HIV-1 Infection
Conditions
Brief summary
The primary objectives of this study are to evaluate the safety and tolerability of a switch to Doravirine/Islatravir (DOR/ISL) compared with continued baseline antiretroviral therapy (ART), through Week 48; and to evaluate the antiretroviral activity of a switch to DOR/ISL compared with continued baseline ART at Week 48. The primary hypothesis is that DOR/ISL is non-inferior to continued baseline ART, as assessed by the percentage of participants with HIV-1 ribonucleic acid (RNA) ≥50 copies/mL at Week 48, with a margin of 4 percentage points used to define non-inferiority.
Interventions
DRUGDOR/ISL
Single tablet combination of 100 mg doravirine (DOR) with 0.25 mg Islatravir (ISL) in tablet form, taken orally, once daily.
DRUGART
Standard of care ART, per approved product list, taken orally
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-1 (HIV-1) positive with plasma HIV-1 Ribonucleic Acid (RNA) \<50 copies/mL at screening * Has been receiving continuous, stable oral 2-drug or 3-drug combination (± PK booster) antiretroviral therapy ART with documented viral suppression (HIV-1 RNA \<50 copies/mL) for ≥3 consecutive months prior to providing documented informed consent and has no history of prior virologic treatment failure on any past or current regimen * Female is not a participant of childbearing potential (POCBP); or if a POCBP uses an acceptable contraceptive method or abstains from penile-vaginal intercourse as their preferred and usual lifestyle; has a negative highly sensitive pregnancy test; and whose medical history, menstrual history, and recent sexual activity has been reviewed by the investigator
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 a diagnosis of an active acquired immunodeficiency syndrome (AIDS)-defining opportunistic infection within 30 days prior to screening * Has active hepatitis B virus (HBV) infection * Has chronic hepatitis C virus (HCV) infection consistent with cirrhosis * Has a ≤5 years prior history of malignancy * Is taking or is anticipated to require systemic immunosuppressive therapy, immune modulators, or strong and moderate cytochrome P450 3A (CYP3A) inducers * Has taken long-acting HIV therapy at any time * Is currently participating in or has participated in a clinical study and received (or is receiving) 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 Doravine (DOR)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With HIV-1 RNA ≥50 Copies/mL at Week 48 | Week 48 | HIV-1 RNA levels in plasma were measured by polymerase chain reaction (PCR) assay with a reliable lower limit of quantification of \<50 copies/mL. The percentage of participants with HIV-1 RNA ≥50 copies/mL at Week 48 is presented using the FDA Snapshot missing data approach. |
| Percentage of Participants With One or More Adverse Events (AEs) at Week 48 | Up to Week 48 | An AE is defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The percentage of participants who experienced at least one AE from Day 1 up to Week 48 are reported. |
| Percentage of Participants With an AE Leading to Discontinuation of Study Intervention at Week 48 | Up to Week 48 | An AE is defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The percentage of participants who experienced at least one AE leading to discontinuation of study intervention from Day 1 up to Week 48 are reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With HIV-1 RNA <200 Copies/mL at Week 96 | Week 96 | HIV-1 RNA levels in plasma were measured by a polymerase chain reaction (PCR) assay with a reliable lower limit of quantification of \<50 copies/mL. The percentage of participants with HIV-1 RNA \<200 copies/mL at Week 96 is presented using the FDA Snapshot missing data approach. |
| Participants With HIV-1 RNA <200 Copies/mL at Week 144 | Week 144 | HIV-1 RNA levels in plasma were measured by a polymerase chain reaction (PCR) assay with a reliable lower limit of quantification of \<50 copies/mL. The percentage of participants with HIV-1 RNA \<200 copies/mL at Week 144 is presented using the FDA Snapshot missing data approach. |
| Percentage of Participants With HIV-1 RNA ≥50 Copies/mL at Week 96 | Week 96 | HIV-1 RNA levels in plasma were measured by a polymerase chain reaction (PCR) assay with a reliable lower limit of quantification of \<50 copies/mL. The percentage of participants with HIV-1 RNA ≥50 copies/mL at Week 96 is presented using the FDA Snapshot missing data approach. |
| Percentage of Participants With HIV-1 RNA ≥50 Copies/mL at Week 144 | Week 144 | HIV-1 RNA levels in plasma were measured by a polymerase chain reaction (PCR) assay with a reliable lower limit of quantification of \<50 copies/mL. The percentage of participants with HIV-1 RNA ≥50 copies/mL at Week 144 is presented using the FDA Snapshot missing data approach. |
| Percentage of Participants With HIV-1 RNA <50 Copies/mL at Week 96 | Week 96 | HIV-1 RNA levels in plasma were measured by a polymerase chain reaction (PCR) assay with a reliable lower limit of quantification of \<50 copies/mL. The percentage of participants with HIV-1 RNA \<50 copies/mL at Week 96 is presented using the FDA Snapshot missing data approach. |
| Percentage of Participants With HIV-1 RNA <50 Copies/mL at Week 144 | Week 144 | HIV-1 RNA levels in plasma were measured by a polymerase chain reaction (PCR) assay with a reliable lower limit of quantification of \<50 copies/mL. The percentage of participants with HIV-1 RNA \<50 copies/mL at Week 144 is presented using the FDA Snapshot missing data approach. |
| Mean Change of Plasma Cluster of Differentiation 4 (CD4+) T-Cell Count From Baseline Day 1 to Week 48 | Baseline at Day 1 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 mean change of plasma CD4+ T-Cell count from baseline to Week 48 is presented. |
| Mean Change of Plasma CD4+ T-Cell Count From Baseline Week 48 to Week 96 | Baseline at Week 48 and Week 96 | Mean change from baseline at Week 48 in CD4+ T-cell count at Week 96. This outcome measure is applicable to participants who were randomized to switch to DOR/ISL at Week 48. |
| Mean Change of Plasma CD4+ T-Cell Count From Baseline Day 1 to Week 96 | Baseline at Day 1 and Week 96 | Mean change from baseline at Day 1 in CD4+ T-cell count at Week 96. This outcome measure is applicable to those randomized to start DOR/ISL on Day 1. |
| Mean Change of Plasma CD4+ T-Cell Count From Baseline Day 1 to Week 144 | Baseline at Day 1 and Week 144 | Mean change from baseline at Day 1 in CD4+ T-cell count at Week 144. This outcome measure is applicable to those randomized to start DOR/ISL on Day 1. |
| Mean Change of Plasma CD4+ T-Cell Count From Baseline Day 48 to Week 144 | Baseline at Week 48 and Week 144 | Mean change from baseline at Week 48 in CD4+ T-cell count at Week 144. This outcome measure is applicable to participants who were randomized to switch to DOR/ISL at Week 48. |
| Mean Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) at Week 48 | Baseline and Week 48 | Blood serum samples were taken at baseline and Week 48. The mean change from baseline in fasting Low density lipoprotein cholesterol (LDL-C) at Week 48 is presented for PI-containing regimens (including PI- + InSTI-containing regimens), non-PI- and non-InSTI-containing regimens, and InSTI-containing regimens (non-PI-containing regimens) are presented. |
| Mean Change From Baseline in Fasting Non-High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 48 | Baseline and Week 48 | Blood serum samples were taken at baseline and Week 48. The mean change from baseline in fasting Non-HDL-C at Week 48 is presented for PI-containing regimens (including PI- + InSTI-containing regimens), non-PI- and non-InSTI-containing regimens, and InSTI-containing regimens (non-PI-containing regimens) are presented. |
| Participants With One or More AEs at Week 96 | Up to Week 96 | An AE is defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The percentage of participants who experienced at least one AE from Day 1 up to Week 96 is reported. |
| Participants With One or More AEs at Week 144 | Up to Week 144 | An AE is defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The percentage of participants who experienced at least one AE from Day 1 up to Week 144 is reported. |
| Percentage of Participants With AEs Leading to Discontinuation of Study Intervention at Week 96 | Up to Week 96 | An AE is defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The percentage of participants who experienced at least one AE leading to discontinuation of study intervention from Day 1 up to Week 96 are reported. |
| Percentage of Participants With AEs Leading to Discontinuation of Study Intervention at Week 144 | Up to Week 144 | An AE is defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The percentage of participants who experienced at least one AE leading to discontinuation of study intervention from Day 1 up to Week 144 are reported. |
| Percentage of Participants With One or More AEs From Week 48 up to Week 96 | Week 48 up to Week 96 | An AE is defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The percentage of participants who experienced at least one AE from Week 48 up to Week 96 is reported. |
| Percentage of Participants With One or More AEs From Week 48 up to Week 144 | Week 48 up to Week 144 | An AE is defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The percentage of participants who experienced at least one AE from Week 48 up to Week 144 is presented. |
| Percentage of Participants With AEs Leading to Discontinuation of Study Intervention From Week 48 up to Week 96 | Week 48 up to Week 96 | An AE is defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The percentage of participants who experienced at least one AE leading to discontinuation of study intervention from Week 48 up to Week 96 are reported. |
| Percentage of Participants With AEs Leading to Discontinuation of Study Intervention From Week 48 up to Week 144 | Week 48 up to Week 144 | An AE is defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The percentage of participants who experienced at least one AE leading to discontinuation of study intervention from Week 48 up to Week 144 are reported. |
| Percentage of Participants With Treatment-Emergent, Resistance-associated Substitutions at Week 48 | Up to Week 48 | Participants with clinically significant confirmed viremia \[2 consecutive occurences 4 weeks (+-1 week) apart of HIV-1 RNA \>=200 copies/mL at any time during the study\] or who discontinue study intervention for another reason with HIV-1 RNA \>=200 copies/mL at the time of discontinuation met the criteria for post-baseline resistance testing. Participants with HIV-1 RNA \>=400 copies/mL or any participant for whom available genotypic or phenotypic data show evidence of resistance, irrespective of viral load were included in the resistance analysis subset. Plasma samples were collected for genotypic and phenotypic HIV-1 viral drug resistance testing and used to assess resistance-associated substitutions and virus susceptibility to study intervention. The percentage of participants in the resistance analysis subset with treatment-emergent resistance-associated substitutions to the study intervention is presented. |
| Percentage of Participants With HIV-1 RNA <200 Copies/mL at Week 48 | Week 48 | HIV-1 RNA levels in plasma were measured by a polymerase chain reaction (PCR) assay with a reliable lower limit of quantification of \<50 copies/mL. The percentage of participants with HIV-1 RNA \<200 copies/mL at Week 48 is presented using the FDA Snapshot missing data approach. |
| Percentage of Participants With HIV-1 RNA <50 Copies/mL at Week 48 | Week 48 | HIV-1 RNA levels in plasma were measured by a polymerase chain reaction (PCR) assay with a reliable lower limit of quantification of \<50 copies/mL. The percentage of participants with HIV-1 RNA \<50 copies/mL at Week 48 is presented using the FDA Snapshot missing data approach. |
Countries
Australia, Canada, Colombia, Japan, South Africa, Switzerland, United Kingdom, United States
Participant flow
Recruitment details
Adults living with human immunodeficiency virus-1 (HIV-1) receiving baseline antiretroviral therapy (ART) were enrolled.
Pre-assignment details
Of the 553 participants randomly assigned in a 2:1 ratio to either Group 1: participants switched from baseline ART to doravirine (DOR)/islatravir (ISL) on Day 1 to Week 144; or Group 2: participants continued baseline ART until Week 48 then switch to DOR/ISL from Week 48 to Week 144, 551 participants received treatment.
Participants by arm
| Arm | Count |
|---|---|
| Doravirine/Islatravir (DOR/ISL) Participants with Human Immunodeficiency Virus-1 (HIV-1) that have been virologically suppressed for ≥3 consecutive months who were previously treated with continuous baseline antiretroviral therapy (ART) received doravine/islatravir (DOR/ISL), a fixed dose combination (FDC) of 100 mg DOR/0.25 mg ISL orally once daily (qd) for 144 weeks. At Week 144, participants who consent to enter the optional study extension will continue to receive DOR/ISL qd (100 mg/0.25 mg) for an additional 96 weeks or until it is commercially accessible (whichever comes first). | 368 |
| Baseline ART + DOR/ISL Participants with HIV-1 that has been virologically suppressed for ≥3 consecutive months who were previously treated with continuous baseline ART received standard of care (SOC) ART for 48 weeks, followed by treatment with DOR/ISL as a FDC of 100 mg DOR/0.25 mg ISL orally qd until Week 144. At Week 144, participants who consent to enter the optional study extension will continue to receive DOR/ISL qd (100 mg/0.25 mg) for an additional 96 weeks or until it is commercially accessible (whichever comes first). | 185 |
| Total | 553 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 |
| Overall Study | Death | 0 | 1 |
| Overall Study | Lost to Follow-up | 1 | 2 |
| Overall Study | Ongoing | 353 | 177 |
| Overall Study | Physician Decision | 1 | 0 |
| Overall Study | Withdrawal by Subject | 4 | 1 |
Baseline characteristics
| Characteristic | Total | Doravirine/Islatravir (DOR/ISL) | Baseline ART + DOR/ISL |
|---|---|---|---|
| Age, Continuous | 49.8 Years STANDARD_DEVIATION 12.3 | 49.9 Years STANDARD_DEVIATION 12.6 | 49.5 Years STANDARD_DEVIATION 11.8 |
| Baseline Antiretroviral (ART) Stratification at Randomization All other non-PI- and non-InSTI containing regimens | 167 Count of Participants | 111 Count of Participants | 56 Count of Participants |
| Baseline Antiretroviral (ART) Stratification at Randomization InSTI-based regimens (non-PI containing regimens) | 354 Count of Participants | 233 Count of Participants | 121 Count of Participants |
| Baseline Antiretroviral (ART) Stratification at Randomization PI-containing regimens (including PI- and InSTI-containing regimens) | 30 Count of Participants | 22 Count of Participants | 8 Count of Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 80 Participants | 54 Participants | 26 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 467 Participants | 310 Participants | 157 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 6 Participants | 4 Participants | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 28 Participants | 18 Participants | 10 Participants |
| Race (NIH/OMB) Black or African American | 250 Participants | 166 Participants | 84 Participants |
| Race (NIH/OMB) More than one race | 54 Participants | 38 Participants | 16 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 2 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) White | 217 Participants | 143 Participants | 74 Participants |
| Sex: Female, Male Female | 219 Participants | 152 Participants | 67 Participants |
| Sex: Female, Male Male | 334 Participants | 216 Participants | 118 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 368 | 1 / 185 |
| other Total, other adverse events | 123 / 366 | 73 / 185 |
| serious Total, serious adverse events | 23 / 366 | 9 / 185 |
Outcome results
Primary
Percentage of Participants With an AE Leading to Discontinuation of Study Intervention at Week 48
An AE is defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The percentage of participants who experienced at least one AE leading to discontinuation of study intervention from Day 1 up to Week 48 are reported.
Time frame: Up to Week 48
Population: All randomized participants who received at least one dose of study intervention.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Doravirine/Islatravir (DOR/ISL) | Percentage of Participants With an AE Leading to Discontinuation of Study Intervention at Week 48 | 0.5 Percentage of Participants |
| Baseline ART + DOR/ISL | Percentage of Participants With an AE Leading to Discontinuation of Study Intervention at Week 48 | 2.2 Percentage of Participants |
95% CI: [-4.9, 0.2]
Primary
Percentage of Participants With HIV-1 RNA ≥50 Copies/mL at Week 48
HIV-1 RNA levels in plasma were measured by polymerase chain reaction (PCR) assay with a reliable lower limit of quantification of \<50 copies/mL. The percentage of participants with HIV-1 RNA ≥50 copies/mL at Week 48 is presented using the FDA Snapshot missing data approach.
Time frame: Week 48
Population: All randomized participants who received at least one dose of study intervention and had data for analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Doravirine/Islatravir (DOR/ISL) | Percentage of Participants With HIV-1 RNA ≥50 Copies/mL at Week 48 | 1.4 Percentage of Participants |
| Baseline ART + DOR/ISL | Percentage of Participants With HIV-1 RNA ≥50 Copies/mL at Week 48 | 4.9 Percentage of Participants |
p-value: <0.00195% CI: [-7.81, -0.77]Miettinen and Nurminen
Primary
Percentage of Participants With One or More Adverse Events (AEs) at Week 48
An AE is defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The percentage of participants who experienced at least one AE from Day 1 up to Week 48 are reported.
Time frame: Up to Week 48
Population: All randomized participants who received at least one dose of study intervention.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Doravirine/Islatravir (DOR/ISL) | Percentage of Participants With One or More Adverse Events (AEs) at Week 48 | 79.5 Percentage of Participants |
| Baseline ART + DOR/ISL | Percentage of Participants With One or More Adverse Events (AEs) at Week 48 | 83.8 Percentage of Participants |
95% CI: [-10.7, 2.8]
Secondary
Mean Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) at Week 48
Blood serum samples were taken at baseline and Week 48. The mean change from baseline in fasting Low density lipoprotein cholesterol (LDL-C) at Week 48 is presented for PI-containing regimens (including PI- + InSTI-containing regimens), non-PI- and non-InSTI-containing regimens, and InSTI-containing regimens (non-PI-containing regimens) are presented.
Time frame: Baseline and Week 48
Population: All randomized participants who received at least one dose of study intervention and had baseline data and at least one post-baseline test result in the specified analysis window.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Doravirine/Islatravir (DOR/ISL) | Mean Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) at Week 48 | PI-containing regimens (including PI- + InSTI-containing regimens) | -7.10 mg/dL |
| Doravirine/Islatravir (DOR/ISL) | Mean Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) at Week 48 | non-PI- and non-InSTI-containing regimens | 5.07 mg/dL |
| Doravirine/Islatravir (DOR/ISL) | Mean Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) at Week 48 | InSTI-containing regimens (non-PI-containing regimens) | 2.45 mg/dL |
| Baseline ART + DOR/ISL | Mean Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) at Week 48 | PI-containing regimens (including PI- + InSTI-containing regimens) | -2.75 mg/dL |
| Baseline ART + DOR/ISL | Mean Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) at Week 48 | non-PI- and non-InSTI-containing regimens | 0.29 mg/dL |
| Baseline ART + DOR/ISL | Mean Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) at Week 48 | InSTI-containing regimens (non-PI-containing regimens) | -0.37 mg/dL |
Comparison: PI-containing regimens (including PI- + InSTI-containing regimens)p-value: 0.83495% CI: [-24.91, 20.49]ANCOVA
Comparison: non-PI- and non-InSTI-containing regimensp-value: 0.42595% CI: [-5.08, 11.97]ANCOVA
Comparison: InSTI-containing regimens (non-PI-containing regimens)p-value: 0.161895% CI: [-1.5, 8.95]ANCOVA
Secondary
Mean Change From Baseline in Fasting Non-High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 48
Blood serum samples were taken at baseline and Week 48. The mean change from baseline in fasting Non-HDL-C at Week 48 is presented for PI-containing regimens (including PI- + InSTI-containing regimens), non-PI- and non-InSTI-containing regimens, and InSTI-containing regimens (non-PI-containing regimens) are presented.
Time frame: Baseline and Week 48
Population: All randomized participants who received at least one dose of study intervention and had baseline data and at least one post-baseline test result in the specified analysis window.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Doravirine/Islatravir (DOR/ISL) | Mean Change From Baseline in Fasting Non-High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 48 | PI-containing regimens (including PI- + InSTI-containing regimens) | -11.80 mg/dL |
| Doravirine/Islatravir (DOR/ISL) | Mean Change From Baseline in Fasting Non-High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 48 | non-PI- and non-InSTI-containing regimens | 5.78 mg/dL |
| Doravirine/Islatravir (DOR/ISL) | Mean Change From Baseline in Fasting Non-High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 48 | InSTI-containing regimens (non-PI-containing regimens) | 3.60 mg/dL |
| Baseline ART + DOR/ISL | Mean Change From Baseline in Fasting Non-High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 48 | PI-containing regimens (including PI- + InSTI-containing regimens) | -2.75 mg/dL |
| Baseline ART + DOR/ISL | Mean Change From Baseline in Fasting Non-High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 48 | non-PI- and non-InSTI-containing regimens | 0.44 mg/dL |
| Baseline ART + DOR/ISL | Mean Change From Baseline in Fasting Non-High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 48 | InSTI-containing regimens (non-PI-containing regimens) | 3.29 mg/dL |
Comparison: PI-containing regimens (including PI- + InSTI-containing regimens)95% CI: [-29.8, 15.77]
Comparison: non-PI- and non-InSTI-containing regimens95% CI: [-5.22, 13.21]
Comparison: InSTI-containing regimens (non-PI-containing regimens)95% CI: [-6.83, 8.87]
Secondary
Mean Change of Plasma CD4+ T-Cell Count From Baseline Day 1 to Week 144
Mean change from baseline at Day 1 in CD4+ T-cell count at Week 144. This outcome measure is applicable to those randomized to start DOR/ISL on Day 1.
Time frame: Baseline at Day 1 and Week 144
Secondary
Mean Change of Plasma CD4+ T-Cell Count From Baseline Day 1 to Week 96
Mean change from baseline at Day 1 in CD4+ T-cell count at Week 96. This outcome measure is applicable to those randomized to start DOR/ISL on Day 1.
Time frame: Baseline at Day 1 and Week 96
Secondary
Mean Change of Plasma CD4+ T-Cell Count From Baseline Day 48 to Week 144
Mean change from baseline at Week 48 in CD4+ T-cell count at Week 144. This outcome measure is applicable to participants who were randomized to switch to DOR/ISL at Week 48.
Time frame: Baseline at Week 48 and Week 144
Secondary
Mean Change of Plasma CD4+ T-Cell Count From Baseline Week 48 to Week 96
Mean change from baseline at Week 48 in CD4+ T-cell count at Week 96. This outcome measure is applicable to participants who were randomized to switch to DOR/ISL at Week 48.
Time frame: Baseline at Week 48 and Week 96
Secondary
Mean Change of Plasma Cluster of Differentiation 4 (CD4+) T-Cell Count From Baseline Day 1 to 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 mean change of plasma CD4+ T-Cell count from baseline to Week 48 is presented.
Time frame: Baseline at Day 1 and Week 48
Population: All randomized participants who received at least one dose of study intervention and who have baseline data.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Doravirine/Islatravir (DOR/ISL) | Mean Change of Plasma Cluster of Differentiation 4 (CD4+) T-Cell Count From Baseline Day 1 to Week 48 | 5.41 cells/mm^3 |
| Baseline ART + DOR/ISL | Mean Change of Plasma Cluster of Differentiation 4 (CD4+) T-Cell Count From Baseline Day 1 to Week 48 | 18.22 cells/mm^3 |
95% CI: [-46.32, 15.47]
Secondary
Participants With HIV-1 RNA <200 Copies/mL at Week 144
HIV-1 RNA levels in plasma were measured by a polymerase chain reaction (PCR) assay with a reliable lower limit of quantification of \<50 copies/mL. The percentage of participants with HIV-1 RNA \<200 copies/mL at Week 144 is presented using the FDA Snapshot missing data approach.
Time frame: Week 144
Secondary
Participants With One or More AEs at Week 144
An AE is defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The percentage of participants who experienced at least one AE from Day 1 up to Week 144 is reported.
Time frame: Up to Week 144
Secondary
Participants With One or More AEs at Week 96
An AE is defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The percentage of participants who experienced at least one AE from Day 1 up to Week 96 is reported.
Time frame: Up to Week 96
Secondary
Percentage of Participants With AEs Leading to Discontinuation of Study Intervention at Week 144
An AE is defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The percentage of participants who experienced at least one AE leading to discontinuation of study intervention from Day 1 up to Week 144 are reported.
Time frame: Up to Week 144
Secondary
Percentage of Participants With AEs Leading to Discontinuation of Study Intervention at Week 96
An AE is defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The percentage of participants who experienced at least one AE leading to discontinuation of study intervention from Day 1 up to Week 96 are reported.
Time frame: Up to Week 96
Secondary
Percentage of Participants With AEs Leading to Discontinuation of Study Intervention From Week 48 up to Week 144
An AE is defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The percentage of participants who experienced at least one AE leading to discontinuation of study intervention from Week 48 up to Week 144 are reported.
Time frame: Week 48 up to Week 144
Secondary
Percentage of Participants With AEs Leading to Discontinuation of Study Intervention From Week 48 up to Week 96
An AE is defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The percentage of participants who experienced at least one AE leading to discontinuation of study intervention from Week 48 up to Week 96 are reported.
Time frame: Week 48 up to Week 96
Secondary
Percentage of Participants With HIV-1 RNA <200 Copies/mL at Week 48
HIV-1 RNA levels in plasma were measured by a polymerase chain reaction (PCR) assay with a reliable lower limit of quantification of \<50 copies/mL. The percentage of participants with HIV-1 RNA \<200 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 and had data for analysis excluding participants who had at least one major deviation that may substantially affect the results of the outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Doravirine/Islatravir (DOR/ISL) | Percentage of Participants With HIV-1 RNA <200 Copies/mL at Week 48 | 95.6 Percentage of Participants |
| Baseline ART + DOR/ISL | Percentage of Participants With HIV-1 RNA <200 Copies/mL at Week 48 | 95.7 Percentage of Participants |
95% CI: [-3.49, 4.21]
Secondary
Percentage of Participants With HIV-1 RNA <200 Copies/mL at Week 96
HIV-1 RNA levels in plasma were measured by a polymerase chain reaction (PCR) assay with a reliable lower limit of quantification of \<50 copies/mL. The percentage of participants with HIV-1 RNA \<200 copies/mL at Week 96 is presented using the FDA Snapshot missing data approach.
Time frame: Week 96
Secondary
Percentage of Participants With HIV-1 RNA <50 Copies/mL at Week 144
HIV-1 RNA levels in plasma were measured by a polymerase chain reaction (PCR) assay with a reliable lower limit of quantification of \<50 copies/mL. The percentage of participants with HIV-1 RNA \<50 copies/mL at Week 144 is presented using the FDA Snapshot missing data approach.
Time frame: Week 144
Secondary
Percentage of Participants With HIV-1 RNA ≥50 Copies/mL at Week 144
HIV-1 RNA levels in plasma were measured by a polymerase chain reaction (PCR) assay with a reliable lower limit of quantification of \<50 copies/mL. The percentage of participants with HIV-1 RNA ≥50 copies/mL at Week 144 is presented using the FDA Snapshot missing data approach.
Time frame: Week 144
Secondary
Percentage of Participants With HIV-1 RNA <50 Copies/mL at Week 48
HIV-1 RNA levels in plasma were measured by a polymerase chain reaction (PCR) assay with a reliable lower limit of quantification of \<50 copies/mL. The percentage of participants with HIV-1 RNA \<50 copies/mL at Week 48 is presented using the FDA Snapshot missing data approach.
Time frame: Week 48
Population: All randomized participants who received at least one dose of study intervention and had data for analysis excluding participants who had at least one major deviation that may substantially affect the results of the outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Doravirine/Islatravir (DOR/ISL) | Percentage of Participants With HIV-1 RNA <50 Copies/mL at Week 48 | 95.6 Percentage of Participants |
| Baseline ART + DOR/ISL | Percentage of Participants With HIV-1 RNA <50 Copies/mL at Week 48 | 91.9 Percentage of Participants |
95% CI: [-0.31, 8.89]
Secondary
Percentage of Participants With HIV-1 RNA <50 Copies/mL at Week 96
HIV-1 RNA levels in plasma were measured by a polymerase chain reaction (PCR) assay with a reliable lower limit of quantification of \<50 copies/mL. The percentage of participants with HIV-1 RNA \<50 copies/mL at Week 96 is presented using the FDA Snapshot missing data approach.
Time frame: Week 96
Secondary
Percentage of Participants With HIV-1 RNA ≥50 Copies/mL at Week 96
HIV-1 RNA levels in plasma were measured by a polymerase chain reaction (PCR) assay with a reliable lower limit of quantification of \<50 copies/mL. The percentage of participants with HIV-1 RNA ≥50 copies/mL at Week 96 is presented using the FDA Snapshot missing data approach.
Time frame: Week 96
Secondary
Percentage of Participants With One or More AEs From Week 48 up to Week 144
An AE is defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The percentage of participants who experienced at least one AE from Week 48 up to Week 144 is presented.
Time frame: Week 48 up to Week 144
Secondary
Percentage of Participants With One or More AEs From Week 48 up to Week 96
An AE is defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The percentage of participants who experienced at least one AE from Week 48 up to Week 96 is reported.
Time frame: Week 48 up to Week 96
Secondary
Percentage of Participants With Treatment-Emergent, Resistance-associated Substitutions at Week 48
Participants with clinically significant confirmed viremia \[2 consecutive occurences 4 weeks (+-1 week) apart of HIV-1 RNA \>=200 copies/mL at any time during the study\] or who discontinue study intervention for another reason with HIV-1 RNA \>=200 copies/mL at the time of discontinuation met the criteria for post-baseline resistance testing. Participants with HIV-1 RNA \>=400 copies/mL or any participant for whom available genotypic or phenotypic data show evidence of resistance, irrespective of viral load were included in the resistance analysis subset. Plasma samples were collected for genotypic and phenotypic HIV-1 viral drug resistance testing and used to assess resistance-associated substitutions and virus susceptibility to study intervention. The percentage of participants in the resistance analysis subset with treatment-emergent resistance-associated substitutions to the study intervention is presented.
Time frame: Up to Week 48
Population: Participants with HIV-1 RNA \>=400 copies/mL or any participant for whom available genotypic or phenotypic data show evidence of resistance, irrespective of viral load were included in the resistance analysis subset.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Doravirine/Islatravir (DOR/ISL) | Percentage of Participants With Treatment-Emergent, Resistance-associated Substitutions at Week 48 | 0 Percentage of participants |