The purpose of this study is to determine if the combination of atazanavir and raltegravir taken together is safe and effective in the treatment of human immunodeficiency virus (HIV).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
167
Capsules, Oral, 300 mg, twice daily, 96 weeks
Tablet, Oral, 400 mg, twice daily, 96 weeks
Capsules, Oral, 300 mg, once daily, 96 weeks
Southwest Center For HIV/AIDS
Phoenix, Arizona, United States
Yale University School Of Medicine
New Haven, Connecticut, United States
Number of Participants With Human Immunodeficiency Virus (HIV) Ribonucleic Acid (RNA) Level <50 Copies/mL at Week 24
The number of HIV 1-infected treatment-naive participants with an HIV RNA level \<50 copies/mL after 24 weeks of treatment. Confirmed virologic response noncompleter=failure (NC=F); noncompleter=missing (NC=M); virologic response-observed cases (VR-OC).
Time frame: At Week 24 from Baseline
Number of Nonresponders at Week 8
Participants were classified as nonresponders if they had an HIV RNA level ≥400 copies/mL and a decrease from baseline \<2 log10 copies/mL.
Time frame: At Week 8 from Baseline
Number of Participants With HIV RNA Levels <50 Copies/mL at Weeks 48 and 96
Participant HIV RNA level was determined at Weeks 48 and 96 using the Roche Amplicor® Ultrasensitive Assay Version 1. VR-OC=Virologic response-observed cases.
Time frame: At Weeks 48 and 96 from Baseline
Number of Participants With HIV RNA Levels <400 Copies/mL at Week 24
NC=F: noncompleter=failure; NC=M: noncompleter=missing; VR-OC: virologic response-observed
Time frame: At Week 24 from Baseline
Number of Participants With HIV RNA Levels <400 Copies/mL at Week 48
Time frame: At Week 48 from Baseline
Number of Participants With HIV RNA Levels <400 Copies/mL at Week 96
Time frame: At Week 96 from Baseline
Mean Change From Baseline in Absolute Cluster of Differentiation 4 Cell Count
Time frame: From Baseline to Weeks 2, 4, 8, 12, 16, 20, and 24
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Capsules, Oral, 100 mg, once daily, 96 weeks
Tablet, Oral, 300-mg Tenofovir/200-mg Emtricitabine, once daily, 96 weeks
Dupont Circle Physicians Group
Washington D.C., District of Columbia, United States
Orlando Immunology Center
Orlando, Florida, United States
The Aaron Diamond AIDS Research Center
New York, New York, United States
University Of Cincinnati
Cincinnati, Ohio, United States
Tarrant County Infectious Disease Associates
Fort Worth, Texas, United States
Therapeutic Concepts, P.A.
Houston, Texas, United States
Diversified Medical Practices, P.A.
Houston, Texas, United States
Local Institution
Buenos Aires, Bs As, Buenos Aires, Argentina
...and 6 more locations
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Death as Outcome, AEs Leading to Discontinuation, SAEs Leading to Discontinuation
AE=any new untoward medical occurrence or worsening of a preexisting medical condition that does not necessarily have a causal relationship with this treatment. SAE=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 congenital anomaly/birth defect, results in drug dependency or drug abuse, or is an important medical event.
Time frame: Week 1 to Week 96, continuously
Baseline and Mean Change From Baseline in Total Cholesterol Levels
The mean change from baseline in participant fasting lipids was determined using fasting serum samples.
Time frame: From Baseline to Week 24 and Week 48
Mean Change From Baseline in Total Bilirubin Level
Time frame: From Baseline to Week 24 and Week 48
Mean Change From Baseline in Electrocardiogram Findings
The incidence of QRS wave widening and QT and PR prolongation on participant electrocardiogram findings were evaluated at study Week 24.
Time frame: From Baseline to Week 24
Atazanavir Maximum Observed Plasma Concentration (Cmax) in 1 Dosing Interval
Serial blood samples were collected over a 12-hour period after the morning dose at Week 2.
Time frame: At Week 2 from Baseline
Raltegravir Cmax in 1 Dosing Interval
Serial blood samples were collected over a 12-hour period after the morning dose at Week 2.
Time frame: At Week 2 from Baseline
Atazanavir Time of Maximum Observed Plasma Concentration (Tmax)
Serial blood samples were collected over a 12-hour period after the morning dose at Week 2.
Time frame: At Week 2 from Baseline
Raltegravir Tmax
Serial blood samples were collected over a 12-hour period after the morning dose at Week 2.
Time frame: At Week 2 from Baseline
Atazanavir Trough Plasma Concentration (Cmin) 12 Hours Postdose
Time frame: At Week 2 from Baseline
Raltegravir Cmin 12 Hours Postdose
Time frame: At Week 2 from Baseline
Atazanavir Cmin Prior to the Morning Dose
Time frame: At Week 2 from Baseline
Raltegravir Cmin Prior to the Morning Dose
Time frame: At Week 2 from Baseline
Atazanavir Area Under the Concentration Curve From Time 0 to 12 Hours (AUC [0-12h]) in 1 Dosing Interval
Time frame: At Week 2 from Baseline
Raltegravir AUC (0-12h) in 1 Dosing Interval
Time frame: At Week 2 from Baseline
Atazanavir Area Under the Concentration Curve From Time 0 to 24 Hours (AUC [0-24h]) in 1 Dosing Interval
AUC (0-24h) was estimated by multiplying AUC (0-12h) by 2.
Time frame: At Week 2 from Baseline
Atazanavir Individual Inhibitory Quotient (IQ)
Individual IQ was defined at Cmin at Week 2 divided by the protein binding adjusted EC90 (ie, the drug concentration observed to inhibit virion production by 90% in a cell-based assay) values for Atazanavir that were derived from individual participant clinical isolates.
Time frame: At Week 2 from Baseline
Atazanavir Terminal Elimination Half Life
Time frame: At Week 2 from Baseline
Raltegravir Terminal Elimination Half Life
Time frame: At Week 2 from Baseline
Number of Participants With Hematology Laboratory Test Results With Worst Toxicity of Grades 1 to 4 Among All Treated Participants
ULN=upper limit of normal. Hematocrit(%) Grade (Gr) 1: ≥28.5-\<31; Gr 2: ≥24-\<28.5; Gr 3: ≥19.5-\<24; Gr 4: \<19.5. Hemoglobin (g/dL) Gr 1: 9.5-11; Gr 2: 8-9.4; Gr 3: 6.5-7.9; Gr 4: \<6.5. Platelets (/mm\^3) Gr 1: 75,000-99,000; Gr 2: 50,000-74,999; Gr 3: 20,000-49,999; Gr 4: \<20,000. White Blood Cells (/mm\^3) Gr 1: \>2500-4000; Gr 2: \>1000-\<2500; Gr 3: \>800-\<1000; Gr 4: \<800. . Prothrombin time (seconds) Gr 1: 1.01-1.25\*ULN; Gr 2: 1.26-1.5\*ULN; Gr 3: 1.51-3\*ULN; Gr 4: \>3\*ULN.
Time frame: While on treatment from Baseline through Week 96
Number of Participants With Blood Chemistry Laboratory Test Results With Worst Toxicity of Grades 1 to 4
Blood urea nitrogen Gr 1:1.25-2.5\*ULN;Gr 2:2.6-5.0\*ULN; Gr 3:5.1-10\*ULN; Gr 4:\>10\*ULN. Creatinine (mg/dL) Gr 1: 1.1-1.5 \*ULN; Gr 2: 1.6-3\*ULN: Gr 3: 3.1-6\*ULN; Gr 4: \>6\*ULN. Hypercarbia (meq/L)Gr 1: 33-36; Gr 2:37-40; Gr 3: 41-45; Gr 4:\>45. Hypocarbia (meq/L)Gr 1:19-21; Gr 2: 15-18; Gr 3: 10-14; Gr 4:\<10. Hypercalcemia (mg/dL)Gr 1:10.6-11.5;Gr 2:11.6-12.5; Gr 3:12.6-13.5;Gr 4: \>13.5. Hypocalcemia (mg/dL)Gr 1: 8.4-7.8;Gr 2:7.7-7; Gr 3:6.9-6.1; Gr 4: \<6.1.Hyperchloremia(meq/L)Gr 1:113-116; Gr 2:117-120; Gr 3:121-125; Gr 4: \>125.Hypochloremia(meq/L)Gr 1: 90-93; Gr 2: 85-89; Gr 3:80-84; Gr 4:\<80.
Time frame: While on treatment from Baseline through Week 96
Number of Participants With Blood Chemistry Laboratory Test Results With Worst Toxicity of Grades 1 to 4 (Continued)
Hyperkalemia(meq/L) Gr 1: 5.6-6; Gr 2: 6.1-6.5; Gr 3: 6.6-7; Gr4: \>7. Hypokalemia(meq/L) Gr 1: 3-3.4; Gr 2: 2.5-2.9; Gr 3: 2-2.4; Gr 4:\<2. Hypernatremia (meq/L) Gr 1: 148-150; Gr 2: 151-157; Gr 3: 148-165; Gr 4: \>165. Hyponatremia (meq/L) Gr 1: 130-132; Gr 2: 123-129; Gr 3: 116-122; Gr 4: \>115.Hyperglycemia(mg/dL)Gr 1: 116-160; Gr 2: 161-250; Gr 3: 251-500; Gr 4: \>500. Hypoglycemia(mg/dL)Gr 1: 55-64; Gr 2: 40-54; Gr 3:30-39;Gr 4:\<30.Creatine kinase (IU/L) Gr 1: \>ULN-1.5\*ULN; Gr 2: 1.5-3\*ULN; Gr 3: \>3-6\*ULN; Gr 4: \>6.0\*ULN. Albumin (g/dL) Gr 1: \<LLN-30; Gr 2: \<30-20; Gr 3\&4: \<20.
Time frame: While on treatment from Baseline through Week 96
Number of Participants With Enzyme and Urine Laboratory Test Results With Worst Toxicity of Grades 1 to 4
AST/SGOT=Aspartate aminotransferase/serum glutamate oxaloacetate transaminase; ALT/SGPT=Alanine transaminase/serum glutamic pyruvic transaminase. Bilirubin (mg/dL)Gr 1: 1.1-1.5\*ULN;Gr 2:1.6-2.5\*ULN;Gr3:2.6-5\*ULN;Gr4:\>5\*ULN.AST/SGOT(U/L)Gr 1:1.25-2.5\*ULN;Gr 2: 2.6-5\*ULN;Gr 3:5.1-10\*ULN;Gr4:\>10\*ULN.ALT/SGPT (U/L)Gr 1:1.25-2.5\*ULN;Gr 2:1.4-2.09\*ULN;Gr 3:5.1-10\*ULN;Gr4:\>10\*ULN. Lipase(U/L)Gr 1:1.1-1.39\*ULN;Gr 2:\>1.5-2\*ULN;Gr 3:2.5-5;Gr 4:5\*ULN.Proteinuria(g/24 hr loss)Gr 1:1+or \<1;Gr 2:2-3+or\>1-2; Gr 3:4+or\>2-3.5;Gr4:\>3.5.Creatine kinase(IU/L)Gr1:2-3\*ULN;Gr 2:3.1-5\*ULN;Gr 3:5.1-10\*ULN;Gr4:\>10\*ULN.
Time frame: While on treatment from Baseline through Week 96