HIV-1 Infection
Conditions
Brief summary
This is a phase 3, randomized, controlled, double-blind, multisite clinical study of a once-daily fixed dose combination (FDC) of 100 mg doravirine/0.75 mg islatravir (DOR/ISL \[also known as MK-8591A\]) in treatment-naïve participants living with human immunodeficiency virus type-1 (HIV-1) infection. The primary objectives are to evaluate the antiretroviral activity, safety, and tolerability of DOR/ISL compared to bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF). The primary hypothesis is that DOR/ISL is noninferior or superior to BIC/FTC/TAF treatment based on the percentage of participants with HIV-1 ribonucleic acid (RNA) \<50 copies/mL at Week 48.
Detailed description
Double-blind treatment with the assigned intervention occurs from Day 1 to Week 96, followed by an open-label portion up to Week 144. Participants who benefit from treatment in the opinion of the Investigator may continue their assigned intervention up to Week 168 (or until they have the option to enroll in a DOR/ISL 100 mg/0.25 mg study, whichever is sooner).
Interventions
DRUGDOR/ISL
100 mg DOR/0.75 mg ISL FDC single tablet taken once daily by mouth.
DRUGBIC/FTC/TAF
BIC/FTC/TAF 50/200/25 mg FDC single tablet taken once daily by mouth.
Placebo single tablet matched to BIC/FTC/TAF taken by mouth.
Placebo single tablet matched to DOR/ISL taken by mouth.
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Is human immunodeficiency virus type 1 (HIV-1) positive * Is naïve to antiretroviral therapy (ART) defined as having received ≤10 days of prior therapy with any antiretroviral agent following a diagnosis of HIV-1 infection including prevention of mother-to-child transmission up to 1 month prior to screening. * A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies: 1) Is not a woman of childbearing potential (WOCBP); 2) Is a WOCBP and using an acceptable contraceptive method, or be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis); 3) A WOCBP must have a negative highly sensitive pregnancy test (\[urine or serum\] as required by local regulations) within 24 hours before the first dose of study intervention; 4) If a urine test cannot be confirmed as negative (eg, an ambiguous result), a serum pregnancy test is required
Exclusion criteria
* Has human immunodeficiency virus type 2 (HIV-2) infection * Has hypersensitivity or other contraindication to any of the components of the study interventions as determined by the investigator * Has an active diagnosis of hepatitis due to any cause, including active hepatitis B virus (HBV) infection (defined as hepatitis B surface antigen \[HBsAg\]-positive or hepatitis B virus deoxyribonucleic acid \[HBV DNA\]-positive) * Has a history of malignancy ≤5 years prior to signing informed consent except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or cutaneous Kaposi's sarcoma * Has a history or current evidence of any condition (including active tuberculosis infection), therapy, laboratory abnormality or other circumstance (including drug or alcohol use or dependence) that might, in the opinion of the investigator, confound the results of the study or interfere with the participant's participation for the full duration of the study * Has been treated for a viral infection other than HIV-1, such as hepatitis B, with an agent that is active against HIV-1 * Is taking or is anticipated to require systemic immunosuppressive therapy, immune modulators, or any prohibited therapy from 45 days prior to Day 1 through the study intervention period * Is currently participating in or has participated in a clinical study with an investigational compound or device from 45 days prior to Day 1 through the study intervention period * Has a documented or known virologic resistance to any approved HIV-1 reverse transcriptase inhibitor, or any study intervention * Has exclusionary laboratory values within 45 days prior to Day 1 * Is female and is expecting to conceive or donate eggs at any time during the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Human Immunodeficiency Virus (HIV)-1 Ribonucleic Acid (RNA) <50 Copies/mL at Week 48 | 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. The percentage of participants with HIV-1 RNA \<50 copies/mL at Week 48 was presented using the Food and Drug Administration (FDA) Snapshot missing data approach. The final analysis for this outcome is presented here. |
| Percentage of Participants Who Experienced an Adverse Event (AE) up to Week 48 | Up to approximately 48 weeks | An AE was any untoward medical occurrence in a study participant administered a study drug, which does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the study drug whether or not it is considered related to the study drug. The percentage of participants who experienced at least one AE up to Week 48 was reported. The final analysis for this outcome is presented here. |
| Percentage of Participants Who Discontinued Study Treatment Due to an AE up to Week 48 | Up to approximately 48 weeks | An AE was any untoward medical occurrence in a study participant administered a study drug, which does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the study drug whether or not it is considered related to the study drug. The percentage of participants who discontinued study treatment due to an AE up to Week 48 were reported. The final analysis for this outcome is presented here. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With HIV-1 RNA <50 Copies/mL at Week 96 | 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. The percentage of participants with HIV-1 RNA \<50 copies/mL at Week 96 was presented using the FDA Snapshot missing data approach. The final analysis for this outcome is presented here. |
| Percentage of Participants With HIV-1 RNA <50 Copies/mL at Week 144 | 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. The percentage of participants with HIV-1 RNA \<50 copies/mL at Week 144 was presented using the Data as Observed (DAO) missing data approach. The final analysis for this outcome is presented here. |
| Percentage of Participants With HIV-1 RNA <40 Copies/mL at Week 48 | Week 48 | The percentage of participants with HIV-1 RNA \<40 copies/mL was determined. 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 was presented using the FDA Snapshot missing data approach. The final analysis for this outcome is presented here. |
| Percentage of Participants With HIV-1 RNA <200 Copies/mL at Week 48 | Week 48 | The percentage of participants with HIV-1 RNA \<200 copies/mL was determined. 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 \<200 copies/mL at Week 48 was presented using the FDA Snapshot missing data approach. The final analysis for this outcome is presented here. |
| Percentage of Participants With HIV-1 RNA <40 Copies/mL at Week 96 | 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. The percentage of participants with HIV-1 RNA \<40 copies/mL at Week 96 was presented using the FDA Snapshot missing data approach. The final analysis for this outcome is presented here. |
| Percentage of Participants With HIV-1 RNA <200 Copies/mL at Week 96 | 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. The percentage of participants with HIV-1 RNA \<200 copies/mL at Week 96 was presented using the FDA Snapshot missing data approach. The final analysis for this outcome is presented here. |
| Percentage of Participants With HIV-1 RNA <40 Copies/mL at Week 144 | 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. The percentage of participants with HIV-1 RNA \<40 copies/mL at Week 144 was presented using the DAO missing data approach. The final analysis for this outcome is presented here. |
| Percentage of Participants With HIV-1 RNA <200 Copies/mL at Week 144 | 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. The percentage of participants with HIV-1 RNA \<200 copies/mL at Week 144 was presented using the DAO missing data approach. The final analysis for this outcome is presented here. |
| Mean Change From Baseline in Cluster of Differentiation 4+ (CD4+) T-Cell Counts at Week 48 | Baseline (Day 1) and Week 48 | Plasma CD4+ T-cell count was measured in cells/mm\^3 for baseline and at Week 48 by a central laboratory. Baseline measurements were defined as the Day 1 value of each participant. The mean change from baseline in CD4+ T-cell count at Week 48 using the Data as Observed (DAO) approach was presented. The final analysis for this outcome is presented here. |
| Mean Change From Baseline in Cluster of Differentiation 4+ (CD4+) T-Cell Counts at Week 96 | Baseline (Day 1) and Week 96 | Plasma CD4+ T-cell count was measured in cells/mm\^3 for baseline and at Week 96 by a central laboratory. Baseline measurements were defined as the Day 1 value of each participant. The mean change from baseline in CD4+ T-cell count at Week 96 using the Data as Observed (DAO) approach was presented. The final analysis for this outcome is presented here. |
| Mean Change From Baseline in Cluster of Differentiation 4+ (CD4+) T-Cell Counts at Week 144 | Baseline (Day 1) and Week 144 | Plasma CD4+ T-cell count was measured in cells/mm\^3 for baseline and at Week 144 by a central laboratory. Baseline measurements were defined as the Day 1 value of each participant. The mean change from baseline in CD4+ T-cell count at Week 144 using the Data as Observed (DAO) approach was presented. The final analysis for this outcome is presented here. |
| Incidence of Viral Resistance-Associated Substitutions (RASs) at Week 48 | Week 48 | RASs was defined as participants with confirmed HIV-1 RNA ≥200 copies/mL and/or genotypic or phenotypic analysis of data showing evidence of resistance to the study drug administered. The number of participants who demonstrated RASs at Week 48 was presented. The final analysis for this outcome is presented here. |
| Incidence of Viral RASs at Week 96 | Week 96 | RASs was defined as participants with confirmed HIV-1 RNA ≥200 copies/mL and/or genotypic or phenotypic analysis of data showing evidence of resistance to the study drug administered. The number of participants who demonstrated RASs at Week 96 was presented. The final analysis for this outcome is presented here. |
| Incidence of Viral RASs at Week 144 | Week 144 | RASs was defined as participants with confirmed HIV-1 RNA ≥200 copies/mL and/or genotypic or phenotypic analysis of data showing evidence of resistance to the study drug administered. The number of participants who demonstrated RASs at Week 144 was presented. The final analysis for this outcome is presented here. |
| Mean Change From Baseline in Body Weight at Week 48 | Baseline (Day 1) and Week 48 | Body weight was measured at baseline and at Week 48. Participants removed their shoes and wore a single layer of clothing at each measurement. Baseline measurements were defined as the Day 1 value of each participant. The mean change from baseline in body weight at Week 48 was presented. The final analysis for this outcome is presented here. |
| Mean Change From Baseline in Body Weight at Week 96 | Baseline (Day 1) and Week 96 | Body weight was measured at baseline and at Week 96. Participants removed their shoes and wore a single layer of clothing at each measurement. Baseline measurements were defined as the Day 1 value of each participant. The mean change from baseline in body weight at Week 96 was presented. The final analysis for this outcome is presented here. |
| Mean Change From Baseline in Body Weight at Week 144 | Baseline (Day 1) and Week 144 | Body weight was measured at baseline and at Week 144. Participants removed their shoes and wore a single layer of clothing at each measurement. Baseline measurements were defined as the Day 1 value of each participant. The mean change from baseline in body weight at Week 144 was presented. The final analysis for this outcome is presented here. |
| Percentage of Participants Who Experienced an Adverse Event (AE) | Up to approximately 47 months | An AE was any untoward medical occurrence in a study participant administered a study drug, which does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the study drug whether or not it is considered related to the study drug. 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. The final analysis for this outcome is presented here. |
| Percentage of Participants Who Discontinued Study Treatment Due to an AE | Up to approximately 38 months | An AE was any untoward medical occurrence in a study participant administered a study drug, which does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the study drug whether or not it is considered related to the study drug. 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. The final analysis for this outcome is presented here. |
Countries
Argentina, Canada, Chile, Colombia, France, Germany, Israel, Italy, Japan, South Africa, Spain, Taiwan, United States
Contacts
STUDY_DIRECTORMedical Director
Merck Sharp & Dohme LLC
Participant flow
Recruitment details
Treatment-naïve participants living with Human Immunodeficiency Virus-1 (HIV-1) that had not received ≤10 days of prior antiretroviral therapy were enrolled.
Pre-assignment details
A total of 599 participants were randomized in the study and 597 received at least 1 dose of study intervention. The safety analyses were conducted using all participants as treated population, which included all randomized participants who received at least 1 dose of study intervention.
Participants by arm
| Arm | Count |
|---|---|
| Group 1: DOR/ISL Treatment-naïve participants with HIV-1 received blinded Doravirine/Islatravir (DOR/ISL) and placebo to Bictegravir/Tenofovir Alafenamide/Emtricitabine (BIC/FTC/TAF) once daily (QD) from Day 1 to Week 96, and open-label DOR/ISL up to Week 144. Participants who were benefitting from treatment were then eligible to continue on open-label DOR/ISL up to Week 168. | 298 |
| Group 2: BIC/FTC/TAF Treatment-naïve participants with HIV-1 received blinded BIC/FTC/TAF and placebo to DOR/ISL QD from Day 1 to Week 96, and open-label BIC/FTC/TAF up to Week 144. Participants who were benefitting from treatment were then eligible to continue on open-label BIC/FTC/TAF up to Week 168. | 301 |
| Total | 599 |
Baseline characteristics
| Characteristic | Group 2: BIC/FTC/TAF | Total | Group 1: DOR/ISL |
|---|---|---|---|
| Age, Continuous | 35.7 Years STANDARD_DEVIATION 10.9 | 35.2 Years STANDARD_DEVIATION 10.9 | 34.7 Years STANDARD_DEVIATION 11 |
| Baseline Cluster of Differentiation 4+ (CD4+) T-Cell Count <200 cells/mm^3 | 60 Participants | 121 Participants | 61 Participants |
| Baseline Cluster of Differentiation 4+ (CD4+) T-Cell Count ≥200 cells/mm^3 | 239 Participants | 476 Participants | 237 Participants |
| Baseline Cluster of Differentiation 4+ (CD4+) T-Cell Count Missing | 2 Participants | 2 Participants | 0 Participants |
| Baseline Human Immunodeficiency Virus (HIV)-1 Ribonucleic Acid (RNA) Level ≤100,000 copies/mL | 239 Participants | 483 Participants | 244 Participants |
| Baseline Human Immunodeficiency Virus (HIV)-1 Ribonucleic Acid (RNA) Level >100,000 copies/mL | 60 Participants | 114 Participants | 54 Participants |
| Baseline Human Immunodeficiency Virus (HIV)-1 Ribonucleic Acid (RNA) Level Missing | 2 Participants | 2 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 112 Participants | 235 Participants | 123 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 184 Participants | 355 Participants | 171 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 5 Participants | 9 Participants | 4 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 2 Participants | 4 Participants | 2 Participants |
| Race (NIH/OMB) Asian | 20 Participants | 36 Participants | 16 Participants |
| Race (NIH/OMB) Black or African American | 90 Participants | 176 Participants | 86 Participants |
| Race (NIH/OMB) More than one race | 19 Participants | 42 Participants | 23 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) White | 169 Participants | 340 Participants | 171 Participants |
| Sex: Female, Male Female | 71 Participants | 148 Participants | 77 Participants |
| Sex: Female, Male Male | 230 Participants | 451 Participants | 221 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 2 / 298 | 0 / 266 | 0 / 146 | 0 / 301 | 0 / 267 | 0 / 143 | 0 / 21 | 0 / 27 | 1 / 112 | 0 / 128 |
| other Total, other adverse events | 146 / 298 | 115 / 266 | 42 / 146 | 141 / 299 | 124 / 267 | 37 / 143 | 3 / 21 | 2 / 27 | 8 / 112 | 2 / 128 |
| serious Total, serious adverse events | 19 / 298 | 14 / 266 | 3 / 146 | 16 / 299 | 13 / 267 | 1 / 143 | 0 / 21 | 0 / 27 | 3 / 112 | 1 / 128 |
Outcome results
Primary
Percentage of Participants Who Discontinued Study Treatment Due to an AE up to Week 48
An AE is any untoward medical occurrence in a study participant administered a study drug, which does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the study drug whether or not it is considered related to the study drug. The percentage of participants who discontinued study treatment due to an AE were reported.
Time frame: Up to approximately 48 weeks
Population: All randomized participants who received at least one dose of study intervention.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group 1: DOR/ISL | Percentage of Participants Who Discontinued Study Treatment Due to an AE up to Week 48 | 7.4 Percentage of participants |
| Group 2: BIC/FTC/TAF | Percentage of Participants Who Discontinued Study Treatment Due to an AE up to Week 48 | 3.3 Percentage of participants |
95% CI: [0.4, 7.9]
Primary
Percentage of Participants Who Experienced an Adverse Event (AE) up to Week 48
An AE is any untoward medical occurrence in a study participant administered a study drug, which does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the study drug whether or not it is considered related to the study drug. The percentage of participants who experience an AE was reported.
Time frame: Up to approximately 48 weeks
Population: All randomized participants who received at least one dose of study intervention.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group 1: DOR/ISL | Percentage of Participants Who Experienced an Adverse Event (AE) up to Week 48 | 90.6 Percentage of participants |
| Group 2: BIC/FTC/TAF | Percentage of Participants Who Experienced an Adverse Event (AE) up to Week 48 | 86.3 Percentage of participants |
95% CI: [-0.8, 9.6]
Primary
Percentage of Participants With Human Immunodeficiency Virus (HIV)-1 Ribonucleic Acid (RNA) <50 Copies/mL at Week 48
HIV-1 RNA levels in blood samples taken at each visit were measured by the Abbott Real Time 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 was presented using the FDA Snapshot missing data approach.
Time frame: Week 48
Population: All randomized participants who received at least one dose of study intervention.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group 1: DOR/ISL | Percentage of Participants With Human Immunodeficiency Virus (HIV)-1 Ribonucleic Acid (RNA) <50 Copies/mL at Week 48 | 88.9 Percentage of participants |
| Group 2: BIC/FTC/TAF | Percentage of Participants With Human Immunodeficiency Virus (HIV)-1 Ribonucleic Acid (RNA) <50 Copies/mL at Week 48 | 88.3 Percentage of participants |
95% CI: [-4.5, 5.8]
Secondary
Change From Baseline in Body Weight at Week 144
Body weight was measured at baseline and at Week 144. Baseline measurements were defined as the Day 1 value of each participant. The change from baseline in body weight at Week 144 will be presented.
Time frame: Baseline (Day 1) and Week 144
Secondary
Change From Baseline in Body Weight at Week 48
Body weight was measured at baseline and at Week 48. Baseline measurements were defined as the Day 1 value of each participant. The change from baseline in body weight at Week 48 was presented.
Time frame: Baseline (Day 1) and Week 48
Population: All randomized participants who received at least one dose of study intervention and had Week 48 data available for body weight.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Group 1: DOR/ISL | Change From Baseline in Body Weight at Week 48 | 3.45 kilogram |
| Group 2: BIC/FTC/TAF | Change From Baseline in Body Weight at Week 48 | 3.32 kilogram |
p-value: 0.7395% CI: [-0.71, 1.02]ANCOVA
Secondary
Change From Baseline in Body Weight at Week 96
Body weight was measured at baseline and at Week 96. Baseline measurements were defined as the Day 1 value of each participant. The change from baseline in body weight at Week 96 will be presented.
Time frame: Baseline (Day 1) and Week 96
Secondary
Change From Baseline in Cluster of Differentiation 4+ (CD4+) T-Cell Counts at Week 144
Plasma CD4+ T-cell count will be measured in cells/mm\^3 for baseline and 144 weeks by a central laboratory. Baseline measurements were defined as the Day 1 value of each participant. The mean change from baseline in CD4+ T-cell count at Week 144 will be presented.
Time frame: Baseline (Day 1) and Week 144
Secondary
Change From Baseline in Cluster of Differentiation 4+ (CD4+) T-Cell Counts at Week 48
Plasma CD4+ T-cell count was measured in cells/mm\^3 for baseline and 48 weeks by a central laboratory. Baseline measurements were defined as the Day 1 value of each participant. The mean change from baseline in CD4+ T-cell count at Week 48 was presented.
Time frame: Baseline (Day 1) and Week 48
Population: All randomized participants who received at least one dose of study intervention and who have baseline data.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Group 1: DOR/ISL | Change From Baseline in Cluster of Differentiation 4+ (CD4+) T-Cell Counts at Week 48 | 182.4 cells/mm^3 |
| Group 2: BIC/FTC/TAF | Change From Baseline in Cluster of Differentiation 4+ (CD4+) T-Cell Counts at Week 48 | 233.5 cells/mm^3 |
Secondary
Change From Baseline in Cluster of Differentiation 4+ (CD4+) T-Cell Counts at Week 96
Plasma CD4+ T-cell count will be measured in cells/mm\^3 for baseline and 96 weeks by a central laboratory. Baseline measurements were defined as the Day 1 value of each participant. The mean change from baseline in CD4+ T-cell count at Week 96 will be presented.
Time frame: Baseline (Day 1) and Week 96
Secondary
Incidence of Viral RASs at Week 144
RASs was defined as participants with confirmed HIV-1 RNA ≥200 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 viral RASs at Week 144 will be presented.
Time frame: Week 144
Secondary
Incidence of Viral RASs at Week 96
RASs was defined as participants with confirmed HIV-1 RNA ≥200 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 viral RASs at Week 96 will be presented.
Time frame: Week 96
Secondary
Incidence of Viral Resistance-Associated Substitutions (RASs) at Week 48
RASs was defined as participants with confirmed HIV-1 RNA ≥200 copies/mL and/or genotypic or phenotypic analysis of data showing evidence of resistance to the study drug administered. The number of participants who demonstrated RASs at Week 48 was presented.
Time frame: Week 48
Population: Participants who meet the definition of confirmed virologic rebound or incomplete virologic response, or who discontinue study intervention for another reason and have HIV-1 RNA ≥200 copies/mL at the time of discontinuation. Among such participants, those with HIV-1 RNA ≥400 copies/mL were included. Participants for whom available genotypic or phenotypic data showed evidence of resistance, irrespective of viral load, were also included.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Group 1: DOR/ISL | Incidence of Viral Resistance-Associated Substitutions (RASs) at Week 48 | 1 Participants |
| Group 2: BIC/FTC/TAF | Incidence of Viral Resistance-Associated Substitutions (RASs) at Week 48 | 0 Participants |
Secondary
Percentage of Participants Who Discontinued Study Treatment Due to an AE up to Week 156
An AE is any untoward medical occurrence in a study participant administered a study drug, which does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the study drug whether or not it is considered related to the study drug. The percentage of participants who discontinued study treatment due to an AE will be reported.
Time frame: Up to approximately 156 weeks
Secondary
Percentage of Participants Who Experienced an Adverse Event (AE) up to Week 156
An AE is any untoward medical occurrence in a study participant administered a study drug, which does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the study drug whether or not it is considered related to the study drug. The percentage of participants who experience an AE will be reported.
Time frame: Up to approximately 156 weeks
Secondary
Percentage of Participants With HIV-1 RNA <200 Copies/mL at Week 144
The percentage of participants with HIV-1 RNA \<200 copies/mL will be determined. The central laboratory will measure plasma HIV-1 RNA using an Abbott Real Time PCR assay with a LLOD of 40 copies/mL. The percentage of participants with HIV-1 RNA \<200 copies/mL at Week 144 will be presented using the FDA Snapshot missing data approach.
Time frame: Week 144
Secondary
Percentage of Participants With HIV-1 RNA <200 Copies/mL at Week 48
The percentage of participants with HIV-1 RNA \<200 copies/mL will be determined. The central laboratory will measure plasma HIV-1 RNA using an Abbott Real Time PCR assay with a LLOD of 40 copies/mL. The percentage of participants with HIV-1 RNA \<200 copies/mL at Week 48 will be presented using the FDA Snapshot missing data approach.
Time frame: Week 48
Population: All randomized participants who received at least one dose of study intervention.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group 1: DOR/ISL | Percentage of Participants With HIV-1 RNA <200 Copies/mL at Week 48 | 89.6 Percentage of participants |
| Group 2: BIC/FTC/TAF | Percentage of Participants With HIV-1 RNA <200 Copies/mL at Week 48 | 88.6 Percentage of participants |
95% CI: [-4.1, 6.1]
Secondary
Percentage of Participants With HIV-1 RNA <200 Copies/mL at Week 96
The percentage of participants with HIV-1 RNA \<200 copies/mL will be determined. The central laboratory will measure plasma HIV-1 RNA using an Abbott Real Time PCR assay with a LLOD of 40 copies/mL. The percentage of participants with HIV-1 RNA \<200 copies/mL at Week 96 will be presented using the FDA Snapshot missing data approach.
Time frame: Week 96
Secondary
Percentage of Participants With HIV-1 RNA <40 Copies/mL at Week 144
The percentage of participants with HIV-1 RNA \<40 copies/mL will be determined. The central laboratory will measure plasma HIV-1 RNA using an Abbott Real Time PCR assay with a LLOD of 40 copies/mL. The percentage of participants with HIV-1 RNA \<40 copies/mL at Week 144 will be presented using the FDA Snapshot missing data approach.
Time frame: Week 144
Secondary
Percentage of Participants With HIV-1 RNA <40 Copies/mL at Week 48
The percentage of participants with HIV-1 RNA \<40 copies/mL will be determined. The central laboratory will measure plasma HIV-1 RNA using an Abbott Real Time PCR assay with a LLOD of 40 copies/mL. The percentage of participants with HIV-1 RNA \<40 copies/mL at Week 48 will be presented using the FDA Snapshot missing data approach.
Time frame: Week 48
Population: All randomized participants who received at least one dose of study intervention.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group 1: DOR/ISL | Percentage of Participants With HIV-1 RNA <40 Copies/mL at Week 48 | 88.6 Percentage of participants |
| Group 2: BIC/FTC/TAF | Percentage of Participants With HIV-1 RNA <40 Copies/mL at Week 48 | 86.3 Percentage of participants |
95% CI: [-3.1, 7.7]
Secondary
Percentage of Participants With HIV-1 RNA <40 Copies/mL at Week 96
The percentage of participants with HIV-1 RNA \<40 copies/mL will be determined. The central laboratory will measure plasma HIV-1 RNA using an Abbott Real Time PCR assay with a LLOD of 40 copies/mL. The percentage of participants with HIV-1 RNA \<40 copies/mL at Week 96 will be presented using the FDA Snapshot missing data approach.
Time frame: Week 96
Secondary
Percentage of Participants With HIV-1 RNA <50 Copies/mL at Week 144
The percentage of participants with HIV-1 RNA \<50 copies/mL will be determined. The central laboratory will measure plasma HIV-1 RNA using an Abbott Real Time PCR assay with a LLOD of 40 copies/mL. The percentage of participants with HIV-1 RNA \<50 copies/mL at Week 144 will be presented using the FDA Snapshot missing data approach.
Time frame: Week 144
Secondary
Percentage of Participants With HIV-1 RNA <50 Copies/mL at Week 96
The percentage of participants with HIV-1 RNA \<50 copies/mL will be determined. The central laboratory will measure plasma HIV-1 RNA using an Abbott Real Time PCR assay with a LLOD of 40 copies/mL. The percentage of participants with HIV-1 RNA \<50 copies/mL at Week 96 will be presented using the FDA Snapshot missing data approach.
Time frame: Week 96