HIV
Conditions
Keywords
HIV, AIDS, Immunodeficiency Virus, Human, PREZISTA, darunavir, TMC114, Protease Inhibitor, Truvada, Atazanavir, REYATAZ, HIV Infections, Treatment Naïve
Brief summary
The purpose of this research study is to compare changes in triglyceride and other lipids (levels of fats found in the blood) from Baseline (Day 1) to Week 12 for darunavir/ritonavir 800/100 mg once daily versus atazanavir/ritonavir 300/100 mg once daily in combination with a fixed-dose background regimen consisting of emtricitabine \[FTC\]/tenofovir \[TDF\] 200/300 mg once daily). This study will also evaluate the safety (adverse events), effectiveness, and tolerability of darunavir/ritonavir and atazanivir/ritonavir over 48 weeks.
Detailed description
The purpose of this study is to expand our understanding of the metabolic effects of darunavir/ritonavir (DRV/r) in HIV-infected patients. This is a phase 4, multicenter, open-label, randomized (study drug assigned by chance), comparative study designed to compare changes in lipid, glucose, and insulin parameters in HIV-infected, anti-retroviral (ARV) naive patients treated with DRV/r 800/100 mg once daily (QD) versus atazanavir/ritonavir (ATV/r) 300/100 mg QD in combination with a common background of emtricitabine (FTC)/ tenofovir (TDF) 200/300 mg QD. In addition, changes in inflammatory markers will be measured. A substudy of the parent study TMC114HIV4023 will evaluate insulin sensitivity and endothelial function in a subset of patients. The study will be conducted at approximately 16 study sites in the United States. Approximately 60 HIV-1 infected, treatment-naive adult patients will be enrolled in the study. Screening will take place during a 4-week period. At the baseline visit, eligible patients will be randomized in a 1:1 ratio to receive DRV/r 800/100 mg QD or ATV/r 300/100 mg QD administered in combination with a fixed-dose background regimen consisting of emtricitabine (FTC)/tenofovir (TDF) 200/300 mg once daily. The treatment period is 48 weeks. Study assessments will be performed at clinic visits at the end of weeks 4, 8, 12, 24, 36, and 48. The primary endpoint will be assessed at week 12. All patients will return for follow up visits 1 week and 4 weeks after the completion of study treatment. During the treatment period, the patient will be seen at regular visits during which the investigator will assess the patient's medical condition, any Adverse Events and study drug compliance. Laboratory evaluations for efficacy and safety will be done at regular visits as well as blood pressure monitoring. Up to twenty patients (evenly randomized to receive DRV/r or ATV/r) who meet additional entry criteria will be enrolled in the substudy. The study hypothesis is the change in triglycerides and other lipids from baseline to week 12 will be similar in the DRV/r arm versus the ATV/r arm. The substudy hypothesis is that DRV/r will not adversely affect insulin sensitivity or endothelial function during 12 weeks of therapy, and the change from baseline in insulin sensitivity and endothelial function will be similar in the DRV/r arm versus the ATV/r arm. During the treatment period, the patient will be seen at regular visits during which the investigator will assess the patient's medical condition, any Adverse Events and study drug compliance. Laboratory evaluations for efficacy and safety will be done at regular visits as well as blood pressure monitoring. Patients will be randomized in a 1:1 ratio to receive darunavir/ritonavir 800/100 mg once daily (QD) plus emtricitabine (FTC)/tenofovir (TDF) 200/300 mg QD or atazanavir/ritonavir 300/100 mg QD plus emtricitabine (FTC)/tenofovir (TDF) for 48 weeks.
Interventions
DRUGritonavir
100 mg capsule or tablet once daily for 48 weeks
DRUGdarunavir
800 mg tablet once daily for 48 weeks
DRUGemtricitabine [FTC]/tenofovir [TDF]
200/300 mg tablet once daily for 48 weeks
DRUGatazanavir
300 mg capsule once daily for 48 weeks
Sponsors
Tibotec Therapeutics, a Division of Ortho Biotech Products, L.P., USA
Tibotec, Inc
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
No
Inclusion criteria
* HIV-1 RNA of 1000 copies/mL or more * No previous treatment with antiretroviral drugs for more than 10 days * Demonstrated sensitivity \[Fold Change (FC) = lower Clinical Cut Off (CCO)\] to tenofovir, darunavir and atazanavir * Demonstrated sensitivity to emtricitabine defined as absence of M184V/I mutation * Any CD4 (Cluster of Differentiation 4) cell count
Exclusion criteria
* Body mass index \>30 kg/m2 * Laboratory parameters as follows: fasting glucose \>110 mg/dL, Low-Density Lipoprotein (LDL) cholesterol \>130 mg/dL, triglycerides \>200 mg/dL * Presence of any currently active AIDS-defining illness * Treatment for primary HIV infection or postexposure prophylaxis for HIV * Patients with acute or chronic hepatitis A, B or C infection
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Fasting Triglyceride (TG) Levels in the Lipid Evaluable (LE) Set at Week12 | Baseline, Week 12 | Observed values. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Low Density Lipoprotein (LDL) Direct in the LE Set at Week 12 and 48. | Baseline, Week 12 and 48 | Observed Values |
| Change From Baseline in High Density Lipoprotein (HDL) in the LE Set at Week 12 and 48. | Baseline, Week 12 and 48 | Observed Values |
| Change From Baseline in Apolipoprotein A1 in the LE Set at Week 12 and 48. | Baseline, Week 12 and 48 | Observed Values |
| Change From Baseline in Apolipoprotein B in the LE Set at Week 12 and 48. | Baseline, Week 12 and 48 | Observed Values |
| Change From Baseline in TC/HDL Ratio in the LE Set at Week 12 and 48. | Baseline, Week 12 and 48 | Participants TC and HDL was analyzed at Baseline and Week 12 and 48. Change from Baseline at Week 12 and 48 was calculated as ratio using observed values. |
| Change From Baseline in Glucose at Week 12 and 48. | Baseline, Week 12 and 48 | Participants glucose level was analyzed at Baseline and Week 12 and 48. Change from Baseline at Week 12 and 48 was reported. |
| Change From Baseline in Insulin at Week 12 and 48. | Baseline, Week 12 and 48 | Participants insulin was analyzed at Baseline and Week 12 and 48 and change from Baseline at Week 12 and 48 were reported. |
| Change From Baseline in Total Cholesterol (TC) Levels in the LE Set at Week 12 and 48 | Baseline, Week 12 and 48 | Observed Values |
| Antiviral Activity, Human Immunodeficiency Virus Type 1 (HIV-1) RNA. | Week 12 and 48 | Number of Participants with antiviral activity, human immunodeficiency virus Type 1 (HIV-1) RNA less than (\<) 50 copies per milliliters (copies/mL) or \< 400 copies/mL. |
| Number of Participants With Antiviral Activity, HIV-1 RNA, Missing Values as Treatment Failure (M=F) | Week 12 and 48 | Number of participants with antiviral activity, HIV-1 RNA, missing values as treatment failure (Missing = Failure) were observed. |
| Change From Baseline in HIV-1 RNA Viral Load at Week 12 and 48. | Baseline, Week 12 and 48 | the HIV-1 RNA viral load was calculated using Log Base 10 transformed HIV-1 RNA observed values. |
| Change From Baseline in CD4 Cell Count at Week 12 and 48, Observed Values. | Baseline, Week 12 and 48 | Participants' Cluster of Differentiation (CD) 4 Cell Count were at baseline and the change values at Week 12 and 48 were observed. |
| Change From Baseline in Cluster of Differentiation (CD) 4 Cell Count at Week 12 and 48, Last Observation Carried Forward (LOCF). | Baseline, Week 12 and 48 | Participants' Cluster of Differentiation (CD) 4 Cell Count were observed at baseline and the change values at Week 12 and 48 was calculated using LOCF. |
| Change From Baseline in Cluster of Differentiation (CD) 4 Percent at Week 12 and 48, Last Observation Carried Forward (LOCF). | Baseline, Week 12 and 48 | Participants' Cluster of Differentiation (CD) 4 percent were observed at baseline and the change values at Week 12 and 48 was calculated using LOCF. |
| Change From Baseline in Homeostasis Model Assessment-Insulin Resistance (HOMA-IR) at Week 12 and 48. | Baseline, Week 12 and 48 | Participants homeostasis model assessment-insulin resistance (HOMA-IR) were observed and change from Baseline were reported. HOMA-IR score was calculated as: (fasting plasma glucose\*fasting serum insulin)/22.5. Low HOMA IR values indicate high insulin sensitivity and high HOMA IR values indicate low insulin sensitivity (insulin resistance). |
Countries
United States
Participant flow
Pre-assignment details
A total of 68 participants were enrolled in the study, and out of which 65 were treated.
Participants by arm
| Arm | Count |
|---|---|
| Darunavir Darunavir;emtricitabine \[FTC\]/tenofovir \[TDF\];ritonavir. 800 mg tablet once daily for 48 weeks;200/300 mg tablet once daily for 48 weeks;100 mg capsule or tablet once daily for 48 weeks. | 34 |
| Atazanavir atazanavir;emtricitabine \[FTC\]/tenofovir \[TDF\];ritonavir. 300 mg capsule once daily for 48 weeks;200/300 mg once daily for 48 weeks;100 mg capsule or tablet once daily for 48 weeks | 31 |
| Total | 65 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 2 |
| Overall Study | Lost to Follow-up | 1 | 1 |
| Overall Study | Other | 1 | 2 |
| Overall Study | Protocol Violation | 1 | 0 |
| Overall Study | Withdrawal by Subject | 2 | 1 |
Baseline characteristics
| Characteristic | Darunavir | Atazanavir | Total |
|---|---|---|---|
| Age, Continuous | 35.9 years STANDARD_DEVIATION 10.35 | 36.9 years STANDARD_DEVIATION 11.66 | 36.4 years STANDARD_DEVIATION 10.92 |
| Region of Enrollment US | 34 participants | 31 participants | 65 participants |
| Sex: Female, Male Female | 5 Participants | 4 Participants | 9 Participants |
| Sex: Female, Male Male | 29 Participants | 27 Participants | 56 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 28 / 31 | 25 / 29 |
| serious Total, serious adverse events | 5 / 31 | 5 / 29 |
Outcome results
Primary
Change From Baseline in Fasting Triglyceride (TG) Levels in the Lipid Evaluable (LE) Set at Week12
Observed values.
Time frame: Baseline, Week 12
Population: The LE set consisted of all subjects in the PP analysis set who remained on study through Week 48 and had a fasting lipid assessment at baseline and at least once post first dose of DRV or ATV prior to or on the Week 48 visit. Here, 'n' signifies those participants evaluable for this measure at specified time points for each group, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Darunavir | Change From Baseline in Fasting Triglyceride (TG) Levels in the Lipid Evaluable (LE) Set at Week12 | Baseline (n=28,27) | 113.7 milligram per deciliters (mg/dL) | Standard Deviation 57.4 |
| Darunavir | Change From Baseline in Fasting Triglyceride (TG) Levels in the Lipid Evaluable (LE) Set at Week12 | Change at Week 12 (n=27,27) | 22.0 milligram per deciliters (mg/dL) | Standard Deviation 62.72 |
| Atazanavir | Change From Baseline in Fasting Triglyceride (TG) Levels in the Lipid Evaluable (LE) Set at Week12 | Baseline (n=28,27) | 114.2 milligram per deciliters (mg/dL) | Standard Deviation 84.05 |
| Atazanavir | Change From Baseline in Fasting Triglyceride (TG) Levels in the Lipid Evaluable (LE) Set at Week12 | Change at Week 12 (n=27,27) | 8.1 milligram per deciliters (mg/dL) | Standard Deviation 81.15 |
Secondary
Antiviral Activity, Human Immunodeficiency Virus Type 1 (HIV-1) RNA.
Number of Participants with antiviral activity, human immunodeficiency virus Type 1 (HIV-1) RNA less than (\<) 50 copies per milliliters (copies/mL) or \< 400 copies/mL.
Time frame: Week 12 and 48
Population: The ITT population included participants who remained on study through Week 48 and had an assessment at baseline and at least once post first dose of DRV or ATV prior to or on the Week 48 visit.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Darunavir | Antiviral Activity, Human Immunodeficiency Virus Type 1 (HIV-1) RNA. | Week12: HIV-1 RNA Less Than (<) 50 copies/mL | 13 number of participants |
| Darunavir | Antiviral Activity, Human Immunodeficiency Virus Type 1 (HIV-1) RNA. | Week 12: HIV-1 RNA < 400 copies/mL | 28 number of participants |
| Darunavir | Antiviral Activity, Human Immunodeficiency Virus Type 1 (HIV-1) RNA. | Week 48: HIV-1 RNA < 50 copies/mL | 25 number of participants |
| Darunavir | Antiviral Activity, Human Immunodeficiency Virus Type 1 (HIV-1) RNA. | Week 48: HIV-1 RNA < 400 copies/mL | 28 number of participants |
| Atazanavir | Antiviral Activity, Human Immunodeficiency Virus Type 1 (HIV-1) RNA. | Week 48: HIV-1 RNA < 400 copies/mL | 24 number of participants |
| Atazanavir | Antiviral Activity, Human Immunodeficiency Virus Type 1 (HIV-1) RNA. | Week12: HIV-1 RNA Less Than (<) 50 copies/mL | 19 number of participants |
| Atazanavir | Antiviral Activity, Human Immunodeficiency Virus Type 1 (HIV-1) RNA. | Week 48: HIV-1 RNA < 50 copies/mL | 22 number of participants |
| Atazanavir | Antiviral Activity, Human Immunodeficiency Virus Type 1 (HIV-1) RNA. | Week 12: HIV-1 RNA < 400 copies/mL | 29 number of participants |
Secondary
Change From Baseline in Apolipoprotein A1 in the LE Set at Week 12 and 48.
Observed Values
Time frame: Baseline, Week 12 and 48
Population: The LE set consisted of all subjects in the PP analysis set who remained on study through Week 48 and had a fasting lipid assessment at baseline and at least once post first dose of DRV or ATV prior to or on the Week 48 visit. Here, 'n' signifies those participants evaluable for this measure at specified time points for each group, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Darunavir | Change From Baseline in Apolipoprotein A1 in the LE Set at Week 12 and 48. | Baseline (n=28,27) | 1.1 grams per liters (g/L) | Standard Deviation 0.26 |
| Darunavir | Change From Baseline in Apolipoprotein A1 in the LE Set at Week 12 and 48. | Change at Week 12 (n=27,27) | 0.1 grams per liters (g/L) | Standard Deviation 0.21 |
| Darunavir | Change From Baseline in Apolipoprotein A1 in the LE Set at Week 12 and 48. | Change at Week 48 (n=26,22) | 0.1 grams per liters (g/L) | Standard Deviation 0.16 |
| Atazanavir | Change From Baseline in Apolipoprotein A1 in the LE Set at Week 12 and 48. | Baseline (n=28,27) | 1.3 grams per liters (g/L) | Standard Deviation 0.22 |
| Atazanavir | Change From Baseline in Apolipoprotein A1 in the LE Set at Week 12 and 48. | Change at Week 12 (n=27,27) | -0.007 grams per liters (g/L) | Standard Deviation 0.18 |
| Atazanavir | Change From Baseline in Apolipoprotein A1 in the LE Set at Week 12 and 48. | Change at Week 48 (n=26,22) | 0.0 grams per liters (g/L) | Standard Deviation 0.19 |
Secondary
Change From Baseline in Apolipoprotein B in the LE Set at Week 12 and 48.
Observed Values
Time frame: Baseline, Week 12 and 48
Population: The LE set consisted of all subjects in the PP analysis set who remained on study through Week 48 and had a fasting lipid assessment at baseline and at least once post first dose of DRV or ATV prior to or on the Week 48 visit. Here, 'n' signifies those participants evaluable for this measure at specified time points for each group, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Darunavir | Change From Baseline in Apolipoprotein B in the LE Set at Week 12 and 48. | Baseline (n=28,27) | 0.7 g/L | Standard Deviation 0.19 |
| Darunavir | Change From Baseline in Apolipoprotein B in the LE Set at Week 12 and 48. | Change at Week 12 (n=27,27) | -0.004 g/L | Standard Deviation 0.2 |
| Darunavir | Change From Baseline in Apolipoprotein B in the LE Set at Week 12 and 48. | Change at Week 48 (n=26,22) | 0.0 g/L | Standard Deviation 0.21 |
| Atazanavir | Change From Baseline in Apolipoprotein B in the LE Set at Week 12 and 48. | Baseline (n=28,27) | 0.8 g/L | Standard Deviation 0.19 |
| Atazanavir | Change From Baseline in Apolipoprotein B in the LE Set at Week 12 and 48. | Change at Week 12 (n=27,27) | -0.05 g/L | Standard Deviation 0.16 |
| Atazanavir | Change From Baseline in Apolipoprotein B in the LE Set at Week 12 and 48. | Change at Week 48 (n=26,22) | 0.0 g/L | Standard Deviation 0.17 |
Secondary
Change From Baseline in CD4 Cell Count at Week 12 and 48, Observed Values.
Participants' Cluster of Differentiation (CD) 4 Cell Count were at baseline and the change values at Week 12 and 48 were observed.
Time frame: Baseline, Week 12 and 48
Population: The ITT population included participants who remained on study through Week 48 and had an assessment at baseline and at least once post first dose of DRV or ATV prior to or on the Week 48 visit. Here, 'n' signifies those participants evaluable for this measure at specified time points for each group, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Darunavir | Change From Baseline in CD4 Cell Count at Week 12 and 48, Observed Values. | Baseline (n=34,31) | 268.3 cells/micro L | Standard Deviation 144.17 |
| Darunavir | Change From Baseline in CD4 Cell Count at Week 12 and 48, Observed Values. | Change at Week 12 (n=32,29) | 111.1 cells/micro L | Standard Deviation 97.25 |
| Darunavir | Change From Baseline in CD4 Cell Count at Week 12 and 48, Observed Values. | Change at Week 48 (n=29,25) | 217.4 cells/micro L | Standard Deviation 116.76 |
| Atazanavir | Change From Baseline in CD4 Cell Count at Week 12 and 48, Observed Values. | Baseline (n=34,31) | 326.7 cells/micro L | Standard Deviation 174.13 |
| Atazanavir | Change From Baseline in CD4 Cell Count at Week 12 and 48, Observed Values. | Change at Week 12 (n=32,29) | 68.3 cells/micro L | Standard Deviation 134.6 |
| Atazanavir | Change From Baseline in CD4 Cell Count at Week 12 and 48, Observed Values. | Change at Week 48 (n=29,25) | 205.3 cells/micro L | Standard Deviation 153.54 |
Secondary
Change From Baseline in Cluster of Differentiation (CD) 4 Cell Count at Week 12 and 48, Last Observation Carried Forward (LOCF).
Participants' Cluster of Differentiation (CD) 4 Cell Count were observed at baseline and the change values at Week 12 and 48 was calculated using LOCF.
Time frame: Baseline, Week 12 and 48
Population: The ITT population included participants who remained on study through Week 48 and had an assessment at baseline and at least once post first dose of DRV or ATV prior to or on the Week 48 visit. LOCF was applied. Here, 'n' signifies those participants evaluable for this measure at specified time points for each group, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Darunavir | Change From Baseline in Cluster of Differentiation (CD) 4 Cell Count at Week 12 and 48, Last Observation Carried Forward (LOCF). | Baseline (n=34,31) | 268.3 cells/uL | Standard Deviation 144.17 |
| Darunavir | Change From Baseline in Cluster of Differentiation (CD) 4 Cell Count at Week 12 and 48, Last Observation Carried Forward (LOCF). | Change at Week 12 (n=34,31) | 103.4 cells/uL | Standard Deviation 101.01 |
| Darunavir | Change From Baseline in Cluster of Differentiation (CD) 4 Cell Count at Week 12 and 48, Last Observation Carried Forward (LOCF). | Change at Week 48 (n=34,31) | 194.9 cells/uL | Standard Deviation 139.68 |
| Atazanavir | Change From Baseline in Cluster of Differentiation (CD) 4 Cell Count at Week 12 and 48, Last Observation Carried Forward (LOCF). | Baseline (n=34,31) | 326.7 cells/uL | Standard Deviation 174.13 |
| Atazanavir | Change From Baseline in Cluster of Differentiation (CD) 4 Cell Count at Week 12 and 48, Last Observation Carried Forward (LOCF). | Change at Week 12 (n=34,31) | 74.6 cells/uL | Standard Deviation 132.49 |
| Atazanavir | Change From Baseline in Cluster of Differentiation (CD) 4 Cell Count at Week 12 and 48, Last Observation Carried Forward (LOCF). | Change at Week 48 (n=34,31) | 187.7 cells/uL | Standard Deviation 146.28 |
Secondary
Change From Baseline in Cluster of Differentiation (CD) 4 Percent at Week 12 and 48, Last Observation Carried Forward (LOCF).
Participants' Cluster of Differentiation (CD) 4 percent were observed at baseline and the change values at Week 12 and 48 was calculated using LOCF.
Time frame: Baseline, Week 12 and 48
Population: The ITT population included participants who remained on study through Week 48 and had an assessment at baseline and at least once post first dose of DRV or ATV prior to or on the Week 48 visit. LOCF was applied. Here, 'n' signifies those participants evaluable for this measure at specified time points for each group, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Darunavir | Change From Baseline in Cluster of Differentiation (CD) 4 Percent at Week 12 and 48, Last Observation Carried Forward (LOCF). | Baseline (n=34,31) | 18.6 percentage of CD4 cells | Standard Deviation 9.89 |
| Darunavir | Change From Baseline in Cluster of Differentiation (CD) 4 Percent at Week 12 and 48, Last Observation Carried Forward (LOCF). | Change at Week 12 (n=32,30) | 5.9 percentage of CD4 cells | Standard Deviation 6.02 |
| Darunavir | Change From Baseline in Cluster of Differentiation (CD) 4 Percent at Week 12 and 48, Last Observation Carried Forward (LOCF). | Change at Week 48 (n=29,25) | 9.6 percentage of CD4 cells | Standard Deviation 7.24 |
| Atazanavir | Change From Baseline in Cluster of Differentiation (CD) 4 Percent at Week 12 and 48, Last Observation Carried Forward (LOCF). | Baseline (n=34,31) | 21.4 percentage of CD4 cells | Standard Deviation 9.25 |
| Atazanavir | Change From Baseline in Cluster of Differentiation (CD) 4 Percent at Week 12 and 48, Last Observation Carried Forward (LOCF). | Change at Week 12 (n=32,30) | 4.5 percentage of CD4 cells | Standard Deviation 5.25 |
| Atazanavir | Change From Baseline in Cluster of Differentiation (CD) 4 Percent at Week 12 and 48, Last Observation Carried Forward (LOCF). | Change at Week 48 (n=29,25) | 8.5 percentage of CD4 cells | Standard Deviation 5.51 |
Secondary
Change From Baseline in Glucose at Week 12 and 48.
Participants glucose level was analyzed at Baseline and Week 12 and 48. Change from Baseline at Week 12 and 48 was reported.
Time frame: Baseline, Week 12 and 48
Population: Intent-to-treat (ITT) population included participants who remained on study through Week 48 and had an assessment at baseline and at least once post first dose of DRV or ATV prior to or on the Week 48 visit. 'N'=participants evaluable for this measure and 'n'=participants evaluable for this outcome measure at specified time points for each group.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Darunavir | Change From Baseline in Glucose at Week 12 and 48. | Baseline (n=33,30) | 88.5 mg/dL | Standard Deviation 12.37 |
| Darunavir | Change From Baseline in Glucose at Week 12 and 48. | Change at Week 12 (n=30,29) | 1.5 mg/dL | Standard Deviation 12.52 |
| Darunavir | Change From Baseline in Glucose at Week 12 and 48. | Change at Week 48 (n=28,24) | 2.8 mg/dL | Standard Deviation 9.1 |
| Atazanavir | Change From Baseline in Glucose at Week 12 and 48. | Baseline (n=33,30) | 89.7 mg/dL | Standard Deviation 10.84 |
| Atazanavir | Change From Baseline in Glucose at Week 12 and 48. | Change at Week 12 (n=30,29) | 5.8 mg/dL | Standard Deviation 14.55 |
| Atazanavir | Change From Baseline in Glucose at Week 12 and 48. | Change at Week 48 (n=28,24) | 6.4 mg/dL | Standard Deviation 22.07 |
Secondary
Change From Baseline in High Density Lipoprotein (HDL) in the LE Set at Week 12 and 48.
Observed Values
Time frame: Baseline, Week 12 and 48
Population: The LE set consisted of all subjects in the PP analysis set who remained on study through Week 48 and had a fasting lipid assessment at baseline and at least once post first dose of DRV or ATV prior to or on the Week 48 visit. Here, 'n' signifies those participants evaluable for this measure at specified time points for each group, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Darunavir | Change From Baseline in High Density Lipoprotein (HDL) in the LE Set at Week 12 and 48. | Baseline (n=28,27) | 37.9 mg/dL | Standard Deviation 13.36 |
| Darunavir | Change From Baseline in High Density Lipoprotein (HDL) in the LE Set at Week 12 and 48. | Change at Week 12 (n=27,27) | 6.6 mg/dL | Standard Deviation 11.58 |
| Darunavir | Change From Baseline in High Density Lipoprotein (HDL) in the LE Set at Week 12 and 48. | Change at Week 48 (n=26,22) | 6.0 mg/dL | Standard Deviation 7.43 |
| Atazanavir | Change From Baseline in High Density Lipoprotein (HDL) in the LE Set at Week 12 and 48. | Baseline (n=28,27) | 45.0 mg/dL | Standard Deviation 13.56 |
| Atazanavir | Change From Baseline in High Density Lipoprotein (HDL) in the LE Set at Week 12 and 48. | Change at Week 12 (n=27,27) | 2.2 mg/dL | Standard Deviation 8.74 |
| Atazanavir | Change From Baseline in High Density Lipoprotein (HDL) in the LE Set at Week 12 and 48. | Change at Week 48 (n=26,22) | 3.7 mg/dL | Standard Deviation 9.89 |
Secondary
Change From Baseline in HIV-1 RNA Viral Load at Week 12 and 48.
the HIV-1 RNA viral load was calculated using Log Base 10 transformed HIV-1 RNA observed values.
Time frame: Baseline, Week 12 and 48
Population: The ITT population included participants who remained on study through Week 48 and had an assessment at baseline and at least once post first dose of DRV or ATV prior to or on the Week 48 visit. Here, 'n' signifies those participants evaluable for this measure at specified time points for each group, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Darunavir | Change From Baseline in HIV-1 RNA Viral Load at Week 12 and 48. | Change at Week 12 (n=32,30) | -2.955 Log10 HIV RNA | Standard Deviation 0.8081 |
| Darunavir | Change From Baseline in HIV-1 RNA Viral Load at Week 12 and 48. | Change at Week 48 (n=29,24) | -3.269 Log10 HIV RNA | Standard Deviation 0.8304 |
| Darunavir | Change From Baseline in HIV-1 RNA Viral Load at Week 12 and 48. | Baseline (n=34,31) | 5.016 Log10 HIV RNA | Standard Deviation 0.7846 |
| Atazanavir | Change From Baseline in HIV-1 RNA Viral Load at Week 12 and 48. | Baseline (n=34,31) | 4.562 Log10 HIV RNA | Standard Deviation 0.6535 |
| Atazanavir | Change From Baseline in HIV-1 RNA Viral Load at Week 12 and 48. | Change at Week 12 (n=32,30) | -2.605 Log10 HIV RNA | Standard Deviation 0.7035 |
| Atazanavir | Change From Baseline in HIV-1 RNA Viral Load at Week 12 and 48. | Change at Week 48 (n=29,24) | -2.902 Log10 HIV RNA | Standard Deviation 0.662 |
Secondary
Change From Baseline in Homeostasis Model Assessment-Insulin Resistance (HOMA-IR) at Week 12 and 48.
Participants homeostasis model assessment-insulin resistance (HOMA-IR) were observed and change from Baseline were reported. HOMA-IR score was calculated as: (fasting plasma glucose\*fasting serum insulin)/22.5. Low HOMA IR values indicate high insulin sensitivity and high HOMA IR values indicate low insulin sensitivity (insulin resistance).
Time frame: Baseline, Week 12 and 48
Population: The ITT population included participants who remained on study through Week 48 and had an assessment at baseline and at least once post first dose of DRV or ATV prior to or on the Week 48 visit. 'N'=participants evaluable for this measure and 'n'=participants evaluable for this outcome measure at specified time points for each group, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Darunavir | Change From Baseline in Homeostasis Model Assessment-Insulin Resistance (HOMA-IR) at Week 12 and 48. | Baseline (n=27,22) | 1.624 HOMA-IR score | Standard Deviation 1.6962 |
| Darunavir | Change From Baseline in Homeostasis Model Assessment-Insulin Resistance (HOMA-IR) at Week 12 and 48. | Change at Week 12 (n=20,21) | -0.483 HOMA-IR score | Standard Deviation 2.0243 |
| Darunavir | Change From Baseline in Homeostasis Model Assessment-Insulin Resistance (HOMA-IR) at Week 12 and 48. | Change at Week 48 (n=19,14) | 0.035 HOMA-IR score | Standard Deviation 2.258 |
| Atazanavir | Change From Baseline in Homeostasis Model Assessment-Insulin Resistance (HOMA-IR) at Week 12 and 48. | Baseline (n=27,22) | 2.943 HOMA-IR score | Standard Deviation 6.0204 |
| Atazanavir | Change From Baseline in Homeostasis Model Assessment-Insulin Resistance (HOMA-IR) at Week 12 and 48. | Change at Week 12 (n=20,21) | 0.105 HOMA-IR score | Standard Deviation 7.5121 |
| Atazanavir | Change From Baseline in Homeostasis Model Assessment-Insulin Resistance (HOMA-IR) at Week 12 and 48. | Change at Week 48 (n=19,14) | -1.236 HOMA-IR score | Standard Deviation 8.0114 |
Secondary
Change From Baseline in Insulin at Week 12 and 48.
Participants insulin was analyzed at Baseline and Week 12 and 48 and change from Baseline at Week 12 and 48 were reported.
Time frame: Baseline, Week 12 and 48
Population: The ITT population included participants who remained on study through Week 48 and had an assessment at baseline and at least once post first dose of DRV or ATV prior to or on the Week 48 visit. 'N'=participants evaluable for this measure and 'n'=participants evaluable for this outcome measure at specified time points for each group, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Darunavir | Change From Baseline in Insulin at Week 12 and 48. | Baseline (n=33,30) | 5.96 IU/mL | Standard Deviation 5.566 |
| Darunavir | Change From Baseline in Insulin at Week 12 and 48. | Change at Week 12 (n=30,29) | -1.07 IU/mL | Standard Deviation 4.97 |
| Darunavir | Change From Baseline in Insulin at Week 12 and 48. | Change at Week 48 (n=28,24) | 0.95 IU/mL | Standard Deviation 6.006 |
| Atazanavir | Change From Baseline in Insulin at Week 12 and 48. | Baseline (n=33,30) | 8.59 IU/mL | Standard Deviation 14.278 |
| Atazanavir | Change From Baseline in Insulin at Week 12 and 48. | Change at Week 12 (n=30,29) | 0.70 IU/mL | Standard Deviation 18.79 |
| Atazanavir | Change From Baseline in Insulin at Week 12 and 48. | Change at Week 48 (n=28,24) | -2.88 IU/mL | Standard Deviation 16.731 |
Secondary
Change From Baseline in Low Density Lipoprotein (LDL) Direct in the LE Set at Week 12 and 48.
Observed Values
Time frame: Baseline, Week 12 and 48
Population: The LE set consisted of all subjects in the PP analysis set who remained on study through Week 48 and had a fasting lipid assessment at baseline and at least once post first dose of DRV or ATV prior to or on the Week 48 visit. Here, 'n' signifies those participants evaluable for this measure at specified time points for each group, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Darunavir | Change From Baseline in Low Density Lipoprotein (LDL) Direct in the LE Set at Week 12 and 48. | Baseline (n=28, 27) | 84.6 mg/dL | Standard Deviation 21.93 |
| Darunavir | Change From Baseline in Low Density Lipoprotein (LDL) Direct in the LE Set at Week 12 and 48. | Change at Week 12 (n=27, 27) | 13.6 mg/dL | Standard Deviation 25.12 |
| Darunavir | Change From Baseline in Low Density Lipoprotein (LDL) Direct in the LE Set at Week 12 and 48. | Change at Week 48 (n=26, 22) | 14.7 mg/dL | Standard Deviation 25.91 |
| Atazanavir | Change From Baseline in Low Density Lipoprotein (LDL) Direct in the LE Set at Week 12 and 48. | Baseline (n=28, 27) | 100.2 mg/dL | Standard Deviation 23.89 |
| Atazanavir | Change From Baseline in Low Density Lipoprotein (LDL) Direct in the LE Set at Week 12 and 48. | Change at Week 12 (n=27, 27) | 9.6 mg/dL | Standard Deviation 20.78 |
| Atazanavir | Change From Baseline in Low Density Lipoprotein (LDL) Direct in the LE Set at Week 12 and 48. | Change at Week 48 (n=26, 22) | 13.9 mg/dL | Standard Deviation 27.14 |
Secondary
Change From Baseline in TC/HDL Ratio in the LE Set at Week 12 and 48.
Participants TC and HDL was analyzed at Baseline and Week 12 and 48. Change from Baseline at Week 12 and 48 was calculated as ratio using observed values.
Time frame: Baseline, Week 12 and 48
Population: The LE set consisted of all subjects in the PP analysis set who remained on study through Week 48 and had a fasting lipid assessment at baseline and at least once post first dose of DRV or ATV prior to or on the Week 48 visit. Here, 'n' signifies those participants evaluable for this measure at specified time points for each group, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Darunavir | Change From Baseline in TC/HDL Ratio in the LE Set at Week 12 and 48. | Baseline (n=28,27) | 4.1 ratio | Standard Deviation 1.14 |
| Darunavir | Change From Baseline in TC/HDL Ratio in the LE Set at Week 12 and 48. | Change at Week 12 (n=27,27) | -0.1 ratio | Standard Deviation 0.91 |
| Darunavir | Change From Baseline in TC/HDL Ratio in the LE Set at Week 12 and 48. | Change at Week 48 (n=26,22) | 0.1 ratio | Standard Deviation 1.06 |
| Atazanavir | Change From Baseline in TC/HDL Ratio in the LE Set at Week 12 and 48. | Baseline (n=28,27) | 3.9 ratio | Standard Deviation 1.02 |
| Atazanavir | Change From Baseline in TC/HDL Ratio in the LE Set at Week 12 and 48. | Change at Week 12 (n=27,27) | -0.1 ratio | Standard Deviation 0.67 |
| Atazanavir | Change From Baseline in TC/HDL Ratio in the LE Set at Week 12 and 48. | Change at Week 48 (n=26,22) | -0.1 ratio | Standard Deviation 0.75 |
Secondary
Change From Baseline in Total Cholesterol (TC) Levels in the LE Set at Week 12 and 48
Observed Values
Time frame: Baseline, Week 12 and 48
Population: The LE set consisted of all subjects in the PP analysis set who remained on study through Week 48 and had a fasting lipid assessment at baseline and at least once post first dose of DRV or ATV prior to or on the Week 48 visit. Here, 'n' signifies those participants evaluable for this measure at specified time points for each group, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Darunavir | Change From Baseline in Total Cholesterol (TC) Levels in the LE Set at Week 12 and 48 | Baseline (n= 28, 27) | 141.8 mg/dL | Standard Deviation 28.3 |
| Darunavir | Change From Baseline in Total Cholesterol (TC) Levels in the LE Set at Week 12 and 48 | Change at Week 12 (n= 27, 27) | 20.3 mg/dL | Standard Deviation 30.48 |
| Darunavir | Change From Baseline in Total Cholesterol (TC) Levels in the LE Set at Week 12 and 48 | Change at Week 48 (n= 26, 22) | 22.3 mg/dL | Standard Deviation 30.74 |
| Atazanavir | Change From Baseline in Total Cholesterol (TC) Levels in the LE Set at Week 12 and 48 | Baseline (n= 28, 27) | 165.1 mg/dL | Standard Deviation 29.93 |
| Atazanavir | Change From Baseline in Total Cholesterol (TC) Levels in the LE Set at Week 12 and 48 | Change at Week 12 (n= 27, 27) | 4.6 mg/dL | Standard Deviation 26.66 |
| Atazanavir | Change From Baseline in Total Cholesterol (TC) Levels in the LE Set at Week 12 and 48 | Change at Week 48 (n= 26, 22) | 11.8 mg/dL | Standard Deviation 31.93 |
Secondary
Number of Participants With Antiviral Activity, HIV-1 RNA, Missing Values as Treatment Failure (M=F)
Number of participants with antiviral activity, HIV-1 RNA, missing values as treatment failure (Missing = Failure) were observed.
Time frame: Week 12 and 48
Population: The ITT population included participants who remained on study through Week 48 and had an assessment at baseline and at least once post first dose of DRV or ATV prior to or on the Week 48 visit.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Darunavir | Number of Participants With Antiviral Activity, HIV-1 RNA, Missing Values as Treatment Failure (M=F) | Week 12: HIV-1 RNA Less Than (<) 50 copies/mL | 13 number of participants |
| Darunavir | Number of Participants With Antiviral Activity, HIV-1 RNA, Missing Values as Treatment Failure (M=F) | Week 12: HIV-1 RNA < 400 copies/mL | 28 number of participants |
| Darunavir | Number of Participants With Antiviral Activity, HIV-1 RNA, Missing Values as Treatment Failure (M=F) | Week 48: HIV-1 RNA < 50 copies/mL | 25 number of participants |
| Darunavir | Number of Participants With Antiviral Activity, HIV-1 RNA, Missing Values as Treatment Failure (M=F) | Week 48: HIV-1 RNA < 400 copies/mL | 28 number of participants |
| Atazanavir | Number of Participants With Antiviral Activity, HIV-1 RNA, Missing Values as Treatment Failure (M=F) | Week 48: HIV-1 RNA < 400 copies/mL | 24 number of participants |
| Atazanavir | Number of Participants With Antiviral Activity, HIV-1 RNA, Missing Values as Treatment Failure (M=F) | Week 12: HIV-1 RNA Less Than (<) 50 copies/mL | 19 number of participants |
| Atazanavir | Number of Participants With Antiviral Activity, HIV-1 RNA, Missing Values as Treatment Failure (M=F) | Week 48: HIV-1 RNA < 50 copies/mL | 22 number of participants |
| Atazanavir | Number of Participants With Antiviral Activity, HIV-1 RNA, Missing Values as Treatment Failure (M=F) | Week 12: HIV-1 RNA < 400 copies/mL | 28 number of participants |