Trial Outcomes & Findings for Switch to Doravirine/Islatravir (DOR/ISL) in Human Immunodeficiency Virus 1 (HIV-1) Participants Treated With Bictegravir/Emtricitabine/Tenofovir Alafenamide (BIC/FTC/TAF) (MK-8591A-018) (NCT NCT04223791)

Last Updated: 2025-03-30

Results Overview

The Abbott RealTime PCR assay with a reliable lower limit of quantification of 40 copies/mL was used to measure the HIV-1 RNA level in blood samples obtained at each visit. 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

COMPLETED

Study phase

PHASE3

Target enrollment

643 participants

Primary outcome timeframe

Week 48

Results posted on

2025-03-30

Participant Flow

Participant milestones

Participant milestones
Measure	DOR/ISL A fixed dose combination (FDC) of 100 mg doravirine (DOR)/0.75 mg islatravir (ISL) for 144 weeks; and placebo to Bictegravir/Emtricitabine/Tenofovir Alafenamide (BIC/FTC/TAF) for 96 weeks.	BIC/FTC/TAF 50 mg bictegravir (BIC), 200 mg emtricitabine (FTC), 25 mg tenofovir alafenamide (TAF) for 144 weeks, and placebo to FDC DOR/ISL for 96 weeks. Participants will be offered the option to receive open-label FDC DOR/ISL from Week 144 to Week 156.
Overall Study STARTED	322	321
Overall Study Treated	322	319
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	322	321

Reasons for withdrawal

Reasons for withdrawal
Measure	DOR/ISL A fixed dose combination (FDC) of 100 mg doravirine (DOR)/0.75 mg islatravir (ISL) for 144 weeks; and placebo to Bictegravir/Emtricitabine/Tenofovir Alafenamide (BIC/FTC/TAF) for 96 weeks.	BIC/FTC/TAF 50 mg bictegravir (BIC), 200 mg emtricitabine (FTC), 25 mg tenofovir alafenamide (TAF) for 144 weeks, and placebo to FDC DOR/ISL for 96 weeks. Participants will be offered the option to receive open-label FDC DOR/ISL from Week 144 to Week 156.
Overall Study Lost to Follow-up	0	4
Overall Study Physician Decision	5	1
Overall Study Protocol Violation	1	1
Overall Study Withdrawal by Subject	10	12
Overall Study Pregnancy	1	1
Overall Study Ongoing in Study	305	302

Baseline Characteristics

Switch to Doravirine/Islatravir (DOR/ISL) in Human Immunodeficiency Virus 1 (HIV-1) Participants Treated With Bictegravir/Emtricitabine/Tenofovir Alafenamide (BIC/FTC/TAF) (MK-8591A-018)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	DOR/ISL n=322 Participants An FDC of 100 mg DOR/0.75 mg ISL for 144 weeks; and placebo to BIC/FTC/TAF for 96 weeks.	BIC/FTC/TAF n=321 Participants 50 mg BIC, 200 mg FTC, 25 mg TAF for 144 weeks, and placebo to FDC DOR/ISL for 96 weeks. Participants will be offered the option to receive open-label FDC DOR/ISL from Week 144 to Week 156.	Total n=643 Participants Total of all reporting groups
Age, Continuous	47.6 Years STANDARD_DEVIATION 12.6 • n=93 Participants	48.0 Years STANDARD_DEVIATION 11.8 • n=4 Participants	47.8 Years STANDARD_DEVIATION 12.2 • n=27 Participants
Sex: Female, Male Female	105 Participants n=93 Participants	78 Participants n=4 Participants	183 Participants n=27 Participants
Sex: Female, Male Male	217 Participants n=93 Participants	243 Participants n=4 Participants	460 Participants n=27 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	64 Participants n=93 Participants	55 Participants n=4 Participants	119 Participants n=27 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	256 Participants n=93 Participants	261 Participants n=4 Participants	517 Participants n=27 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	2 Participants n=93 Participants	5 Participants n=4 Participants	7 Participants n=27 Participants
Race (NIH/OMB) American Indian or Alaska Native	3 Participants n=93 Participants	2 Participants n=4 Participants	5 Participants n=27 Participants
Race (NIH/OMB) Asian	14 Participants n=93 Participants	13 Participants n=4 Participants	27 Participants n=27 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	2 Participants n=93 Participants	0 Participants n=4 Participants	2 Participants n=27 Participants
Race (NIH/OMB) Black or African American	58 Participants n=93 Participants	56 Participants n=4 Participants	114 Participants n=27 Participants
Race (NIH/OMB) White	240 Participants n=93 Participants	240 Participants n=4 Participants	480 Participants n=27 Participants
Race (NIH/OMB) More than one race	5 Participants n=93 Participants	7 Participants n=4 Participants	12 Participants n=27 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants	3 Participants n=4 Participants	3 Participants n=27 Participants

PRIMARY outcome

Timeframe: Week 48

Population: All participants who received ≥1 dose of study intervention. Participants were included in the treatment group to which they were randomized.

Outcome measures

Outcome measures
Measure	DOR/ISL n=322 Participants An FDC of 100 mg DOR/0.75 mg ISL for 144 weeks; and placebo to BIC/FTC/TAF for 96 weeks.	BIC/FTC/TAF n=319 Participants 50 mg BIC, 200 mg FTC, 25 mg TAF for 144 weeks, and placebo to FDC DOR/ISL for 96 weeks. Participants will be offered the option to receive open-label FDC DOR/ISL from Week 144 to Week 156.
Participants With Human Immunodeficiency Virus 1 Ribonucleic Acid (HIV-1 RNA) ≥50 Copies/mL at Week 48	0.6 Percentage of Participants	0.3 Percentage of Participants

PRIMARY outcome

Timeframe: Up to 48 weeks

Population: All randomized participants who received ≥1 dose of study intervention. Participants were included in the treatment group corresponding to the study intervention received.

An AE is 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. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The percentage of participants who experienced an AE up to week 48 is presented.

Outcome measures

Outcome measures
Measure	DOR/ISL n=322 Participants An FDC of 100 mg DOR/0.75 mg ISL for 144 weeks; and placebo to BIC/FTC/TAF for 96 weeks.	BIC/FTC/TAF n=319 Participants 50 mg BIC, 200 mg FTC, 25 mg TAF for 144 weeks, and placebo to FDC DOR/ISL for 96 weeks. Participants will be offered the option to receive open-label FDC DOR/ISL from Week 144 to Week 156.
Percentage of Participants With One or More Adverse Events (AEs) up to Week 48	71.1 Percentage of Participants	74.6 Percentage of Participants

PRIMARY outcome

Timeframe: Up to 48 weeks

Population: All randomized participants who received ≥1 dose of study intervention. Participants were included in the treatment group corresponding to the study intervention received.

Outcome measures

Outcome measures
Measure	DOR/ISL n=322 Participants An FDC of 100 mg DOR/0.75 mg ISL for 144 weeks; and placebo to BIC/FTC/TAF for 96 weeks.	BIC/FTC/TAF n=319 Participants 50 mg BIC, 200 mg FTC, 25 mg TAF for 144 weeks, and placebo to FDC DOR/ISL for 96 weeks. Participants will be offered the option to receive open-label FDC DOR/ISL from Week 144 to Week 156.
Percentage of Participants Who Discontinued Study Intervention Due to an AE up to Week 48	2.5 Percentage of Participants	2.5 Percentage of Participants

SECONDARY outcome

Timeframe: Week 96

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Week 144

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Week 48

Population: All participants who received ≥1 dose of study intervention. Participants were included in the treatment group to which they were randomized.

The Abbott RealTime PCR assay with a reliable lower limit of quantification of 40 copies/mL was used to measure the HIV-1 RNA level in blood samples obtained at each visit. 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	DOR/ISL n=322 Participants An FDC of 100 mg DOR/0.75 mg ISL for 144 weeks; and placebo to BIC/FTC/TAF for 96 weeks.	BIC/FTC/TAF n=319 Participants 50 mg BIC, 200 mg FTC, 25 mg TAF for 144 weeks, and placebo to FDC DOR/ISL for 96 weeks. Participants will be offered the option to receive open-label FDC DOR/ISL from Week 144 to Week 156.
Percentage of Participants With HIV-1 RNA <50 Copies/mL at Week 48	93.8 Percentage of Participants	94.4 Percentage of Participants

SECONDARY outcome

Timeframe: Week 48

Population: All participants who received ≥1 dose of study intervention. Participants were included in the treatment group to which they were randomized.

The Abbott RealTime PCR assay with a reliable lower limit of quantification of 40 copies/mL was used to measure the HIV-1 RNA level in blood samples obtained at each visit. The percentage of participants with HIV-1 RNA \<40 copies/mL at Week 48 is presented using the FDA snapshot missing data approach.

Outcome measures

Outcome measures
Measure	DOR/ISL n=322 Participants An FDC of 100 mg DOR/0.75 mg ISL for 144 weeks; and placebo to BIC/FTC/TAF for 96 weeks.	BIC/FTC/TAF n=319 Participants 50 mg BIC, 200 mg FTC, 25 mg TAF for 144 weeks, and placebo to FDC DOR/ISL for 96 weeks. Participants will be offered the option to receive open-label FDC DOR/ISL from Week 144 to Week 156.
Percentage of Participants With HIV-1 RNA <40 Copies/mL at Week 48	93.2 Percentage of Participants	94.0 Percentage of Participants

SECONDARY outcome

Timeframe: Week 96

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Week 144

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline and Week 48

Population: All participants who received ≥1 dose of study intervention and who had baseline data for CD4+ T-cell count. Participants were included in the treatment group to which they were randomized.

Blood samples were used to measure CD4+ T-cell count. Baseline measurement of CD4+ T-cell count is defined as the day 1 value for each participant. Change from baseline in CD4+ T-cell count at week 48 using the data as observed (DAO) approach is presented. A negative value indicates a mean decrease in CD4+ T-cell count from baseline and a positive value indicates a mean increase in CD4+ T-cell count from baseline.

Outcome measures

Outcome measures
Measure	DOR/ISL n=301 Participants An FDC of 100 mg DOR/0.75 mg ISL for 144 weeks; and placebo to BIC/FTC/TAF for 96 weeks.	BIC/FTC/TAF n=298 Participants 50 mg BIC, 200 mg FTC, 25 mg TAF for 144 weeks, and placebo to FDC DOR/ISL for 96 weeks. Participants will be offered the option to receive open-label FDC DOR/ISL from Week 144 to Week 156.
Change From Baseline in Cluster of Differentiation-positive (CD4+) T-cell Count at Week 48	-19.66 cells/mm^3 Interval -39.78 to 0.45	40.51 cells/mm^3 Interval 20.66 to 60.36

SECONDARY outcome

Timeframe: Baseline and Week 96

Blood samples were used to measure CD4+ T-cell count. Baseline measurement of CD4+ T-cell count is defined as the day 1 value for each participant. Change from baseline in CD4+ T-cell count at week 96 using the data as observed (DAO) approach is presented. A negative value indicates a mean decrease in CD4+ T-cell count from baseline and a positive value indicates a mean increase in CD4+ T-cell count from baseline.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline and Week 144

Blood samples were used to measure CD4+ T-cell count. Baseline measurement of CD4+ T-cell count is defined as the day 1 value for each participant. Change from baseline in CD4+ T-cell count at week 144 using the data as observed (DAO) approach is presented. A negative value indicates a mean decrease in CD4+ T-cell count from baseline and a positive value indicates a mean increase in CD4+ T-cell count from baseline.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Week 48

Population: 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.

Viral drug resistance is defined as participants with confirmed HIV-1 RNA ≥400 copies/mL having genotypic or phenotypic evidence of resistance to the study drug administered. The number of participants who demonstrate drug resistance is presented.

Outcome measures

Outcome measures
Measure	DOR/ISL n=1 Participants An FDC of 100 mg DOR/0.75 mg ISL for 144 weeks; and placebo to BIC/FTC/TAF for 96 weeks.	BIC/FTC/TAF 50 mg BIC, 200 mg FTC, 25 mg TAF for 144 weeks, and placebo to FDC DOR/ISL for 96 weeks. Participants will be offered the option to receive open-label FDC DOR/ISL from Week 144 to Week 156.
Participants With Viral Drug Resistance-associated Substitutions at Week 48	0 Participants	—

SECONDARY outcome

Timeframe: Week 96

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 number of participants who demonstrate drug resistance is presented.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Week 144

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline and Week 48

Population: Participants who received ≥1 dose of study intervention and were included in the treatment group corresponding to the study intervention received. The analysis population included participants with baseline and at least one postbaseline test result in the specified analysis window.

Body weight was measured and recorded at baseline and week 48. Participants removed their shoes and wore a single layer of clothing at each measurement. The mean change from baseline in body weight at week 48 is presented.

Outcome measures

Outcome measures
Measure	DOR/ISL n=306 Participants An FDC of 100 mg DOR/0.75 mg ISL for 144 weeks; and placebo to BIC/FTC/TAF for 96 weeks.	BIC/FTC/TAF n=302 Participants 50 mg BIC, 200 mg FTC, 25 mg TAF for 144 weeks, and placebo to FDC DOR/ISL for 96 weeks. Participants will be offered the option to receive open-label FDC DOR/ISL from Week 144 to Week 156.
Change From Baseline in Body Weight at Week 48	0.23 kilogram (kg) Standard Deviation 4.19	0.55 kilogram (kg) Standard Deviation 4.40

SECONDARY outcome

Timeframe: Baseline and Week 96

Body weight was measured and recorded at baseline and week 96. Participants removed their shoes and wore a single layer of clothing at each measurement.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline and Week 144

Body weight was measured and recorded at baseline and week 144. Participants removed their shoes and wore a single layer of clothing at each measurement.

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 144

Outcome measures

Outcome data not reported

Adverse Events

DOR/ISL

Serious events: 13 serious events

Other events: 71 other events

Deaths: 1 deaths

BIC/FTC/TAF

Serious events: 15 serious events

Other events: 80 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	DOR/ISL n=322 participants at risk An FDC of 100 mg DOR/0.75 mg ISL for 144 weeks; and placebo to BIC/FTC/TAF for 96 weeks.	BIC/FTC/TAF n=319 participants at risk 50 mg BIC, 200 mg FTC, 25 mg TAF for 144 weeks, and placebo to FDC DOR/ISL for 96 weeks. Participants will be offered the option to receive open-label FDC DOR/ISL from Week 144 to Week 156.
Gastrointestinal disorders Diarrhoea	2.5% 8/322 • Number of events 8 • Up to 48 weeks All-cause mortality population includes all randomized participants in their planned treatment groups. Adverse event population includes all randomized participants who received ≥1 dose of study intervention and were included in the treatment group corresponding to the study intervention received.	6.3% 20/319 • Number of events 21 • Up to 48 weeks All-cause mortality population includes all randomized participants in their planned treatment groups. Adverse event population includes all randomized participants who received ≥1 dose of study intervention and were included in the treatment group corresponding to the study intervention received.
Infections and infestations COVID-19	5.6% 18/322 • Number of events 18 • Up to 48 weeks All-cause mortality population includes all randomized participants in their planned treatment groups. Adverse event population includes all randomized participants who received ≥1 dose of study intervention and were included in the treatment group corresponding to the study intervention received.	5.6% 18/319 • Number of events 19 • Up to 48 weeks All-cause mortality population includes all randomized participants in their planned treatment groups. Adverse event population includes all randomized participants who received ≥1 dose of study intervention and were included in the treatment group corresponding to the study intervention received.
Musculoskeletal and connective tissue disorders Arthralgia	5.3% 17/322 • Number of events 22 • Up to 48 weeks All-cause mortality population includes all randomized participants in their planned treatment groups. Adverse event population includes all randomized participants who received ≥1 dose of study intervention and were included in the treatment group corresponding to the study intervention received.	6.0% 19/319 • Number of events 21 • Up to 48 weeks All-cause mortality population includes all randomized participants in their planned treatment groups. Adverse event population includes all randomized participants who received ≥1 dose of study intervention and were included in the treatment group corresponding to the study intervention received.
Musculoskeletal and connective tissue disorders Back pain	4.0% 13/322 • Number of events 14 • Up to 48 weeks All-cause mortality population includes all randomized participants in their planned treatment groups. Adverse event population includes all randomized participants who received ≥1 dose of study intervention and were included in the treatment group corresponding to the study intervention received.	5.3% 17/319 • Number of events 17 • Up to 48 weeks All-cause mortality population includes all randomized participants in their planned treatment groups. Adverse event population includes all randomized participants who received ≥1 dose of study intervention and were included in the treatment group corresponding to the study intervention received.
Nervous system disorders Headache	7.8% 25/322 • Number of events 42 • Up to 48 weeks All-cause mortality population includes all randomized participants in their planned treatment groups. Adverse event population includes all randomized participants who received ≥1 dose of study intervention and were included in the treatment group corresponding to the study intervention received.	7.2% 23/319 • Number of events 23 • Up to 48 weeks All-cause mortality population includes all randomized participants in their planned treatment groups. Adverse event population includes all randomized participants who received ≥1 dose of study intervention and were included in the treatment group corresponding to the study intervention received.

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.
Publication restrictions are in place

Restriction type: OTHER