This study will evaluate the safety and efficacy of a switch to Doravirine/Islatravir (DOR/ISL) (MK-8591A) (a fixed dose combination of doravirine 100 mg and islatravir 0.75 mg) in participants living with human immunodeficiency virus-1 (HIV-1) virologically suppressed on a regimen of bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF). The primary hypothesis is that a switch to DOR/ISL (MK-8591A) will be non-inferior to continued treatment with BIC/FTC/TAF as assessed by the proportion of participants with HIV-1 ribonucleic acid (RNA) ≥50 copies/mL at Week 48. Participants who benefit from their assigned intervention (as determined by investigator) will be able to continue treatment through a 24-week study extension.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
643
100 mg DOR/ 0.75 ISL FDC single tablet taken orally once daily
50 mg BIC, 200 mg FTC, and 25 mg TAF combined in a single tablet, taken orally once daily
Placebo to BIC/FTC/TAF in a single tablet taken orally, once daily
Placebo to FDC DOR/ISL in a single tablet taken orally, once daily
Pueblo Family Physicians ( Site 2717)
Phoenix, Arizona, United States
Pacific Oaks Medical Group ( Site 2765)
Beverly Hills, California, United States
Men's Health Foundation ( Site 2749)
Los Angeles, California, United States
Kaiser Permanente Los Angeles Medical Center ( Site 2775)
Los Angeles, California, United States
Eisenhower Medical Center ( Site 2744)
Palm Springs, California, United States
Percentage of Participants With Human Immunodeficiency Virus 1 Ribonucleic Acid (HIV-1 RNA) ≥50 Copies/mL at Week 48
The Abbott RealTime polymerase chain reaction (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. Per protocol, the primary outcome measure, the percentage of participants with HIV-1 RNA ≥50 copies/mL at Week 48, is presented using the Food and Drug Administration (FDA) Snapshot missing data approach. The percentage values were rounded to the nearest tenth digit.
Time frame: Week 48
Percentage of Participants With One or More Adverse Events (AEs) up to Week 48
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.
Time frame: Up to 48 weeks
Percentage of Participants Who Discontinued Study Intervention Due to an AE up to Week 48
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 discontinued study intervention due to an AE up to week 48 is presented.
Time frame: Up to 48 weeks
Percentage of Participants With HIV-1 RNA ≥50 Copies/mL at Week 96
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. Per protocol, the secondary outcome measure, percentage of participants with HIV-1 RNA ≥50 copies/mL at Week 96, is presented using the Food and Drug Administration (FDA) Snapshot missing data approach. The percentage values were rounded to the nearest tenth digit.
Time frame: Week 96
Percentage of Participants With HIV-1 RNA ≥50 Copies/mL at Week 144
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. Per protocol, the secondary outcome measure, percentage of participants with HIV-1 RNA ≥50 copies/mL at Week 144, is presented using the FDA snapshot missing data approach. The percentage values were rounded to the nearest tenth digit.
Time frame: Week 144
Percentage of Participants With HIV-1 RNA <50 Copies/mL at Week 48
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. Per protocol, the secondary outcome measure, the percentage of participants with HIV-1 RNA \<50 copies/mL at Week 48, is presented using the FDA snapshot missing data approach. The percentage values were rounded to the nearest tenth digit.
Time frame: Week 48
Percentage of Participants With HIV-1 RNA <40 Copies/mL at Week 48
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. Per protocol, the secondary outcome measure, the percentage of participants with HIV-1 RNA \<40 copies/mL at Week 48, is presented using the FDA snapshot missing data approach.
Time frame: Week 48
Percentage of Participants With HIV-1 RNA <50 Copies/mL at Week 96
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. Per protocol, the secondary outcome measure, the percentage of participants with HIV-1 RNA \<50 copies/mL at Week 96, is presented using the FDA snapshot missing data approach. The percentage values were rounded to the nearest tenth digit.
Time frame: Week 96
Percentage of Participants With HIV-1 RNA <40 Copies/mL at Week 96
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. Per protocol, the secondary outcome measure, the percentage of participants with HIV-1 RNA \<40 copies/mL at Week 96, is presented using the FDA snapshot missing data approach.
Time frame: Week 96
Percentage of Participants With HIV-1 RNA <50 Copies/mL at Week 144
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. Per protocol, the secondary outcome measure, the percentage of participants with HIV-1 RNA \<50 copies/mL at Week 144 is presented using the FDA snapshot missing data approach. The percentage values were rounded to the nearest tenth digit.
Time frame: Week 144
Percentage of Participants With HIV-1 RNA <40 Copies/mL at Week 144
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. Per protocol, the secondary outcome measure, percentage of participants with HIV-1 RNA \<40 copies/mL at Week 144, is presented using the FDA snapshot missing data approach.
Time frame: Week 144
Mean Change From Baseline in Cluster of Differentiation-positive (CD4+) T-cell Count at Week 48
Plasma CD4+ T-cell count was measured in cells/mm\^3 for baseline and 48 weeks by a central laboratory. Baseline measurement of CD4+ T-cell count is defined as the day 1 value for each participant. The mean 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.
Time frame: Baseline and Week 48
Mean Change From Baseline in CD4+ T-cell Count at Week 96
Plasma CD4+ T-cell count was measured in cells/mm\^3 for baseline and 96 weeks by a central laboratory. Baseline measurement of CD4+ T-cell count is defined as the day 1 value for each participant. The mean 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.
Time frame: Baseline and Week 96
Mean Change From Baseline in CD4+ T-cell Count at Week 144
Plasma CD4+ T-cell count was measured in cells/mm\^3 for baseline and 144 weeks by a central laboratory. Baseline measurement of CD4+ T-cell count is defined as the day 1 value for each participant. The mean 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.
Time frame: Baseline and Week 144
Number of Participants With Viral Drug Resistance-associated Substitutions at Week 48
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.
Time frame: Week 48
Number of Participants With Evidence of Viral Drug Resistance-associated Substitutions at 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 at week 96 is presented.
Time frame: Week 96
Number of Participants With Evidence of Viral Drug Resistance-associated Substitutions at Week 144
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 at week 144 is presented.
Time frame: Week 144
Change From Baseline in Body Weight at Week 48
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.
Time frame: Baseline and Week 48
Change From Baseline in Body Weight at 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. The mean change from baseline in body weight at week 96 is presented.
Time frame: Baseline and Week 96
Change From Baseline in Body Weight at 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. The mean change from baseline in body weight at week 144 is presented.
Time frame: Baseline and Week 144
Percentage of Participants With One or More AEs
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 at least one or more AEs is presented. Per protocol, pregnancy-related AEs collected for enrolled participants are reported separately and are presented in the AE module.
Time frame: Up to approximately 55 months
Percentage of Participants Who Discontinued Study Intervention Due to an AE
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 discontinued study intervention due to an AE is presented. Per protocol, pregnancy-related AEs collected for enrolled participants are reported separately and are presented in the AE module.
Time frame: Up to approximately 40 months
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University of California, Davis, Division of ID Research ( Site 2702)
Sacramento, California, United States
Zuckerberg San Francisco General Hospital UCSF ( Site 2743)
San Francisco, California, United States
Whitman-Walker Clinic ( Site 2728)
Washington D.C., District of Columbia, United States
TheraFirst Medical Center ( Site 2742)
Fort Lauderdale, Florida, United States
Midway Immunology and Research ( Site 2759)
Ft. Pierce, Florida, United States
...and 79 more locations