Study of Reyataz in HIV-infected Patients With Lipodystrophy Syndrome

Study Overview
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Brief Summary
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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.

Official Title
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A Phase IV, Open-Label, Randomized, Multicenter Trial Assessing a Reyataz-Based Substitution Approach in the Management of Lipodystrophy Syndrome. Research Into Atazanavir in Lipodystrophy (The REAL Study)

Conditions
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HIV-Associated Lipodystrophy Syndrome

Intervention / Treatment
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* Drug: Atazanavir (ATV) + ritonavir (RTV), continuation of backbone 2 nucleoside reverse transcriptase inhibitor (NRTIs)
* Drug: continuation of current HAART (boosted protease inhibitor [PI] combination + 2 NRTIs)


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Switch arm<br> | Drug: Atazanavir (ATV) + ritonavir (RTV), continuation of backbone 2 nucleoside reverse transcriptase inhibitor (NRTIs)<br>* Capsules, Oral, ATV 300 mg + RTV 100 mg once daily up to 96 weeks<br>* Other names: Reyataz;|
| Active Comparator: Control Arm<br> | Drug: continuation of current HAART (boosted protease inhibitor [PI] combination + 2 NRTIs)<br>* Protease inhibitor [PI] combination + 2 NRTIs<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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.) | Baseline, Week 48 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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.) | Baseline, Week 96 | 
| 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.) | Baseline, Week 48, Week 96 | 
| 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.) | Baseline, Week 48, Week 96 | 
| 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.) | Baseline, Week 48, Week 96 | 
| 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 | Baseline, Week 48, Week 96 | 
| 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 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. | Baseline, Week 48, Week 96 | 
| Mean Changes From Baseline in Body Weight 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 | Mean changes from baseline in proportion of waist to hip measurements. | Baseline, Week 48, Week 96 | 
| 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. | Through Week 96 of study therapy | 
| 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. | Week 48, Week 96 | 
| 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). | Through Week 96 | 
| 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. | Weeks 8-12, Weeks 20-24, Weeks 32-36, Weeks 44-48, Weeks 56-60, Weeks 68-72, Weeks 80-84, Weeks 92-96 | 
| Mean Change From Baseline in CD4 Count | Mean change from baseline in CD4 count among treated subjects | Baseline, Week 48, Week 96 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV infections