Islatravir (DOR/ISL) n=366 participants at risk Participants with Human Immunodeficiency Virus-1 (HIV-1) that have been virologically suppressed for ≥3 consecutive months who were previously treated with continuous baseline antiretroviral therapy (ART) received doravine/islatravir (DOR/ISL), a fixed dose combination (FDC) of 100 mg DOR/0.25 mg ISL orally once daily (qd) for 144 weeks. At Week 144, participants who consent to enter the optional study extension will continue to receive DOR/ISL qd (100 mg/0.25 mg) for an additional 96 weeks or until it is commercially accessible (whichever comes first).	Baseline ART + DOR/ISL n=185 participants at risk Participants with HIV-1 that has been virologically suppressed for ≥3 consecutive months who were previously treated with continuous baseline ART received standard of care (SOC) ART for 48 weeks, followed by treatment with DOR/ISL as a FDC of 100 mg DOR/0.25 mg ISL orally qd until Week 144. At Week 144, participants who consent to enter the optional study extension will continue to receive DOR/ISL qd (100 mg/0.25 mg) for an additional 96 weeks or until it is commercially accessible (whichever comes first).
Blood and lymphatic system disorders Agranulocytosis	0.00% 0/366 • All-cause mortality and adverse events up to 48 weeks. All-cause mortality (ACM): all randomized participants; AEs: all randomized participants who received at least one dose of study treatment.	0.54% 1/185 • Number of events 1 • All-cause mortality and adverse events up to 48 weeks. All-cause mortality (ACM): all randomized participants; AEs: all randomized participants who received at least one dose of study treatment.
Blood and lymphatic system disorders Blood loss anaemia	0.00% 0/366 • All-cause mortality and adverse events up to 48 weeks. All-cause mortality (ACM): all randomized participants; AEs: all randomized participants who received at least one dose of study treatment.	0.54% 1/185 • Number of events 1 • All-cause mortality and adverse events up to 48 weeks. All-cause mortality (ACM): all randomized participants; AEs: all randomized participants who received at least one dose of study treatment.
Cardiac disorders Atrial fibrillation	0.55% 2/366 • Number of events 2 • All-cause mortality and adverse events up to 48 weeks. All-cause mortality (ACM): all randomized participants; AEs: all randomized participants who received at least one dose of study treatment.	0.00% 0/185 • All-cause mortality and adverse events up to 48 weeks. All-cause mortality (ACM): all randomized participants; AEs: all randomized participants who received at least one dose of study treatment.
Cardiac disorders Cardiac failure congestive	0.27% 1/366 • Number of events 1 • All-cause mortality and adverse events up to 48 weeks. All-cause mortality (ACM): all randomized participants; AEs: all randomized participants who received at least one dose of study treatment.	0.00% 0/185 • All-cause mortality and adverse events up to 48 weeks. All-cause mortality (ACM): all randomized participants; AEs: all randomized participants who received at least one dose of study treatment.
Gastrointestinal disorders Abdominal pain	0.27% 1/366 • Number of events 1 • All-cause mortality and adverse events up to 48 weeks. All-cause mortality (ACM): all randomized participants; AEs: all randomized participants who received at least one dose of study treatment.	0.00% 0/185 • All-cause mortality and adverse events up to 48 weeks. All-cause mortality (ACM): all randomized participants; AEs: all randomized participants who received at least one dose of study treatment.
Gastrointestinal disorders Constipation	0.27% 1/366 • Number of events 1 • All-cause mortality and adverse events up to 48 weeks. All-cause mortality (ACM): all randomized participants; AEs: all randomized participants who received at least one dose of study treatment.	0.00% 0/185 • All-cause mortality and adverse events up to 48 weeks. All-cause mortality (ACM): all randomized participants; AEs: all randomized participants who received at least one dose of study treatment.
Gastrointestinal disorders Gastrointestinal haemorrhage	0.27% 1/366 • Number of events 1 • All-cause mortality and adverse events up to 48 weeks. All-cause mortality (ACM): all randomized participants; AEs: all randomized participants who received at least one dose of study treatment.	0.00% 0/185 • All-cause mortality and adverse events up to 48 weeks. All-cause mortality (ACM): all randomized participants; AEs: all randomized participants who received at least one dose of study treatment.
Hepatobiliary disorders Cholelithiasis	0.27% 1/366 • Number of events 1 • All-cause mortality and adverse events up to 48 weeks. All-cause mortality (ACM): all randomized participants; AEs: all randomized participants who received at least one dose of study treatment.	0.00% 0/185 • All-cause mortality and adverse events up to 48 weeks. All-cause mortality (ACM): all randomized participants; AEs: all randomized participants who received at least one dose of study treatment.
Infections and infestations Cellulitis	0.00% 0/366 • All-cause mortality and adverse events up to 48 weeks. All-cause mortality (ACM): all randomized participants; AEs: all randomized participants who received at least one dose of study treatment.	0.54% 1/185 • Number of events 1 • All-cause mortality and adverse events up to 48 weeks. All-cause mortality (ACM): all randomized participants; AEs: all randomized participants who received at least one dose of study treatment.
Infections and infestations Gastroenteritis	0.27% 1/366 • Number of events 1 • All-cause mortality and adverse events up to 48 weeks. All-cause mortality (ACM): all randomized participants; AEs: all randomized participants who received at least one dose of study treatment.	0.00% 0/185 • All-cause mortality and adverse events up to 48 weeks. All-cause mortality (ACM): all randomized participants; AEs: all randomized participants who received at least one dose of study treatment.
Infections and infestations Osteomyelitis	0.27% 1/366 • Number of events 1 • All-cause mortality and adverse events up to 48 weeks. All-cause mortality (ACM): all randomized participants; AEs: all randomized participants who received at least one dose of study treatment.	0.00% 0/185 • All-cause mortality and adverse events up to 48 weeks. All-cause mortality (ACM): all randomized participants; AEs: all randomized participants who received at least one dose of study treatment.
Infections and infestations Pneumonia	0.82% 3/366 • Number of events 3 • All-cause mortality and adverse events up to 48 weeks. All-cause mortality (ACM): all randomized participants; AEs: all randomized participants who received at least one dose of study treatment.	0.00% 0/185 • All-cause mortality and adverse events up to 48 weeks. All-cause mortality (ACM): all randomized participants; AEs: all randomized participants who received at least one dose of study treatment.
Infections and infestations Sinusitis	0.27% 1/366 • Number of events 1 • All-cause mortality and adverse events up to 48 weeks. All-cause mortality (ACM): all randomized participants; AEs: all randomized participants who received at least one dose of study treatment.	0.00% 0/185 • All-cause mortality and adverse events up to 48 weeks. All-cause mortality (ACM): all randomized participants; AEs: all randomized participants who received at least one dose of study treatment.
Infections and infestations Viral upper respiratory tract infection	0.00% 0/366 • All-cause mortality and adverse events up to 48 weeks. All-cause mortality (ACM): all randomized participants; AEs: all randomized participants who received at least one dose of study treatment.	0.54% 1/185 • Number of events 1 • All-cause mortality and adverse events up to 48 weeks. All-cause mortality (ACM): all randomized participants; AEs: all randomized participants who received at least one dose of study treatment.
Injury, poisoning and procedural complications Concussion	0.27% 1/366 • Number of events 1 • All-cause mortality and adverse events up to 48 weeks. All-cause mortality (ACM): all randomized participants; AEs: all randomized participants who received at least one dose of study treatment.	0.00% 0/185 • All-cause mortality and adverse events up to 48 weeks. All-cause mortality (ACM): all randomized participants; AEs: all randomized participants who received at least one dose of study treatment.
Injury, poisoning and procedural complications Fibula fracture	0.27% 1/366 • Number of events 1 • All-cause mortality and adverse events up to 48 weeks. All-cause mortality (ACM): all randomized participants; AEs: all randomized participants who received at least one dose of study treatment.	0.00% 0/185 • All-cause mortality and adverse events up to 48 weeks. All-cause mortality (ACM): all randomized participants; AEs: all randomized participants who received at least one dose of study treatment.
Injury, poisoning and procedural complications Head injury	0.27% 1/366 • Number of events 1 • All-cause mortality and adverse events up to 48 weeks. All-cause mortality (ACM): all randomized participants; AEs: all randomized participants who received at least one dose of study treatment.	0.00% 0/185 • All-cause mortality and adverse events up to 48 weeks. All-cause mortality (ACM): all randomized participants; AEs: all randomized participants who received at least one dose of study treatment.
Injury, poisoning and procedural complications Ligament rupture	0.00% 0/366 • All-cause mortality and adverse events up to 48 weeks. All-cause mortality (ACM): all randomized participants; AEs: all randomized participants who received at least one dose of study treatment.	0.54% 1/185 • Number of events 1 • All-cause mortality and adverse events up to 48 weeks. All-cause mortality (ACM): all randomized participants; AEs: all randomized participants who received at least one dose of study treatment.
Injury, poisoning and procedural complications Lower limb fracture	0.27% 1/366 • Number of events 1 • All-cause mortality and adverse events up to 48 weeks. All-cause mortality (ACM): all randomized participants; AEs: all randomized participants who received at least one dose of study treatment.	0.00% 0/185 • All-cause mortality and adverse events up to 48 weeks. All-cause mortality (ACM): all randomized participants; AEs: all randomized participants who received at least one dose of study treatment.
Injury, poisoning and procedural complications Meniscus injury	0.00% 0/366 • All-cause mortality and adverse events up to 48 weeks. All-cause mortality (ACM): all randomized participants; AEs: all randomized participants who received at least one dose of study treatment.	0.54% 1/185 • Number of events 1 • All-cause mortality and adverse events up to 48 weeks. All-cause mortality (ACM): all randomized participants; AEs: all randomized participants who received at least one dose of study treatment.
Injury, poisoning and procedural complications Wrist fracture	0.27% 1/366 • Number of events 1 • All-cause mortality and adverse events up to 48 weeks. All-cause mortality (ACM): all randomized participants; AEs: all randomized participants who received at least one dose of study treatment.	0.00% 0/185 • All-cause mortality and adverse events up to 48 weeks. All-cause mortality (ACM): all randomized participants; AEs: all randomized participants who received at least one dose of study treatment.
Investigations Troponin I increased	0.27% 1/366 • Number of events 1 • All-cause mortality and adverse events up to 48 weeks. All-cause mortality (ACM): all randomized participants; AEs: all randomized participants who received at least one dose of study treatment.	0.00% 0/185 • All-cause mortality and adverse events up to 48 weeks. All-cause mortality (ACM): all randomized participants; AEs: all randomized participants who received at least one dose of study treatment.
Metabolism and nutrition disorders Diabetes mellitus inadequate control	0.27% 1/366 • Number of events 1 • All-cause mortality and adverse events up to 48 weeks. All-cause mortality (ACM): all randomized participants; AEs: all randomized participants who received at least one dose of study treatment.	0.00% 0/185 • All-cause mortality and adverse events up to 48 weeks. All-cause mortality (ACM): all randomized participants; AEs: all randomized participants who received at least one dose of study treatment.
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	0.27% 1/366 • Number of events 1 • All-cause mortality and adverse events up to 48 weeks. All-cause mortality (ACM): all randomized participants; AEs: all randomized participants who received at least one dose of study treatment.	0.00% 0/185 • All-cause mortality and adverse events up to 48 weeks. All-cause mortality (ACM): all randomized participants; AEs: all randomized participants who received at least one dose of study treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Cervix carcinoma	0.00% 0/366 • All-cause mortality and adverse events up to 48 weeks. All-cause mortality (ACM): all randomized participants; AEs: all randomized participants who received at least one dose of study treatment.	0.54% 1/185 • Number of events 1 • All-cause mortality and adverse events up to 48 weeks. All-cause mortality (ACM): all randomized participants; AEs: all randomized participants who received at least one dose of study treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Invasive breast carcinoma	0.00% 0/366 • All-cause mortality and adverse events up to 48 weeks. All-cause mortality (ACM): all randomized participants; AEs: all randomized participants who received at least one dose of study treatment.	0.54% 1/185 • Number of events 1 • All-cause mortality and adverse events up to 48 weeks. All-cause mortality (ACM): all randomized participants; AEs: all randomized participants who received at least one dose of study treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Kaposi's sarcoma	0.27% 1/366 • Number of events 1 • All-cause mortality and adverse events up to 48 weeks. All-cause mortality (ACM): all randomized participants; AEs: all randomized participants who received at least one dose of study treatment.	0.00% 0/185 • All-cause mortality and adverse events up to 48 weeks. All-cause mortality (ACM): all randomized participants; AEs: all randomized participants who received at least one dose of study treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Sarcoma	0.00% 0/366 • All-cause mortality and adverse events up to 48 weeks. All-cause mortality (ACM): all randomized participants; AEs: all randomized participants who received at least one dose of study treatment.	0.54% 1/185 • Number of events 1 • All-cause mortality and adverse events up to 48 weeks. All-cause mortality (ACM): all randomized participants; AEs: all randomized participants who received at least one dose of study treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Transitional cell carcinoma	0.00% 0/366 • All-cause mortality and adverse events up to 48 weeks. All-cause mortality (ACM): all randomized participants; AEs: all randomized participants who received at least one dose of study treatment.	0.54% 1/185 • Number of events 1 • All-cause mortality and adverse events up to 48 weeks. All-cause mortality (ACM): all randomized participants; AEs: all randomized participants who received at least one dose of study treatment.
Nervous system disorders Subarachnoid haemorrhage	0.27% 1/366 • Number of events 1 • All-cause mortality and adverse events up to 48 weeks. All-cause mortality (ACM): all randomized participants; AEs: all randomized participants who received at least one dose of study treatment.	0.00% 0/185 • All-cause mortality and adverse events up to 48 weeks. All-cause mortality (ACM): all randomized participants; AEs: all randomized participants who received at least one dose of study treatment.
Nervous system disorders Syncope	0.27% 1/366 • Number of events 1 • All-cause mortality and adverse events up to 48 weeks. All-cause mortality (ACM): all randomized participants; AEs: all randomized participants who received at least one dose of study treatment.	0.00% 0/185 • All-cause mortality and adverse events up to 48 weeks. All-cause mortality (ACM): all randomized participants; AEs: all randomized participants who received at least one dose of study treatment.
Psychiatric disorders Depression	0.00% 0/366 • All-cause mortality and adverse events up to 48 weeks. All-cause mortality (ACM): all randomized participants; AEs: all randomized participants who received at least one dose of study treatment.	0.54% 1/185 • Number of events 2 • All-cause mortality and adverse events up to 48 weeks. All-cause mortality (ACM): all randomized participants; AEs: all randomized participants who received at least one dose of study treatment.
Psychiatric disorders Psychotic disorder	0.00% 0/366 • All-cause mortality and adverse events up to 48 weeks. All-cause mortality (ACM): all randomized participants; AEs: all randomized participants who received at least one dose of study treatment.	0.54% 1/185 • Number of events 1 • All-cause mortality and adverse events up to 48 weeks. All-cause mortality (ACM): all randomized participants; AEs: all randomized participants who received at least one dose of study treatment.
Psychiatric disorders Suicide attempt	0.27% 1/366 • Number of events 1 • All-cause mortality and adverse events up to 48 weeks. All-cause mortality (ACM): all randomized participants; AEs: all randomized participants who received at least one dose of study treatment.	0.00% 0/185 • All-cause mortality and adverse events up to 48 weeks. All-cause mortality (ACM): all randomized participants; AEs: all randomized participants who received at least one dose of study treatment.
Renal and urinary disorders Proteinuria	0.27% 1/366 • Number of events 1 • All-cause mortality and adverse events up to 48 weeks. All-cause mortality (ACM): all randomized participants; AEs: all randomized participants who received at least one dose of study treatment.	0.00% 0/185 • All-cause mortality and adverse events up to 48 weeks. All-cause mortality (ACM): all randomized participants; AEs: all randomized participants who received at least one dose of study treatment.
Renal and urinary disorders Urinary tract obstruction	0.27% 1/366 • Number of events 1 • All-cause mortality and adverse events up to 48 weeks. All-cause mortality (ACM): all randomized participants; AEs: all randomized participants who received at least one dose of study treatment.	0.00% 0/185 • All-cause mortality and adverse events up to 48 weeks. All-cause mortality (ACM): all randomized participants; AEs: all randomized participants who received at least one dose of study treatment.
Reproductive system and breast disorders Cervix disorder	0.27% 1/366 • Number of events 1 • All-cause mortality and adverse events up to 48 weeks. All-cause mortality (ACM): all randomized participants; AEs: all randomized participants who received at least one dose of study treatment.	0.00% 0/185 • All-cause mortality and adverse events up to 48 weeks. All-cause mortality (ACM): all randomized participants; AEs: all randomized participants who received at least one dose of study treatment.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.27% 1/366 • Number of events 1 • All-cause mortality and adverse events up to 48 weeks. All-cause mortality (ACM): all randomized participants; AEs: all randomized participants who received at least one dose of study treatment.	0.00% 0/185 • All-cause mortality and adverse events up to 48 weeks. All-cause mortality (ACM): all randomized participants; AEs: all randomized participants who received at least one dose of study treatment.