HIV-Associated Lipodystrophy Syndrome
Conditions
Keywords
HIV infections
Brief summary
The purpose of this clinical research study is to learn if human immunodeficiency virus (HIV)-infected subjects with abdominal fat accumulation on their highly active antiretroviral treatment (HAART) regimen have better changes in fat distribution after switching to atazanavir-ritonavir than those remaining on their current protease inhibitor boosted HAART regimen.
Interventions
DRUGAtazanavir (ATV) + ritonavir (RTV), continuation of backbone 2 nucleoside reverse transcriptase inhibitor (NRTIs)
Capsules, Oral, ATV 300 mg + RTV 100 mg once daily up to 96 weeks
DRUGcontinuation of current HAART (boosted protease inhibitor [PI] combination + 2 NRTIs)
Protease inhibitor \[PI\] combination + 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
* HIV-1 infected on HAART regimen containing 2 NRTI and boosted PI for at least 12 weeks prior to screening. Subjects may not have experienced virological failure to more than one prior PI-containing regimen. Must be able to swallow tablets * Viral load \<400 c/mL at screening and stable for at least 6 months * Signs of fat redistribution and lipohypertrophy (abdominal) Waist to Hip Ratio \>0.90 and Waist Circumference \>88.2 cm for men and Waist Circumference \>75.3 for women
Exclusion criteria
* Pregnant or breastfeeding women * New HIV-related opportunistic infections * Active alcohol or substance use * Grade 4 lab toxicity * History of taking atazanavir (ATV) * Prohibited therapies, including non-nucleoside reverse transcriptase inhibitors (NNRTI)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Trunk-to-limb Fat Ratio as Measured by Dual Energy X-Ray Absortiometry (DEXA) at Week 48 | Baseline, Week 48 | Mean changes from Baseline in trunk-to-limb fat ratio as measured by DEXA, an x-ray scan used to measure bone mineral density. Clinical improvement is associated with a decrease in values. (Baseline trunk-to-limb fat ratio values can be found in the Baseline Characteristics section.) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Trunk-to-limb Fat Ratio as Measured by DEXA at Week 96 | Baseline, Week 96 | Mean changes from baseline in trunk-to-limb fat ratio as measured by DEXA, an x-ray scan used to measure bone mineral density. Clinical improvement is associated with a decrease in values.(Baseline trunk-to-limb fat ratio values can be found in the Baseline Characteristics section.) |
| Mean Percent Change From Baseline in Visceral Adipose Tissue (VAT) Area by Computed Tomography (CT) Scans and in Trunk Fat by DEXA. | Baseline, Week 48, Week 96 | The mean percent change from baseline in physical signs of lipohypertrophy, as assessed objectively by changes in visceral adipose tissue (VAT) area (cm2) by computed tomography (CT) scans and by changes in trunk fat (kg) by DEXA. Clinical improvement is associated with a decrease in values. (Baseline values can be found in the Baseline Characteristics section.) |
| Mean Percent Change From Baseline in Peripheral Adipose Tissue (Limb Fat) by DEXA and by Changes in Subcutaneous Adipose Tissue (SAT) Area by CT Scans | Baseline, Week 48, Week 96 | The mean percent change from baseline in physical signs of lipoatrophy, as assessed objectively by changes in peripheral adipose tissue (ie, limb fat (kg) by DEXA and in subcutaneous adipose tissue (SAT) area by CT scans. Clinical improvement is associated with stable values, or an increase in values. (Baseline values can be found in the Baseline Characteristics section.) |
| Mean Percent Change From Baseline in Total Body Fat by DEXA and in Total Adipose Tissue (TAT) Area by CT Scans | Baseline, Week 48, Week 96 | The mean percent change from baseline in total body fat by DEXA and in total adipose tissue (TAT) area by CT scans. Total body fat and TAT are both associated many factors (trunk fat + limb fat + other \[weight, etc\]), and thus clinical improvement cannot be predicted based solely an increase or decrease of these values. (Baseline values can be found in the Baseline Characteristics section.) |
| Mean Percent Changes From Baseline in Fasting Lipids | Baseline, Week 48, Week 96 | Mean percent changes from baseline in fasting total, low-density lipoprotein (LDL), high-density lipoprotein (HDL), and non-HDL cholesterol, triglycerides, and apolipoprotein B |
| Mean Changes From Baseline in Fasting Glucose at Week 48 and Week 96 | Baseline, Week 48, Week 96 | — |
| Mean Changes From Baseline in Fasting Insulin at Week 48 and Week 96 | Baseline, Week 48, Week 96 | — |
| Mean Changes From Baseline in Waist Circumference at Week 48 and Week 96 | Baseline, Week 48, Week 96 | — |
| Mean Changes From Baseline in Body Mass Index at Week 48 and Week 96 | Baseline, Week 48, Week 96 | — |
| Mean Changes From Baseline in Waist-to-Hip Ratio at Week 48 and Week 96 | Baseline, Week 48, Week 96 | Mean changes from baseline in proportion of waist to hip measurements. |
| Mean Changes From Baseline in Fasting Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) | Baseline, Week 48, Week 96 | HOMA-IR is an index used in evaluation of obese patients at risk for type 2 diabetes which requires fasting glucose and insulin concentrations. It is a mathematical model based on the theory of a negative feedback loop between the liver and β-cells that regulates both fasting glucose and insulin concentrations and can be used to estimate pancreatic β-cell function and degree of insulin resistance. HOMA-IR normal values are between 2 and 2.5. HOMA-IR ≥ 2.5 indicates insulin-resistance. |
| Mean Changes From Baseline in Body Weight at Week 48 and Week 96 | Baseline, Week 48, Week 96 | — |
| Percentage of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths, and AEs Leading to Discontinuation | Through Week 96 of study therapy | Percentage of Participants with AEs, Serious AEs (SAEs), Deaths, and AEs leading to 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. |
| Percentage of Participants With Abnormal Liver Function Tests | Week 48, Week 96 | Percentage of participants with Abnormal Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), and Total Bilirubin (TBILI) measurements. Values for liver tests are graded using the modified World Health Organization (WHO) criteria. Grade 1 is mild, grade 2 is moderate, grade 3 is severe, grade 4 is life threatening or disabling. |
| Percentage of Participants With Adverse Events (AEs) Leading to Discontinuation | Through Week 96 | Percentage of Participants with AEs leading to discontinuation of study therapy. An AE is defined as any new untoward medical occurrence or worsening of a pre-existing medical condition. All events listed in this table were SAEs, except for renal impairment and hypertriglycerideamia, which were an AEs (and did not meet the 5 percent threshold reported in Adverse Event module of this record). |
| Kaplan-Meier Cumulative Proportion of Participants Without Virologic Rebound (HIV RNA ≥400 c/mL) at Timepoints up to Week 96 in Treated Participants With HIV RNA <400 c/mL at Baseline | Weeks 8-12, Weeks 20-24, Weeks 32-36, Weeks 44-48, Weeks 56-60, Weeks 68-72, Weeks 80-84, Weeks 92-96 | Virologic rebound was measured from the first dose of study therapy to the first of the 2 consecutive measurements ≥400 c/mL. Time to virologic rebound was analyzed using life tables. Measured Values show the Kaplan-Meier cumulative proportion of participants without virologic rebound up to the end of the respective interval. |
| Mean Change From Baseline in CD4 Count | Baseline, Week 48, Week 96 | Mean change from baseline in CD4 count among treated subjects |
Countries
Canada, France, Germany, Italy, Mexico, Poland, Spain, United Kingdom, United States
Participant flow
Pre-assignment details
A total of 219 participants were enrolled and 18 were never randomized (1 poor/noncompliance; 10 no longer met study criteria; 5 withdrew consent). 201 participants were randomized; however, 1 participant was never treated and is not included in the participant flow.
Participants by arm
| Arm | Count |
|---|---|
| ATV/RTV Switch Arm Participants switching their current treatment with a ritonavir (RTV)-boosted protease inhibitor (PI)-containing highly active antiretroviral therapy (HAART) regimen to atazanavir (ATV)/RTV (ATV: 2 x 150 mg capsules once daily (QD) / RTV: 1 x 100 mg capsule QD) while continuing their background nucleoside reverse transcriptase inhibitors (NRTIs). | 131 |
| PI/RTV Control Arm Participants continued on their current treatment with an RTV-boosted, PI-containing HAART regimen while continuing their background NRTIs. | 69 |
| Total | 200 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 6 | 2 |
| Overall Study | Change in antiviral regimen | 0 | 1 |
| Overall Study | Lack of Efficacy | 2 | 0 |
| Overall Study | Lost to Follow-up | 3 | 1 |
| Overall Study | No longer meets study criteria | 2 | 0 |
| Overall Study | Poor/noncompliance | 1 | 1 |
| Overall Study | Surgery for abdominal fat | 1 | 0 |
| Overall Study | Withdrawal by Subject | 2 | 4 |
Baseline characteristics
| Characteristic | Total | PI/RTV Control Arm | ATV/RTV Switch Arm |
|---|---|---|---|
| Adipose Tissue at Baseline SAT | 193.6 cm2 | 183.9 cm2 | 209.5 cm2 |
| Adipose Tissue at Baseline TAT | 352.0 cm2 | 328.6 cm2 | 356.2 cm2 |
| Adipose Tissue at Baseline VAT | 129.4 cm2 | 128.1 cm2 | 131.9 cm2 |
| Age Continuous | 43 Years | 42 Years | 43 Years |
| Body Mass Index (BMI) | 25.9 kg/m2 | 25.7 kg/m2 | 25.9 kg/m2 |
| Body Weight | 76 kg | 77 kg | 75 kg |
| CD4 Cell Count | 459 cells/mm3 | 437 cells/mm3 | 470 cells/mm3 |
| Cluster of Differentiation 4 (CD4) Distribution 100 to <200 cells/mm3 | 17 Participants | 3 Participants | 14 Participants |
| Cluster of Differentiation 4 (CD4) Distribution 200 to <350 cells/mm3 | 46 Participants | 22 Participants | 24 Participants |
| Cluster of Differentiation 4 (CD4) Distribution 350 to <500 cells/mm3 | 47 Participants | 16 Participants | 31 Participants |
| Cluster of Differentiation 4 (CD4) Distribution ≥500 cells/mm3 | 87 Participants | 27 Participants | 60 Participants |
| Cluster of Differentiation 4 (CD4) Distribution 50 to <100 cells/mm3 | 2 Participants | 0 Participants | 2 Participants |
| Cluster of Differentiation 4 (CD4) Distribution Missing | 1 Participants | 1 Participants | 0 Participants |
| Fasting Glucose <100 mg/dL | 145 participants | 49 participants | 96 participants |
| Fasting Glucose 100 mg/dL to <126 mg/dL | 36 participants | 13 participants | 23 participants |
| Fasting Glucose >=126 mg/dL | 9 participants | 4 participants | 5 participants |
| Fasting Lipids HDL Cholesterol <40 mg/dL | 44 participants | 21 participants | 23 participants |
| Fasting Lipids HDL Cholesterol 40 mg/dL to <60 mg/dL | 112 participants | 32 participants | 80 participants |
| Fasting Lipids HDL Cholesterol >=60 mg/dL | 29 participants | 9 participants | 20 participants |
| Fasting Lipids LDL Cholesterol <100 mg/dL | 62 participants | 22 participants | 40 participants |
| Fasting Lipids LDL Cholesterol 100 mg/dL to <130 mg/dL | 61 participants | 25 participants | 36 participants |
| Fasting Lipids LDL Cholesterol 130 mg/dL to <160 mg/dL | 41 participants | 11 participants | 30 participants |
| Fasting Lipids LDL Cholesterol 160 mg/dL to <190 mg/dL | 12 participants | 1 participants | 11 participants |
| Fasting Lipids LDL Cholesterol >=190 mg/dL | 8 participants | 2 participants | 6 participants |
| Fasting Lipids Non-HDL Cholesterol <130 mg/dL | 38 participants | 16 participants | 22 participants |
| Fasting Lipids Non-HDL Cholesterol 130 mg/dL to <160 mg/dL | 45 participants | 14 participants | 31 participants |
| Fasting Lipids Non-HDL Cholesterol 160 mg/dL to <190 mg/dL | 47 participants | 15 participants | 32 participants |
| Fasting Lipids Non-HDL Cholesterol 190 mg/dL to <220 mg/dL | 31 participants | 9 participants | 22 participants |
| Fasting Lipids Non-HDL Cholesterol >=220 mg/dL | 24 participants | 8 participants | 16 participants |
| Fasting Lipids Total Cholesterol <200 mg/dL | 73 participants | 28 participants | 45 participants |
| Fasting Lipids Total Cholesterol 200 mg/dL to 240 mg/dL | 61 participants | 19 participants | 42 participants |
| Fasting Lipids Total Cholesterol 240 mg/dL to 300 mg/dL | 40 participants | 11 participants | 29 participants |
| Fasting Lipids Total Cholesterol >=300 mg/dL | 11 participants | 4 participants | 7 participants |
| Fasting Lipids Triglycerides <150 mg/dL | 43 participants | 14 participants | 29 participants |
| Fasting Lipids Triglycerides 150 mg/dL to <200 mg/dL | 37 participants | 9 participants | 28 participants |
| Fasting Lipids Triglycerides 200 mg/dL to <500 mg/dL | 79 participants | 27 participants | 52 participants |
| Fasting Lipids Triglycerides >=500 mg/dL | 26 participants | 12 participants | 14 participants |
| Human Immunodeficiency Virus Ribonucleic Acid (HIV RNA) Distribution ≥1000 c/mL | 2 Participants | 0 Participants | 2 Participants |
| Human Immunodeficiency Virus Ribonucleic Acid (HIV RNA) Distribution 400 to <1000 c/mL | 2 Participants | 0 Participants | 2 Participants |
| Human Immunodeficiency Virus Ribonucleic Acid (HIV RNA) Distribution <50 c/mL | 181 Participants | 64 Participants | 117 Participants |
| Human Immunodeficiency Virus Ribonucleic Acid (HIV RNA) Distribution 50 to <400 c/mL | 15 Participants | 5 Participants | 10 Participants |
| Race/Ethnicity, Customized American Indian/Alaska Native | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Black/African American | 25 Participants | 10 Participants | 15 Participants |
| Race/Ethnicity, Customized Latino/Hispanic | 2 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Mestizo | 46 Participants | 15 Participants | 31 Participants |
| Race/Ethnicity, Customized White | 126 Participants | 43 Participants | 83 Participants |
| Region of Enrollment Europe | 116 participants | 39 participants | 77 participants |
| Region of Enrollment North America | 84 participants | 30 participants | 54 participants |
| Sex: Female, Male Female | 49 Participants | 14 Participants | 35 Participants |
| Sex: Female, Male Male | 151 Participants | 55 Participants | 96 Participants |
| Trunk Fat, Limb Fat, Total Body Fat Limb Fat | 7.0 kg | 6.7 kg | 7.1 kg |
| Trunk Fat, Limb Fat, Total Body Fat Total Body Fat | 19.8 kg | 18.7 kg | 20.8 kg |
| Trunk Fat, Limb Fat, Total Body Fat Trunk Fat | 11.4 kg | 10.9 kg | 11.8 kg |
| Trunk-to-Limb Fat Ratio | 1.62 ratio | 1.73 ratio | 1.59 ratio |
| Waist Circumference | 94 cm | 95 cm | 94 cm |
| Waist-to-Hip Ratio | 0.99 ratio | 0.97 ratio | 0.99 ratio |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 94 / 131 | 35 / 69 |
| serious Total, serious adverse events | 11 / 131 | 5 / 69 |
Outcome results
Primary
Change From Baseline in Trunk-to-limb Fat Ratio as Measured by Dual Energy X-Ray Absortiometry (DEXA) at Week 48
Mean changes from Baseline in trunk-to-limb fat ratio as measured by DEXA, an x-ray scan used to measure bone mineral density. Clinical improvement is associated with a decrease in values. (Baseline trunk-to-limb fat ratio values can be found in the Baseline Characteristics section.)
Time frame: Baseline, Week 48
Population: Treated participants. Observed case (OC) analysis: n=participants with fat measurement at baseline and at the analysis timepoint. Last observation carried forward (LOCF): n=participants with fat measurement at baseline and at or before the analysis timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ATV/RTV Switch Arm | Change From Baseline in Trunk-to-limb Fat Ratio as Measured by Dual Energy X-Ray Absortiometry (DEXA) at Week 48 | LOCF Population (n=112; n=54) | 0.02 ratio | Standard Error 0.027 |
| ATV/RTV Switch Arm | Change From Baseline in Trunk-to-limb Fat Ratio as Measured by Dual Energy X-Ray Absortiometry (DEXA) at Week 48 | OCPopulation (n=105; n=51) | 0.02 ratio | Standard Error 0.029 |
| PI/RTV Control Arm | Change From Baseline in Trunk-to-limb Fat Ratio as Measured by Dual Energy X-Ray Absortiometry (DEXA) at Week 48 | LOCF Population (n=112; n=54) | -0.02 ratio | Standard Error 0.036 |
| PI/RTV Control Arm | Change From Baseline in Trunk-to-limb Fat Ratio as Measured by Dual Energy X-Ray Absortiometry (DEXA) at Week 48 | OCPopulation (n=105; n=51) | -0.01 ratio | Standard Error 0.038 |
Comparison: LOCFp-value: 0.4895% CI: [-0.06, 0.12]t-test, 2 sided
Comparison: OCp-value: 0.5795% CI: [-0.07, 12]t-test, 2 sided
Secondary
Change From Baseline in Trunk-to-limb Fat Ratio as Measured by DEXA at Week 96
Mean changes from baseline in trunk-to-limb fat ratio as measured by DEXA, an x-ray scan used to measure bone mineral density. Clinical improvement is associated with a decrease in values.(Baseline trunk-to-limb fat ratio values can be found in the Baseline Characteristics section.)
Time frame: Baseline, Week 96
Population: Observed case (OC) analysis: n=participants with fat measurement at baseline and at the analysis timepoint. Last observation carried forward (LOCF): n=participants with fat measurement at baseline and at or before the analysis timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ATV/RTV Switch Arm | Change From Baseline in Trunk-to-limb Fat Ratio as Measured by DEXA at Week 96 | LOCF Population (n=112; n=54) | 0.04 ratio | Standard Error 0.035 |
| ATV/RTV Switch Arm | Change From Baseline in Trunk-to-limb Fat Ratio as Measured by DEXA at Week 96 | OC Population (n=94; n=45) | 0.04 ratio | Standard Error 0.041 |
| PI/RTV Control Arm | Change From Baseline in Trunk-to-limb Fat Ratio as Measured by DEXA at Week 96 | LOCF Population (n=112; n=54) | 0.02 ratio | Standard Error 0.046 |
| PI/RTV Control Arm | Change From Baseline in Trunk-to-limb Fat Ratio as Measured by DEXA at Week 96 | OC Population (n=94; n=45) | 0.05 ratio | Standard Error 0.051 |
Comparison: LOCFp-value: 0.7395% CI: [-0.1, 0.14]t-test, 2 sided
Comparison: OCp-value: 0.9195% CI: [-0.14, 0.13]t-test, 2 sided
Secondary
Kaplan-Meier Cumulative Proportion of Participants Without Virologic Rebound (HIV RNA ≥400 c/mL) at Timepoints up to Week 96 in Treated Participants With HIV RNA <400 c/mL at Baseline
Virologic rebound was measured from the first dose of study therapy to the first of the 2 consecutive measurements ≥400 c/mL. Time to virologic rebound was analyzed using life tables. Measured Values show the Kaplan-Meier cumulative proportion of participants without virologic rebound up to the end of the respective interval.
Time frame: Weeks 8-12, Weeks 20-24, Weeks 32-36, Weeks 44-48, Weeks 56-60, Weeks 68-72, Weeks 80-84, Weeks 92-96
Population: Treated subjects with HIV RNA \<400 c/mL at baseline.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| ATV/RTV Switch Arm | Kaplan-Meier Cumulative Proportion of Participants Without Virologic Rebound (HIV RNA ≥400 c/mL) at Timepoints up to Week 96 in Treated Participants With HIV RNA <400 c/mL at Baseline | By Weeks 8-12 | 0.9837 Proportion of participants |
| ATV/RTV Switch Arm | Kaplan-Meier Cumulative Proportion of Participants Without Virologic Rebound (HIV RNA ≥400 c/mL) at Timepoints up to Week 96 in Treated Participants With HIV RNA <400 c/mL at Baseline | By Weeks 56-60 | 0.9585 Proportion of participants |
| ATV/RTV Switch Arm | Kaplan-Meier Cumulative Proportion of Participants Without Virologic Rebound (HIV RNA ≥400 c/mL) at Timepoints up to Week 96 in Treated Participants With HIV RNA <400 c/mL at Baseline | By Weeks 32-36 | 0.9753 Proportion of participants |
| ATV/RTV Switch Arm | Kaplan-Meier Cumulative Proportion of Participants Without Virologic Rebound (HIV RNA ≥400 c/mL) at Timepoints up to Week 96 in Treated Participants With HIV RNA <400 c/mL at Baseline | By Weeks 68-72 | 0.9585 Proportion of participants |
| ATV/RTV Switch Arm | Kaplan-Meier Cumulative Proportion of Participants Without Virologic Rebound (HIV RNA ≥400 c/mL) at Timepoints up to Week 96 in Treated Participants With HIV RNA <400 c/mL at Baseline | By Weeks 80-84 | 0.9585 Proportion of participants |
| ATV/RTV Switch Arm | Kaplan-Meier Cumulative Proportion of Participants Without Virologic Rebound (HIV RNA ≥400 c/mL) at Timepoints up to Week 96 in Treated Participants With HIV RNA <400 c/mL at Baseline | By Weeks 20-24 | 0.9837 Proportion of participants |
| ATV/RTV Switch Arm | Kaplan-Meier Cumulative Proportion of Participants Without Virologic Rebound (HIV RNA ≥400 c/mL) at Timepoints up to Week 96 in Treated Participants With HIV RNA <400 c/mL at Baseline | By Weeks 92-96 | 0.9585 Proportion of participants |
| ATV/RTV Switch Arm | Kaplan-Meier Cumulative Proportion of Participants Without Virologic Rebound (HIV RNA ≥400 c/mL) at Timepoints up to Week 96 in Treated Participants With HIV RNA <400 c/mL at Baseline | By Weeks 44-48 | 0.9669 Proportion of participants |
| PI/RTV Control Arm | Kaplan-Meier Cumulative Proportion of Participants Without Virologic Rebound (HIV RNA ≥400 c/mL) at Timepoints up to Week 96 in Treated Participants With HIV RNA <400 c/mL at Baseline | By Weeks 92-96 | 0.9309 Proportion of participants |
| PI/RTV Control Arm | Kaplan-Meier Cumulative Proportion of Participants Without Virologic Rebound (HIV RNA ≥400 c/mL) at Timepoints up to Week 96 in Treated Participants With HIV RNA <400 c/mL at Baseline | By Weeks 8-12 | 1.000 Proportion of participants |
| PI/RTV Control Arm | Kaplan-Meier Cumulative Proportion of Participants Without Virologic Rebound (HIV RNA ≥400 c/mL) at Timepoints up to Week 96 in Treated Participants With HIV RNA <400 c/mL at Baseline | By Weeks 20-24 | 1.000 Proportion of participants |
| PI/RTV Control Arm | Kaplan-Meier Cumulative Proportion of Participants Without Virologic Rebound (HIV RNA ≥400 c/mL) at Timepoints up to Week 96 in Treated Participants With HIV RNA <400 c/mL at Baseline | By Weeks 32-36 | 0.9841 Proportion of participants |
| PI/RTV Control Arm | Kaplan-Meier Cumulative Proportion of Participants Without Virologic Rebound (HIV RNA ≥400 c/mL) at Timepoints up to Week 96 in Treated Participants With HIV RNA <400 c/mL at Baseline | By Weeks 44-48 | 0.9841 Proportion of participants |
| PI/RTV Control Arm | Kaplan-Meier Cumulative Proportion of Participants Without Virologic Rebound (HIV RNA ≥400 c/mL) at Timepoints up to Week 96 in Treated Participants With HIV RNA <400 c/mL at Baseline | By Weeks 56-60 | 0.9841 Proportion of participants |
| PI/RTV Control Arm | Kaplan-Meier Cumulative Proportion of Participants Without Virologic Rebound (HIV RNA ≥400 c/mL) at Timepoints up to Week 96 in Treated Participants With HIV RNA <400 c/mL at Baseline | By Weeks 80-84 | 0.9674 Proportion of participants |
| PI/RTV Control Arm | Kaplan-Meier Cumulative Proportion of Participants Without Virologic Rebound (HIV RNA ≥400 c/mL) at Timepoints up to Week 96 in Treated Participants With HIV RNA <400 c/mL at Baseline | By Weeks 68-72 | 0.9841 Proportion of participants |
95% CI: [0.3, 3.72]
Secondary
Mean Change From Baseline in CD4 Count
Mean change from baseline in CD4 count among treated subjects
Time frame: Baseline, Week 48, Week 96
Population: Observed Cases (OC)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ATV/RTV Switch Arm | Mean Change From Baseline in CD4 Count | Week 48 (n=114; n=56) | 14 cells/mm3 | Standard Error 13.1 |
| ATV/RTV Switch Arm | Mean Change From Baseline in CD4 Count | Week 96 (n=96; n=54) | 3 cells/mm3 | Standard Error 16.9 |
| PI/RTV Control Arm | Mean Change From Baseline in CD4 Count | Week 48 (n=114; n=56) | 44 cells/mm3 | Standard Error 19.4 |
| PI/RTV Control Arm | Mean Change From Baseline in CD4 Count | Week 96 (n=96; n=54) | 82 cells/mm3 | Standard Error 22 |
Secondary
Mean Changes From Baseline in Body Mass Index at Week 48 and Week 96
Time frame: Baseline, Week 48, Week 96
Population: LOCF; n=number of participants with baseline value and value at or before analysis timepoint
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ATV/RTV Switch Arm | Mean Changes From Baseline in Body Mass Index at Week 48 and Week 96 | Week 48 (n=130; n=67) | 0.3 kg/m2 | Standard Error 0.12 |
| ATV/RTV Switch Arm | Mean Changes From Baseline in Body Mass Index at Week 48 and Week 96 | Week 96 (n=130; n=67) | 0.2 kg/m2 | Standard Error 0.13 |
| PI/RTV Control Arm | Mean Changes From Baseline in Body Mass Index at Week 48 and Week 96 | Week 48 (n=130; n=67) | -0.2 kg/m2 | Standard Error 0.13 |
| PI/RTV Control Arm | Mean Changes From Baseline in Body Mass Index at Week 48 and Week 96 | Week 96 (n=130; n=67) | -0.5 kg/m2 | Standard Error 0.25 |
Secondary
Mean Changes From Baseline in Body Weight at Week 48 and Week 96
Time frame: Baseline, Week 48, Week 96
Population: LOCF; n=number of participants with baseline value and value at or before analysis timepoint
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ATV/RTV Switch Arm | Mean Changes From Baseline in Body Weight at Week 48 and Week 96 | Week 48 (n=130; n=68) | 1 kg | Standard Error 0.3 |
| ATV/RTV Switch Arm | Mean Changes From Baseline in Body Weight at Week 48 and Week 96 | Week 96 (n=130; n=68) | 0 kg | Standard Error 0.4 |
| PI/RTV Control Arm | Mean Changes From Baseline in Body Weight at Week 48 and Week 96 | Week 48 (n=130; n=68) | -1 kg | Standard Error 0.4 |
| PI/RTV Control Arm | Mean Changes From Baseline in Body Weight at Week 48 and Week 96 | Week 96 (n=130; n=68) | -1 kg | Standard Error 0.7 |
Secondary
Mean Changes From Baseline in Fasting Glucose at Week 48 and Week 96
Time frame: Baseline, Week 48, Week 96
Population: Treated participants (LOCF); n=number of participants with baseline value at or before analysis timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ATV/RTV Switch Arm | Mean Changes From Baseline in Fasting Glucose at Week 48 and Week 96 | Week 48 (n=124; n=63) | 3.6 mg/dL | Standard Error 2.6 |
| ATV/RTV Switch Arm | Mean Changes From Baseline in Fasting Glucose at Week 48 and Week 96 | Week 96 (n=124; n=64) | 1.2 mg/dL | Standard Error 2.82 |
| PI/RTV Control Arm | Mean Changes From Baseline in Fasting Glucose at Week 48 and Week 96 | Week 48 (n=124; n=63) | -3.3 mg/dL | Standard Error 2.92 |
| PI/RTV Control Arm | Mean Changes From Baseline in Fasting Glucose at Week 48 and Week 96 | Week 96 (n=124; n=64) | 3.0 mg/dL | Standard Error 2.88 |
Secondary
Mean Changes From Baseline in Fasting Homeostasis Model Assessment of Insulin Resistance (HOMA-IR)
HOMA-IR is an index used in evaluation of obese patients at risk for type 2 diabetes which requires fasting glucose and insulin concentrations. It is a mathematical model based on the theory of a negative feedback loop between the liver and β-cells that regulates both fasting glucose and insulin concentrations and can be used to estimate pancreatic β-cell function and degree of insulin resistance. HOMA-IR normal values are between 2 and 2.5. HOMA-IR ≥ 2.5 indicates insulin-resistance.
Time frame: Baseline, Week 48, Week 96
Population: Treated participants (LOCF); n=number of participants with baseline value at or before analysis timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ATV/RTV Switch Arm | Mean Changes From Baseline in Fasting Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) | Baseline (n=115; n=59) | 3.42 mg/dL x uU/mL | Standard Error 0.309 |
| ATV/RTV Switch Arm | Mean Changes From Baseline in Fasting Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) | Week 48 (n=115; n=57) | 0.74 mg/dL x uU/mL | Standard Error 0.589 |
| ATV/RTV Switch Arm | Mean Changes From Baseline in Fasting Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) | Week 96 (n=115; n=57) | 0.28 mg/dL x uU/mL | Standard Error 0.5 |
| PI/RTV Control Arm | Mean Changes From Baseline in Fasting Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) | Baseline (n=115; n=59) | 5.43 mg/dL x uU/mL | Standard Error 1.233 |
| PI/RTV Control Arm | Mean Changes From Baseline in Fasting Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) | Week 48 (n=115; n=57) | -1.73 mg/dL x uU/mL | Standard Error 1.223 |
| PI/RTV Control Arm | Mean Changes From Baseline in Fasting Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) | Week 96 (n=115; n=57) | 1.00 mg/dL x uU/mL | Standard Error 1.648 |
Secondary
Mean Changes From Baseline in Fasting Insulin at Week 48 and Week 96
Time frame: Baseline, Week 48, Week 96
Population: Treated participants (LOCF); n=number of participants with baseline value at or before analysis timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ATV/RTV Switch Arm | Mean Changes From Baseline in Fasting Insulin at Week 48 and Week 96 | Baseline (n=124; n=62) | 14.1 microunits per milliliter | Standard Error 1.04 |
| ATV/RTV Switch Arm | Mean Changes From Baseline in Fasting Insulin at Week 48 and Week 96 | Week 48 (n=124; n=59) | 1.3 microunits per milliliter | Standard Error 1.46 |
| ATV/RTV Switch Arm | Mean Changes From Baseline in Fasting Insulin at Week 48 and Week 96 | Week 96 (n=124; n=59) | 0.0 microunits per milliliter | Standard Error 1.2 |
| PI/RTV Control Arm | Mean Changes From Baseline in Fasting Insulin at Week 48 and Week 96 | Baseline (n=124; n=62) | 21.8 microunits per milliliter | Standard Error 3.36 |
| PI/RTV Control Arm | Mean Changes From Baseline in Fasting Insulin at Week 48 and Week 96 | Week 48 (n=124; n=59) | -4.1 microunits per milliliter | Standard Error 3.79 |
| PI/RTV Control Arm | Mean Changes From Baseline in Fasting Insulin at Week 48 and Week 96 | Week 96 (n=124; n=59) | 0.3 microunits per milliliter | Standard Error 4.76 |
Secondary
Mean Changes From Baseline in Waist Circumference at Week 48 and Week 96
Time frame: Baseline, Week 48, Week 96
Population: LOCF; n=number of participants with baseline value and value at or before analysis timepoint
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ATV/RTV Switch Arm | Mean Changes From Baseline in Waist Circumference at Week 48 and Week 96 | Week 48 (n=123; n=66) | -1 cm | Standard Error 0.5 |
| ATV/RTV Switch Arm | Mean Changes From Baseline in Waist Circumference at Week 48 and Week 96 | Week 96 (n=124; n=66) | -1 cm | Standard Error 0.6 |
| PI/RTV Control Arm | Mean Changes From Baseline in Waist Circumference at Week 48 and Week 96 | Week 48 (n=123; n=66) | -1 cm | Standard Error 0.6 |
| PI/RTV Control Arm | Mean Changes From Baseline in Waist Circumference at Week 48 and Week 96 | Week 96 (n=124; n=66) | -1 cm | Standard Error 0.8 |
Secondary
Mean Changes From Baseline in Waist-to-Hip Ratio at Week 48 and Week 96
Mean changes from baseline in proportion of waist to hip measurements.
Time frame: Baseline, Week 48, Week 96
Population: LOCF; n=number of participants with baseline value and value at or before analysis timepoint
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ATV/RTV Switch Arm | Mean Changes From Baseline in Waist-to-Hip Ratio at Week 48 and Week 96 | Week 48 (n=123; n=65) | -0.01 ratio | Standard Error 0.005 |
| ATV/RTV Switch Arm | Mean Changes From Baseline in Waist-to-Hip Ratio at Week 48 and Week 96 | Week 96 (n=124; n=65) | -0.01 ratio | Standard Error 0.006 |
| PI/RTV Control Arm | Mean Changes From Baseline in Waist-to-Hip Ratio at Week 48 and Week 96 | Week 48 (n=123; n=65) | -0.01 ratio | Standard Error 0.007 |
| PI/RTV Control Arm | Mean Changes From Baseline in Waist-to-Hip Ratio at Week 48 and Week 96 | Week 96 (n=124; n=65) | -0.01 ratio | Standard Error 0.007 |
Secondary
Mean Percent Change From Baseline in Peripheral Adipose Tissue (Limb Fat) by DEXA and by Changes in Subcutaneous Adipose Tissue (SAT) Area by CT Scans
The mean percent change from baseline in physical signs of lipoatrophy, as assessed objectively by changes in peripheral adipose tissue (ie, limb fat (kg) by DEXA and in subcutaneous adipose tissue (SAT) area by CT scans. Clinical improvement is associated with stable values, or an increase in values. (Baseline values can be found in the Baseline Characteristics section.)
Time frame: Baseline, Week 48, Week 96
Population: SAT analysis population=treated subjects with adipose tissue pairs (LOCF); trunk fat analysis population=treated subjects with fat pairs (LOCF); n=number of subjects with measurement at baseline and at or before analysis timepoint.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| ATV/RTV Switch Arm | Mean Percent Change From Baseline in Peripheral Adipose Tissue (Limb Fat) by DEXA and by Changes in Subcutaneous Adipose Tissue (SAT) Area by CT Scans | Week 48 SAT (n=108; n=59) | -2.2 percent change |
| ATV/RTV Switch Arm | Mean Percent Change From Baseline in Peripheral Adipose Tissue (Limb Fat) by DEXA and by Changes in Subcutaneous Adipose Tissue (SAT) Area by CT Scans | Week 96 SAT (n=111; n=59) | -3.5 percent change |
| ATV/RTV Switch Arm | Mean Percent Change From Baseline in Peripheral Adipose Tissue (Limb Fat) by DEXA and by Changes in Subcutaneous Adipose Tissue (SAT) Area by CT Scans | Week 48 Limb Fat (n=112; 54) | 0.9 percent change |
| ATV/RTV Switch Arm | Mean Percent Change From Baseline in Peripheral Adipose Tissue (Limb Fat) by DEXA and by Changes in Subcutaneous Adipose Tissue (SAT) Area by CT Scans | Week 48 Limb Fat (n=112; n=54) | -0.8 percent change |
| PI/RTV Control Arm | Mean Percent Change From Baseline in Peripheral Adipose Tissue (Limb Fat) by DEXA and by Changes in Subcutaneous Adipose Tissue (SAT) Area by CT Scans | Week 48 Limb Fat (n=112; n=54) | -6.1 percent change |
| PI/RTV Control Arm | Mean Percent Change From Baseline in Peripheral Adipose Tissue (Limb Fat) by DEXA and by Changes in Subcutaneous Adipose Tissue (SAT) Area by CT Scans | Week 48 SAT (n=108; n=59) | -5.9 percent change |
| PI/RTV Control Arm | Mean Percent Change From Baseline in Peripheral Adipose Tissue (Limb Fat) by DEXA and by Changes in Subcutaneous Adipose Tissue (SAT) Area by CT Scans | Week 48 Limb Fat (n=112; 54) | -3.6 percent change |
| PI/RTV Control Arm | Mean Percent Change From Baseline in Peripheral Adipose Tissue (Limb Fat) by DEXA and by Changes in Subcutaneous Adipose Tissue (SAT) Area by CT Scans | Week 96 SAT (n=111; n=59) | -9.7 percent change |
Comparison: SAT, Week 48, LOCFp-value: 0.1695% CI: [-1.6, 10]t-test, 2 sided
Comparison: Week 96 SATp-value: 0.0695% CI: [-0.2, 14.2]t-test, 2 sided
Comparison: Week 48, Limb Fatp-value: 0.1595% CI: [-1.7, 11.4]t-test, 2 sided
Comparison: Week 96, Limb Fatp-value: 0.1795% CI: [-2.3, 14.4]t-test, 2 sided
Secondary
Mean Percent Change From Baseline in Total Body Fat by DEXA and in Total Adipose Tissue (TAT) Area by CT Scans
The mean percent change from baseline in total body fat by DEXA and in total adipose tissue (TAT) area by CT scans. Total body fat and TAT are both associated many factors (trunk fat + limb fat + other \[weight, etc\]), and thus clinical improvement cannot be predicted based solely an increase or decrease of these values. (Baseline values can be found in the Baseline Characteristics section.)
Time frame: Baseline, Week 48, Week 96
Population: TAT analysis population=treated subjects with adipose tissue pairs (LOCF); trunk fat analysis population=treated subjects with fat pairs (LOCF); n=number of subjects with measurement at baseline and at or before the analysis timepoint
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| ATV/RTV Switch Arm | Mean Percent Change From Baseline in Total Body Fat by DEXA and in Total Adipose Tissue (TAT) Area by CT Scans | Week 48 TAT (n=108; n= 59) | 0.0 percent change |
| ATV/RTV Switch Arm | Mean Percent Change From Baseline in Total Body Fat by DEXA and in Total Adipose Tissue (TAT) Area by CT Scans | Week 96 TAT (n=111; n=59) | -0.9 percent change |
| ATV/RTV Switch Arm | Mean Percent Change From Baseline in Total Body Fat by DEXA and in Total Adipose Tissue (TAT) Area by CT Scans | Week 48 Total Body Fat (n=105; n=51) | 1.9 percent change |
| ATV/RTV Switch Arm | Mean Percent Change From Baseline in Total Body Fat by DEXA and in Total Adipose Tissue (TAT) Area by CT Scans | Week 96 Total Body Fat (n=94; n=45) | 0.5 percent change |
| PI/RTV Control Arm | Mean Percent Change From Baseline in Total Body Fat by DEXA and in Total Adipose Tissue (TAT) Area by CT Scans | Week 96 Total Body Fat (n=94; n=45) | -7.4 percent change |
| PI/RTV Control Arm | Mean Percent Change From Baseline in Total Body Fat by DEXA and in Total Adipose Tissue (TAT) Area by CT Scans | Week 48 TAT (n=108; n= 59) | -3.5 percent change |
| PI/RTV Control Arm | Mean Percent Change From Baseline in Total Body Fat by DEXA and in Total Adipose Tissue (TAT) Area by CT Scans | Week 48 Total Body Fat (n=105; n=51) | -3.7 percent change |
| PI/RTV Control Arm | Mean Percent Change From Baseline in Total Body Fat by DEXA and in Total Adipose Tissue (TAT) Area by CT Scans | Week 96 TAT (n=111; n=59) | -5.0 percent change |
Comparison: Week 48 TATp-value: 0.1995% CI: [-1.8, 9.4]t-test, 2 sided
Comparison: Week 96 TATp-value: 0.1695% CI: [-1.7, 10.7]Wilcoxon (Mann-Whitney)
Comparison: Week 48 Total Body Fatp-value: 0.038595% CI: [0.3, 9.7]t-test, 2 sided
Comparison: Week 96 Total Body Fatp-value: 0.195% CI: [-1, 13.2]t-test, 2 sided
Secondary
Mean Percent Change From Baseline in Visceral Adipose Tissue (VAT) Area by Computed Tomography (CT) Scans and in Trunk Fat by DEXA.
The mean percent change from baseline in physical signs of lipohypertrophy, as assessed objectively by changes in visceral adipose tissue (VAT) area (cm2) by computed tomography (CT) scans and by changes in trunk fat (kg) by DEXA. Clinical improvement is associated with a decrease in values. (Baseline values can be found in the Baseline Characteristics section.)
Time frame: Baseline, Week 48, Week 96
Population: VAT analysis population=treated subjects with adipose tissue pairs (LOCF); trunk fat analysis population=treated subjects with fat pairs (LOCF); n=number of subjects with measurement at baseline and at or before the analysis timepoint.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| ATV/RTV Switch Arm | Mean Percent Change From Baseline in Visceral Adipose Tissue (VAT) Area by Computed Tomography (CT) Scans and in Trunk Fat by DEXA. | Week 48 VAT (n=98; n=53) | 6.5 Percent change |
| ATV/RTV Switch Arm | Mean Percent Change From Baseline in Visceral Adipose Tissue (VAT) Area by Computed Tomography (CT) Scans and in Trunk Fat by DEXA. | Week 96 VAT (n=101; n=53) | 4.3 Percent change |
| ATV/RTV Switch Arm | Mean Percent Change From Baseline in Visceral Adipose Tissue (VAT) Area by Computed Tomography (CT) Scans and in Trunk Fat by DEXA. | Week 48 Trunk Fat (n=112; n=57) | 2.6 Percent change |
| ATV/RTV Switch Arm | Mean Percent Change From Baseline in Visceral Adipose Tissue (VAT) Area by Computed Tomography (CT) Scans and in Trunk Fat by DEXA. | Week 96 Trunk Fat (n=112; n=57) | 1.6 Percent change |
| PI/RTV Control Arm | Mean Percent Change From Baseline in Visceral Adipose Tissue (VAT) Area by Computed Tomography (CT) Scans and in Trunk Fat by DEXA. | Week 96 Trunk Fat (n=112; n=57) | -3.6 Percent change |
| PI/RTV Control Arm | Mean Percent Change From Baseline in Visceral Adipose Tissue (VAT) Area by Computed Tomography (CT) Scans and in Trunk Fat by DEXA. | Week 48 VAT (n=98; n=53) | -0.4 Percent change |
| PI/RTV Control Arm | Mean Percent Change From Baseline in Visceral Adipose Tissue (VAT) Area by Computed Tomography (CT) Scans and in Trunk Fat by DEXA. | Week 48 Trunk Fat (n=112; n=57) | -1.8 Percent change |
| PI/RTV Control Arm | Mean Percent Change From Baseline in Visceral Adipose Tissue (VAT) Area by Computed Tomography (CT) Scans and in Trunk Fat by DEXA. | Week 96 VAT (n=101; n=53) | 2.1 Percent change |
Comparison: Week 48 VAT LOCFp-value: 0.2795% CI: [-3.9, 15.1]t-test, 2 sided
Comparison: VAT, Week 96 LOCFp-value: 0.6895% CI: [-6.7, 11.2]t-test, 2 sided
Comparison: Week 48 Trunk Fat LOCFp-value: 0.1495% CI: [-1.4, 10.6]t-test, 2 sided
Comparison: Week 96 Trunk Fat LOCFp-value: 0.1495% CI: [-1.7, 12.9]t-test, 2 sided
Secondary
Mean Percent Changes From Baseline in Fasting Lipids
Mean percent changes from baseline in fasting total, low-density lipoprotein (LDL), high-density lipoprotein (HDL), and non-HDL cholesterol, triglycerides, and apolipoprotein B
Time frame: Baseline, Week 48, Week 96
Population: Treated Subjects (LOCF). n=56 for LDL cholesterol in the PI/RTV arm at both timepoints
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| ATV/RTV Switch Arm | Mean Percent Changes From Baseline in Fasting Lipids | Week 48 - Total Cholesterol | -13.0 Percent change |
| ATV/RTV Switch Arm | Mean Percent Changes From Baseline in Fasting Lipids | Week 48 - HDL Cholesterol | -6.2 Percent change |
| ATV/RTV Switch Arm | Mean Percent Changes From Baseline in Fasting Lipids | Week 48 - Non-HDL Cholesterol | -14.8 Percent change |
| ATV/RTV Switch Arm | Mean Percent Changes From Baseline in Fasting Lipids | Week 48 - LDL Cholesterol | -10.4 Percent change |
| ATV/RTV Switch Arm | Mean Percent Changes From Baseline in Fasting Lipids | Week 48 - Triglycerides | -23.8 Percent change |
| ATV/RTV Switch Arm | Mean Percent Changes From Baseline in Fasting Lipids | Week 48 - Apolipoprotein B | -7.6 Percent change |
| ATV/RTV Switch Arm | Mean Percent Changes From Baseline in Fasting Lipids | Week 96 - Total Cholesterol | -12.5 Percent change |
| ATV/RTV Switch Arm | Mean Percent Changes From Baseline in Fasting Lipids | Week 96 - HDL Cholesterol | -6.8 Percent change |
| ATV/RTV Switch Arm | Mean Percent Changes From Baseline in Fasting Lipids | Week 96 - Non-HDL Cholesterol | -14.0 Percent change |
| ATV/RTV Switch Arm | Mean Percent Changes From Baseline in Fasting Lipids | Week 96 - LDL Cholesterol | -8.4 Percent change |
| ATV/RTV Switch Arm | Mean Percent Changes From Baseline in Fasting Lipids | Week 96 - Triglycerides | -25.0 Percent change |
| ATV/RTV Switch Arm | Mean Percent Changes From Baseline in Fasting Lipids | Week 96 - Apolipoprotein B | -8.3 Percent change |
| PI/RTV Control Arm | Mean Percent Changes From Baseline in Fasting Lipids | Week 96 - Triglycerides | -12.2 Percent change |
| PI/RTV Control Arm | Mean Percent Changes From Baseline in Fasting Lipids | Week 48 - Total Cholesterol | -1.0 Percent change |
| PI/RTV Control Arm | Mean Percent Changes From Baseline in Fasting Lipids | Week 96 - Total Cholesterol | -0.1 Percent change |
| PI/RTV Control Arm | Mean Percent Changes From Baseline in Fasting Lipids | Week 48 - HDL Cholesterol | -2.6 Percent change |
| PI/RTV Control Arm | Mean Percent Changes From Baseline in Fasting Lipids | Week 96 - LDL Cholesterol | 3.6 Percent change |
| PI/RTV Control Arm | Mean Percent Changes From Baseline in Fasting Lipids | Week 48 - Non-HDL Cholesterol | -0.6 Percent change |
| PI/RTV Control Arm | Mean Percent Changes From Baseline in Fasting Lipids | Week 96 - HDL Cholesterol | -4.6 Percent change |
| PI/RTV Control Arm | Mean Percent Changes From Baseline in Fasting Lipids | Week 48 - LDL Cholesterol | 2.6 Percent change |
| PI/RTV Control Arm | Mean Percent Changes From Baseline in Fasting Lipids | Week 96 - Apolipoprotein B | 8.3 Percent change |
| PI/RTV Control Arm | Mean Percent Changes From Baseline in Fasting Lipids | Week 48 - Triglycerides | -11.7 Percent change |
| PI/RTV Control Arm | Mean Percent Changes From Baseline in Fasting Lipids | Week 96 - Non-HDL Cholesterol | 1.2 Percent change |
| PI/RTV Control Arm | Mean Percent Changes From Baseline in Fasting Lipids | Week 48 - Apolipoprotein B | 1.1 Percent change |
Secondary
Percentage of Participants With Abnormal Liver Function Tests
Percentage of participants with Abnormal Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), and Total Bilirubin (TBILI) measurements. Values for liver tests are graded using the modified World Health Organization (WHO) criteria. Grade 1 is mild, grade 2 is moderate, grade 3 is severe, grade 4 is life threatening or disabling.
Time frame: Week 48, Week 96
Population: All treated participants
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| ATV/RTV Switch Arm | Percentage of Participants With Abnormal Liver Function Tests | Wk 48 ALT Grades 1-4 | 34 Percentage of Participants |
| ATV/RTV Switch Arm | Percentage of Participants With Abnormal Liver Function Tests | Wk 48 ALT Grades 3-4 | 1 Percentage of Participants |
| ATV/RTV Switch Arm | Percentage of Participants With Abnormal Liver Function Tests | Wk 48 ALT Grade 4 | 0 Percentage of Participants |
| ATV/RTV Switch Arm | Percentage of Participants With Abnormal Liver Function Tests | Wk 96 ALT Grades 1-4 | 37 Percentage of Participants |
| ATV/RTV Switch Arm | Percentage of Participants With Abnormal Liver Function Tests | Wk 96 ALT Grades 3-4 | 2 Percentage of Participants |
| ATV/RTV Switch Arm | Percentage of Participants With Abnormal Liver Function Tests | Wk 96 ALT Grade 4 | 0 Percentage of Participants |
| ATV/RTV Switch Arm | Percentage of Participants With Abnormal Liver Function Tests | Wk 48 AST Grade 1-4 | 19 Percentage of Participants |
| ATV/RTV Switch Arm | Percentage of Participants With Abnormal Liver Function Tests | Wk 48 AST Grades 3-4 | 1 Percentage of Participants |
| ATV/RTV Switch Arm | Percentage of Participants With Abnormal Liver Function Tests | Wk 48 AST Grade 4 | 0 Percentage of Participants |
| ATV/RTV Switch Arm | Percentage of Participants With Abnormal Liver Function Tests | Wk 96 AST Grades 1-4 | 24 Percentage of Participants |
| ATV/RTV Switch Arm | Percentage of Participants With Abnormal Liver Function Tests | Wk 96 AST Grades 3-4 | 1 Percentage of Participants |
| ATV/RTV Switch Arm | Percentage of Participants With Abnormal Liver Function Tests | Wk 96 AST Grade 4 | 0 Percentage of Participants |
| ATV/RTV Switch Arm | Percentage of Participants With Abnormal Liver Function Tests | Wk 48 TBILI Grades 1-4 | 94 Percentage of Participants |
| ATV/RTV Switch Arm | Percentage of Participants With Abnormal Liver Function Tests | Wk 48 TBILI Grades 3-4 | 53 Percentage of Participants |
| ATV/RTV Switch Arm | Percentage of Participants With Abnormal Liver Function Tests | Wk 48 TBILI Grade 4 | 13 Percentage of Participants |
| ATV/RTV Switch Arm | Percentage of Participants With Abnormal Liver Function Tests | Wk 96 TBILI Grades 1-4 | 95 Percentage of Participants |
| ATV/RTV Switch Arm | Percentage of Participants With Abnormal Liver Function Tests | Wk 96 TBILI Grades 3-4 | 60 Percentage of Participants |
| ATV/RTV Switch Arm | Percentage of Participants With Abnormal Liver Function Tests | Wk 96 TBILI Grade 4 | 17 Percentage of Participants |
| PI/RTV Control Arm | Percentage of Participants With Abnormal Liver Function Tests | Wk 48 TBILI Grades 3-4 | 0 Percentage of Participants |
| PI/RTV Control Arm | Percentage of Participants With Abnormal Liver Function Tests | Wk 48 ALT Grades 1-4 | 23 Percentage of Participants |
| PI/RTV Control Arm | Percentage of Participants With Abnormal Liver Function Tests | Wk 96 AST Grades 1-4 | 19 Percentage of Participants |
| PI/RTV Control Arm | Percentage of Participants With Abnormal Liver Function Tests | Wk 48 ALT Grades 3-4 | 0 Percentage of Participants |
| PI/RTV Control Arm | Percentage of Participants With Abnormal Liver Function Tests | Wk 96 TBILI Grade 4 | 0 Percentage of Participants |
| PI/RTV Control Arm | Percentage of Participants With Abnormal Liver Function Tests | Wk 48 ALT Grade 4 | 0 Percentage of Participants |
| PI/RTV Control Arm | Percentage of Participants With Abnormal Liver Function Tests | Wk 96 AST Grades 3-4 | 0 Percentage of Participants |
| PI/RTV Control Arm | Percentage of Participants With Abnormal Liver Function Tests | Wk 96 ALT Grades 1-4 | 32 Percentage of Participants |
| PI/RTV Control Arm | Percentage of Participants With Abnormal Liver Function Tests | Wk 48 TBILI Grade 4 | 0 Percentage of Participants |
| PI/RTV Control Arm | Percentage of Participants With Abnormal Liver Function Tests | Wk 96 ALT Grades 3-4 | 0 Percentage of Participants |
| PI/RTV Control Arm | Percentage of Participants With Abnormal Liver Function Tests | Wk 96 AST Grade 4 | 0 Percentage of Participants |
| PI/RTV Control Arm | Percentage of Participants With Abnormal Liver Function Tests | Wk 96 ALT Grade 4 | 0 Percentage of Participants |
| PI/RTV Control Arm | Percentage of Participants With Abnormal Liver Function Tests | Wk 96 TBILI Grades 3-4 | 0 Percentage of Participants |
| PI/RTV Control Arm | Percentage of Participants With Abnormal Liver Function Tests | Wk 48 AST Grade 1-4 | 15 Percentage of Participants |
| PI/RTV Control Arm | Percentage of Participants With Abnormal Liver Function Tests | Wk 48 TBILI Grades 1-4 | 19 Percentage of Participants |
| PI/RTV Control Arm | Percentage of Participants With Abnormal Liver Function Tests | Wk 48 AST Grades 3-4 | 0 Percentage of Participants |
| PI/RTV Control Arm | Percentage of Participants With Abnormal Liver Function Tests | Wk 96 TBILI Grades 1-4 | 21 Percentage of Participants |
| PI/RTV Control Arm | Percentage of Participants With Abnormal Liver Function Tests | Wk 48 AST Grade 4 | 0 Percentage of Participants |
Secondary
Percentage of Participants With Adverse Events (AEs) Leading to Discontinuation
Percentage of Participants with AEs leading to discontinuation of study therapy. An AE is defined as any new untoward medical occurrence or worsening of a pre-existing medical condition. All events listed in this table were SAEs, except for renal impairment and hypertriglycerideamia, which were an AEs (and did not meet the 5 percent threshold reported in Adverse Event module of this record).
Time frame: Through Week 96
Population: Treated subjects
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| ATV/RTV Switch Arm | Percentage of Participants With Adverse Events (AEs) Leading to Discontinuation | Any adverse experience leading to discontinuation | 5 Percent of Participants |
| ATV/RTV Switch Arm | Percentage of Participants With Adverse Events (AEs) Leading to Discontinuation | Hyperbilirubinemia | 2 Percent of Participants |
| ATV/RTV Switch Arm | Percentage of Participants With Adverse Events (AEs) Leading to Discontinuation | Jaundice | 1 Percent of Participants |
| ATV/RTV Switch Arm | Percentage of Participants With Adverse Events (AEs) Leading to Discontinuation | Drug abuse | 1 Percent of Participants |
| ATV/RTV Switch Arm | Percentage of Participants With Adverse Events (AEs) Leading to Discontinuation | Renal impairment | 1 Percent of Participants |
| ATV/RTV Switch Arm | Percentage of Participants With Adverse Events (AEs) Leading to Discontinuation | Stevens-Johnson syndrome | 1 Percent of Participants |
| ATV/RTV Switch Arm | Percentage of Participants With Adverse Events (AEs) Leading to Discontinuation | Hypertriglyceridemia | 0 Percent of Participants |
| ATV/RTV Switch Arm | Percentage of Participants With Adverse Events (AEs) Leading to Discontinuation | Squamous cell carcinoma | 0 Percent of Participants |
| PI/RTV Control Arm | Percentage of Participants With Adverse Events (AEs) Leading to Discontinuation | Squamous cell carcinoma | 1 Percent of Participants |
| PI/RTV Control Arm | Percentage of Participants With Adverse Events (AEs) Leading to Discontinuation | Any adverse experience leading to discontinuation | 3 Percent of Participants |
| PI/RTV Control Arm | Percentage of Participants With Adverse Events (AEs) Leading to Discontinuation | Renal impairment | 0 Percent of Participants |
| PI/RTV Control Arm | Percentage of Participants With Adverse Events (AEs) Leading to Discontinuation | Hyperbilirubinemia | 0 Percent of Participants |
| PI/RTV Control Arm | Percentage of Participants With Adverse Events (AEs) Leading to Discontinuation | Hypertriglyceridemia | 1 Percent of Participants |
| PI/RTV Control Arm | Percentage of Participants With Adverse Events (AEs) Leading to Discontinuation | Jaundice | 0 Percent of Participants |
| PI/RTV Control Arm | Percentage of Participants With Adverse Events (AEs) Leading to Discontinuation | Stevens-Johnson syndrome | 0 Percent of Participants |
| PI/RTV Control Arm | Percentage of Participants With Adverse Events (AEs) Leading to Discontinuation | Drug abuse | 0 Percent of Participants |
Secondary
Percentage of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths, and AEs Leading to Discontinuation
Percentage of Participants with AEs, Serious AEs (SAEs), Deaths, and AEs leading to 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: Through Week 96 of study therapy
Population: Treated participants
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| ATV/RTV Switch Arm | Percentage of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths, and AEs Leading to Discontinuation | Death | 0 Percentage of Participants |
| ATV/RTV Switch Arm | Percentage of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths, and AEs Leading to Discontinuation | SAE | 8 Percentage of Participants |
| ATV/RTV Switch Arm | Percentage of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths, and AEs Leading to Discontinuation | AE Leading to Discontinuation | 5 Percentage of Participants |
| ATV/RTV Switch Arm | Percentage of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths, and AEs Leading to Discontinuation | Any AEs (all grades) through Week 96 | 90 Percentage of Participants |
| PI/RTV Control Arm | Percentage of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths, and AEs Leading to Discontinuation | Any AEs (all grades) through Week 96 | 83 Percentage of Participants |
| PI/RTV Control Arm | Percentage of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths, and AEs Leading to Discontinuation | Death | 0 Percentage of Participants |
| PI/RTV Control Arm | Percentage of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths, and AEs Leading to Discontinuation | AE Leading to Discontinuation | 3 Percentage of Participants |
| PI/RTV Control Arm | Percentage of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths, and AEs Leading to Discontinuation | SAE | 7 Percentage of Participants |