HIV Infections
Conditions
Keywords
Treatment Naive, HIV-1 infected treatment naive patients
Brief summary
The purpose of this study is to compare the proportion of subjects with HIV-1 RNA viral load \< 50 c/mL through Week 48 of the Maintenance Phase among HIV-infected subjects with an initial undetectable viral load following an Induction Phase with an ATV/RTV containing HAART regimen, when switched to ATV versus remaining on ATV/RTV, whilst continuing their previous NRTI backbone.
Interventions
DRUGAtazanavir + 2 NRTIs
Capsules, tablets, Oral, 48 weeks (after a 26-to-30-week induction phase with ATV 300 mg + RTV 100 mg + 2 NRTIs)
DRUGAtazanavir + Ritonavir + 2 NRTIs
Capsules, tablets, Oral, 48 weeks (after a 26-to-30-week induction phase with ATV 300 mg + RTV 100 mg + 2 NRTIs)
Sponsors
Bristol-Myers Squibb
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
* Treatment naive HIV-1 infected subjects ( \< 10 days of treatment with any ARV). * Subjects who have an HIV-1 RNA level ≥ 5000 c/mL at screening. * Subjects who have a CD4 count ≥ 50 cells/mm3. * Men and women, ages 18 years of age or older (or minimum age as determined by local regulatory or as legal requirements dictate). * Both females of child-bearing potential and males must utilize effective barrier contraception. Other contraception in addition to barrier methods is permitted; refer to the Investigator Brochure for details regarding potential interactions with ATV and some oral contraceptives
Exclusion criteria
* WOCBP who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for up to 8 weeks after the study. * WOCBP using a prohibited contraceptive method. Caution is warranted with coadministration of oral contraceptives (ethinyl estradiol and norethindrone) - see Investigator Brochure for details * Women who are pregnant or breastfeeding * Women with a positive pregnancy test on enrollment or prior to study drug administration. * Presence of a newly diagnosed HIV-related opportunistic infection or any medical condition requiring acute therapy at the time of enrollment * Primary HIV infection * Medical History and Concurrent Diseases * Active alcohol or substance use sufficient, in the investigator's opinion, to prevent adequate compliance with study therapy or to increase the risk of developing pancreatitis or chemical hepatitis Physical and Laboratory Test Findings * Screening laboratory values measured as follows: * Grade IV glucose, * Grade IV electrolytes, * Grade IV transaminases, * Grade IV hematology. * Hypersensitivity to any component of the formulation of study drug * Prior history of taking any ARV for more than 10 days * Concomitant administration of tenofovir (TDF). * Refer to Section 6.4.1 which details all prohibited therapies
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With HIV-1 RNA <50 Copies/mL (c/mL) Through Week 48 of the Maintenance Phase | From the end of Induction Phase (Week 26 to Week 30 of Induction Phase treatment) through Week 48 of Maintenance Phase | Participants were considered successes unless they experienced treatment failure, or had missing Week 48 HIV-1 RNA. Treatment failure: virologic rebound (ie, 2 consecutive on-treatment HIV-1 RNA ≥ 50 c/mL, or last HIV-1 RNA ≥ 50 c/mL followed by discontinuation), or discontinuation before Week 48. Denominator included all randomized participants. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Kaplan-Meier Cumulative Proportion for Treatment Failure (HIV-1 RNA ≥50 c/mL) at Different Time Points Through Week 48 of the Maintenance Phase | Weeks 6-8, Weeks 14-16, Weeks 22-24, Weeks 30-32, Weeks 38-40, Weeks 46-48 | Treatment failure based on HIV-1 RNA ≥ 50 c/mL was defined as virologic rebound on or before Week 48 or discontinuation of study therapy before Week 48 for any reason. Time to treatment failure was analyzed using life tables. Measured Values shows the Kaplan-Meier cumulative proportion of participants without treatment failure up to the end of the respective interval. |
| Kaplan-Meier Cumulative Proportion for Treatment Failure (HIV-1 RNA ≥400 c/mL) at Different Time Points Through Week 48 of the Maintenance Phase | Weeks 6-8, Weeks 14-16, Weeks 22-24, Weeks 30-32, Weeks 38-40, Weeks 46-48 | Treatment failure based on HIV-1 RNA ≥ 400 c/mL was defined as virologic rebound on or before Week 48 or discontinuation of study therapy before Week 48 for any reason. Time to treatment failure was analyzed using life tables. Measured Values shows the Kaplan-Meier cumulative proportion of participants without treatment failure up to the end of the respective interval. |
| Change From End of Induction Phase in CD4 Cell Count at Week 48 of Maintenance Phase | End of Induction Phase (Week 26 to Week 30 of Induction Phase treatment), Week 48 of Maintenance Phase | Change in CD4 Cell Count From End of Induction Phase at Week 48 of Maintenance Phase. Change=Week 48 maintenance Phase value - end of Induction Phase value; a decrease signifies worsening. |
| Change From Baseline in CD4 Cell Count at Week 24 of Induction Phase | Baseline, Week 24 of Induction Phase | Change From Baseline in CD4 Count at Week 24 of Induction Phase. Change=Week 24 Induction Phase value - Baseline value; a decrease signifies worsening. |
| Change From Baseline in CD4 Cell Count at Week 48 of Rescue Phase | Baseline, Week 48 of Rescue Phase | Change From Baseline in CD4 Count at Week 48 of Rescue Phase. Change=Week 48 Rescue Phase value - Baseline value; a decrease signifies worsening. |
| Change From Baseline in HIV-1 RNA at Week 24 of the Induction Phase | Baseline, Week 24 of Induction Phase | Change From Baseline in HIV-1 RNA at Week 24 of the Induction Phase. Change=Week 24 Induction Phase value - Baseline value; a decrease signifies improvement. |
| Change From Baseline in HIV-1 RNA at Week 48 of the Rescue Phase | \Baseline, Week 48 of Rescue Phase | Change From Baseline in HIV-1 RNA at Week 48 of the Rescue Phase. Change=Week 48 Rescue Phase value - Baseline value; a decrease signifies improvement. |
| Percentage of Participants With HIV-1 RNA <400 c/mL Through Week 48 of the Maintenance Phase | From the end of Induction Phase (Week 26 to Week 30 of Induction Phase treatment) through Week 48 of Maintenance Phase | Participants were considered successes unless they experienced treatment failure, or had missing Week 48 HIV-1 RNA. Treatment failure: virologic rebound (ie, 2 consecutive on-treatment HIV-1 RNA ≥ 400 c/mL, or last HIV-1 RNA ≥ 400 c/mL followed by discontinuation), or discontinuation before Week 48. Denominator included all randomized participants. |
| Treatment Outcomes Based on Viral Loads (HIV-1 RNA ≥400 c/mL) Through the End of Rescue Phase | Baseline, Week 48 of Rescue Phase | Treatment outcome is based on the first reason of failure. These analyses were performed using HIV-1 RNA of 400 c/mL to define suppression and virologic rebound. |
| Time to Suppression (Confirmed HIV-1 RNA < 50 c/mL) During Treatment Phase | Week 16-18, Week 24-26, Week 38-40, Week 64-66 | Description: Time to suppression was measured from the first dose of Induction Phase study therapy to the first of the 2 consecutive measurements \< 50 c/mL. Time to suppression was analyzed using life tables. Measured Values show the Kaplan-Meier cumulative number of treated participants without suppression up to the end of the respective interval. |
| Time to Suppression (Confirmed HIV-1 RNA < 400 c/mL) During Treatment Phase | Week 16-18, Week 24-26, Week 30-32 | Time to suppression was measured from the first dose of Induction Phase study therapy to the first of the 2 consecutive measurements \<400 c/mL. Time to suppression was analyzed using life tables. Measured Values show the Kaplan-Meier cumulative number of treated participants without suppression up to the end of the respective interval. |
| Summary of Adverse Events During Induction Phase | Measurements are included through the earlier of the last dose of Induction Phase study therapy plus 30 days or the first dose of Maintenance/Rescue Phase therapy (ie, up until 26 to 31 weeks + 30 days). | Summary of Adverse Events (AEs), Deaths, Serious AEs (SAEs), and AEs leading to study discontinuation. An AE is defined as any new untoward medical occurrence or worsening of a pre-existing medical condition. An SAE is any untoward medical occurrence that at any dose results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a cancer, is a congenital anomaly/birth defect, results in the development of drug dependency or drug abuse, is an important medical event. |
| Summary of Adverse Events During Maintenance Phase | Measurements are included from the end of Induction Phase (26 to 30 weeks after first dose) through the last dose of Maintenance Phase study therapy plus 30 days. | Summary of Adverse Events (AEs), Deaths, Serious AEs (SAEs), and AEs leading to study discontinuation. An AE is defined as any new untoward medical occurrence or worsening of a pre-existing medical condition. An SAE is any untoward medical occurrence that at any dose results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a cancer, is a congenital anomaly/birth defect, results in the development of drug dependency or drug abuse, is an important medical event. |
| Summary of Adverse Events During Rescue Phase | Measurements are included from the end of Induction Phase (26 to 30 weeks after the first dose therapy) through the last dose of Rescue Phase study therapy plus 30 days. | Summary of Adverse Events (AEs), Deaths, Serious AEs (SAEs), and AEs leading to study discontinuation. An AE is defined as any new untoward medical occurrence or worsening of a pre-existing medical condition. An SAE is any untoward medical occurrence that at any dose results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a cancer, is a congenital anomaly/birth defect, results in the development of drug dependency or drug abuse, is an important medical event. |
| Percent Change From End of Induction Phase in Fasting Lipids at Week 48 of Maintenance Phase | Measurements were included from the end of Induction Phase (Week 26 to Week 30 of Induction therapy) through Week 48 of Maintenance Phase. | Percent change in fasting lipids from end of Induction Phase to Week 48 of Maintenance Phase.Percent changes were calculated on the log scale and then back transformed to the original scale.Change=Week 48 maintenance Phase value - end of Induction Phase value; a decrease signifies worsening for HDL cholesterol and improvement for all other lipds. |
| Treatment Outcomes Based on Viral Loads (HIV-1 RNA ≥50 c/mL) Through the End of Rescue Phase | Through Week 48 of Rescue Phase. Measurements were included from the end of Induction Phase through the last dose of Rescue Phase study therapy plus 4 days. | Treatment outcome is based on the first reason of failure. These analyses were performed using HIV-1 RNA of 50 c/mL to define suppression and virologic rebound. |
Countries
Estonia, France, Germany, Ireland, Italy, Latvia, Portugal, Russia, Spain, United Kingdom
Participant flow
Pre-assignment details
288 subjects were enrolled, of which 36 did not start Induction Phase Therapy (22 did not meet study criteria, 6 withdrew consent, 4 lost to follow-up, 3 had missing information, and 1 for investigator's decision).
Participants by arm
| Arm | Count |
|---|---|
| Randomized Subjects: Switch Regimen ATV 400 mg QD + 2 NRTIs | 87 |
| Randomized Subjects: Continuation Regimen ATV 300 mg + RTV 100 mg QD + 2 NRTIs | 85 |
| Nonrandomized Subjects All participants entering Rescue Phase after Induction Phase or discontinued during Induction Phase: ATV 300 mg + RTV 100 mg QD + 2 NRTIs | 80 |
| Total | 252 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Induction Phase | Adverse Event | 9 | 0 | 0 | 0 |
| Induction Phase | Death | 1 | 0 | 0 | 0 |
| Induction Phase | Incarceration | 1 | 0 | 0 | 0 |
| Induction Phase | Lack of Efficacy | 1 | 0 | 0 | 0 |
| Induction Phase | Lost to Follow-up | 5 | 0 | 0 | 0 |
| Induction Phase | Missing lab data | 1 | 0 | 0 | 0 |
| Induction Phase | Physician Decision | 2 | 0 | 0 | 0 |
| Induction Phase | Poor/noncompliance | 2 | 0 | 0 | 0 |
| Induction Phase | Pregnancy | 1 | 0 | 0 | 0 |
| Induction Phase | Subject no longer meets study criteria | 3 | 0 | 0 | 0 |
| Induction Phase | Withdrawal by Subject | 4 | 0 | 0 | 0 |
| Maintenance Phase/Rescue Phase | Adverse Event | 0 | 1 | 4 | 1 |
| Maintenance Phase/Rescue Phase | Death | 0 | 0 | 0 | 1 |
| Maintenance Phase/Rescue Phase | Lack of Efficacy | 0 | 0 | 0 | 1 |
| Maintenance Phase/Rescue Phase | Lost to Follow-up | 0 | 1 | 1 | 2 |
| Maintenance Phase/Rescue Phase | Poor/noncompliance | 0 | 3 | 2 | 3 |
| Maintenance Phase/Rescue Phase | Pregnancy | 0 | 2 | 2 | 0 |
| Maintenance Phase/Rescue Phase | RTV intake impossible | 0 | 0 | 1 | 0 |
| Maintenance Phase/Rescue Phase | Subject no longer meets study criteria | 0 | 0 | 1 | 0 |
| Maintenance Phase/Rescue Phase | Withdrawal by Subject | 0 | 2 | 2 | 1 |
Baseline characteristics
| Characteristic | Total | Nonrandomized Subjects | Randomized Subjects: Continuation Regimen | Randomized Subjects: Switch Regimen |
|---|---|---|---|---|
| Age, Customized | 36 years | 36 years | 35 years | 35 years |
| Baseline CD4 | 245 cells/mm3 | 227 cells/mm3 | 265 cells/mm3 | 255 cells/mm3 |
| Baseline HIV-1 RNA | 4.95 log10c/mL | 5.46 log10c/mL | 4.86 log10c/mL | 4.85 log10c/mL |
| Hepatitis B or C Hepatitis B/C negative | 193 Participants | 57 Participants | 65 Participants | 71 Participants |
| Hepatitis B or C Hepatitis B/C positive | 59 Participants | 23 Participants | 20 Participants | 16 Participants |
| Race/Ethnicity, Customized Black | 39 Participants | 11 Participants | 14 Participants | 14 Participants |
| Race/Ethnicity, Customized Other | 4 Participants | 3 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized White | 209 Participants | 66 Participants | 70 Participants | 73 Participants |
| Region of Enrollment Europe | 196 participants | 60 participants | 68 participants | 68 participants |
| Region of Enrollment Russian Federation | 56 participants | 20 participants | 17 participants | 19 participants |
| Sex: Female, Male Female | 62 Participants | 16 Participants | 24 Participants | 22 Participants |
| Sex: Female, Male Male | 190 Participants | 64 Participants | 61 Participants | 65 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 72 / 87 | 75 / 85 | 52 / 80 |
| serious Total, serious adverse events | 7 / 87 | 5 / 85 | 11 / 80 |
Outcome results
Primary
Percentage of Participants With HIV-1 RNA <50 Copies/mL (c/mL) Through Week 48 of the Maintenance Phase
Participants were considered successes unless they experienced treatment failure, or had missing Week 48 HIV-1 RNA. Treatment failure: virologic rebound (ie, 2 consecutive on-treatment HIV-1 RNA ≥ 50 c/mL, or last HIV-1 RNA ≥ 50 c/mL followed by discontinuation), or discontinuation before Week 48. Denominator included all randomized participants.
Time frame: From the end of Induction Phase (Week 26 to Week 30 of Induction Phase treatment) through Week 48 of Maintenance Phase
Population: As-randomized population (as-randomized refers to the treatment regimen assigned at randomization).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Switch Regimen | Percentage of Participants With HIV-1 RNA <50 Copies/mL (c/mL) Through Week 48 of the Maintenance Phase | 78 Percentage of participants |
| Continuation Regimen | Percentage of Participants With HIV-1 RNA <50 Copies/mL (c/mL) Through Week 48 of the Maintenance Phase | 75 Percentage of participants |
Comparison: The planned sample size of 178 randomized subjects (89 on each regimen) provides at least 80% power to demonstrate that the response rate on ATV is within a 15% margin of the response rate on ATV/RTV assuming: a 2-sided 95% confidence interval for the difference in response rate between treatment regimens (switch-continuation); a response rate of 85% in both the Continuation and Switch regimens; a margin of -15% for the difference in response rates between treatment regimens.95% CI: [-9.8, 15.5]Normal approximation
Secondary
Change From Baseline in CD4 Cell Count at Week 24 of Induction Phase
Change From Baseline in CD4 Count at Week 24 of Induction Phase. Change=Week 24 Induction Phase value - Baseline value; a decrease signifies worsening.
Time frame: Baseline, Week 24 of Induction Phase
Population: Analyses use observed values (participants included are those with CD4 measurements at Baseline and at the end of Induction Phase).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Switch Regimen | Change From Baseline in CD4 Cell Count at Week 24 of Induction Phase | 170 cells/mm3 | Standard Error 10 |
| Continuation Regimen | Change From Baseline in CD4 Cell Count at Week 24 of Induction Phase | 201 cells/mm3 | Standard Error 18.5 |
| Total | Change From Baseline in CD4 Cell Count at Week 24 of Induction Phase | 177 cells/mm3 | Standard Error 8.8 |
Secondary
Change From Baseline in CD4 Cell Count at Week 48 of Rescue Phase
Change From Baseline in CD4 Count at Week 48 of Rescue Phase. Change=Week 48 Rescue Phase value - Baseline value; a decrease signifies worsening.
Time frame: Baseline, Week 48 of Rescue Phase
Population: Analyses use observed values (participants included are those with CD4 measurements at Baseline and Week 48 of Rescue Phase).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Switch Regimen | Change From Baseline in CD4 Cell Count at Week 48 of Rescue Phase | 313 cells/mm3 | Standard Error 26.6 |
Secondary
Change From Baseline in HIV-1 RNA at Week 24 of the Induction Phase
Change From Baseline in HIV-1 RNA at Week 24 of the Induction Phase. Change=Week 24 Induction Phase value - Baseline value; a decrease signifies improvement.
Time frame: Baseline, Week 24 of Induction Phase
Population: Analyses use observed values (participants included are those with HIV-1 RNA measurements at baseline and at Week 24 of Induction Phase).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Switch Regimen | Change From Baseline in HIV-1 RNA at Week 24 of the Induction Phase | -3.16 log10 c/mL | Standard Error 0.046 |
| Continuation Regimen | Change From Baseline in HIV-1 RNA at Week 24 of the Induction Phase | -3.35 log10 c/mL | Standard Error 0.135 |
| Total | Change From Baseline in HIV-1 RNA at Week 24 of the Induction Phase | -3.21 log10 c/mL | Standard Error 0.048 |
Secondary
Change From Baseline in HIV-1 RNA at Week 48 of the Rescue Phase
Change From Baseline in HIV-1 RNA at Week 48 of the Rescue Phase. Change=Week 48 Rescue Phase value - Baseline value; a decrease signifies improvement.
Time frame: \Baseline, Week 48 of Rescue Phase
Population: Analyses use observed values (participants included are those with HIV-1 RNA measurements at baseline and at Week 48 of Rescue Phase)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Switch Regimen | Change From Baseline in HIV-1 RNA at Week 48 of the Rescue Phase | -3.71 log10 c/mL | Standard Error 0.078 |
Secondary
Change From End of Induction Phase in CD4 Cell Count at Week 48 of Maintenance Phase
Change in CD4 Cell Count From End of Induction Phase at Week 48 of Maintenance Phase. Change=Week 48 maintenance Phase value - end of Induction Phase value; a decrease signifies worsening.
Time frame: End of Induction Phase (Week 26 to Week 30 of Induction Phase treatment), Week 48 of Maintenance Phase
Population: As-randomized population (as-randomized refers to the treatment regimen assigned at randomization). Analysis uses observed values (participants included are those with CD4 measurements at end of Induction Phase and at Week 48 of Maintenance Phase).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Switch Regimen | Change From End of Induction Phase in CD4 Cell Count at Week 48 of Maintenance Phase | 100 cells/mm3 | Standard Error 14.7 |
| Continuation Regimen | Change From End of Induction Phase in CD4 Cell Count at Week 48 of Maintenance Phase | 92 cells/mm3 | Standard Error 18.1 |
95% CI: [-38, 53]Normal approximation
Secondary
Kaplan-Meier Cumulative Proportion for Treatment Failure (HIV-1 RNA ≥400 c/mL) at Different Time Points Through Week 48 of the Maintenance Phase
Treatment failure based on HIV-1 RNA ≥ 400 c/mL was defined as virologic rebound on or before Week 48 or discontinuation of study therapy before Week 48 for any reason. Time to treatment failure was analyzed using life tables. Measured Values shows the Kaplan-Meier cumulative proportion of participants without treatment failure up to the end of the respective interval.
Time frame: Weeks 6-8, Weeks 14-16, Weeks 22-24, Weeks 30-32, Weeks 38-40, Weeks 46-48
Population: As-randomized population. (As-randomized refers to the treatment regimen assigned at randomization.)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Switch Regimen | Kaplan-Meier Cumulative Proportion for Treatment Failure (HIV-1 RNA ≥400 c/mL) at Different Time Points Through Week 48 of the Maintenance Phase | Proportion by Week 14-16 | 0.9176 Proportion of participants |
| Switch Regimen | Kaplan-Meier Cumulative Proportion for Treatment Failure (HIV-1 RNA ≥400 c/mL) at Different Time Points Through Week 48 of the Maintenance Phase | Proportion by Week 30-32 | 0.8824 Proportion of participants |
| Switch Regimen | Kaplan-Meier Cumulative Proportion for Treatment Failure (HIV-1 RNA ≥400 c/mL) at Different Time Points Through Week 48 of the Maintenance Phase | Proportion by Week 38-40 | 0.8585 Proportion of participants |
| Switch Regimen | Kaplan-Meier Cumulative Proportion for Treatment Failure (HIV-1 RNA ≥400 c/mL) at Different Time Points Through Week 48 of the Maintenance Phase | Proportion by Week 6-8 | 0.9412 Proportion of participants |
| Switch Regimen | Kaplan-Meier Cumulative Proportion for Treatment Failure (HIV-1 RNA ≥400 c/mL) at Different Time Points Through Week 48 of the Maintenance Phase | Proportion by Week 46-48 | 0.8585 Proportion of participants |
| Switch Regimen | Kaplan-Meier Cumulative Proportion for Treatment Failure (HIV-1 RNA ≥400 c/mL) at Different Time Points Through Week 48 of the Maintenance Phase | Proportion by Week 22-24 | 0.9059 Proportion of participants |
| Continuation Regimen | Kaplan-Meier Cumulative Proportion for Treatment Failure (HIV-1 RNA ≥400 c/mL) at Different Time Points Through Week 48 of the Maintenance Phase | Proportion by Week 46-48 | 0.8823 Proportion of participants |
| Continuation Regimen | Kaplan-Meier Cumulative Proportion for Treatment Failure (HIV-1 RNA ≥400 c/mL) at Different Time Points Through Week 48 of the Maintenance Phase | Proportion by Week 6-8 | 0.9885 Proportion of participants |
| Continuation Regimen | Kaplan-Meier Cumulative Proportion for Treatment Failure (HIV-1 RNA ≥400 c/mL) at Different Time Points Through Week 48 of the Maintenance Phase | Proportion by Week 14-16 | 0.9885 Proportion of participants |
| Continuation Regimen | Kaplan-Meier Cumulative Proportion for Treatment Failure (HIV-1 RNA ≥400 c/mL) at Different Time Points Through Week 48 of the Maintenance Phase | Proportion by Week 22-24 | 0.9770 Proportion of participants |
| Continuation Regimen | Kaplan-Meier Cumulative Proportion for Treatment Failure (HIV-1 RNA ≥400 c/mL) at Different Time Points Through Week 48 of the Maintenance Phase | Proportion by Week 38-40 | 0.8966 Proportion of participants |
| Continuation Regimen | Kaplan-Meier Cumulative Proportion for Treatment Failure (HIV-1 RNA ≥400 c/mL) at Different Time Points Through Week 48 of the Maintenance Phase | Proportion by Week 30-32 | 0.9540 Proportion of participants |
Comparison: Covariate in the model: treatment regimen95% CI: [0.37, 1.9]Cox Proportional Hazards Model
Secondary
Kaplan-Meier Cumulative Proportion for Treatment Failure (HIV-1 RNA ≥50 c/mL) at Different Time Points Through Week 48 of the Maintenance Phase
Treatment failure based on HIV-1 RNA ≥ 50 c/mL was defined as virologic rebound on or before Week 48 or discontinuation of study therapy before Week 48 for any reason. Time to treatment failure was analyzed using life tables. Measured Values shows the Kaplan-Meier cumulative proportion of participants without treatment failure up to the end of the respective interval.
Time frame: Weeks 6-8, Weeks 14-16, Weeks 22-24, Weeks 30-32, Weeks 38-40, Weeks 46-48
Population: As-randomized population (as-randomized refers to the treatment regimen assigned at randomization).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Switch Regimen | Kaplan-Meier Cumulative Proportion for Treatment Failure (HIV-1 RNA ≥50 c/mL) at Different Time Points Through Week 48 of the Maintenance Phase | Proportion by Week 6-8 | 0.9655 Proportion of participants |
| Switch Regimen | Kaplan-Meier Cumulative Proportion for Treatment Failure (HIV-1 RNA ≥50 c/mL) at Different Time Points Through Week 48 of the Maintenance Phase | Proportion by Week 14-16 | 0.9655 Proportion of participants |
| Switch Regimen | Kaplan-Meier Cumulative Proportion for Treatment Failure (HIV-1 RNA ≥50 c/mL) at Different Time Points Through Week 48 of the Maintenance Phase | Proportion by Week 22-24 | 0.9540 Proportion of participants |
| Switch Regimen | Kaplan-Meier Cumulative Proportion for Treatment Failure (HIV-1 RNA ≥50 c/mL) at Different Time Points Through Week 48 of the Maintenance Phase | Proportion by Week 30-32 | 0.9310 Proportion of participants |
| Switch Regimen | Kaplan-Meier Cumulative Proportion for Treatment Failure (HIV-1 RNA ≥50 c/mL) at Different Time Points Through Week 48 of the Maintenance Phase | Proportion by Week 38-40 | 0.8506 Proportion of participants |
| Switch Regimen | Kaplan-Meier Cumulative Proportion for Treatment Failure (HIV-1 RNA ≥50 c/mL) at Different Time Points Through Week 48 of the Maintenance Phase | Proportion by Week 46-48 | 0.8273 Proportion of participants |
| Continuation Regimen | Kaplan-Meier Cumulative Proportion for Treatment Failure (HIV-1 RNA ≥50 c/mL) at Different Time Points Through Week 48 of the Maintenance Phase | Proportion by Week 38-40 | 0.8343 Proportion of participants |
| Continuation Regimen | Kaplan-Meier Cumulative Proportion for Treatment Failure (HIV-1 RNA ≥50 c/mL) at Different Time Points Through Week 48 of the Maintenance Phase | Proportion by Week 6-8 | 0.9412 Proportion of participants |
| Continuation Regimen | Kaplan-Meier Cumulative Proportion for Treatment Failure (HIV-1 RNA ≥50 c/mL) at Different Time Points Through Week 48 of the Maintenance Phase | Proportion by Week 30-32 | 0.8824 Proportion of participants |
| Continuation Regimen | Kaplan-Meier Cumulative Proportion for Treatment Failure (HIV-1 RNA ≥50 c/mL) at Different Time Points Through Week 48 of the Maintenance Phase | Proportion by Week 14-16 | 0.9176 Proportion of participants |
| Continuation Regimen | Kaplan-Meier Cumulative Proportion for Treatment Failure (HIV-1 RNA ≥50 c/mL) at Different Time Points Through Week 48 of the Maintenance Phase | Proportion by Week 46-48 | 0.8176 Proportion of participants |
| Continuation Regimen | Kaplan-Meier Cumulative Proportion for Treatment Failure (HIV-1 RNA ≥50 c/mL) at Different Time Points Through Week 48 of the Maintenance Phase | Proportion by Week 22-24 | 0.9059 Proportion of participants |
Comparison: Covariate in the model: treatment regimen.95% CI: [0.5, 1.88]Cox Proportional Hazards Model
Secondary
Percentage of Participants With HIV-1 RNA <400 c/mL Through Week 48 of the Maintenance Phase
Participants were considered successes unless they experienced treatment failure, or had missing Week 48 HIV-1 RNA. Treatment failure: virologic rebound (ie, 2 consecutive on-treatment HIV-1 RNA ≥ 400 c/mL, or last HIV-1 RNA ≥ 400 c/mL followed by discontinuation), or discontinuation before Week 48. Denominator included all randomized participants.
Time frame: From the end of Induction Phase (Week 26 to Week 30 of Induction Phase treatment) through Week 48 of Maintenance Phase
Population: As-randomized population. (As-randomized refers to the treatment regimen assigned at randomization.)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Switch Regimen | Percentage of Participants With HIV-1 RNA <400 c/mL Through Week 48 of the Maintenance Phase | 86 Percentage of participants |
| Continuation Regimen | Percentage of Participants With HIV-1 RNA <400 c/mL Through Week 48 of the Maintenance Phase | 81 Percentage of participants |
95% CI: [-6, 16.1]Normal Approximation
Secondary
Percent Change From End of Induction Phase in Fasting Lipids at Week 48 of Maintenance Phase
Percent change in fasting lipids from end of Induction Phase to Week 48 of Maintenance Phase.Percent changes were calculated on the log scale and then back transformed to the original scale.Change=Week 48 maintenance Phase value - end of Induction Phase value; a decrease signifies worsening for HDL cholesterol and improvement for all other lipds.
Time frame: Measurements were included from the end of Induction Phase (Week 26 to Week 30 of Induction therapy) through Week 48 of Maintenance Phase.
Population: Participants who received at least 1 dose of Maintenance Phase study therapy. As-treated population (as-treated refers to the actual treatment received during the Maintenance Phase). Analysis used last observation carried forward (LOCF) to replace missing values.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Switch Regimen | Percent Change From End of Induction Phase in Fasting Lipids at Week 48 of Maintenance Phase | HDL Cholesterol | 3.7 percent change |
| Switch Regimen | Percent Change From End of Induction Phase in Fasting Lipids at Week 48 of Maintenance Phase | Triglycerides | -27.0 percent change |
| Switch Regimen | Percent Change From End of Induction Phase in Fasting Lipids at Week 48 of Maintenance Phase | LDL Cholesterol | -0.7 percent change |
| Switch Regimen | Percent Change From End of Induction Phase in Fasting Lipids at Week 48 of Maintenance Phase | Non-HDL Cholesterol | -7.4 percent change |
| Switch Regimen | Percent Change From End of Induction Phase in Fasting Lipids at Week 48 of Maintenance Phase | Total Cholesterol | -4.7 percent change |
| Continuation Regimen | Percent Change From End of Induction Phase in Fasting Lipids at Week 48 of Maintenance Phase | Non-HDL Cholesterol | 1.1 percent change |
| Continuation Regimen | Percent Change From End of Induction Phase in Fasting Lipids at Week 48 of Maintenance Phase | Total Cholesterol | 1.4 percent change |
| Continuation Regimen | Percent Change From End of Induction Phase in Fasting Lipids at Week 48 of Maintenance Phase | HDL Cholesterol | 0.8 percent change |
| Continuation Regimen | Percent Change From End of Induction Phase in Fasting Lipids at Week 48 of Maintenance Phase | LDL Cholesterol | -2.1 percent change |
| Continuation Regimen | Percent Change From End of Induction Phase in Fasting Lipids at Week 48 of Maintenance Phase | Triglycerides | 9.8 percent change |
Secondary
Summary of Adverse Events During Induction Phase
Summary of Adverse Events (AEs), Deaths, Serious AEs (SAEs), and AEs leading to study discontinuation. An AE is defined as any new untoward medical occurrence or worsening of a pre-existing medical condition. An SAE is any untoward medical occurrence that at any dose results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a cancer, is a congenital anomaly/birth defect, results in the development of drug dependency or drug abuse, is an important medical event.
Time frame: Measurements are included through the earlier of the last dose of Induction Phase study therapy plus 30 days or the first dose of Maintenance/Rescue Phase therapy (ie, up until 26 to 31 weeks + 30 days).
Population: Participants who received at least 1 dose of Induction Phase study therapy.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Switch Regimen | Summary of Adverse Events During Induction Phase | SAEs related to study therapy | 0 Participants |
| Switch Regimen | Summary of Adverse Events During Induction Phase | AEs leading to discontinuation | 0 Participants |
| Switch Regimen | Summary of Adverse Events During Induction Phase | Deaths | 0 Participants |
| Switch Regimen | Summary of Adverse Events During Induction Phase | SAEs | 7 Participants |
| Continuation Regimen | Summary of Adverse Events During Induction Phase | SAEs related to study therapy | 2 Participants |
| Continuation Regimen | Summary of Adverse Events During Induction Phase | SAEs | 9 Participants |
| Continuation Regimen | Summary of Adverse Events During Induction Phase | AEs leading to discontinuation | 9 Participants |
| Continuation Regimen | Summary of Adverse Events During Induction Phase | Deaths | 3 Participants |
| Total | Summary of Adverse Events During Induction Phase | AEs leading to discontinuation | 9 Participants |
| Total | Summary of Adverse Events During Induction Phase | Deaths | 3 Participants |
| Total | Summary of Adverse Events During Induction Phase | SAEs | 16 Participants |
| Total | Summary of Adverse Events During Induction Phase | SAEs related to study therapy | 2 Participants |
Secondary
Summary of Adverse Events During Maintenance Phase
Summary of Adverse Events (AEs), Deaths, Serious AEs (SAEs), and AEs leading to study discontinuation. An AE is defined as any new untoward medical occurrence or worsening of a pre-existing medical condition. An SAE is any untoward medical occurrence that at any dose results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a cancer, is a congenital anomaly/birth defect, results in the development of drug dependency or drug abuse, is an important medical event.
Time frame: Measurements are included from the end of Induction Phase (26 to 30 weeks after first dose) through the last dose of Maintenance Phase study therapy plus 30 days.
Population: Participants who received at least 1 dose of Maintenance Phase study therapy. As-treated population (as-treated refers to the actual treatment received during the Maintenance Phase).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Switch Regimen | Summary of Adverse Events During Maintenance Phase | Deaths | 0 Participants |
| Switch Regimen | Summary of Adverse Events During Maintenance Phase | Serious Adverse Events (SAEs) | 4 Participants |
| Switch Regimen | Summary of Adverse Events During Maintenance Phase | SAEs related to study therapy | 0 Participants |
| Switch Regimen | Summary of Adverse Events During Maintenance Phase | AEs leading to discontinuation | 1 Participants |
| Continuation Regimen | Summary of Adverse Events During Maintenance Phase | AEs leading to discontinuation | 4 Participants |
| Continuation Regimen | Summary of Adverse Events During Maintenance Phase | Deaths | 0 Participants |
| Continuation Regimen | Summary of Adverse Events During Maintenance Phase | SAEs related to study therapy | 0 Participants |
| Continuation Regimen | Summary of Adverse Events During Maintenance Phase | Serious Adverse Events (SAEs) | 3 Participants |
Secondary
Summary of Adverse Events During Rescue Phase
Summary of Adverse Events (AEs), Deaths, Serious AEs (SAEs), and AEs leading to study discontinuation. An AE is defined as any new untoward medical occurrence or worsening of a pre-existing medical condition. An SAE is any untoward medical occurrence that at any dose results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a cancer, is a congenital anomaly/birth defect, results in the development of drug dependency or drug abuse, is an important medical event.
Time frame: Measurements are included from the end of Induction Phase (26 to 30 weeks after the first dose therapy) through the last dose of Rescue Phase study therapy plus 30 days.
Population: Participants who received at least 1 dose of Rescue Phase study therapy
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Switch Regimen | Summary of Adverse Events During Rescue Phase | Deaths | 1 Participants |
| Switch Regimen | Summary of Adverse Events During Rescue Phase | SAEs | 2 Participants |
| Switch Regimen | Summary of Adverse Events During Rescue Phase | SAEs related to study therapy | 0 Participants |
| Switch Regimen | Summary of Adverse Events During Rescue Phase | AEs leading to discontinuation | 1 Participants |
Secondary
Time to Suppression (Confirmed HIV-1 RNA < 400 c/mL) During Treatment Phase
Time to suppression was measured from the first dose of Induction Phase study therapy to the first of the 2 consecutive measurements \<400 c/mL. Time to suppression was analyzed using life tables. Measured Values show the Kaplan-Meier cumulative number of treated participants without suppression up to the end of the respective interval.
Time frame: Week 16-18, Week 24-26, Week 30-32
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Switch Regimen | Time to Suppression (Confirmed HIV-1 RNA < 400 c/mL) During Treatment Phase | Number of Participants Suppressed by Week 16-18 | 168 Participants |
| Switch Regimen | Time to Suppression (Confirmed HIV-1 RNA < 400 c/mL) During Treatment Phase | Number of Participants Suppressed by Wk 24-26 | 171 Participants |
| Switch Regimen | Time to Suppression (Confirmed HIV-1 RNA < 400 c/mL) During Treatment Phase | Number of Participants Suppressed by Wk 30-32 | 172 Participants |
| Continuation Regimen | Time to Suppression (Confirmed HIV-1 RNA < 400 c/mL) During Treatment Phase | Number of Participants Suppressed by Week 16-18 | 39 Participants |
| Continuation Regimen | Time to Suppression (Confirmed HIV-1 RNA < 400 c/mL) During Treatment Phase | Number of Participants Suppressed by Wk 24-26 | 54 Participants |
| Continuation Regimen | Time to Suppression (Confirmed HIV-1 RNA < 400 c/mL) During Treatment Phase | Number of Participants Suppressed by Wk 30-32 | 55 Participants |
Secondary
Time to Suppression (Confirmed HIV-1 RNA < 50 c/mL) During Treatment Phase
Description: Time to suppression was measured from the first dose of Induction Phase study therapy to the first of the 2 consecutive measurements \< 50 c/mL. Time to suppression was analyzed using life tables. Measured Values show the Kaplan-Meier cumulative number of treated participants without suppression up to the end of the respective interval.
Time frame: Week 16-18, Week 24-26, Week 38-40, Week 64-66
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Switch Regimen | Time to Suppression (Confirmed HIV-1 RNA < 50 c/mL) During Treatment Phase | Number of Participants Suppressed by Wk 16-18 | 131 Participants |
| Switch Regimen | Time to Suppression (Confirmed HIV-1 RNA < 50 c/mL) During Treatment Phase | Number of Participants Suppressed by Wk 24-26 | 171 Participants |
| Switch Regimen | Time to Suppression (Confirmed HIV-1 RNA < 50 c/mL) During Treatment Phase | Number of Participants Suppressed by Wk 38-40 | 172 Participants |
| Switch Regimen | Time to Suppression (Confirmed HIV-1 RNA < 50 c/mL) During Treatment Phase | Number of Participants Suppressed by Wk 64-66 | 172 Participants |
| Continuation Regimen | Time to Suppression (Confirmed HIV-1 RNA < 50 c/mL) During Treatment Phase | Number of Participants Suppressed by Wk 64-66 | 42 Participants |
| Continuation Regimen | Time to Suppression (Confirmed HIV-1 RNA < 50 c/mL) During Treatment Phase | Number of Participants Suppressed by Wk 16-18 | 3 Participants |
| Continuation Regimen | Time to Suppression (Confirmed HIV-1 RNA < 50 c/mL) During Treatment Phase | Number of Participants Suppressed by Wk 38-40 | 31 Participants |
| Continuation Regimen | Time to Suppression (Confirmed HIV-1 RNA < 50 c/mL) During Treatment Phase | Number of Participants Suppressed by Wk 24-26 | 5 Participants |
Secondary
Treatment Outcomes Based on Viral Loads (HIV-1 RNA ≥400 c/mL) Through the End of Rescue Phase
Treatment outcome is based on the first reason of failure. These analyses were performed using HIV-1 RNA of 400 c/mL to define suppression and virologic rebound.
Time frame: Baseline, Week 48 of Rescue Phase
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Switch Regimen | Treatment Outcomes Based on Viral Loads (HIV-1 RNA ≥400 c/mL) Through the End of Rescue Phase | Suppression, then Virologic Rebound at/before Wk48 | 2 Participants |
| Switch Regimen | Treatment Outcomes Based on Viral Loads (HIV-1 RNA ≥400 c/mL) Through the End of Rescue Phase | Suppression Maintained Through Week 48 | 39 Participants |
| Switch Regimen | Treatment Outcomes Based on Viral Loads (HIV-1 RNA ≥400 c/mL) Through the End of Rescue Phase | Discontinuation Before Week 48 | 9 Participants |
| Switch Regimen | Treatment Outcomes Based on Viral Loads (HIV-1 RNA ≥400 c/mL) Through the End of Rescue Phase | Viral Suppression Never Achieved | 0 Participants |
Secondary
Treatment Outcomes Based on Viral Loads (HIV-1 RNA ≥50 c/mL) Through the End of Rescue Phase
Treatment outcome is based on the first reason of failure. These analyses were performed using HIV-1 RNA of 50 c/mL to define suppression and virologic rebound.
Time frame: Through Week 48 of Rescue Phase. Measurements were included from the end of Induction Phase through the last dose of Rescue Phase study therapy plus 4 days.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Switch Regimen | Treatment Outcomes Based on Viral Loads (HIV-1 RNA ≥50 c/mL) Through the End of Rescue Phase | Suppression Maintained Through Week 48 | 29 Participants |
| Switch Regimen | Treatment Outcomes Based on Viral Loads (HIV-1 RNA ≥50 c/mL) Through the End of Rescue Phase | Suppression, then Virologic Rebound at/before Wk48 | 7 Participants |
| Switch Regimen | Treatment Outcomes Based on Viral Loads (HIV-1 RNA ≥50 c/mL) Through the End of Rescue Phase | Discontinuation Before Week 48 | 8 Participants |
| Switch Regimen | Treatment Outcomes Based on Viral Loads (HIV-1 RNA ≥50 c/mL) Through the End of Rescue Phase | Viral Suppression Never Achieved | 6 Participants |