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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
68
100 mg capsule or tablet once daily for 48 weeks
100 mg capsule or tablet once daily for 48 weeks
800 mg tablet once daily for 48 weeks
200/300 mg tablet once daily for 48 weeks
200/300 mg once daily for 48 weeks
300 mg capsule once daily for 48 weeks
Unnamed facility
Los Angeles, California, United States
Unnamed facility
Glastonbury, Connecticut, United States
Unnamed facility
Washington D.C., District of Columbia, United States
Unnamed facility
Fort Lauderdale, Florida, United States
Unnamed facility
Miami, Florida, United States
Unnamed facility
Orlando, Florida, United States
Unnamed facility
Indianapolis, Indiana, United States
Unnamed facility
Boston, Massachusetts, United States
Unnamed facility
Minneapolis, Minnesota, United States
Unnamed facility
St Louis, Missouri, United States
...and 5 more locations
Change From Baseline in Fasting Triglyceride (TG) Levels in the Lipid Evaluable (LE) Set at Week12
Observed values.
Time frame: Baseline, Week 12
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
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
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
Change From Baseline in Apolipoprotein A1 in the LE Set at Week 12 and 48.
Observed Values
Time frame: Baseline, Week 12 and 48
Change From Baseline in Apolipoprotein B in the LE Set at Week 12 and 48.
Observed Values
Time frame: Baseline, Week 12 and 48
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
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
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
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
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
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
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
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
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
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
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.