HIV
Conditions
Keywords
Combination Therapy
Brief summary
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).
Interventions
DRUGAtazanavir
Capsules, Oral, 300 mg, twice daily, 96 weeks
DRUGRaltegravir
Tablet, Oral, 400 mg, twice daily, 96 weeks
DRUGRitonavir
Capsules, Oral, 100 mg, once daily, 96 weeks
Tablet, Oral, 300-mg Tenofovir/200-mg Emtricitabine, once daily, 96 weeks
Sponsors
Merck Sharp & Dohme LLC
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
* Human Immunodeficiency Virus (HIV)-1 positive status * HIV ribonucleic acid (RNA) level \>=5000 copies/mL * Antiretroviral treatment-naive * Absolute Cluster of Differentiation 4 (CD4) cell count meeting 1 of the following criteria: * \<350 cells/mm\^3 * Screening CD4 \>=350 and \<=500 cells/mm\^3 ONLY if at least 1 of the following conditions apply: * Screening HIV RNA level \>100,000 copies/mL, or * CD4 decline \>50-100 cells/mm\^3/year, or * Age \>=55 years * Any CD4 cell count, if participant has a history of an acquired immune deficiency syndrome-defining illness * Medically stable
Exclusion criteria
* Screening HIV genotype showing resistance to any component of the study regimen (Atazanavir, Raltegravir, Tenofovir/Emtricitabine) * Hepatitis B or hepatitis C coinfection * History of or current cardiac disease * Electrocardiogram findings: * PR Interval \>260 msec (severe 1st degree atrioventricular block) * QRS Interval \>120 msec
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Human Immunodeficiency Virus (HIV) Ribonucleic Acid (RNA) Level <50 Copies/mL at Week 24 | At Week 24 from Baseline | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With HIV RNA Levels <50 Copies/mL at Weeks 48 and 96 | At Weeks 48 and 96 from Baseline | 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. |
| Number of Participants With HIV RNA Levels <400 Copies/mL at Week 24 | At Week 24 from Baseline | NC=F: noncompleter=failure; NC=M: noncompleter=missing; VR-OC: virologic response-observed |
| Number of Participants With HIV RNA Levels <400 Copies/mL at Week 48 | At Week 48 from Baseline | — |
| Number of Participants With HIV RNA Levels <400 Copies/mL at Week 96 | At Week 96 from Baseline | — |
| Mean Change From Baseline in Absolute Cluster of Differentiation 4 Cell Count | From Baseline to Weeks 2, 4, 8, 12, 16, 20, and 24 | — |
| Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Death as Outcome, AEs Leading to Discontinuation, SAEs Leading to Discontinuation | Week 1 to Week 96, continuously | 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. |
| Baseline and Mean Change From Baseline in Total Cholesterol Levels | From Baseline to Week 24 and Week 48 | The mean change from baseline in participant fasting lipids was determined using fasting serum samples. |
| Mean Change From Baseline in Total Bilirubin Level | From Baseline to Week 24 and Week 48 | — |
| Mean Change From Baseline in Electrocardiogram Findings | From Baseline to Week 24 | The incidence of QRS wave widening and QT and PR prolongation on participant electrocardiogram findings were evaluated at study Week 24. |
| Atazanavir Maximum Observed Plasma Concentration (Cmax) in 1 Dosing Interval | At Week 2 from Baseline | Serial blood samples were collected over a 12-hour period after the morning dose at Week 2. |
| Raltegravir Cmax in 1 Dosing Interval | At Week 2 from Baseline | Serial blood samples were collected over a 12-hour period after the morning dose at Week 2. |
| Atazanavir Time of Maximum Observed Plasma Concentration (Tmax) | At Week 2 from Baseline | Serial blood samples were collected over a 12-hour period after the morning dose at Week 2. |
| Raltegravir Tmax | At Week 2 from Baseline | Serial blood samples were collected over a 12-hour period after the morning dose at Week 2. |
| Number of Nonresponders at Week 8 | At Week 8 from Baseline | Participants were classified as nonresponders if they had an HIV RNA level ≥400 copies/mL and a decrease from baseline \<2 log10 copies/mL. |
| Raltegravir Cmin 12 Hours Postdose | At Week 2 from Baseline | — |
| Atazanavir Cmin Prior to the Morning Dose | At Week 2 from Baseline | — |
| Raltegravir Cmin Prior to the Morning Dose | At Week 2 from Baseline | — |
| Atazanavir Area Under the Concentration Curve From Time 0 to 12 Hours (AUC [0-12h]) in 1 Dosing Interval | At Week 2 from Baseline | — |
| Raltegravir AUC (0-12h) in 1 Dosing Interval | At Week 2 from Baseline | — |
| Atazanavir Area Under the Concentration Curve From Time 0 to 24 Hours (AUC [0-24h]) in 1 Dosing Interval | At Week 2 from Baseline | AUC (0-24h) was estimated by multiplying AUC (0-12h) by 2. |
| Atazanavir Individual Inhibitory Quotient (IQ) | At Week 2 from Baseline | 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. |
| Atazanavir Terminal Elimination Half Life | At Week 2 from Baseline | — |
| Raltegravir Terminal Elimination Half Life | 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 | While on treatment from Baseline through Week 96 | 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. |
| Number of Participants With Blood Chemistry Laboratory Test Results With Worst Toxicity of Grades 1 to 4 | While on treatment from Baseline through Week 96 | 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. |
| Number of Participants With Blood Chemistry Laboratory Test Results With Worst Toxicity of Grades 1 to 4 (Continued) | While on treatment from Baseline through Week 96 | 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. |
| Number of Participants With Enzyme and Urine Laboratory Test Results With Worst Toxicity of Grades 1 to 4 | While on treatment from Baseline through Week 96 | 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. |
| Atazanavir Trough Plasma Concentration (Cmin) 12 Hours Postdose | At Week 2 from Baseline | — |
Countries
Argentina, France, United States
Participant flow
Recruitment details
Participants were enrolled from sites in Argentina (n=21 randomized), France (n=26 randomized), and the United States (n=47 randomized).
Pre-assignment details
Of 167 participants enrolled, 94 were randomized to treatment; 1 withdrew consent after randomization but prior to study dosing. Of the 73 not randomized, 5 withdrew consent, 1 lost to follow up; 1 poor/noncompliance; 61 no longer met study criteria, and 5 for other reasons. The trial was terminated early.
Participants by arm
| Arm | Count |
|---|---|
| Atazanavir + Raltegravir Atazanavir 300 mg twice daily plus Raltegravir 400 mg twice daily | 63 |
| Atazanavir + Ritonavir + Tenofovir/Emtricitabine Atazanavir, 300 mg once daily, plus Ritonavir, 100 mg once daily, plus fixed-dose Tenofovir/emtricitabine, 300 mg/200 mg once daily | 30 |
| Total | 93 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| On or After Week 36 | Adverse Event | 0 | 1 |
| On or After Week 36 | Did not attend termination visit | 2 | 0 |
| On or After Week 36 | Lack of Efficacy | 1 | 0 |
| On or After Week 36 | Lost to Follow-up | 1 | 0 |
| On or After Week 36 | Poor Compliance | 1 | 0 |
| On or After Week 36 | Protocol Violation | 1 | 0 |
| On or After Week 36 | Sponsor Termination | 45 | 26 |
| Prior to Week 24 | Adverse Event | 3 | 0 |
| Prior to Week 24 | Lost to Follow-up | 0 | 1 |
| Prior to Week 24 | Protocol Violation | 0 | 2 |
| Prior to Week 24 | Withdrawal by Subject | 1 | 0 |
| Week 24 to Prior to Week 36 | Adverse Event | 1 | 0 |
| Week 24 to Prior to Week 36 | Lack of Efficacy | 6 | 0 |
| Week 24 to Prior to Week 36 | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Atazanavir + Raltegravir | Atazanavir + Ritonavir + Tenofovir/Emtricitabine | Total |
|---|---|---|---|
| Age Continuous | 39.5 years STANDARD_DEVIATION 10.9 | 41.6 years STANDARD_DEVIATION 10.87 | 40.2 years STANDARD_DEVIATION 10.88 |
| CD4 Distribution at Baseline 100 to < 200 cells/mm^3 | 13 Participants | 3 Participants | 16 Participants |
| CD4 Distribution at Baseline 200 to < 350 cells/mm^3 | 29 Participants | 13 Participants | 42 Participants |
| CD4 Distribution at Baseline 350 to < 500 cells/mm^3 | 14 Participants | 9 Participants | 23 Participants |
| CD4 Distribution at Baseline >= 500 cells/mm^3 | 1 Participants | 0 Participants | 1 Participants |
| CD4 Distribution at Baseline < 50 cells/mm^3 | 5 Participants | 4 Participants | 9 Participants |
| CD4 Distribution at Baseline 50 to < 100 cells/mm^3 | 1 Participants | 1 Participants | 2 Participants |
| HIV RNA Distribution at Baseline 100,000 to <500,000 copies/mL | 26 Participants | 10 Participants | 36 Participants |
| HIV RNA Distribution at Baseline < 30,000 copies/mL | 14 Participants | 7 Participants | 21 Participants |
| HIV RNA Distribution at Baseline 30,000 to <100,000 copies/mL | 15 Participants | 10 Participants | 25 Participants |
| HIV RNA Distribution at Baseline >=500,000 copies/mL | 8 Participants | 3 Participants | 11 Participants |
| HIV RNA Level at Baseline | 4.9 log10 copies/mL STANDARD_DEVIATION 0.57 | 4.9 log10 copies/mL STANDARD_DEVIATION 0.66 | 4.9 log10 copies/mL STANDARD_DEVIATION 0.6 |
| Mean Cluster of Differentiation 4 (CD4) Cell Count at Baseline | 256.2 cells/mm^3 STANDARD_DEVIATION 116.79 | 261.2 cells/mm^3 STANDARD_DEVIATION 134.93 | 257.8 cells/mm^3 STANDARD_DEVIATION 122.21 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 8 Participants | 6 Participants | 14 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 54 Participants | 23 Participants | 77 Participants |
| Sex: Female, Male Female | 8 Participants | 2 Participants | 10 Participants |
| Sex: Female, Male Male | 55 Participants | 28 Participants | 83 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 58 / 63 | 27 / 30 |
| serious Total, serious adverse events | 7 / 63 | 2 / 30 |
Outcome results
Primary
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
Population: All randomized participants who received at least 1 dose of study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Atazanavir + Raltegravir | Number of Participants With Human Immunodeficiency Virus (HIV) Ribonucleic Acid (RNA) Level <50 Copies/mL at Week 24 | NC=F (n=63, 30) | 47 Participants |
| Atazanavir + Raltegravir | Number of Participants With Human Immunodeficiency Virus (HIV) Ribonucleic Acid (RNA) Level <50 Copies/mL at Week 24 | NC=M (n=58, 27) | 47 Participants |
| Atazanavir + Raltegravir | Number of Participants With Human Immunodeficiency Virus (HIV) Ribonucleic Acid (RNA) Level <50 Copies/mL at Week 24 | VR-OC (n=52, 25) | 41 Participants |
| Atazanavir + Ritonavir + Tenofovir/Emtricitabine | Number of Participants With Human Immunodeficiency Virus (HIV) Ribonucleic Acid (RNA) Level <50 Copies/mL at Week 24 | NC=F (n=63, 30) | 19 Participants |
| Atazanavir + Ritonavir + Tenofovir/Emtricitabine | Number of Participants With Human Immunodeficiency Virus (HIV) Ribonucleic Acid (RNA) Level <50 Copies/mL at Week 24 | NC=M (n=58, 27) | 19 Participants |
| Atazanavir + Ritonavir + Tenofovir/Emtricitabine | Number of Participants With Human Immunodeficiency Virus (HIV) Ribonucleic Acid (RNA) Level <50 Copies/mL at Week 24 | VR-OC (n=52, 25) | 19 Participants |
Secondary
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
Population: All randomized participants who received at least 1 dose of study medication and who were evaluable.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Atazanavir + Raltegravir | Atazanavir Area Under the Concentration Curve From Time 0 to 12 Hours (AUC [0-12h]) in 1 Dosing Interval | 19903.4 ng•h/mL | Standard Deviation 8088 |
Secondary
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
Population: All randomized participants who received at least 1 dose of study medication and who were evaluable.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Atazanavir + Raltegravir | Atazanavir Area Under the Concentration Curve From Time 0 to 24 Hours (AUC [0-24h]) in 1 Dosing Interval | 39806.7 ng•h/mL | Standard Deviation 16176 |
Secondary
Atazanavir Cmin Prior to the Morning Dose
Time frame: At Week 2 from Baseline
Population: All randomized participants who received at least 1 dose of study medication and who were evaluable.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Atazanavir + Raltegravir | Atazanavir Cmin Prior to the Morning Dose | 879.25 ng*h / mL | Standard Deviation 495 |
Secondary
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
Population: All randomized participants who received at least 1 dose of study medication and who were evaluable.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Atazanavir + Raltegravir | Atazanavir Individual Inhibitory Quotient (IQ) | 23.47 Units on a Scale |
Secondary
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
Population: All randomized participants who received at least 1 dose of study medication and were evaluable.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Atazanavir + Raltegravir | Atazanavir Maximum Observed Plasma Concentration (Cmax) in 1 Dosing Interval | 3506.5 ng/mL | Standard Deviation 1366 |
Secondary
Atazanavir Terminal Elimination Half Life
Time frame: At Week 2 from Baseline
Population: All randomized participants who received at least 1 dose of study medication and who were evaluable.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Atazanavir + Raltegravir | Atazanavir Terminal Elimination Half Life | 5.0 Hours | Standard Deviation 2.2 |
Secondary
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
Population: All randomized participants who received at least 1 dose of study medication and who were evaluable.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Atazanavir + Raltegravir | Atazanavir Time of Maximum Observed Plasma Concentration (Tmax) | 3.0 Hours |
Secondary
Atazanavir Trough Plasma Concentration (Cmin) 12 Hours Postdose
Time frame: At Week 2 from Baseline
Population: All randomized participants who received at least 1 dose of study medication and who were evaluable.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Atazanavir + Raltegravir | Atazanavir Trough Plasma Concentration (Cmin) 12 Hours Postdose | 687.1 ng•h/mL | Standard Deviation 402 |
Secondary
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
Population: All randomized participants who received at least 1 dose of study medication. N=number of participants analyzed; n=number of participants with measurements for that time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Atazanavir + Raltegravir | Baseline and Mean Change From Baseline in Total Cholesterol Levels | Baseline (n=56, 26) | 164.6 mg/dL | Standard Error 3.833 |
| Atazanavir + Raltegravir | Baseline and Mean Change From Baseline in Total Cholesterol Levels | Mean change from Baseline at Week 24 (n=51, 20) | 14.7 mg/dL | Standard Error 4.367 |
| Atazanavir + Raltegravir | Baseline and Mean Change From Baseline in Total Cholesterol Levels | Mean change from Baseline at Week 48 (n=38, 20) | 18.0 mg/dL | Standard Error 3.04 |
| Atazanavir + Ritonavir + Tenofovir/Emtricitabine | Baseline and Mean Change From Baseline in Total Cholesterol Levels | Baseline (n=56, 26) | 169.6 mg/dL | Standard Error 6.756 |
| Atazanavir + Ritonavir + Tenofovir/Emtricitabine | Baseline and Mean Change From Baseline in Total Cholesterol Levels | Mean change from Baseline at Week 24 (n=51, 20) | 15.1 mg/dL | Standard Error 6.827 |
| Atazanavir + Ritonavir + Tenofovir/Emtricitabine | Baseline and Mean Change From Baseline in Total Cholesterol Levels | Mean change from Baseline at Week 48 (n=38, 20) | 17.1 mg/dL | Standard Error 4.526 |
Secondary
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
Population: All randomized participants who received at least 1 dose of study medication and had baseline and timepoint results.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Atazanavir + Raltegravir | Mean Change From Baseline in Absolute Cluster of Differentiation 4 Cell Count | Mean change from Baseline at Week 24 (n=55, 24) | 166.0 cells/mm^3 | Standard Error 16.954 |
| Atazanavir + Raltegravir | Mean Change From Baseline in Absolute Cluster of Differentiation 4 Cell Count | Mean change from Baseline at Week 2 (n=59, 26) | 81.1 cells/mm^3 | Standard Error 11.886 |
| Atazanavir + Raltegravir | Mean Change From Baseline in Absolute Cluster of Differentiation 4 Cell Count | Mean change from Baseline at Week 4 (n=62, 27) | 82.7 cells/mm^3 | Standard Error 12.238 |
| Atazanavir + Raltegravir | Mean Change From Baseline in Absolute Cluster of Differentiation 4 Cell Count | Mean change from Baseline at Week 8 (n=60, 29) | 111.5 cells/mm^3 | Standard Error 12.297 |
| Atazanavir + Raltegravir | Mean Change From Baseline in Absolute Cluster of Differentiation 4 Cell Count | Mean change from Baseline at Week 12 (n=62, 28) | 128.6 cells/mm^3 | Standard Error 13.964 |
| Atazanavir + Raltegravir | Mean Change From Baseline in Absolute Cluster of Differentiation 4 Cell Count | Mean change from Baseline at Week 16 (n=58, 27) | 143.6 cells/mm^3 | Standard Error 12.789 |
| Atazanavir + Raltegravir | Mean Change From Baseline in Absolute Cluster of Differentiation 4 Cell Count | Mean change from Baseline at Week 20 (n=58, 24) | 166.5 cells/mm^3 | Standard Error 12.189 |
| Atazanavir + Ritonavir + Tenofovir/Emtricitabine | Mean Change From Baseline in Absolute Cluster of Differentiation 4 Cell Count | Mean change from Baseline at Week 24 (n=55, 24) | 127.0 cells/mm^3 | Standard Error 17.788 |
| Atazanavir + Ritonavir + Tenofovir/Emtricitabine | Mean Change From Baseline in Absolute Cluster of Differentiation 4 Cell Count | Mean change from Baseline at Week 12 (n=62, 28) | 129.3 cells/mm^3 | Standard Error 20.46 |
| Atazanavir + Ritonavir + Tenofovir/Emtricitabine | Mean Change From Baseline in Absolute Cluster of Differentiation 4 Cell Count | Mean change from Baseline at Week 2 (n=59, 26) | 63.1 cells/mm^3 | Standard Error 14.248 |
| Atazanavir + Ritonavir + Tenofovir/Emtricitabine | Mean Change From Baseline in Absolute Cluster of Differentiation 4 Cell Count | Mean change from Baseline at Week 20 (n=58, 24) | 140.7 cells/mm^3 | Standard Error 19.919 |
| Atazanavir + Ritonavir + Tenofovir/Emtricitabine | Mean Change From Baseline in Absolute Cluster of Differentiation 4 Cell Count | Mean change from Baseline at Week 4 (n=62, 27) | 100.1 cells/mm^3 | Standard Error 19.481 |
| Atazanavir + Ritonavir + Tenofovir/Emtricitabine | Mean Change From Baseline in Absolute Cluster of Differentiation 4 Cell Count | Mean change from Baseline at Week 16 (n=58, 27) | 127.6 cells/mm^3 | Standard Error 19.336 |
| Atazanavir + Ritonavir + Tenofovir/Emtricitabine | Mean Change From Baseline in Absolute Cluster of Differentiation 4 Cell Count | Mean change from Baseline at Week 8 (n=60, 29) | 111.9 cells/mm^3 | Standard Error 16.845 |
Secondary
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
Population: All randomized participants who received at least 1 dose of study medication.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Atazanavir + Raltegravir | Mean Change From Baseline in Electrocardiogram Findings | QRS Interval | 8.9 msec | Standard Error 1.019 |
| Atazanavir + Raltegravir | Mean Change From Baseline in Electrocardiogram Findings | QTc Friderica Interval | -2.7 msec | Standard Error 2.001 |
| Atazanavir + Raltegravir | Mean Change From Baseline in Electrocardiogram Findings | PR Interval | 17.6 msec | Standard Error 2.101 |
| Atazanavir + Ritonavir + Tenofovir/Emtricitabine | Mean Change From Baseline in Electrocardiogram Findings | QRS Interval | 3.6 msec | Standard Error 1.966 |
| Atazanavir + Ritonavir + Tenofovir/Emtricitabine | Mean Change From Baseline in Electrocardiogram Findings | QTc Friderica Interval | 6.0 msec | Standard Error 3.76 |
| Atazanavir + Ritonavir + Tenofovir/Emtricitabine | Mean Change From Baseline in Electrocardiogram Findings | PR Interval | 4.9 msec | Standard Error 2.248 |
Secondary
Mean Change From Baseline in Total Bilirubin Level
Time frame: From Baseline to Week 24 and Week 48
Population: All randomized participants who received at least 1 dose of study medication.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Atazanavir + Raltegravir | Mean Change From Baseline in Total Bilirubin Level | Mean change from Baseline at Week 24 | 2.15 mg/dL | Standard Error 0.2032 |
| Atazanavir + Raltegravir | Mean Change From Baseline in Total Bilirubin Level | Mean change from Baseline at Week 48 | 2.08 mg/dL | Standard Error 0.2176 |
| Atazanavir + Ritonavir + Tenofovir/Emtricitabine | Mean Change From Baseline in Total Bilirubin Level | Mean change from Baseline at Week 24 | 1.71 mg/dL | Standard Error 0.2234 |
| Atazanavir + Ritonavir + Tenofovir/Emtricitabine | Mean Change From Baseline in Total Bilirubin Level | Mean change from Baseline at Week 48 | 1.52 mg/dL | Standard Error 0.2206 |
Secondary
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
Population: The first 60 participants randomized, who received at least 1 dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Atazanavir + Raltegravir | Number of Nonresponders at Week 8 | 0 Participants |
| Atazanavir + Ritonavir + Tenofovir/Emtricitabine | Number of Nonresponders at Week 8 | 1 Participants |
Secondary
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
Population: All randomized participants who received at least 1 dose of study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Atazanavir + Raltegravir | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Death as Outcome, AEs Leading to Discontinuation, SAEs Leading to Discontinuation | SAEs | 7 Participants |
| Atazanavir + Raltegravir | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Death as Outcome, AEs Leading to Discontinuation, SAEs Leading to Discontinuation | AEs leading to discontinuation | 4 Participants |
| Atazanavir + Raltegravir | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Death as Outcome, AEs Leading to Discontinuation, SAEs Leading to Discontinuation | Deaths | 0 Participants |
| Atazanavir + Raltegravir | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Death as Outcome, AEs Leading to Discontinuation, SAEs Leading to Discontinuation | SAEs leading to discontinuation | 1 Participants |
| Atazanavir + Raltegravir | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Death as Outcome, AEs Leading to Discontinuation, SAEs Leading to Discontinuation | AEs | 60 Participants |
| Atazanavir + Ritonavir + Tenofovir/Emtricitabine | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Death as Outcome, AEs Leading to Discontinuation, SAEs Leading to Discontinuation | SAEs leading to discontinuation | 0 Participants |
| Atazanavir + Ritonavir + Tenofovir/Emtricitabine | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Death as Outcome, AEs Leading to Discontinuation, SAEs Leading to Discontinuation | AEs | 29 Participants |
| Atazanavir + Ritonavir + Tenofovir/Emtricitabine | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Death as Outcome, AEs Leading to Discontinuation, SAEs Leading to Discontinuation | SAEs | 2 Participants |
| Atazanavir + Ritonavir + Tenofovir/Emtricitabine | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Death as Outcome, AEs Leading to Discontinuation, SAEs Leading to Discontinuation | Deaths | 0 Participants |
| Atazanavir + Ritonavir + Tenofovir/Emtricitabine | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Death as Outcome, AEs Leading to Discontinuation, SAEs Leading to Discontinuation | AEs leading to discontinuation | 1 Participants |
Secondary
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
Population: All randomized participants who received at least 1 dose of study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Atazanavir + Raltegravir | Number of Participants With Blood Chemistry Laboratory Test Results With Worst Toxicity of Grades 1 to 4 | Hyperchloremia | 0 Participants |
| Atazanavir + Raltegravir | Number of Participants With Blood Chemistry Laboratory Test Results With Worst Toxicity of Grades 1 to 4 | Hypercarbia | 1 Participants |
| Atazanavir + Raltegravir | Number of Participants With Blood Chemistry Laboratory Test Results With Worst Toxicity of Grades 1 to 4 | Hypochloremia | 1 Participants |
| Atazanavir + Raltegravir | Number of Participants With Blood Chemistry Laboratory Test Results With Worst Toxicity of Grades 1 to 4 | Hypoglycemia | 6 Participants |
| Atazanavir + Raltegravir | Number of Participants With Blood Chemistry Laboratory Test Results With Worst Toxicity of Grades 1 to 4 | Hyperkalemia | 2 Participants |
| Atazanavir + Raltegravir | Number of Participants With Blood Chemistry Laboratory Test Results With Worst Toxicity of Grades 1 to 4 | Hypocarbia | 15 Participants |
| Atazanavir + Raltegravir | Number of Participants With Blood Chemistry Laboratory Test Results With Worst Toxicity of Grades 1 to 4 | Hypokalemia | 6 Participants |
| Atazanavir + Raltegravir | Number of Participants With Blood Chemistry Laboratory Test Results With Worst Toxicity of Grades 1 to 4 | Hypercalcemia | 2 Participants |
| Atazanavir + Raltegravir | Number of Participants With Blood Chemistry Laboratory Test Results With Worst Toxicity of Grades 1 to 4 | Hypernatremia | 0 Participants |
| Atazanavir + Raltegravir | Number of Participants With Blood Chemistry Laboratory Test Results With Worst Toxicity of Grades 1 to 4 | Creatinine | 3 Participants |
| Atazanavir + Raltegravir | Number of Participants With Blood Chemistry Laboratory Test Results With Worst Toxicity of Grades 1 to 4 | Hyponatremia | 3 Participants |
| Atazanavir + Raltegravir | Number of Participants With Blood Chemistry Laboratory Test Results With Worst Toxicity of Grades 1 to 4 | Hypocalcemia | 1 Participants |
| Atazanavir + Raltegravir | Number of Participants With Blood Chemistry Laboratory Test Results With Worst Toxicity of Grades 1 to 4 | Hyperclycemia | 8 Participants |
| Atazanavir + Raltegravir | Number of Participants With Blood Chemistry Laboratory Test Results With Worst Toxicity of Grades 1 to 4 | Blood urea nitrogen | 0 Participants |
| Atazanavir + Ritonavir + Tenofovir/Emtricitabine | Number of Participants With Blood Chemistry Laboratory Test Results With Worst Toxicity of Grades 1 to 4 | Hypoglycemia | 4 Participants |
| Atazanavir + Ritonavir + Tenofovir/Emtricitabine | Number of Participants With Blood Chemistry Laboratory Test Results With Worst Toxicity of Grades 1 to 4 | Hyperclycemia | 5 Participants |
| Atazanavir + Ritonavir + Tenofovir/Emtricitabine | Number of Participants With Blood Chemistry Laboratory Test Results With Worst Toxicity of Grades 1 to 4 | Blood urea nitrogen | 1 Participants |
| Atazanavir + Ritonavir + Tenofovir/Emtricitabine | Number of Participants With Blood Chemistry Laboratory Test Results With Worst Toxicity of Grades 1 to 4 | Creatinine | 2 Participants |
| Atazanavir + Ritonavir + Tenofovir/Emtricitabine | Number of Participants With Blood Chemistry Laboratory Test Results With Worst Toxicity of Grades 1 to 4 | Hypercarbia | 1 Participants |
| Atazanavir + Ritonavir + Tenofovir/Emtricitabine | Number of Participants With Blood Chemistry Laboratory Test Results With Worst Toxicity of Grades 1 to 4 | Hypercalcemia | 1 Participants |
| Atazanavir + Ritonavir + Tenofovir/Emtricitabine | Number of Participants With Blood Chemistry Laboratory Test Results With Worst Toxicity of Grades 1 to 4 | Hypocalcemia | 1 Participants |
| Atazanavir + Ritonavir + Tenofovir/Emtricitabine | Number of Participants With Blood Chemistry Laboratory Test Results With Worst Toxicity of Grades 1 to 4 | Hyperchloremia | 0 Participants |
| Atazanavir + Ritonavir + Tenofovir/Emtricitabine | Number of Participants With Blood Chemistry Laboratory Test Results With Worst Toxicity of Grades 1 to 4 | Hypochloremia | 1 Participants |
| Atazanavir + Ritonavir + Tenofovir/Emtricitabine | Number of Participants With Blood Chemistry Laboratory Test Results With Worst Toxicity of Grades 1 to 4 | Hyperkalemia | 0 Participants |
| Atazanavir + Ritonavir + Tenofovir/Emtricitabine | Number of Participants With Blood Chemistry Laboratory Test Results With Worst Toxicity of Grades 1 to 4 | Hypokalemia | 5 Participants |
| Atazanavir + Ritonavir + Tenofovir/Emtricitabine | Number of Participants With Blood Chemistry Laboratory Test Results With Worst Toxicity of Grades 1 to 4 | Hypernatremia | 0 Participants |
| Atazanavir + Ritonavir + Tenofovir/Emtricitabine | Number of Participants With Blood Chemistry Laboratory Test Results With Worst Toxicity of Grades 1 to 4 | Hyponatremia | 1 Participants |
| Atazanavir + Ritonavir + Tenofovir/Emtricitabine | Number of Participants With Blood Chemistry Laboratory Test Results With Worst Toxicity of Grades 1 to 4 | Hypocarbia | 7 Participants |
Secondary
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
Population: All randomized participants who received at least 1 dose of study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Atazanavir + Raltegravir | Number of Participants With Blood Chemistry Laboratory Test Results With Worst Toxicity of Grades 1 to 4 (Continued) | Hyperkalemia | 2 Participants |
| Atazanavir + Raltegravir | Number of Participants With Blood Chemistry Laboratory Test Results With Worst Toxicity of Grades 1 to 4 (Continued) | Hyperclycemia | 8 Participants |
| Atazanavir + Raltegravir | Number of Participants With Blood Chemistry Laboratory Test Results With Worst Toxicity of Grades 1 to 4 (Continued) | Hypernatremia | 0 Participants |
| Atazanavir + Raltegravir | Number of Participants With Blood Chemistry Laboratory Test Results With Worst Toxicity of Grades 1 to 4 (Continued) | Hypoglycemia | 6 Participants |
| Atazanavir + Raltegravir | Number of Participants With Blood Chemistry Laboratory Test Results With Worst Toxicity of Grades 1 to 4 (Continued) | Hypokalemia | 1 Participants |
| Atazanavir + Raltegravir | Number of Participants With Blood Chemistry Laboratory Test Results With Worst Toxicity of Grades 1 to 4 (Continued) | Creatine kinase | 21 Participants |
| Atazanavir + Raltegravir | Number of Participants With Blood Chemistry Laboratory Test Results With Worst Toxicity of Grades 1 to 4 (Continued) | Hyponatremia | 3 Participants |
| Atazanavir + Raltegravir | Number of Participants With Blood Chemistry Laboratory Test Results With Worst Toxicity of Grades 1 to 4 (Continued) | Albumin | 3 Participants |
| Atazanavir + Ritonavir + Tenofovir/Emtricitabine | Number of Participants With Blood Chemistry Laboratory Test Results With Worst Toxicity of Grades 1 to 4 (Continued) | Albumin | 2 Participants |
| Atazanavir + Ritonavir + Tenofovir/Emtricitabine | Number of Participants With Blood Chemistry Laboratory Test Results With Worst Toxicity of Grades 1 to 4 (Continued) | Hyperkalemia | 1 Participants |
| Atazanavir + Ritonavir + Tenofovir/Emtricitabine | Number of Participants With Blood Chemistry Laboratory Test Results With Worst Toxicity of Grades 1 to 4 (Continued) | Hypokalemia | 1 Participants |
| Atazanavir + Ritonavir + Tenofovir/Emtricitabine | Number of Participants With Blood Chemistry Laboratory Test Results With Worst Toxicity of Grades 1 to 4 (Continued) | Hypernatremia | 0 Participants |
| Atazanavir + Ritonavir + Tenofovir/Emtricitabine | Number of Participants With Blood Chemistry Laboratory Test Results With Worst Toxicity of Grades 1 to 4 (Continued) | Hyponatremia | 1 Participants |
| Atazanavir + Ritonavir + Tenofovir/Emtricitabine | Number of Participants With Blood Chemistry Laboratory Test Results With Worst Toxicity of Grades 1 to 4 (Continued) | Hyperclycemia | 5 Participants |
| Atazanavir + Ritonavir + Tenofovir/Emtricitabine | Number of Participants With Blood Chemistry Laboratory Test Results With Worst Toxicity of Grades 1 to 4 (Continued) | Hypoglycemia | 4 Participants |
| Atazanavir + Ritonavir + Tenofovir/Emtricitabine | Number of Participants With Blood Chemistry Laboratory Test Results With Worst Toxicity of Grades 1 to 4 (Continued) | Creatine kinase | 7 Participants |
Secondary
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
Population: All randomized participants who received at least 1 dose of study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Atazanavir + Raltegravir | Number of Participants With Enzyme and Urine Laboratory Test Results With Worst Toxicity of Grades 1 to 4 | Lipase | 11 Participants |
| Atazanavir + Raltegravir | Number of Participants With Enzyme and Urine Laboratory Test Results With Worst Toxicity of Grades 1 to 4 | Total Bilirubin | 62 Participants |
| Atazanavir + Raltegravir | Number of Participants With Enzyme and Urine Laboratory Test Results With Worst Toxicity of Grades 1 to 4 | Proteinurea | 14 Participants |
| Atazanavir + Raltegravir | Number of Participants With Enzyme and Urine Laboratory Test Results With Worst Toxicity of Grades 1 to 4 | ALT/ SGPT | 10 Participants |
| Atazanavir + Raltegravir | Number of Participants With Enzyme and Urine Laboratory Test Results With Worst Toxicity of Grades 1 to 4 | Creatine kinase | 21 Participants |
| Atazanavir + Raltegravir | Number of Participants With Enzyme and Urine Laboratory Test Results With Worst Toxicity of Grades 1 to 4 | AST/SGOT | 11 Participants |
| Atazanavir + Ritonavir + Tenofovir/Emtricitabine | Number of Participants With Enzyme and Urine Laboratory Test Results With Worst Toxicity of Grades 1 to 4 | Creatine kinase | 7 Participants |
| Atazanavir + Ritonavir + Tenofovir/Emtricitabine | Number of Participants With Enzyme and Urine Laboratory Test Results With Worst Toxicity of Grades 1 to 4 | AST/SGOT | 8 Participants |
| Atazanavir + Ritonavir + Tenofovir/Emtricitabine | Number of Participants With Enzyme and Urine Laboratory Test Results With Worst Toxicity of Grades 1 to 4 | ALT/ SGPT | 8 Participants |
| Atazanavir + Ritonavir + Tenofovir/Emtricitabine | Number of Participants With Enzyme and Urine Laboratory Test Results With Worst Toxicity of Grades 1 to 4 | Lipase | 13 Participants |
| Atazanavir + Ritonavir + Tenofovir/Emtricitabine | Number of Participants With Enzyme and Urine Laboratory Test Results With Worst Toxicity of Grades 1 to 4 | Proteinurea | 11 Participants |
| Atazanavir + Ritonavir + Tenofovir/Emtricitabine | Number of Participants With Enzyme and Urine Laboratory Test Results With Worst Toxicity of Grades 1 to 4 | Total Bilirubin | 28 Participants |
Secondary
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
Population: All randomized participants who received at least 1 dose of study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Atazanavir + Raltegravir | Number of Participants With Hematology Laboratory Test Results With Worst Toxicity of Grades 1 to 4 Among All Treated Participants | Hemoglobin | 2 Participants |
| Atazanavir + Raltegravir | Number of Participants With Hematology Laboratory Test Results With Worst Toxicity of Grades 1 to 4 Among All Treated Participants | Prothrombin Time | 12 Participants |
| Atazanavir + Raltegravir | Number of Participants With Hematology Laboratory Test Results With Worst Toxicity of Grades 1 to 4 Among All Treated Participants | Platelets | 1 Participants |
| Atazanavir + Raltegravir | Number of Participants With Hematology Laboratory Test Results With Worst Toxicity of Grades 1 to 4 Among All Treated Participants | White Blood Cells | 22 Participants |
| Atazanavir + Raltegravir | Number of Participants With Hematology Laboratory Test Results With Worst Toxicity of Grades 1 to 4 Among All Treated Participants | Hematocrit | 1 Participants |
| Atazanavir + Ritonavir + Tenofovir/Emtricitabine | Number of Participants With Hematology Laboratory Test Results With Worst Toxicity of Grades 1 to 4 Among All Treated Participants | White Blood Cells | 14 Participants |
| Atazanavir + Ritonavir + Tenofovir/Emtricitabine | Number of Participants With Hematology Laboratory Test Results With Worst Toxicity of Grades 1 to 4 Among All Treated Participants | Hematocrit | 0 Participants |
| Atazanavir + Ritonavir + Tenofovir/Emtricitabine | Number of Participants With Hematology Laboratory Test Results With Worst Toxicity of Grades 1 to 4 Among All Treated Participants | Hemoglobin | 0 Participants |
| Atazanavir + Ritonavir + Tenofovir/Emtricitabine | Number of Participants With Hematology Laboratory Test Results With Worst Toxicity of Grades 1 to 4 Among All Treated Participants | Platelets | 1 Participants |
| Atazanavir + Ritonavir + Tenofovir/Emtricitabine | Number of Participants With Hematology Laboratory Test Results With Worst Toxicity of Grades 1 to 4 Among All Treated Participants | Prothrombin Time | 7 Participants |
Secondary
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
Population: All randomized participants who received at least 1 dose of study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Atazanavir + Raltegravir | Number of Participants With HIV RNA Levels <400 Copies/mL at Week 24 | NC=F (n= 63, 30) | 52 Participants |
| Atazanavir + Raltegravir | Number of Participants With HIV RNA Levels <400 Copies/mL at Week 24 | NC=M (n=58, 27) | 52 Participants |
| Atazanavir + Raltegravir | Number of Participants With HIV RNA Levels <400 Copies/mL at Week 24 | VR-OC (n=52, 25) | 46 Participants |
| Atazanavir + Ritonavir + Tenofovir/Emtricitabine | Number of Participants With HIV RNA Levels <400 Copies/mL at Week 24 | NC=F (n= 63, 30) | 26 Participants |
| Atazanavir + Ritonavir + Tenofovir/Emtricitabine | Number of Participants With HIV RNA Levels <400 Copies/mL at Week 24 | NC=M (n=58, 27) | 26 Participants |
| Atazanavir + Ritonavir + Tenofovir/Emtricitabine | Number of Participants With HIV RNA Levels <400 Copies/mL at Week 24 | VR-OC (n=52, 25) | 24 Participants |
Secondary
Number of Participants With HIV RNA Levels <400 Copies/mL at Week 48
Time frame: At Week 48 from Baseline
Population: The study terminated early, and this analysis was only done at Week 48 using VR-OC for participants who reached Week 48 when the study was terminated.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Atazanavir + Raltegravir | Number of Participants With HIV RNA Levels <400 Copies/mL at Week 48 | 45 Participants |
| Atazanavir + Ritonavir + Tenofovir/Emtricitabine | Number of Participants With HIV RNA Levels <400 Copies/mL at Week 48 | 25 Participants |
Secondary
Number of Participants With HIV RNA Levels <400 Copies/mL at Week 96
Time frame: At Week 96 from Baseline
Population: This analysis was not preformed due to early termination of the study.
Secondary
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
Population: The study terminated early, and this analysis was done only at Week 48 using VR-OC for participants who reached Week 48 when the study was terminated.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Atazanavir + Raltegravir | Number of Participants With HIV RNA Levels <50 Copies/mL at Weeks 48 and 96 | 37 Participants |
| Atazanavir + Ritonavir + Tenofovir/Emtricitabine | Number of Participants With HIV RNA Levels <50 Copies/mL at Weeks 48 and 96 | 19 Participants |
Secondary
Raltegravir AUC (0-12h) in 1 Dosing Interval
Time frame: At Week 2 from Baseline
Population: All randomized participants who received at least 1 dose of study medication and who were evaluable.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Atazanavir + Raltegravir | Raltegravir AUC (0-12h) in 1 Dosing Interval | 6446.4 ng•h/mL | Standard Deviation 6432 |
Secondary
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
Population: All randomized participants who received at least 1 dose of study medication and were evaluable.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Atazanavir + Raltegravir | Raltegravir Cmax in 1 Dosing Interval | 1577.0 ng/mL | Standard Deviation 2516 |
Secondary
Raltegravir Cmin 12 Hours Postdose
Time frame: At Week 2 from Baseline
Population: All randomized participants who received at least 1 dose of study medication and who were evaluable.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Atazanavir + Raltegravir | Raltegravir Cmin 12 Hours Postdose | 76.2 ng•h/mL | Standard Deviation 94.5 |
Secondary
Raltegravir Cmin Prior to the Morning Dose
Time frame: At Week 2 from Baseline
Population: All randomized participants who received at least 1 dose of study medication and who were evaluable.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Atazanavir + Raltegravir | Raltegravir Cmin Prior to the Morning Dose | 445.42 ng•h/mL | Standard Deviation 577 |
Secondary
Raltegravir Terminal Elimination Half Life
Time frame: At Week 2 from Baseline
Population: All randomized participants who received at least 1 dose of study medication and who were evaluable.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Atazanavir + Raltegravir | Raltegravir Terminal Elimination Half Life | 2.9 Hours | Standard Deviation 2.8 |
Secondary
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
Population: All randomized participants who received at least 1 dose of study medication and who were evaluable.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Atazanavir + Raltegravir | Raltegravir Tmax | 2.08 Hours |