HIV Infection
Conditions
Brief summary
This study will evaluate the safety and efficacy of a switch to MK-8591A (a fixed dose combination of doravirine and islatravir) in human immunodeficiency virus -1 (HIV-1)-infected participants virologically suppressed on a protocol-specified antiretroviral regimen. The primary hypothesis is that a switch to MK-8591A will be non-inferior to continued treatment with baseline antiretroviral therapy (ART) as assessed by the percentage of participants with HIV-1 ribonucleic acid (RNA) ≥50 copies/mL at Week 48.
Interventions
DRUGDOR/ISL
A FDC of 100 mg DOR/ 0.75 mg ISL taken in tablet form, orally, once daily
DRUGART
Baseline ART regimen will be administered as per approved label. ART medication will not be provided by the Sponsor; participants will provide their own ART medications. Allowed drug classes include nucleoside analog reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), integrase strand transferase inhibitors (InSTIs), fusion inhibitors, chemokine receptor 5 (CCR5) antagonists, post-attachment inhibitor, and pharmacokinetic (PK) boosters.
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Is human immunodeficiency virus (HIV-1) positive * Has been receiving continuous, stable oral 2-drug or 3-drug combination (± pharmacokinetic (PK) booster) with documented viral suppression (HIV-1 RNA \<50 copies/mL) for ≥3 months prior to signing informed consent and has no history of prior virologic treatment failure on any past or current regimen. * Females are eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies: is not a woman of childbearing potential (WOCBP); is a WOCBP and using an acceptable contraceptive method, or be abstinent from heterosexual intercourse as their preferred and usual lifestyle; 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; if a urine test cannot be confirmed as negative (e.g. an ambiguous result), a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive
Exclusion criteria
* Has 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) co-infection * 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 * Is taking or is anticipated to require systemic immunosuppressive therapy, immune modulators, or any prohibited therapies * Is currently taking long-acting cabotegravir-rilpivirine * 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 treatment period * Has a documented or known virologic resistance to doravirine (DOR) * Expects 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 | HIV-1 RNA levels in blood samples taken at each visit were measured by the Abbott RealTime polymerase chain reaction (PCR) assay with a reliable lower limit of quantification of 40 copies/mL. The percentage of participants with HIV-1 RNA ≥50 copies/mL at Week 48 is presented using the FDA Snapshot missing data approach. |
| Percentage of Participants With One or More Adverse Events (AEs) up to Week 48 | Up to ~48 Weeks | An AE was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The percentage of participants who experienced at least one AE was reported. |
| Percentage of Participants Who Discontinued Study Intervention Due to an AE up to Week 48 | Up to ~48 Weeks | An AE was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The percentage of participants who discontinued study intervention due to an AE was reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With HIV-1 RNA <40 or <50 Copies/mL at Week 48 | Week 48 | HIV-1 RNA levels in blood samples taken at each visit were measured by the Abbott RealTime PCR assay with a reliable lower limit of quantification of 40 copies/mL. The percentage of participants with HIV-1 RNA \<40 copies/mL or \<50 copies/mL at Week 48 is presented using the FDA Snapshot missing data approach. |
| Group 2 (Switch-Over): Percentage of Participants With HIV-1 RNA ≥50 Copies/mL, <40 Copies/mL or <50 Copies/mL at Week 96 | Week 96 | HIV-1 RNA levels in blood samples taken at each visit was measured by the Abbott RealTime PCR assay with a reliable lower limit of quantification of 40 copies/mL. The percentage of participants with HIV-1 RNA ≥50 copies/mL, \<40 copies/mL, or \<50 copies/mL at Week 96 is reported for Group 2 participants who delayed switch over from baseline ART to DOR/ISL from Week 48 to Week 96. Per protocol, the percentage of participants with HIV-1 RNA ≥50 copies/mL, \<40 copies/mL, or \<50 copies/mL at Week 96 for Group 1 participants is a separate outcome measure and is presented later in the record. |
| Group 1: Percentage of Participants With HIV-1 RNA ≥50 Copies/mL, <40 Copies/mL or <50 Copies/mL at Week 96 | Week 96 | HIV-1 RNA levels in blood samples taken at each visit was measured by the Abbott RealTime PCR assay with a reliable lower limit of quantification of 40 copies/mL. The percentage of participants with HIV-1 RNA ≥50 copies/mL, \<40 copies/mL, or \<50 copies/mL at Week 96 is reported for Group 1 participants. Per protocol, the percentage of participants with HIV-1 RNA ≥50 copies/mL, \<40 copies/mL, or \<50 copies/mL at Week 96 for Group 2 participants who delayed switch over from baseline ART to DOR/ISL from Week 48 to Week 96 is a separate outcome measure and is presented earlier in the record. |
| Percentage Change From Baseline in CD4+ T-cell Count at Week 48 | Baseline and Week 48 | Plasma CD4+ T-Cell Count was measured in cells/mm\^3 for baseline and 48 weeks. Baseline measurements were defined as the Day 1 value of each participant. The percentage change from baseline to Week 48 is presented. |
| Group 1: Percentage Change From Baseline in CD4+ T-cell Count at Week 96 | Baseline and Week 96 | Plasma CD4+ T-Cell Count was measured in cells/mm\^3 for baseline and 96 weeks. Baseline measurements were defined as the Day 1 value of each participant. The mean percent change from baseline to Week 96 in CD4+ T-cell count is reported for Group 1 participants. Per protocol, the mean percentage change from baseline in CD4+ T-cell count at Week 96 for Group 2 participants was not planned or conducted. |
| Group 1 & Group 2 (Switch-Over): Percentage Change From Week 48 in CD4+ T-cell Count at Week 96 | Week 48 and Week 96 | Plasma CD4+ T-Cell Count was measured in cells/mm\^3 for Week 48 and Week 96. The mean percent change from Week 48 to Week 96 is reported for Group 1 and Group 2 participants who delayed switch over from baseline ART to DOR/ISL Week 48 to Week 96. |
| Percentage of Participants With Evidence of Viral Drug Resistance-associated Substitutions at Week 48 | Week 48 | Viral drug resistance is defined as participants with confirmed HIV-1 RNA ≥400 copies/mL and/or genotypic or phenotypic analysis of data showing evidence of resistance to the study drug administered. The percentage of participants who demonstrated drug resistance at Week 48 is presented. |
| Percentage of Participants With Evidence of Viral Drug Resistance-associated Substitutions at Week 96 | Week 96 | Viral drug resistance was defined as participants with confirmed HIV-1 RNA ≥400 copies/mL and/or genotypic or phenotypic analysis of data showing evidence of resistance to the study drug administered. The percentage of participants who demonstrate drug resistance at Week 96 is presented for Group 1 and Group 2 participants who delayed switch over from baseline ART to DOR/ISL from Week 48 to Week 96. Per protocol, the percentage of participants with evidence of viral drug resistance-associated substitutions from week 0 to week 48 for Group 1 and Group 2 participants is a separate outcome measure and is presented earlier in the record. |
| Change From Baseline to Week 24 in Fasting Lipids in Participants on Protease Inhibitor (PI)-Containing Regimens (Including PI- and Integrase Strand Transferase Inhibitor [InSTI]-Containing Regimens) | Baseline and Week 24 | Blood serum samples were taken at baseline and Week 24. Per protocol, this outcome analysis was conducted in participants on PI-containing regimens (including PI- and InSTI-containing regimens), excluding participants who took lipid-lowering therapy during the study. The fasting lipids consisted of fasting cholesterol, fasting high density lipoprotein (HDL) cholesterol, fasting low density lipoprotein (LDL) cholesterol, fasting non-HDL cholesterol, and fasting triglycerides. The mean change from baseline to Week 24 in fasting lipids is presented. |
| Change From Baseline to Week 24 in Fasting Lipids in Participants on InSTI-based Regimens (Non-PI Containing Regimens) | Baseline and Week 24 | Blood serum samples were taken at baseline and Week 24. Per protocol, this outcome analysis was conducted in participants on InSTI-based regimens (non-PI containing regimens), excluding participants who took lipid-lowering therapy during the study. The fasting lipids consisted of fasting cholesterol, fasting HDL cholesterol, fasting LDL cholesterol, fasting non-HDL cholesterol, and fasting triglycerides. The mean change from baseline to Week 24 in fasting lipids is presented. |
| Change From Baseline to Week 24 in Fasting Lipids in Participants on All Other Non-PI- and Non-InSTI Containing Regimens | Baseline and Week 24 | Blood serum samples were taken at baseline and Week 24. Per protocol, this outcome analysis was conducted in participants on all other non-PI- and non-InSTI containing regimens, excluding participants who took lipid-lowering therapy during the study. The fasting lipids consisted of fasting cholesterol, fasting HDL cholesterol, fasting LDL cholesterol, fasting non-HDL cholesterol, and fasting triglycerides. The mean change from baseline to Week 24 in fasting lipids is presented. |
| Change From Baseline to Week 48 in Fasting Lipids in Participants on Protease Inhibitor (PI)-Containing Regimens (Including PI- and Integrase Strand Transferase Inhibitor [InSTI]-Containing Regimens) | Baseline and Week 48 | Blood serum samples were taken at baseline and Week 48. Per protocol, this outcome analysis was conducted in participants on PI-containing regimens (including PI- and InSTI-containing regimens), excluding participants who took lipid-lowering therapy during the study. The fasting lipids consisted of fasting cholesterol, fasting high density lipoprotein (HDL) cholesterol, fasting low density lipoprotein (LDL) cholesterol, fasting non-HDL cholesterol, and fasting triglycerides. The mean change from baseline to Week 48 in fasting lipids is presented. |
| Change From Baseline to Week 48 in Fasting Lipids in Participants on InSTI-based Regimens (Non-PI Containing Regimens) | Baseline and Week 48 | Blood serum samples were taken at baseline and Week 48. Per protocol, this outcome analysis was conducted in participants on InSTI-based regimens (non-PI containing regimens), excluding participants who took lipid-lowering therapy during the study. The fasting lipids consisted of fasting cholesterol, fasting HDL cholesterol, fasting LDL cholesterol, fasting non-HDL cholesterol, and fasting triglycerides. The mean change from baseline to Week 48 in fasting lipids is presented. |
| Change From Baseline to Week 48 in Fasting Lipids in Participants on All Other Non-PI- and Non-InSTI Containing Regimens | Baseline and Week 48 | Blood serum samples were taken at baseline and Week 48. Per protocol, this outcome analysis was conducted in participants on all other non-PI- and non-InSTI containing regimens, excluding participants who took lipid-lowering therapy during the study. The fasting lipids consisted of fasting cholesterol, fasting HDL cholesterol, fasting LDL cholesterol, fasting non-HDL cholesterol, and fasting triglycerides. The mean change from baseline to Week 48 in fasting lipids is presented. |
| Change From Baseline in Body Weight at Week 48 for InSTI-based Regimens (Non-PI-containing Regimens) | Baseline and Week 48 | Baseline measurements were defined as the Day 1 value of each participant. The change from baseline in body weight to Week 48 is presented for participants who received InSTI- based regimens. |
| Group 1: Percentage of Participants With One or More AEs up to Week 96 | Up to ~96 Weeks | An AE was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The percentage of participants who experienced at least one AE up to Week 96 is reported for Group 1 participants. Per protocol, the percentage of participants with one or more AEs for Group 2 participants is a separate outcome measure and is presented later in the record. |
| Group 1: Percentage of Participants Who Discontinued Study Intervention Due to an AE up to Week 96 | Up to ~96 Weeks | An AE was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The percentage of participants who discontinued study intervention due to an AE up to Week 96 is reported for Group 1 participants. Per protocol, the percentage of participants who discontinued study intervention for Group 2 participants is a separate outcome measure and is presented later in the record. |
| Group 1 & Group 2 (Switch-Over): Percentage of Participants With One or More AEs From Week 48 to Week 96 | Weeks 48-96 (up to ~48 weeks) | An AE was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The percentage of participants who experienced at least one AE from Week 48 up to Week 96 is reported for Group 1 participants and Group 2 participants who delayed switch over from baseline ART to DOR/ISL from Week 48 to Week 96. |
| Group 1 & Group 2 (Switch-Over): Percentage of Participants Who Discontinued Study Intervention Due to an AE From Week 48 to Week 96 | Weeks 48-96 (up to ~48 weeks) | An AE was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The percentage of participants who discontinued study intervention due to an AE from Week 48 up to Week 96 is reported for Group 1 participants and Group 2 participants who delayed switch over from baseline ART to DOR/ISL from Week 48 to Week 96. |
Countries
Australia, Canada, Chile, Colombia, France, Italy, Japan, New Zealand, Poland, Russia, South Africa, Spain, Switzerland, United Kingdom, United States
Contacts
STUDY_DIRECTORMedical Director
Merck Sharp & Dohme LLC
Participant flow
Pre-assignment details
Adult human immunodeficiency virus-1 (HIV-1)-infected participants receiving baseline antiretroviral therapy (ART) were enrolled. 672 participants were randomly assigned in a 1:1 ratio to either Group 1: participants switched from baseline ART to doravirine (DOR)/islatravir (ISL) on Day 1 to Week 96; or Group 2: participants continued baseline ART until Week 48 then delayed switch to DOR/ISL from Week 48 to Week 96.
Participants by arm
| Arm | Count |
|---|---|
| Group 1: Doravirine/Islatravir (DOR/ISL) Participants who were previously treated with continuous baseline antiretroviral therapy (ART) received DOR/ISL, a fixed dose combination (FDC) of 100 mg doravirine (DOR)/0.75 mg islatravir (ISL) orally once daily for 96 weeks. | 336 |
| Group 2: Baseline Antiretroviral Therapy (ART) Participants received continuous baseline ART for 48 weeks. Continuing participants delayed switch over from baseline ART to DOR/ISL, fixed dose combination of 100 mg DOR/0.75 mg ISL orally once daily, from Week 48 to Week 96, a total DOR/ISL treatment duration of 48 Weeks. | 336 |
| Total | 672 |
Baseline characteristics
| Characteristic | Group 2: Baseline Antiretroviral Therapy (ART) | Total | Group 1: Doravirine/Islatravir (DOR/ISL) |
|---|---|---|---|
| Age, Continuous | 45.4 Years STANDARD_DEVIATION 11.7 | 45.5 Years STANDARD_DEVIATION 11.7 | 45.5 Years STANDARD_DEVIATION 11.7 |
| ART Regimen Stratification All other non-PI- and non-InSTI containing regimens | 116 Participants | 232 Participants | 116 Participants |
| ART Regimen Stratification InSTI-based regimens (non-PI containing regimens) | 174 Participants | 348 Participants | 174 Participants |
| ART Regimen Stratification PI-containing regimens (including PI- and InSTI-containing regimens) | 46 Participants | 92 Participants | 46 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 64 Participants | 131 Participants | 67 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 270 Participants | 536 Participants | 266 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants | 5 Participants | 3 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 8 Participants | 12 Participants | 4 Participants |
| Race (NIH/OMB) Asian | 19 Participants | 38 Participants | 19 Participants |
| Race (NIH/OMB) Black or African American | 91 Participants | 179 Participants | 88 Participants |
| Race (NIH/OMB) More than one race | 16 Participants | 29 Participants | 13 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 2 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 4 Participants | 2 Participants |
| Race (NIH/OMB) White | 198 Participants | 408 Participants | 210 Participants |
| Sex: Female, Male Female | 126 Participants | 249 Participants | 123 Participants |
| Sex: Female, Male Male | 210 Participants | 423 Participants | 213 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 336 | 1 / 322 | 1 / 336 | 0 / 326 |
| other Total, other adverse events | 85 / 336 | 115 / 322 | 52 / 336 | 120 / 326 |
| serious Total, serious adverse events | 16 / 336 | 13 / 322 | 15 / 336 | 12 / 326 |
Outcome results
Primary
Percentage of Participants Who Discontinued Study Intervention Due to an AE up to Week 48
An AE was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The percentage of participants who discontinued study intervention due to an AE was reported.
Time frame: Up to ~48 Weeks
Population: All randomized participants who received at least one dose of study intervention.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group 1: Doravirine/Islatravir (DOR/ISL) | Percentage of Participants Who Discontinued Study Intervention Due to an AE up to Week 48 | 2.1 Percentage of Participants |
| Group 2: Baseline Antiretroviral Therapy (ART) | Percentage of Participants Who Discontinued Study Intervention Due to an AE up to Week 48 | 0.3 Percentage of Participants |
95% CI: [0.2, 4]
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 RealTime polymerase chain reaction (PCR) assay with a reliable lower limit of quantification of 40 copies/mL. The percentage of participants with HIV-1 RNA ≥50 copies/mL at Week 48 is presented using the FDA Snapshot missing data approach.
Time frame: Week 48
Population: All randomized participants who received at least one dose of study intervention.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group 1: Doravirine/Islatravir (DOR/ISL) | Percentage of Participants With Human Immunodeficiency Virus (HIV)-1 Ribonucleic Acid (RNA) ≥50 Copies/mL at Week 48 | 0.0 Percentage of Participants |
| Group 2: Baseline Antiretroviral Therapy (ART) | Percentage of Participants With Human Immunodeficiency Virus (HIV)-1 Ribonucleic Acid (RNA) ≥50 Copies/mL at Week 48 | 1.5 Percentage of Participants |
p-value: <0.00195% CI: [-3.44, -0.34]Miettinen and Nurminen
Primary
Percentage of Participants With One or More Adverse Events (AEs) up to Week 48
An AE was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The percentage of participants who experienced at least one AE was reported.
Time frame: Up to ~48 Weeks
Population: All randomized participants who received at least one dose of study intervention.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group 1: Doravirine/Islatravir (DOR/ISL) | Percentage of Participants With One or More Adverse Events (AEs) up to Week 48 | 80.1 Percentage of Participants |
| Group 2: Baseline Antiretroviral Therapy (ART) | Percentage of Participants With One or More Adverse Events (AEs) up to Week 48 | 70.2 Percentage of Participants |
95% CI: [3.3, 16.3]
Secondary
Change From Baseline in Body Weight at Week 48 for InSTI-based Regimens (Non-PI-containing Regimens)
Baseline measurements were defined as the Day 1 value of each participant. The change from baseline in body weight to Week 48 is presented for participants who received InSTI- based regimens.
Time frame: Baseline and Week 48
Population: All randomized participants who received at least one dose of study intervention, had baseline and Week 48 data available for body weight, and received InSTI-based regimens.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Group 1: Doravirine/Islatravir (DOR/ISL) | Change From Baseline in Body Weight at Week 48 for InSTI-based Regimens (Non-PI-containing Regimens) | 0.66 kg |
| Group 2: Baseline Antiretroviral Therapy (ART) | Change From Baseline in Body Weight at Week 48 for InSTI-based Regimens (Non-PI-containing Regimens) | 0.10 kg |
95% CI: [-0.59, 1.46]
Secondary
Change From Baseline to Week 24 in Fasting Lipids in Participants on All Other Non-PI- and Non-InSTI Containing Regimens
Blood serum samples were taken at baseline and Week 24. Per protocol, this outcome analysis was conducted in participants on all other non-PI- and non-InSTI containing regimens, excluding participants who took lipid-lowering therapy during the study. The fasting lipids consisted of fasting cholesterol, fasting HDL cholesterol, fasting LDL cholesterol, fasting non-HDL cholesterol, and fasting triglycerides. The mean change from baseline to Week 24 in fasting lipids is presented.
Time frame: Baseline and Week 24
Population: All randomized participants on all other non-PI- and non-InSTI containing regimens, who received at least one dose of study intervention and had baseline and Week 24 data available for each lipid type, excluding participants who took lipid-lowering therapy during the study, per protocol.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Group 1: Doravirine/Islatravir (DOR/ISL) | Change From Baseline to Week 24 in Fasting Lipids in Participants on All Other Non-PI- and Non-InSTI Containing Regimens | Fasting HDL Cholesterol | -3.43 mg/dL |
| Group 1: Doravirine/Islatravir (DOR/ISL) | Change From Baseline to Week 24 in Fasting Lipids in Participants on All Other Non-PI- and Non-InSTI Containing Regimens | Fasting Non-HDL Cholesterol | 11.07 mg/dL |
| Group 1: Doravirine/Islatravir (DOR/ISL) | Change From Baseline to Week 24 in Fasting Lipids in Participants on All Other Non-PI- and Non-InSTI Containing Regimens | Fasting Cholesterol | 7.18 mg/dL |
| Group 1: Doravirine/Islatravir (DOR/ISL) | Change From Baseline to Week 24 in Fasting Lipids in Participants on All Other Non-PI- and Non-InSTI Containing Regimens | Fasting Triglycerides | -1.16 mg/dL |
| Group 1: Doravirine/Islatravir (DOR/ISL) | Change From Baseline to Week 24 in Fasting Lipids in Participants on All Other Non-PI- and Non-InSTI Containing Regimens | Fasting LDL Cholesterol | 11.33 mg/dL |
| Group 2: Baseline Antiretroviral Therapy (ART) | Change From Baseline to Week 24 in Fasting Lipids in Participants on All Other Non-PI- and Non-InSTI Containing Regimens | Fasting Triglycerides | 4.45 mg/dL |
| Group 2: Baseline Antiretroviral Therapy (ART) | Change From Baseline to Week 24 in Fasting Lipids in Participants on All Other Non-PI- and Non-InSTI Containing Regimens | Fasting Cholesterol | 7.35 mg/dL |
| Group 2: Baseline Antiretroviral Therapy (ART) | Change From Baseline to Week 24 in Fasting Lipids in Participants on All Other Non-PI- and Non-InSTI Containing Regimens | Fasting HDL Cholesterol | -0.72 mg/dL |
| Group 2: Baseline Antiretroviral Therapy (ART) | Change From Baseline to Week 24 in Fasting Lipids in Participants on All Other Non-PI- and Non-InSTI Containing Regimens | Fasting LDL Cholesterol | 7.19 mg/dL |
| Group 2: Baseline Antiretroviral Therapy (ART) | Change From Baseline to Week 24 in Fasting Lipids in Participants on All Other Non-PI- and Non-InSTI Containing Regimens | Fasting Non-HDL Cholesterol | 8.07 mg/dL |
Comparison: Fasting Cholesterol95% CI: [-7.6, 9.7]
Comparison: Fasting HDL Cholesterol95% CI: [-6.37, 0.05]
Comparison: Fasting LDL Cholesterol95% CI: [-2.27, 11.03]
Comparison: Fasting Non-HDL Cholesterol95% CI: [-3.93, 11.19]
Comparison: Fasting Triglycerides95% CI: [-15.89, 12.31]
Secondary
Change From Baseline to Week 24 in Fasting Lipids in Participants on InSTI-based Regimens (Non-PI Containing Regimens)
Blood serum samples were taken at baseline and Week 24. Per protocol, this outcome analysis was conducted in participants on InSTI-based regimens (non-PI containing regimens), excluding participants who took lipid-lowering therapy during the study. The fasting lipids consisted of fasting cholesterol, fasting HDL cholesterol, fasting LDL cholesterol, fasting non-HDL cholesterol, and fasting triglycerides. The mean change from baseline to Week 24 in fasting lipids is presented.
Time frame: Baseline and Week 24
Population: All randomized participants on InSTI-based regimens (non-PI containing regimens) who received at least one dose of study intervention and had baseline and Week 24 data available for each lipid type, excluding participants who took lipid-lowering therapy during the study, per protocol.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Group 1: Doravirine/Islatravir (DOR/ISL) | Change From Baseline to Week 24 in Fasting Lipids in Participants on InSTI-based Regimens (Non-PI Containing Regimens) | Fasting HDL Cholesterol | 0.84 mg/dL |
| Group 1: Doravirine/Islatravir (DOR/ISL) | Change From Baseline to Week 24 in Fasting Lipids in Participants on InSTI-based Regimens (Non-PI Containing Regimens) | Fasting Non-HDL Cholesterol | 2.14 mg/dL |
| Group 1: Doravirine/Islatravir (DOR/ISL) | Change From Baseline to Week 24 in Fasting Lipids in Participants on InSTI-based Regimens (Non-PI Containing Regimens) | Fasting LDL Cholesterol | 3.21 mg/dL |
| Group 1: Doravirine/Islatravir (DOR/ISL) | Change From Baseline to Week 24 in Fasting Lipids in Participants on InSTI-based Regimens (Non-PI Containing Regimens) | Fasting Triglycerides | -0.97 mg/dL |
| Group 1: Doravirine/Islatravir (DOR/ISL) | Change From Baseline to Week 24 in Fasting Lipids in Participants on InSTI-based Regimens (Non-PI Containing Regimens) | Fasting Cholesterol | 2.98 mg/dL |
| Group 2: Baseline Antiretroviral Therapy (ART) | Change From Baseline to Week 24 in Fasting Lipids in Participants on InSTI-based Regimens (Non-PI Containing Regimens) | Fasting Triglycerides | -1.56 mg/dL |
| Group 2: Baseline Antiretroviral Therapy (ART) | Change From Baseline to Week 24 in Fasting Lipids in Participants on InSTI-based Regimens (Non-PI Containing Regimens) | Fasting Cholesterol | 8.74 mg/dL |
| Group 2: Baseline Antiretroviral Therapy (ART) | Change From Baseline to Week 24 in Fasting Lipids in Participants on InSTI-based Regimens (Non-PI Containing Regimens) | Fasting HDL Cholesterol | 0.27 mg/dL |
| Group 2: Baseline Antiretroviral Therapy (ART) | Change From Baseline to Week 24 in Fasting Lipids in Participants on InSTI-based Regimens (Non-PI Containing Regimens) | Fasting LDL Cholesterol | 8.50 mg/dL |
| Group 2: Baseline Antiretroviral Therapy (ART) | Change From Baseline to Week 24 in Fasting Lipids in Participants on InSTI-based Regimens (Non-PI Containing Regimens) | Fasting Non-HDL Cholesterol | 8.47 mg/dL |
Comparison: Fasting Cholesterol95% CI: [-10.43, 2.09]
Comparison: Fasting HDL Cholesterol95% CI: [-1.46, 3.09]
Comparison: Fasting LDL Cholesterol95% CI: [-9.47, 1.74]
Comparison: Fasting Non-HDL Cholesterol95% CI: [-11.21, 1.38]
Comparison: Fasting Triglycerides95% CI: [-16.14, 19.43]
Secondary
Change From Baseline to Week 24 in Fasting Lipids in Participants on Protease Inhibitor (PI)-Containing Regimens (Including PI- and Integrase Strand Transferase Inhibitor [InSTI]-Containing Regimens)
Blood serum samples were taken at baseline and Week 24. Per protocol, this outcome analysis was conducted in participants on PI-containing regimens (including PI- and InSTI-containing regimens), excluding participants who took lipid-lowering therapy during the study. The fasting lipids consisted of fasting cholesterol, fasting high density lipoprotein (HDL) cholesterol, fasting low density lipoprotein (LDL) cholesterol, fasting non-HDL cholesterol, and fasting triglycerides. The mean change from baseline to Week 24 in fasting lipids is presented.
Time frame: Baseline and Week 24
Population: All randomized participants on PI-containing regimens (including PI- and InSTI-containing regimens) who received at least one dose of study intervention and had baseline and Week 24 data available for each lipid type, excluding participants who took lipid-lowering therapy during the study, per protocol.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Group 1: Doravirine/Islatravir (DOR/ISL) | Change From Baseline to Week 24 in Fasting Lipids in Participants on Protease Inhibitor (PI)-Containing Regimens (Including PI- and Integrase Strand Transferase Inhibitor [InSTI]-Containing Regimens) | Fasting HDL | -0.97 mg/dL |
| Group 1: Doravirine/Islatravir (DOR/ISL) | Change From Baseline to Week 24 in Fasting Lipids in Participants on Protease Inhibitor (PI)-Containing Regimens (Including PI- and Integrase Strand Transferase Inhibitor [InSTI]-Containing Regimens) | Fasting Non-HDL Cholesterol | -11.97 mg/dL |
| Group 1: Doravirine/Islatravir (DOR/ISL) | Change From Baseline to Week 24 in Fasting Lipids in Participants on Protease Inhibitor (PI)-Containing Regimens (Including PI- and Integrase Strand Transferase Inhibitor [InSTI]-Containing Regimens) | Fasting LDL Cholesterol | -7.47 mg/dL |
| Group 1: Doravirine/Islatravir (DOR/ISL) | Change From Baseline to Week 24 in Fasting Lipids in Participants on Protease Inhibitor (PI)-Containing Regimens (Including PI- and Integrase Strand Transferase Inhibitor [InSTI]-Containing Regimens) | Fasting Triglycerides | -22.69 mg/dL |
| Group 1: Doravirine/Islatravir (DOR/ISL) | Change From Baseline to Week 24 in Fasting Lipids in Participants on Protease Inhibitor (PI)-Containing Regimens (Including PI- and Integrase Strand Transferase Inhibitor [InSTI]-Containing Regimens) | Fasting Cholesterol | -12.94 mg/dL |
| Group 2: Baseline Antiretroviral Therapy (ART) | Change From Baseline to Week 24 in Fasting Lipids in Participants on Protease Inhibitor (PI)-Containing Regimens (Including PI- and Integrase Strand Transferase Inhibitor [InSTI]-Containing Regimens) | Fasting Triglycerides | -3.16 mg/dL |
| Group 2: Baseline Antiretroviral Therapy (ART) | Change From Baseline to Week 24 in Fasting Lipids in Participants on Protease Inhibitor (PI)-Containing Regimens (Including PI- and Integrase Strand Transferase Inhibitor [InSTI]-Containing Regimens) | Fasting Cholesterol | 6.20 mg/dL |
| Group 2: Baseline Antiretroviral Therapy (ART) | Change From Baseline to Week 24 in Fasting Lipids in Participants on Protease Inhibitor (PI)-Containing Regimens (Including PI- and Integrase Strand Transferase Inhibitor [InSTI]-Containing Regimens) | Fasting HDL | 0.76 mg/dL |
| Group 2: Baseline Antiretroviral Therapy (ART) | Change From Baseline to Week 24 in Fasting Lipids in Participants on Protease Inhibitor (PI)-Containing Regimens (Including PI- and Integrase Strand Transferase Inhibitor [InSTI]-Containing Regimens) | Fasting LDL Cholesterol | 5.93 mg/dL |
| Group 2: Baseline Antiretroviral Therapy (ART) | Change From Baseline to Week 24 in Fasting Lipids in Participants on Protease Inhibitor (PI)-Containing Regimens (Including PI- and Integrase Strand Transferase Inhibitor [InSTI]-Containing Regimens) | Fasting Non-HDL Cholesterol | 5.44 mg/dL |
Comparison: Fasting Cholesterol95% CI: [-33.07, -6.44]
Comparison: Fasting HDL Cholesterol95% CI: [-6.55, 3.84]
Comparison: Fasting LDL Cholesterol95% CI: [-24.69, -3.2]
Comparison: Fasting Non-HDL Cholesterol95% CI: [-30.02, -5.46]
Comparison: Fasting Triglycerides95% CI: [-45.51, 2.96]
Secondary
Change From Baseline to Week 48 in Fasting Lipids in Participants on All Other Non-PI- and Non-InSTI Containing Regimens
Blood serum samples were taken at baseline and Week 48. Per protocol, this outcome analysis was conducted in participants on all other non-PI- and non-InSTI containing regimens, excluding participants who took lipid-lowering therapy during the study. The fasting lipids consisted of fasting cholesterol, fasting HDL cholesterol, fasting LDL cholesterol, fasting non-HDL cholesterol, and fasting triglycerides. The mean change from baseline to Week 48 in fasting lipids is presented.
Time frame: Baseline and Week 48
Population: All randomized participants on all other non-PI- and non-InSTI containing regimens, who received at least one dose of study intervention and had baseline and Week 48 data available for each lipid type, excluding participants who took lipid-lowering therapy during the study, per protocol.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Group 1: Doravirine/Islatravir (DOR/ISL) | Change From Baseline to Week 48 in Fasting Lipids in Participants on All Other Non-PI- and Non-InSTI Containing Regimens | Fasting HDL Cholesterol | -3.84 mg/dL |
| Group 1: Doravirine/Islatravir (DOR/ISL) | Change From Baseline to Week 48 in Fasting Lipids in Participants on All Other Non-PI- and Non-InSTI Containing Regimens | Fasting Non-HDL Cholesterol | 9.94 mg/dL |
| Group 1: Doravirine/Islatravir (DOR/ISL) | Change From Baseline to Week 48 in Fasting Lipids in Participants on All Other Non-PI- and Non-InSTI Containing Regimens | Fasting LDL Cholesterol | 9.27 mg/dL |
| Group 1: Doravirine/Islatravir (DOR/ISL) | Change From Baseline to Week 48 in Fasting Lipids in Participants on All Other Non-PI- and Non-InSTI Containing Regimens | Fasting Triglycerides | 3.33 mg/dL |
| Group 1: Doravirine/Islatravir (DOR/ISL) | Change From Baseline to Week 48 in Fasting Lipids in Participants on All Other Non-PI- and Non-InSTI Containing Regimens | Fasting Cholesterol | 5.66 mg/dL |
| Group 2: Baseline Antiretroviral Therapy (ART) | Change From Baseline to Week 48 in Fasting Lipids in Participants on All Other Non-PI- and Non-InSTI Containing Regimens | Fasting Triglycerides | -2.97 mg/dL |
| Group 2: Baseline Antiretroviral Therapy (ART) | Change From Baseline to Week 48 in Fasting Lipids in Participants on All Other Non-PI- and Non-InSTI Containing Regimens | Fasting Cholesterol | 4.62 mg/dL |
| Group 2: Baseline Antiretroviral Therapy (ART) | Change From Baseline to Week 48 in Fasting Lipids in Participants on All Other Non-PI- and Non-InSTI Containing Regimens | Fasting HDL Cholesterol | -1.98 mg/dL |
| Group 2: Baseline Antiretroviral Therapy (ART) | Change From Baseline to Week 48 in Fasting Lipids in Participants on All Other Non-PI- and Non-InSTI Containing Regimens | Fasting LDL Cholesterol | 7.30 mg/dL |
| Group 2: Baseline Antiretroviral Therapy (ART) | Change From Baseline to Week 48 in Fasting Lipids in Participants on All Other Non-PI- and Non-InSTI Containing Regimens | Fasting Non-HDL Cholesterol | 6.61 mg/dL |
Comparison: Fasting Cholesterol95% CI: [-5.54, 10.17]
Comparison: Fasting HDL Cholesterol95% CI: [-5.69, 0.65]
Comparison: Fasting LDL Cholesterol95% CI: [-3.73, 8.42]
Comparison: Fasting Non-HDL Cholesterol95% CI: [-2.63, 10.56]
Comparison: Fasting Triglycerides95% CI: [-3.97, 24.96]
Secondary
Change From Baseline to Week 48 in Fasting Lipids in Participants on InSTI-based Regimens (Non-PI Containing Regimens)
Blood serum samples were taken at baseline and Week 48. Per protocol, this outcome analysis was conducted in participants on InSTI-based regimens (non-PI containing regimens), excluding participants who took lipid-lowering therapy during the study. The fasting lipids consisted of fasting cholesterol, fasting HDL cholesterol, fasting LDL cholesterol, fasting non-HDL cholesterol, and fasting triglycerides. The mean change from baseline to Week 48 in fasting lipids is presented.
Time frame: Baseline and Week 48
Population: All randomized participants on InSTI-based regimens (non-PI containing regimens) who received at least one dose of study intervention and had baseline and Week 48 data available for each lipid type, excluding participants who took lipid-lowering therapy during the study, per protocol.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Group 1: Doravirine/Islatravir (DOR/ISL) | Change From Baseline to Week 48 in Fasting Lipids in Participants on InSTI-based Regimens (Non-PI Containing Regimens) | Fasting HDL Cholesterol | 0.23 mg/dL |
| Group 1: Doravirine/Islatravir (DOR/ISL) | Change From Baseline to Week 48 in Fasting Lipids in Participants on InSTI-based Regimens (Non-PI Containing Regimens) | Fasting Non-HDL Cholesterol | 2.00 mg/dL |
| Group 1: Doravirine/Islatravir (DOR/ISL) | Change From Baseline to Week 48 in Fasting Lipids in Participants on InSTI-based Regimens (Non-PI Containing Regimens) | Fasting LDL Cholesterol | 2.74 mg/dL |
| Group 1: Doravirine/Islatravir (DOR/ISL) | Change From Baseline to Week 48 in Fasting Lipids in Participants on InSTI-based Regimens (Non-PI Containing Regimens) | Fasting Triglycerides | -2.29 mg/dL |
| Group 1: Doravirine/Islatravir (DOR/ISL) | Change From Baseline to Week 48 in Fasting Lipids in Participants on InSTI-based Regimens (Non-PI Containing Regimens) | Fasting Cholesterol | 2.23 mg/dL |
| Group 2: Baseline Antiretroviral Therapy (ART) | Change From Baseline to Week 48 in Fasting Lipids in Participants on InSTI-based Regimens (Non-PI Containing Regimens) | Fasting Triglycerides | 4.44 mg/dL |
| Group 2: Baseline Antiretroviral Therapy (ART) | Change From Baseline to Week 48 in Fasting Lipids in Participants on InSTI-based Regimens (Non-PI Containing Regimens) | Fasting Cholesterol | 4.39 mg/dL |
| Group 2: Baseline Antiretroviral Therapy (ART) | Change From Baseline to Week 48 in Fasting Lipids in Participants on InSTI-based Regimens (Non-PI Containing Regimens) | Fasting HDL Cholesterol | 0.13 mg/dL |
| Group 2: Baseline Antiretroviral Therapy (ART) | Change From Baseline to Week 48 in Fasting Lipids in Participants on InSTI-based Regimens (Non-PI Containing Regimens) | Fasting LDL Cholesterol | 3.44 mg/dL |
| Group 2: Baseline Antiretroviral Therapy (ART) | Change From Baseline to Week 48 in Fasting Lipids in Participants on InSTI-based Regimens (Non-PI Containing Regimens) | Fasting Non-HDL Cholesterol | 4.37 mg/dL |
Comparison: Fasting Cholesterol95% CI: [-6.26, 6.18]
Comparison: Fasting HDL Cholesterol95% CI: [-1.84, 2.54]
Comparison: Fasting LDL Cholesterol95% CI: [-4.83, 6.11]
Comparison: Fasting Non-HDL Cholesterol95% CI: [-6.81, 5.83]
Comparison: Fasting Triglycerides95% CI: [-20.46, 9.57]
Comparison: Fasting LDL Cholesterol - Multiplicity Adjustedp-value: 0.409395% CI: [-5.63, 6.9]ANCOVA
Comparison: Fasting Non-HDL Cholesterol - Multiplicity Adjustedp-value: 0.439795% CI: [-7.72, 6.75]ANCOVA
Secondary
Change From Baseline to Week 48 in Fasting Lipids in Participants on Protease Inhibitor (PI)-Containing Regimens (Including PI- and Integrase Strand Transferase Inhibitor [InSTI]-Containing Regimens)
Blood serum samples were taken at baseline and Week 48. Per protocol, this outcome analysis was conducted in participants on PI-containing regimens (including PI- and InSTI-containing regimens), excluding participants who took lipid-lowering therapy during the study. The fasting lipids consisted of fasting cholesterol, fasting high density lipoprotein (HDL) cholesterol, fasting low density lipoprotein (LDL) cholesterol, fasting non-HDL cholesterol, and fasting triglycerides. The mean change from baseline to Week 48 in fasting lipids is presented.
Time frame: Baseline and Week 48
Population: All randomized participants on PI-containing regimens (including PI- and InSTI-containing regimens) who received at least one dose of study intervention and had baseline and Week 48 data available for each lipid type, excluding participants who took lipid-lowering therapy during the study, per protocol.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Group 1: Doravirine/Islatravir (DOR/ISL) | Change From Baseline to Week 48 in Fasting Lipids in Participants on Protease Inhibitor (PI)-Containing Regimens (Including PI- and Integrase Strand Transferase Inhibitor [InSTI]-Containing Regimens) | Fasting HDL Cholesterol | -1.45 mg/dL |
| Group 1: Doravirine/Islatravir (DOR/ISL) | Change From Baseline to Week 48 in Fasting Lipids in Participants on Protease Inhibitor (PI)-Containing Regimens (Including PI- and Integrase Strand Transferase Inhibitor [InSTI]-Containing Regimens) | Fasting Non-HDL Cholesterol | -13.86 mg/dL |
| Group 1: Doravirine/Islatravir (DOR/ISL) | Change From Baseline to Week 48 in Fasting Lipids in Participants on Protease Inhibitor (PI)-Containing Regimens (Including PI- and Integrase Strand Transferase Inhibitor [InSTI]-Containing Regimens) | Fasting LDL Cholesterol | -8.59 mg/dL |
| Group 1: Doravirine/Islatravir (DOR/ISL) | Change From Baseline to Week 48 in Fasting Lipids in Participants on Protease Inhibitor (PI)-Containing Regimens (Including PI- and Integrase Strand Transferase Inhibitor [InSTI]-Containing Regimens) | Fasting Triglycerides | -26.90 mg/dL |
| Group 1: Doravirine/Islatravir (DOR/ISL) | Change From Baseline to Week 48 in Fasting Lipids in Participants on Protease Inhibitor (PI)-Containing Regimens (Including PI- and Integrase Strand Transferase Inhibitor [InSTI]-Containing Regimens) | Fasting Cholesterol | -15.31 mg/dL |
| Group 2: Baseline Antiretroviral Therapy (ART) | Change From Baseline to Week 48 in Fasting Lipids in Participants on Protease Inhibitor (PI)-Containing Regimens (Including PI- and Integrase Strand Transferase Inhibitor [InSTI]-Containing Regimens) | Fasting Triglycerides | 2.28 mg/dL |
| Group 2: Baseline Antiretroviral Therapy (ART) | Change From Baseline to Week 48 in Fasting Lipids in Participants on Protease Inhibitor (PI)-Containing Regimens (Including PI- and Integrase Strand Transferase Inhibitor [InSTI]-Containing Regimens) | Fasting Cholesterol | 1.84 mg/dL |
| Group 2: Baseline Antiretroviral Therapy (ART) | Change From Baseline to Week 48 in Fasting Lipids in Participants on Protease Inhibitor (PI)-Containing Regimens (Including PI- and Integrase Strand Transferase Inhibitor [InSTI]-Containing Regimens) | Fasting HDL Cholesterol | -1.08 mg/dL |
| Group 2: Baseline Antiretroviral Therapy (ART) | Change From Baseline to Week 48 in Fasting Lipids in Participants on Protease Inhibitor (PI)-Containing Regimens (Including PI- and Integrase Strand Transferase Inhibitor [InSTI]-Containing Regimens) | Fasting LDL Cholesterol | 3.37 mg/dL |
| Group 2: Baseline Antiretroviral Therapy (ART) | Change From Baseline to Week 48 in Fasting Lipids in Participants on Protease Inhibitor (PI)-Containing Regimens (Including PI- and Integrase Strand Transferase Inhibitor [InSTI]-Containing Regimens) | Fasting Non-HDL Cholesterol | 2.81 mg/dL |
Comparison: Fasting Cholesterol95% CI: [-32.05, -4.76]
Comparison: Fasting HDL Cholesterol95% CI: [-5.06, 5.08]
Comparison: Fasting LDL Cholesterol95% CI: [-25.81, -2.43]
Comparison: Fasting Non-HDL Cholesterol95% CI: [-30.45, -6]
Comparison: Fasting Triglycerides95% CI: [-51.08, -4.49]
Comparison: Fasting LDL Cholesterol - Multiplicity Adjustedp-value: 0.009495% CI: [-27.56, -0.68]ANCOVA
Comparison: Fasting Non-HDL Cholesterol - Multiplicity Adjustedp-value: 0.002195% CI: [-32.28, -4.17]ANCOVA
Secondary
Group 1 & Group 2 (Switch-Over): Percentage Change From Week 48 in CD4+ T-cell Count at Week 96
Plasma CD4+ T-Cell Count was measured in cells/mm\^3 for Week 48 and Week 96. The mean percent change from Week 48 to Week 96 is reported for Group 1 and Group 2 participants who delayed switch over from baseline ART to DOR/ISL Week 48 to Week 96.
Time frame: Week 48 and Week 96
Population: The analysis population consisted of all randomized participants who received at least one dose of study intervention and had data available for this outcome measure for participants in Group 1 and participants in Group 2 who delayed switch over from baseline ART to DOR/ISL from Week 48 to Week 96.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Group 1: Doravirine/Islatravir (DOR/ISL) | Group 1 & Group 2 (Switch-Over): Percentage Change From Week 48 in CD4+ T-cell Count at Week 96 | 5.29 Percentage Change |
| Group 2: Baseline Antiretroviral Therapy (ART) | Group 1 & Group 2 (Switch-Over): Percentage Change From Week 48 in CD4+ T-cell Count at Week 96 | 0.16 Percentage Change |
Secondary
Group 1 & Group 2 (Switch-Over): Percentage of Participants Who Discontinued Study Intervention Due to an AE From Week 48 to Week 96
An AE was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The percentage of participants who discontinued study intervention due to an AE from Week 48 up to Week 96 is reported for Group 1 participants and Group 2 participants who delayed switch over from baseline ART to DOR/ISL from Week 48 to Week 96.
Time frame: Weeks 48-96 (up to ~48 weeks)
Population: The analysis population consisted of all randomized participants who received at least one dose of study intervention for participants in Group 1 and participants in Group 2 who delayed switch over from baseline ART to DOR/ISL from Week 48 to Week 96.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group 1: Doravirine/Islatravir (DOR/ISL) | Group 1 & Group 2 (Switch-Over): Percentage of Participants Who Discontinued Study Intervention Due to an AE From Week 48 to Week 96 | 3.7 Percentage of Participants |
| Group 2: Baseline Antiretroviral Therapy (ART) | Group 1 & Group 2 (Switch-Over): Percentage of Participants Who Discontinued Study Intervention Due to an AE From Week 48 to Week 96 | 2.5 Percentage of Participants |
Secondary
Group 1 & Group 2 (Switch-Over): Percentage of Participants With One or More AEs From Week 48 to Week 96
An AE was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The percentage of participants who experienced at least one AE from Week 48 up to Week 96 is reported for Group 1 participants and Group 2 participants who delayed switch over from baseline ART to DOR/ISL from Week 48 to Week 96.
Time frame: Weeks 48-96 (up to ~48 weeks)
Population: The analysis population consisted of all randomized participants who received at least one dose of study intervention for participants in Group 1 and participants in Group 2 who delayed switch over from baseline ART to DOR/ISL from Week 48 to Week 96.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group 1: Doravirine/Islatravir (DOR/ISL) | Group 1 & Group 2 (Switch-Over): Percentage of Participants With One or More AEs From Week 48 to Week 96 | 73.0 Percentage of Participants |
| Group 2: Baseline Antiretroviral Therapy (ART) | Group 1 & Group 2 (Switch-Over): Percentage of Participants With One or More AEs From Week 48 to Week 96 | 76.4 Percentage of Participants |
Secondary
Group 1: Percentage 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. Baseline measurements were defined as the Day 1 value of each participant. The mean percent change from baseline to Week 96 in CD4+ T-cell count is reported for Group 1 participants. Per protocol, the mean percentage change from baseline in CD4+ T-cell count at Week 96 for Group 2 participants was not planned or conducted.
Time frame: Baseline and Week 96
Population: The analysis population consisted of all randomized participants in Group 1 who received at least one dose of study intervention and had data, including baseline data, available for this outcome measure. Per protocol, the percentage change from baseline in CD4+ T-cell count at Week 96 for Group 2 participants was not planned or conducted.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Group 1: Doravirine/Islatravir (DOR/ISL) | Group 1: Percentage Change From Baseline in CD4+ T-cell Count at Week 96 | 4.49 Percentage Change |
Secondary
Group 1: Percentage of Participants Who Discontinued Study Intervention Due to an AE up to Week 96
An AE was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The percentage of participants who discontinued study intervention due to an AE up to Week 96 is reported for Group 1 participants. Per protocol, the percentage of participants who discontinued study intervention for Group 2 participants is a separate outcome measure and is presented later in the record.
Time frame: Up to ~96 Weeks
Population: The analysis population consisted of all randomized participants in Group 1 who received at least one dose of study intervention. Per protocol, the percentage of participants who discontinued study intervention for Group 2 participants is a separate outcome measure and is presented later in the record.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group 1: Doravirine/Islatravir (DOR/ISL) | Group 1: Percentage of Participants Who Discontinued Study Intervention Due to an AE up to Week 96 | 5.7 Percentage of Participants |
Secondary
Group 1: Percentage of Participants With HIV-1 RNA ≥50 Copies/mL, <40 Copies/mL or <50 Copies/mL at Week 96
HIV-1 RNA levels in blood samples taken at each visit was measured by the Abbott RealTime PCR assay with a reliable lower limit of quantification of 40 copies/mL. The percentage of participants with HIV-1 RNA ≥50 copies/mL, \<40 copies/mL, or \<50 copies/mL at Week 96 is reported for Group 1 participants. Per protocol, the percentage of participants with HIV-1 RNA ≥50 copies/mL, \<40 copies/mL, or \<50 copies/mL at Week 96 for Group 2 participants who delayed switch over from baseline ART to DOR/ISL from Week 48 to Week 96 is a separate outcome measure and is presented earlier in the record.
Time frame: Week 96
Population: The analysis population consisted of all randomized participants in Group 1 who received at least one dose of study intervention and had data available for this outcome measure. Per protocol, the percentage of participants with HIV-1 RNA ≥50 copies/mL, \<40 copies/mL, or \<50 copies/mL at Week 96 for Group 2 participants who delayed switch over from baseline ART to DOR/ISL from Week 48 to Week 96 is a separate outcome measure and is presented earlier in the record.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Group 1: Doravirine/Islatravir (DOR/ISL) | Group 1: Percentage of Participants With HIV-1 RNA ≥50 Copies/mL, <40 Copies/mL or <50 Copies/mL at Week 96 | HIV-1 RNA ≥50 copies/mL | 1.2 Percentage of Participants |
| Group 1: Doravirine/Islatravir (DOR/ISL) | Group 1: Percentage of Participants With HIV-1 RNA ≥50 Copies/mL, <40 Copies/mL or <50 Copies/mL at Week 96 | HIV-1 RNA <40 copies/mL | 86.0 Percentage of Participants |
| Group 1: Doravirine/Islatravir (DOR/ISL) | Group 1: Percentage of Participants With HIV-1 RNA ≥50 Copies/mL, <40 Copies/mL or <50 Copies/mL at Week 96 | HIV-1 RNA <50 copies/mL | 85.7 Percentage of Participants |
Secondary
Group 1: Percentage of Participants With One or More AEs up to Week 96
An AE was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The percentage of participants who experienced at least one AE up to Week 96 is reported for Group 1 participants. Per protocol, the percentage of participants with one or more AEs for Group 2 participants is a separate outcome measure and is presented later in the record.
Time frame: Up to ~96 Weeks
Population: The analysis population consisted of all randomized participants in Group 1 who received at least one dose of study intervention. Per protocol, the percentage of participants with one or more AEs for Group 2 participants is a separate outcome measure and is presented later in the record.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group 1: Doravirine/Islatravir (DOR/ISL) | Group 1: Percentage of Participants With One or More AEs up to Week 96 | 92.3 Percentage of Participants |
Secondary
Group 2 (Switch-Over): Percentage of Participants With HIV-1 RNA ≥50 Copies/mL, <40 Copies/mL or <50 Copies/mL at Week 96
HIV-1 RNA levels in blood samples taken at each visit was measured by the Abbott RealTime PCR assay with a reliable lower limit of quantification of 40 copies/mL. The percentage of participants with HIV-1 RNA ≥50 copies/mL, \<40 copies/mL, or \<50 copies/mL at Week 96 is reported for Group 2 participants who delayed switch over from baseline ART to DOR/ISL from Week 48 to Week 96. Per protocol, the percentage of participants with HIV-1 RNA ≥50 copies/mL, \<40 copies/mL, or \<50 copies/mL at Week 96 for Group 1 participants is a separate outcome measure and is presented later in the record.
Time frame: Week 96
Population: The analysis population consisted of all randomized participants in Group 2 who delayed switch over from baseline ART to DOR/ISL from Week 48 to Week 96 who received at least one dose of study intervention and had data available for this outcome measure. Per protocol, the percentage of participants with HIV-1 RNA ≥50 copies/mL, \<40 copies/mL, or \<50 copies/mL at Week 96 for Group 1 participants is a separate outcome measure and is presented later in the record.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Group 2: Baseline Antiretroviral Therapy (ART) | Group 2 (Switch-Over): Percentage of Participants With HIV-1 RNA ≥50 Copies/mL, <40 Copies/mL or <50 Copies/mL at Week 96 | HIV-1 RNA ≥50 copies/mL | 0.9 Percentage of Participants |
| Group 2: Baseline Antiretroviral Therapy (ART) | Group 2 (Switch-Over): Percentage of Participants With HIV-1 RNA ≥50 Copies/mL, <40 Copies/mL or <50 Copies/mL at Week 96 | HIV-1 RNA <50 copies/mL | 89.6 Percentage of Participants |
| Group 2: Baseline Antiretroviral Therapy (ART) | Group 2 (Switch-Over): Percentage of Participants With HIV-1 RNA ≥50 Copies/mL, <40 Copies/mL or <50 Copies/mL at Week 96 | HIV-1 RNA <40 copies/mL | 89.6 Percentage of Participants |
Secondary
Percentage Change From Baseline in CD4+ T-cell Count at Week 48
Plasma CD4+ T-Cell Count was measured in cells/mm\^3 for baseline and 48 weeks. Baseline measurements were defined as the Day 1 value of each participant. The percentage change from baseline to Week 48 is presented.
Time frame: Baseline 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: Doravirine/Islatravir (DOR/ISL) | Percentage Change From Baseline in CD4+ T-cell Count at Week 48 | -0.7 Percentage Change |
| Group 2: Baseline Antiretroviral Therapy (ART) | Percentage Change From Baseline in CD4+ T-cell Count at Week 48 | 8.7 Percentage Change |
95% CI: [-13.4, -4.5]
Secondary
Percentage of Participants With Evidence of Viral Drug Resistance-associated Substitutions at Week 48
Viral drug resistance is defined as participants with confirmed HIV-1 RNA ≥400 copies/mL and/or genotypic or phenotypic analysis of data showing evidence of resistance to the study drug administered. The percentage of participants who demonstrated drug resistance at Week 48 is presented.
Time frame: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group 1: Doravirine/Islatravir (DOR/ISL) | Percentage of Participants With Evidence of Viral Drug Resistance-associated Substitutions at Week 48 | 0.0 Percentage of Participants |
| Group 2: Baseline Antiretroviral Therapy (ART) | Percentage of Participants With Evidence of Viral Drug Resistance-associated Substitutions at Week 48 | 0.9 Percentage of Participants |
Secondary
Percentage of Participants With Evidence of Viral Drug Resistance-associated Substitutions at Week 96
Viral drug resistance was defined as participants with confirmed HIV-1 RNA ≥400 copies/mL and/or genotypic or phenotypic analysis of data showing evidence of resistance to the study drug administered. The percentage of participants who demonstrate drug resistance at Week 96 is presented for Group 1 and Group 2 participants who delayed switch over from baseline ART to DOR/ISL from Week 48 to Week 96. Per protocol, the percentage of participants with evidence of viral drug resistance-associated substitutions from week 0 to week 48 for Group 1 and Group 2 participants is a separate outcome measure and is presented earlier in the record.
Time frame: Week 96
Population: Analysis population included participants with virologic rebound (2 repeated incidents of HIV-1 RNA ≥200 copies/mL, 2-4 weeks apart) or who discontinued study intervention with HIV-1 RNA ≥200 copies/mL. Participants with available data showing resistance, despite viral load, are included. Per protocol, percentage of participants with evidence of viral drug resistance associated substitutions from week 0 to week 48 for Groups 1 and 2 is a separate outcome measure reported earlier in the record.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group 1: Doravirine/Islatravir (DOR/ISL) | Percentage of Participants With Evidence of Viral Drug Resistance-associated Substitutions at Week 96 | 0.0 Percentage of Participants |
| Group 2: Baseline Antiretroviral Therapy (ART) | Percentage of Participants With Evidence of Viral Drug Resistance-associated Substitutions at Week 96 | 0.0 Percentage of Participants |
Secondary
Percentage of Participants With HIV-1 RNA <40 or <50 Copies/mL at Week 48
HIV-1 RNA levels in blood samples taken at each visit were measured by the Abbott RealTime PCR assay with a reliable lower limit of quantification of 40 copies/mL. The percentage of participants with HIV-1 RNA \<40 copies/mL or \<50 copies/mL at Week 48 is presented using the FDA Snapshot missing data approach.
Time frame: Week 48
Population: All randomized participants who received at least one dose of study intervention.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Group 1: Doravirine/Islatravir (DOR/ISL) | Percentage of Participants With HIV-1 RNA <40 or <50 Copies/mL at Week 48 | HIV-1 RNA <40 copies/mL | 94.6 Percentage of Participants |
| Group 1: Doravirine/Islatravir (DOR/ISL) | Percentage of Participants With HIV-1 RNA <40 or <50 Copies/mL at Week 48 | HIV-1 RNA <50 copies/mL | 95.2 Percentage of Participants |
| Group 2: Baseline Antiretroviral Therapy (ART) | Percentage of Participants With HIV-1 RNA <40 or <50 Copies/mL at Week 48 | HIV-1 RNA <40 copies/mL | 94.3 Percentage of Participants |
| Group 2: Baseline Antiretroviral Therapy (ART) | Percentage of Participants With HIV-1 RNA <40 or <50 Copies/mL at Week 48 | HIV-1 RNA <50 copies/mL | 94.3 Percentage of Participants |
Comparison: HIV-1 RNA \<40 copies/mL95% CI: [-3.28, 3.9]
Comparison: HIV-1 RNA \<50 copies/mL95% CI: [-2.58, 4.43]