HIV Infections
Conditions
Keywords
HIV, Pediatric
Brief summary
The purpose of this study is to determine whether atazanavir powder combined with ritonavir is safe and well tolerated and produces appropriate drug exposure in children ≥3 months to \<6 years of age.
Interventions
DRUGAtazanavir capsules
Capsules, oral, dosed by weight in Stage 2. Patients who reached the age of 6 years or a weight of ≥25 kg transitioned from the powder to the capsule formulation of atazanavir (ATV). Patients who weighed 15 to \<20 kg received ATV, 150 mg with RTV, 100 mg; those who weighed 20 to \<40 kg received ATV, 200 mg, and RTV, 100 mg; and those who weighed at least 40 kg received ATV, 300 mg with RTV, 100 mg. RTV capsules or tablets were ingested with food immediately before or after ATV intake.
Oral, capsules, 100 mg, administered in Stage 2 with atazanavir capsules, dosed by weight.
DRUGAtazanavir powder
Powder, oral, dosed by weight. Participants who weighed 5 to \<10 kg received atazanavir (ATV), 150 mg, and ritonavir (RTV), 80 mg; those who weighed 10 to \<15 kg received ATV, 200 mg, and RTV, 80 mg; and those who weighed 15 to \<25 kg received ATV, 250 mg, and RTV, 80 mg, once per day for 48 weeks or until pediatric indication is locally approved and participant meets requirements to receive appropriate formulation.
Oral solution, 80 mg/mL, once per day for 48 weeks or until pediatric indication is locally approved and participant meets requirements to receive appropriate formulation.
Sponsors
Bristol-Myers Squibb
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
3 Months to 66 Months
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Confirmed human immunodeficiency virus (HIV)-1 infection diagnosed by a positive virologic test result on 2 separate occasions by: * HIV DNA polymerase chain reaction * HIV RNA with values ≥1,000 copies/mL * Positive HIV enzyme-linked immunosorbent assay at ≥18 months of age, with confirmatory Western blot or indirect immunoflourescence antibody * Infants and children of either sex, aged ≥3 months to \<5 years and 6 months at time of first treatment, and weight \>5 to \<25 kg with any screening baseline plasma viral load * Screening plasma viral load ≥1,000 copies/mL by Roche Amplicor® HIV RNA Assay * Documented genotypic and phenotypic sensitivity at screening to ATV (fold change in susceptibility \<2.2) and to at least 2 nucleoside reverse transcriptase inhibitors (NRTIs) approved in the infant's country * Genotypic sensitivity at screening to atazanavir (ATV) and at least 2 NRTIs * Antiretroviral (ARV) treatment-naive or ARV treatment-experienced. Treatment-experienced participants are defined by previous exposure to ARVs through either prior treatment for HIV infection or through postnatal treatment with ≥1 ARV for the prevention of mother to child transmission. For the purposes of this study, participants exposed to ARVs in utero or intrapartum may be included in the study but will be considered treatment naive. ATV-naive participants must have genotypic sensitivity at screening to ATV (fold change in susceptibility \<2.2) and to both components of the local NRTI backbone. The NRTIs must have been approved for pediatric use at the local country level. Key
Exclusion criteria
* Experienced participants who received ATV or ATV/ritonavir (RTV) at any time prior to study enrollment or with a history of 2 or more protease inhibitor failures * ARV-naïve or -experienced HIV-1 infected patients with contraindication to study medications syncope * Family history of QTc interval syndrome, Brugada syndrome, right ventricular dysplasia, or a corrected QTc interval at screening of \>440 ms * One of the following cardiac rhythm abnormalities documented on screening electrocardiogram: 1st degree atrioventricular (AV) block as defined by protocol, type I 2nd degree AV block while awake, type II 2nd degree AV block at any time, complete AV block at any time, or age-adjusted heart rate \<2nd percentile) History of pancreatitis, peripheral neuropathy, malignancy that requires systemic therapy, or any medical condition which, in the opinion of the investigator, added undue risk to trial participation * Malabsorption syndrome * Presence of a newly diagnosed HIV-related opportunistic infection or any medical condition requiring acute therapy at the time of enrollment * Weight \<5 or ≥25 kg at date of first dose (Day 1). * \>Grade 2 aspartate transaminase or alanine transaminase abnormalities * Hypersensitivity to any component of the study medication formulations (ATV/RTV, or a locally prescribed NRTI with a pediatric indication) * Infants and children of either gender \<3 months or ≥5 years and 6 months at the time of first treatment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Discontinuation | From Day 1 to Week 48 | AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. |
| Number of Participants With Laboratory Test Results With Worst Toxicity of Grade 3-4 | After Day 1 to Week 48 | ALT=alanine aminotransferase; SGPT=serum glutamic-pyruvic transaminase; AST=aspartate aminotransferase; SGOT=serum glutamic-oxaloacetic transaminase; ULN=upper limit of normal. Grading by the National Institute of Health Division of AIDs and World Health Organization criteria. Hemoglobin (g/dL): Grade (Gr)1=9.5-11.0; Gr 2=8.0-9.4; Gr 3=6.5-7.9; Gr 4=\<6.5. Neutrophils, absolute (/mm\^3): Gr 1=\>=1000-\<1500; Gr 2= \>=750-\<1000; Gr 3=\>=500-\<750; Gr 4=\<500. ALT/SGPT (\*ULN): Gr 1=1.25-2.5; Gr 2=2.6-5; Gr 3=5.1-10; Gr 4=\>10. AST/SGOT (\*ULN): Gr 1=1.25-2.5; Gr 2=2.6-5; Gr 3=5.1-10; Gr 4=\>10. Alkaline phosphatase(\*ULN): Gr 1=1.25-2.5; Gr 2=2.6-5: Gr 3=5.1-10; Gr 4=\>10. Total bilirubin (\*ULN): Gr 1=1.1-1; Gr 2=1.6-2.5; Gr 3=2.6-5; Gr 4=\>5. Amylase (\*ULN): Gr 1=1.10-39; Gr 2=1.40-2; Gr 3=2.10-5.0; Gr 4=\>5.0. Lipase (\*ULN): Gr 1=1.10-1.39: Gr 2=1.40-2; Gr 3=2.10-5.0; Gr 4=\>5.0. Uric acid (mg/dL): Gr 1=7.5-10.0; Gr 2=10.1-12.0; Gr 3=12.1-15.0; Gr 4=\>15. |
| Electrocardiogram Changes From Baseline in PR Interval, QTC Bazett, and QTC Fridericia at Week 48 | From Baseline to Week 48 | Electrocardiogram parameters were measured at baseline for QTC Bazett, QTC Fridericia, and PR interval. The mean change from baseline at week 48 is reported by arm in milliseconds. |
| Number of Participants With Centers for Disease Control (CDC) Class C AIDS Events | From Day 1 to Week 48 | CDC Class C events are AIDS-defining events that include recurrent bacterial pneumonia (\>=2 episodes in 12 months); candidiasis of the bronchi, trachea, lungs, or esophagus; invasive cervical carcinoma; disseminated or extrapulmonary coccidioidomycosis; extrapulmonary cryptococcosis; chronic intestinal cryptosporidiosis (\>1 month); cytomegalovirus disease; HIV-related encephalopathy; herpes simplex: chronic ulcers, or bronchitis, pneumonitis, or esophagitis; disseminated or extrapulmonary histoplasmosis; chronic intestinal isosporiasis; Kaposi sarcoma; immunoblastic or primary brain Burkitt lymphoma; mycobacterium avium complex, kansasii, or tuberculosis; mycobacterium, other species; Pneumocystis carinii pneumonia; progressive multifocal leukoencephalopathy; Salmonella septicemia; recurrent toxoplasmosis of brain; HIV wasting syndrome (involuntary weight loss \>10% of baseline body weight) with chronic diarrhea or chronic weakness and documented fever for ≥1 month. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| CD4 Cell Count Changes From Baseline at Week 48 by Treatment/Weight | From Baseline to Week 48 | — |
| CD4 Cell Count Changes From Baseline at Week 48 by Prior Antiretroviral (ARV) Treatment Status | From Baseline to Week 48 | — |
| Mean CD4 Percent Changes From Baseline at Week 48 by Treatment/Weight | From Baseline to Week 48 | — |
| Mean CD4 Percent Changes From Baseline at Week 48 by Antiretroviral (ARV) Treatment Status | From Baseline to Week 48 | — |
| Number of Participants Who Acquired Phenotypic Resistance to Atazanavir or Atazanovir/Ritonavir | After Day 1 to Week 48 | Criteria for resistance testing= meeting at least 1 of the following: \<1 log10 drop from baseline in HIV RNA level by Week 16 and confirmed by a second HIV RNA level; an HIV RNA level \>200 copies/mL after Week 24, confirmed by a second HIV RNA level; repeated HIV RNA levels ≥50 copies/mL after Week 48; an HIV RNA level ≥400 copies/mL confirmed by a second HIV RNA level of ≥400 copies/mL at any time in a participant who had previously achieved a plasma HIV RNA level \<50 copies/mL; or discontinued due to lack of efficacy. Virologic failure was defined as an incomplete virologic response to therapy or as a viral rebound after the achievement of virologic suppression. The phenotypic resistance to a drug is defined as a fold change (ie, ratio of the 50% inhibitory concentration \[IC50\] of the clinical isolate to the IC50 of the reference strain) greater than the cut-off for reduced susceptibility. |
| Percentage of Participants With HIV RNA Levels <50 c/mL and <400 c/mL at Week 48 by Treatment/Weight | At Week 48 | The definition of virologic success included HIV RNA levels \<50 c/mL or 400 c/mL at the Week 48 analysis window. . |
| Area Under the Concentration Curve (in 1 Dosing Interval From Time 0 to 24 Hours Post Observed Dose) (AUC[TAU])of Atazanavir and Ritonavir | At Week 2 at Hour 0 predose and at Hours 1.5, 2.5, 4, 6, 8, 12, and 24 postdose | — |
| Time to Maximum Observed Concentration (Tmax) of Atazanavir and Ritonavir | At Week 2 at Hour 0 predose and at Hours 1.5, 2.5, 4, 6, 8, 12, and 24 postdose | — |
| Apparent Total Body Clearance (CLT/F) of Atazanavir and Ritonavir | At Week 2 | Calculated as dose divided by AUC(TAU). AUC(TAU)=area under the concentration-time curve in 1 dosing interval from time 0 to 24 hours post observed dose. |
| Apparent Total Body Clearance Per Body Weight (CLT/F) Per Kilogram of Atazanavir and Ritonavir | At Week 2 | Calculated as CLT/F divided by body weight |
| Maximum Observed Concentration (Cmax) and Minimum Observed Concentration (Cmin) of Atazanavir and Ritonavir | At Week 2 at Hour 0 predose and at Hours 1.5, 2.5, 4, 6, 8, 12, and 24 postdose | — |
| Percentage of Participants With HIV RNA Levels <50 c/mL and <400 c/mL at Week 48 by Prior Antiretroviral (ARV) Treatment Status | From Day 1 to Week 48 | The definition of virologic success included HIV RNA levels \<50 c/mL or \<400 c/mL at the Week 48 analysis. |
| Mean Change From Baseline in HIV RNA Levels at Week 48 by Treatment/Weight | From Baseline to Week 48 | Participants who received at least 1 dose of atazanavir (ATV) and had an HIV RNA measurement on ATV powder at did not switch to the capsule formulation before Week 48 |
| Mean Change From Baseline in HIV RNA Levels at Week 48 by Prior Antiretroviral (ARV) Treatment Status | From Baseline to Week 48 | — |
Countries
Brazil, Chile, Mexico, Peru, South Africa, Thailand
Participant flow
Pre-assignment details
A total of 82 pediatric patients were enrolled, and 56 received treatment. Reasons for not receiving treatment treated were: no longer met study criteria (23 patients), other reason (2 patients), and withdrew consent (1 patient).
Participants by arm
| Arm | Count |
|---|---|
| Atazanavir Powder, 150 mg/Ritonavir Oral Solution, 80 mg Patients weighing 5 to \<10 kg received atazanavir (ATV), 150-mg powder dosed in 50-mg sachet packets, and ritonavir (RTV) oral solution, 80 mg. Stage 1: Initial dose was determined by the patient's weight on the day of the first on-treatment study visit (Day 1). ATV dispersible powder was mixed with a small amount of food or beverage (water, milk, chocolate milk, liquid infant formula, applesauce, or yogurt). If water was used, mixture must have been taken with food. The entire contents of the mixture must have been consumed to obtain the full dose. The ritonavir oral solution was taken immediately before or after the ATV powder preparation. Stage 2: Patients who reached the age of 6 years or a weight 25 kg were transitioned to the capsule formulation of ATV. RTV capsules or tablets were ingested with food immediately before or after ATV intake. | 21 |
| Atazanavir Powder, 200 mg/Ritonavir Oral Solution, 80 mg Patients weighing 10 to \<15 kg received ATV powder, 200 mg, dosed in 50-mg sachet packets and RTV oral solution, 80 mg. Stage 1: Initial dose was determined by the patient's weight on the day of the first on-treatment study visit (Day 1). ATV dispersible powder was mixed with a small amount of food or beverage (water, milk, chocolate milk, liquid infant formula, applesauce, or yogurt). If water was used, mixture must have been taken with food. All of the mixture must have been consumed to obtain the full dose. The RTV oral solution was taken immediately before or after the ATV powder preparation. Stage 2: Patients who reached the age of 6 years or a weight 25 kg were transitioned to the capsule formulation of ATV. Those who weighed 15 to 20 kg received ATV, 150 mg, with RTV, 100 mg, and those who weighed 20 to 40 mg received ATV, 200 mg with RTV,100 mg. RTV capsules or tablets were ingested with food immediately before or after ATV intake. | 19 |
| Atazanavir Powder, 250 mg/Ritonavir Oral Solution, 80 mg Patients weighing 15 to \<25 kg received 250 mg of ATV powder dosed in 50-mg sachet packets, with 80 mg of RTV solution. Stage 1: Initial dose was determined by the patient's weight on the day of the first on-treatment study visit (Day 1). ATV dispersible powder was mixed with a small amount of food or beverage (water, milk, chocolate milk, liquid infant formula, applesauce, or yogurt). If water was used, mixture must have been taken with food. The entire contents of the mixture must have been consumed to obtain the full dose. The ritonavir oral solution was taken immediately before or after the ATV powder preparation. Stage 2: Patients who reached the age of 6 years or a weight of 25 kg were transitioned to the capsule formulation of ATV. Those who weighed 20 to 40 mg received ATV, 200 mg, with RTV, 100 mg, and those who weighed at least 40 kg received ATV, 300 mg, with RTV, 100 mg. RTV capsules or tablets were ingested with food immediately before or after ATV intake. | 16 |
| Total | 56 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Stage 1 (ATV Powder Formulation) | Adverse Event | 4 | 1 | 0 |
| Stage 1 (ATV Powder Formulation) | Lack of Efficacy | 0 | 2 | 0 |
| Stage 1 (ATV Powder Formulation) | Poor compliance/noncompliance | 0 | 2 | 0 |
| Stage 1 (ATV Powder Formulation) | Withdrawal by Subject | 0 | 0 | 1 |
| Stage 2 (ATV Capsule) | Adverse Event | 0 | 1 | 0 |
| Stage 2 (ATV Capsule) | Lack of Efficacy | 0 | 0 | 2 |
| Stage 2 (ATV Capsule) | Lost to Follow-up | 1 | 1 | 1 |
| Stage 2 (ATV Capsule) | No longer met study criteria | 2 | 2 | 1 |
| Stage 2 (ATV Capsule) | Poor/Non-Compliance | 2 | 0 | 1 |
| Stage 2 (ATV Capsule) | Withdrawal by Subject | 1 | 1 | 1 |
Baseline characteristics
| Characteristic | Total | Atazanavir Powder, 200 mg/Ritonavir Oral Solution, 80 mg | Atazanavir Powder, 150 mg/Ritonavir Oral Solution, 80 mg | Atazanavir Powder, 250 mg/Ritonavir Oral Solution, 80 mg |
|---|---|---|---|---|
| Age, Continuous | 29.6 Months STANDARD_DEVIATION 20.72 | 35.4 Months STANDARD_DEVIATION 11.63 | 7.3 Months STANDARD_DEVIATION 4.05 | 52.1 Months STANDARD_DEVIATION 10.49 |
| CD4 Count | 1192.6 Cells/mm^3 STANDARD_DEVIATION 784.08 | 1107.4 Cells/mm^3 STANDARD_DEVIATION 643.25 | 1594.1 Cells/mm^3 STANDARD_DEVIATION 897.19 | 661.1 Cells/mm^3 STANDARD_DEVIATION 302.6 |
| CD4 Percent <15 | 5 Participants | 2 Participants | 2 Participants | 1 Participants |
| CD4 Percent 15 to <25 | 17 Participants | 6 Participants | 7 Participants | 4 Participants |
| CD4 Percent >=25 | 19 Participants | 6 Participants | 7 Participants | 6 Participants |
| CD4 Percent Not reported | 15 Participants | 5 Participants | 5 Participants | 5 Participants |
| CD4 Percent | 24.8 Percentage STANDARD_DEVIATION 10.61 | 22.0 Percentage STANDARD_DEVIATION 9.35 | 25.4 Percentage STANDARD_DEVIATION 12.11 | 27.5 Percentage STANDARD_DEVIATION 9.85 |
| Country Chile | 6 Participants | 2 Participants | 1 Participants | 3 Participants |
| Country Mexico | 9 Participants | 3 Participants | 2 Participants | 4 Participants |
| Country Peru | 2 Participants | 0 Participants | 1 Participants | 1 Participants |
| Country South Africa | 38 Participants | 13 Participants | 17 Participants | 8 Participants |
| Country Thailand | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| HIV RNA >100,000 c/mL | 32 c/mL | 10 c/mL | 18 c/mL | 4 c/mL |
| HIV RNA <30,000 c/mL | 14 c/mL | 2 c/mL | 3 c/mL | 9 c/mL |
| HIV RNA 30,000 to 100,000 c/mL | 10 c/mL | 7 c/mL | 0 c/mL | 3 c/mL |
| HIV RNA | 4.62 Log10 c/mL STANDARD_DEVIATION 0.617 | 4.83 Log10 c/mL STANDARD_DEVIATION 0.268 | 4.77 Log10 c/mL STANDARD_DEVIATION 0.602 | 4.18 Log10 c/mL STANDARD_DEVIATION 0.727 |
| Prior Antiretroviral (ARV) Treatment Use ARV experienced | 34 Participants | 9 Participants | 14 Participants | 11 Participants |
| Prior Antiretroviral (ARV) Treatment Use ARV naive | 22 Participants | 10 Participants | 7 Participants | 5 Participants |
| Race/Ethnicity, Customized Asian | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Black/African American | 32 Participants | 12 Participants | 13 Participants | 7 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Not reported | 55 Participants | 19 Participants | 21 Participants | 15 Participants |
| Race/Ethnicity, Customized Other | 12 Participants | 3 Participants | 6 Participants | 3 Participants |
| Race/Ethnicity, Customized White | 11 Participants | 3 Participants | 2 Participants | 6 Participants |
| Sex: Female, Male Female | 28 Participants | 12 Participants | 10 Participants | 6 Participants |
| Sex: Female, Male Male | 28 Participants | 7 Participants | 11 Participants | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 21 | 0 / 19 | 0 / 16 |
| other Total, other adverse events | 21 / 21 | 18 / 19 | 15 / 16 |
| serious Total, serious adverse events | 7 / 21 | 5 / 19 | 5 / 16 |
Outcome results
Primary
Electrocardiogram Changes From Baseline in PR Interval, QTC Bazett, and QTC Fridericia at Week 48
Electrocardiogram parameters were measured at baseline for QTC Bazett, QTC Fridericia, and PR interval. The mean change from baseline at week 48 is reported by arm in milliseconds.
Time frame: From Baseline to Week 48
Population: All participants who received at least 1 dose of atazanavir and were evaluable
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Atazanavir Powder, 150 mg/Ritonavir Oral Solution, 80 mg | Electrocardiogram Changes From Baseline in PR Interval, QTC Bazett, and QTC Fridericia at Week 48 | QTC Bazett | 1.7 Milliseconds | Standard Deviation 17.73 |
| Atazanavir Powder, 150 mg/Ritonavir Oral Solution, 80 mg | Electrocardiogram Changes From Baseline in PR Interval, QTC Bazett, and QTC Fridericia at Week 48 | PR Interval | 4.9 Milliseconds | Standard Deviation 21.8 |
| Atazanavir Powder, 150 mg/Ritonavir Oral Solution, 80 mg | Electrocardiogram Changes From Baseline in PR Interval, QTC Bazett, and QTC Fridericia at Week 48 | QTC Fridericia | 7.9 Milliseconds | Standard Deviation 18.36 |
| Atazanavir Powder, 200 mg/Ritonavir Oral Solution, 80 mg | Electrocardiogram Changes From Baseline in PR Interval, QTC Bazett, and QTC Fridericia at Week 48 | QTC Bazett | -3.2 Milliseconds | Standard Deviation 21.78 |
| Atazanavir Powder, 200 mg/Ritonavir Oral Solution, 80 mg | Electrocardiogram Changes From Baseline in PR Interval, QTC Bazett, and QTC Fridericia at Week 48 | PR Interval | 12.0 Milliseconds | Standard Deviation 8.04 |
| Atazanavir Powder, 200 mg/Ritonavir Oral Solution, 80 mg | Electrocardiogram Changes From Baseline in PR Interval, QTC Bazett, and QTC Fridericia at Week 48 | QTC Fridericia | 13.2 Milliseconds | Standard Deviation 18.92 |
| Atazanavir Powder, 250 mg/Ritonavir Oral Solution, 80 mg | Electrocardiogram Changes From Baseline in PR Interval, QTC Bazett, and QTC Fridericia at Week 48 | PR Interval | 6.2 Milliseconds | Standard Deviation 8.54 |
| Atazanavir Powder, 250 mg/Ritonavir Oral Solution, 80 mg | Electrocardiogram Changes From Baseline in PR Interval, QTC Bazett, and QTC Fridericia at Week 48 | QTC Fridericia | 4.8 Milliseconds | Standard Deviation 11.49 |
| Atazanavir Powder, 250 mg/Ritonavir Oral Solution, 80 mg | Electrocardiogram Changes From Baseline in PR Interval, QTC Bazett, and QTC Fridericia at Week 48 | QTC Bazett | -4.2 Milliseconds | Standard Deviation 13.02 |
Primary
Number of Participants With Centers for Disease Control (CDC) Class C AIDS Events
CDC Class C events are AIDS-defining events that include recurrent bacterial pneumonia (\>=2 episodes in 12 months); candidiasis of the bronchi, trachea, lungs, or esophagus; invasive cervical carcinoma; disseminated or extrapulmonary coccidioidomycosis; extrapulmonary cryptococcosis; chronic intestinal cryptosporidiosis (\>1 month); cytomegalovirus disease; HIV-related encephalopathy; herpes simplex: chronic ulcers, or bronchitis, pneumonitis, or esophagitis; disseminated or extrapulmonary histoplasmosis; chronic intestinal isosporiasis; Kaposi sarcoma; immunoblastic or primary brain Burkitt lymphoma; mycobacterium avium complex, kansasii, or tuberculosis; mycobacterium, other species; Pneumocystis carinii pneumonia; progressive multifocal leukoencephalopathy; Salmonella septicemia; recurrent toxoplasmosis of brain; HIV wasting syndrome (involuntary weight loss \>10% of baseline body weight) with chronic diarrhea or chronic weakness and documented fever for ≥1 month.
Time frame: From Day 1 to Week 48
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Atazanavir Powder, 150 mg/Ritonavir Oral Solution, 80 mg | Number of Participants With Centers for Disease Control (CDC) Class C AIDS Events | 1 Participants |
| Atazanavir Powder, 200 mg/Ritonavir Oral Solution, 80 mg | Number of Participants With Centers for Disease Control (CDC) Class C AIDS Events | 1 Participants |
| Atazanavir Powder, 250 mg/Ritonavir Oral Solution, 80 mg | Number of Participants With Centers for Disease Control (CDC) Class C AIDS Events | 0 Participants |
Primary
Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Discontinuation
AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization.
Time frame: From Day 1 to Week 48
Population: All participants who received at least 1 dose of active atazanavir powder.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Atazanavir Powder, 150 mg/Ritonavir Oral Solution, 80 mg | Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Discontinuation | SAEs | 5 Participants |
| Atazanavir Powder, 150 mg/Ritonavir Oral Solution, 80 mg | Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Discontinuation | Deaths | 0 Participants |
| Atazanavir Powder, 150 mg/Ritonavir Oral Solution, 80 mg | Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Discontinuation | AEs leading to discontinuation | 4 Participants |
| Atazanavir Powder, 200 mg/Ritonavir Oral Solution, 80 mg | Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Discontinuation | SAEs | 2 Participants |
| Atazanavir Powder, 200 mg/Ritonavir Oral Solution, 80 mg | Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Discontinuation | Deaths | 0 Participants |
| Atazanavir Powder, 200 mg/Ritonavir Oral Solution, 80 mg | Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Discontinuation | AEs leading to discontinuation | 1 Participants |
| Atazanavir Powder, 250 mg/Ritonavir Oral Solution, 80 mg | Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Discontinuation | Deaths | 0 Participants |
| Atazanavir Powder, 250 mg/Ritonavir Oral Solution, 80 mg | Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Discontinuation | AEs leading to discontinuation | 0 Participants |
| Atazanavir Powder, 250 mg/Ritonavir Oral Solution, 80 mg | Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Discontinuation | SAEs | 4 Participants |
Primary
Number of Participants With Laboratory Test Results With Worst Toxicity of Grade 3-4
ALT=alanine aminotransferase; SGPT=serum glutamic-pyruvic transaminase; AST=aspartate aminotransferase; SGOT=serum glutamic-oxaloacetic transaminase; ULN=upper limit of normal. Grading by the National Institute of Health Division of AIDs and World Health Organization criteria. Hemoglobin (g/dL): Grade (Gr)1=9.5-11.0; Gr 2=8.0-9.4; Gr 3=6.5-7.9; Gr 4=\<6.5. Neutrophils, absolute (/mm\^3): Gr 1=\>=1000-\<1500; Gr 2= \>=750-\<1000; Gr 3=\>=500-\<750; Gr 4=\<500. ALT/SGPT (\*ULN): Gr 1=1.25-2.5; Gr 2=2.6-5; Gr 3=5.1-10; Gr 4=\>10. AST/SGOT (\*ULN): Gr 1=1.25-2.5; Gr 2=2.6-5; Gr 3=5.1-10; Gr 4=\>10. Alkaline phosphatase(\*ULN): Gr 1=1.25-2.5; Gr 2=2.6-5: Gr 3=5.1-10; Gr 4=\>10. Total bilirubin (\*ULN): Gr 1=1.1-1; Gr 2=1.6-2.5; Gr 3=2.6-5; Gr 4=\>5. Amylase (\*ULN): Gr 1=1.10-39; Gr 2=1.40-2; Gr 3=2.10-5.0; Gr 4=\>5.0. Lipase (\*ULN): Gr 1=1.10-1.39: Gr 2=1.40-2; Gr 3=2.10-5.0; Gr 4=\>5.0. Uric acid (mg/dL): Gr 1=7.5-10.0; Gr 2=10.1-12.0; Gr 3=12.1-15.0; Gr 4=\>15.
Time frame: After Day 1 to Week 48
Population: All participants who received at least 1 dose of atazanavir; n=number of evaluable participants.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Atazanavir Powder, 150 mg/Ritonavir Oral Solution, 80 mg | Number of Participants With Laboratory Test Results With Worst Toxicity of Grade 3-4 | AST/SGOT (n=20, 18, 15) | 1 Participants |
| Atazanavir Powder, 150 mg/Ritonavir Oral Solution, 80 mg | Number of Participants With Laboratory Test Results With Worst Toxicity of Grade 3-4 | Uric acid n=20, 18, 15) | 0 Participants |
| Atazanavir Powder, 150 mg/Ritonavir Oral Solution, 80 mg | Number of Participants With Laboratory Test Results With Worst Toxicity of Grade 3-4 | Total bilirubin (n=20, 18, 15) | 2 Participants |
| Atazanavir Powder, 150 mg/Ritonavir Oral Solution, 80 mg | Number of Participants With Laboratory Test Results With Worst Toxicity of Grade 3-4 | Alkaline phosphatase (n=20, 18, 15) | 0 Participants |
| Atazanavir Powder, 150 mg/Ritonavir Oral Solution, 80 mg | Number of Participants With Laboratory Test Results With Worst Toxicity of Grade 3-4 | Hemoglobin (n=20, 17, 15) | 2 Participants |
| Atazanavir Powder, 150 mg/Ritonavir Oral Solution, 80 mg | Number of Participants With Laboratory Test Results With Worst Toxicity of Grade 3-4 | Lipase (n=20, 18, 15) | 0 Participants |
| Atazanavir Powder, 150 mg/Ritonavir Oral Solution, 80 mg | Number of Participants With Laboratory Test Results With Worst Toxicity of Grade 3-4 | ALT/SGPT (n=20, 18, 15) | 5 Participants |
| Atazanavir Powder, 150 mg/Ritonavir Oral Solution, 80 mg | Number of Participants With Laboratory Test Results With Worst Toxicity of Grade 3-4 | Neutrophils, absolute (n=20, 17, 15) | 3 Participants |
| Atazanavir Powder, 150 mg/Ritonavir Oral Solution, 80 mg | Number of Participants With Laboratory Test Results With Worst Toxicity of Grade 3-4 | Amylase (n=20, 18, 15) | 8 Participants |
| Atazanavir Powder, 200 mg/Ritonavir Oral Solution, 80 mg | Number of Participants With Laboratory Test Results With Worst Toxicity of Grade 3-4 | Alkaline phosphatase (n=20, 18, 15) | 1 Participants |
| Atazanavir Powder, 200 mg/Ritonavir Oral Solution, 80 mg | Number of Participants With Laboratory Test Results With Worst Toxicity of Grade 3-4 | Hemoglobin (n=20, 17, 15) | 3 Participants |
| Atazanavir Powder, 200 mg/Ritonavir Oral Solution, 80 mg | Number of Participants With Laboratory Test Results With Worst Toxicity of Grade 3-4 | Neutrophils, absolute (n=20, 17, 15) | 2 Participants |
| Atazanavir Powder, 200 mg/Ritonavir Oral Solution, 80 mg | Number of Participants With Laboratory Test Results With Worst Toxicity of Grade 3-4 | ALT/SGPT (n=20, 18, 15) | 0 Participants |
| Atazanavir Powder, 200 mg/Ritonavir Oral Solution, 80 mg | Number of Participants With Laboratory Test Results With Worst Toxicity of Grade 3-4 | AST/SGOT (n=20, 18, 15) | 0 Participants |
| Atazanavir Powder, 200 mg/Ritonavir Oral Solution, 80 mg | Number of Participants With Laboratory Test Results With Worst Toxicity of Grade 3-4 | Total bilirubin (n=20, 18, 15) | 0 Participants |
| Atazanavir Powder, 200 mg/Ritonavir Oral Solution, 80 mg | Number of Participants With Laboratory Test Results With Worst Toxicity of Grade 3-4 | Amylase (n=20, 18, 15) | 5 Participants |
| Atazanavir Powder, 200 mg/Ritonavir Oral Solution, 80 mg | Number of Participants With Laboratory Test Results With Worst Toxicity of Grade 3-4 | Lipase (n=20, 18, 15) | 1 Participants |
| Atazanavir Powder, 200 mg/Ritonavir Oral Solution, 80 mg | Number of Participants With Laboratory Test Results With Worst Toxicity of Grade 3-4 | Uric acid n=20, 18, 15) | 0 Participants |
| Atazanavir Powder, 250 mg/Ritonavir Oral Solution, 80 mg | Number of Participants With Laboratory Test Results With Worst Toxicity of Grade 3-4 | ALT/SGPT (n=20, 18, 15) | 1 Participants |
| Atazanavir Powder, 250 mg/Ritonavir Oral Solution, 80 mg | Number of Participants With Laboratory Test Results With Worst Toxicity of Grade 3-4 | Hemoglobin (n=20, 17, 15) | 0 Participants |
| Atazanavir Powder, 250 mg/Ritonavir Oral Solution, 80 mg | Number of Participants With Laboratory Test Results With Worst Toxicity of Grade 3-4 | Amylase (n=20, 18, 15) | 1 Participants |
| Atazanavir Powder, 250 mg/Ritonavir Oral Solution, 80 mg | Number of Participants With Laboratory Test Results With Worst Toxicity of Grade 3-4 | Neutrophils, absolute (n=20, 17, 15) | 0 Participants |
| Atazanavir Powder, 250 mg/Ritonavir Oral Solution, 80 mg | Number of Participants With Laboratory Test Results With Worst Toxicity of Grade 3-4 | Uric acid n=20, 18, 15) | 1 Participants |
| Atazanavir Powder, 250 mg/Ritonavir Oral Solution, 80 mg | Number of Participants With Laboratory Test Results With Worst Toxicity of Grade 3-4 | Alkaline phosphatase (n=20, 18, 15) | 0 Participants |
| Atazanavir Powder, 250 mg/Ritonavir Oral Solution, 80 mg | Number of Participants With Laboratory Test Results With Worst Toxicity of Grade 3-4 | AST/SGOT (n=20, 18, 15) | 0 Participants |
| Atazanavir Powder, 250 mg/Ritonavir Oral Solution, 80 mg | Number of Participants With Laboratory Test Results With Worst Toxicity of Grade 3-4 | Lipase (n=20, 18, 15) | 1 Participants |
| Atazanavir Powder, 250 mg/Ritonavir Oral Solution, 80 mg | Number of Participants With Laboratory Test Results With Worst Toxicity of Grade 3-4 | Total bilirubin (n=20, 18, 15) | 3 Participants |
Secondary
Apparent Total Body Clearance (CLT/F) of Atazanavir and Ritonavir
Calculated as dose divided by AUC(TAU). AUC(TAU)=area under the concentration-time curve in 1 dosing interval from time 0 to 24 hours post observed dose.
Time frame: At Week 2
Population: All participants who had received study drug and had adequate pharmacokinetic profiles (n=number evaluable)
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Atazanavir Powder, 150 mg/Ritonavir Oral Solution, 80 mg | Apparent Total Body Clearance (CLT/F) of Atazanavir and Ritonavir | CLT/F Atazanavir | 4.61 L/h |
| Atazanavir Powder, 150 mg/Ritonavir Oral Solution, 80 mg | Apparent Total Body Clearance (CLT/F) of Atazanavir and Ritonavir | CLT/F Ritonavir (n=19, 18, 15 | 4.59 L/h |
| Atazanavir Powder, 200 mg/Ritonavir Oral Solution, 80 mg | Apparent Total Body Clearance (CLT/F) of Atazanavir and Ritonavir | CLT/F Atazanavir | 3.98 L/h |
| Atazanavir Powder, 200 mg/Ritonavir Oral Solution, 80 mg | Apparent Total Body Clearance (CLT/F) of Atazanavir and Ritonavir | CLT/F Ritonavir (n=19, 18, 15 | 3.90 L/h |
| Atazanavir Powder, 250 mg/Ritonavir Oral Solution, 80 mg | Apparent Total Body Clearance (CLT/F) of Atazanavir and Ritonavir | CLT/F Atazanavir | 4.07 L/h |
| Atazanavir Powder, 250 mg/Ritonavir Oral Solution, 80 mg | Apparent Total Body Clearance (CLT/F) of Atazanavir and Ritonavir | CLT/F Ritonavir (n=19, 18, 15 | 5.87 L/h |
Secondary
Apparent Total Body Clearance Per Body Weight (CLT/F) Per Kilogram of Atazanavir and Ritonavir
Calculated as CLT/F divided by body weight
Time frame: At Week 2
Population: All participants who had received study drug and had adequate pharmacokinetic profiles (n=number evaluable)
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Atazanavir Powder, 150 mg/Ritonavir Oral Solution, 80 mg | Apparent Total Body Clearance Per Body Weight (CLT/F) Per Kilogram of Atazanavir and Ritonavir | CLT/F per kilogram Atazanavir | 0.65 L/h per kilogram |
| Atazanavir Powder, 150 mg/Ritonavir Oral Solution, 80 mg | Apparent Total Body Clearance Per Body Weight (CLT/F) Per Kilogram of Atazanavir and Ritonavir | CLT/F per kilogram Ritonavir (n=19, 18, 15) | 0.65 L/h per kilogram |
| Atazanavir Powder, 200 mg/Ritonavir Oral Solution, 80 mg | Apparent Total Body Clearance Per Body Weight (CLT/F) Per Kilogram of Atazanavir and Ritonavir | CLT/F per kilogram Atazanavir | 0.32 L/h per kilogram |
| Atazanavir Powder, 200 mg/Ritonavir Oral Solution, 80 mg | Apparent Total Body Clearance Per Body Weight (CLT/F) Per Kilogram of Atazanavir and Ritonavir | CLT/F per kilogram Ritonavir (n=19, 18, 15) | 0.32 L/h per kilogram |
| Atazanavir Powder, 250 mg/Ritonavir Oral Solution, 80 mg | Apparent Total Body Clearance Per Body Weight (CLT/F) Per Kilogram of Atazanavir and Ritonavir | CLT/F per kilogram Atazanavir | 0.24 L/h per kilogram |
| Atazanavir Powder, 250 mg/Ritonavir Oral Solution, 80 mg | Apparent Total Body Clearance Per Body Weight (CLT/F) Per Kilogram of Atazanavir and Ritonavir | CLT/F per kilogram Ritonavir (n=19, 18, 15) | 0.35 L/h per kilogram |
Secondary
Area Under the Concentration Curve (in 1 Dosing Interval From Time 0 to 24 Hours Post Observed Dose) (AUC[TAU])of Atazanavir and Ritonavir
Time frame: At Week 2 at Hour 0 predose and at Hours 1.5, 2.5, 4, 6, 8, 12, and 24 postdose
Population: All participants who had received study drug and had adequate pharmacokinetic profiles (n=number evaluable)
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Atazanavir Powder, 150 mg/Ritonavir Oral Solution, 80 mg | Area Under the Concentration Curve (in 1 Dosing Interval From Time 0 to 24 Hours Post Observed Dose) (AUC[TAU])of Atazanavir and Ritonavir | AUC(TAU) Atazanavir | 32503 ng*h/mL |
| Atazanavir Powder, 150 mg/Ritonavir Oral Solution, 80 mg | Area Under the Concentration Curve (in 1 Dosing Interval From Time 0 to 24 Hours Post Observed Dose) (AUC[TAU])of Atazanavir and Ritonavir | AUC(TAU) Ritonavir (n=19, 18, 15) | 17439 ng*h/mL |
| Atazanavir Powder, 200 mg/Ritonavir Oral Solution, 80 mg | Area Under the Concentration Curve (in 1 Dosing Interval From Time 0 to 24 Hours Post Observed Dose) (AUC[TAU])of Atazanavir and Ritonavir | AUC(TAU) Atazanavir | 50305 ng*h/mL |
| Atazanavir Powder, 200 mg/Ritonavir Oral Solution, 80 mg | Area Under the Concentration Curve (in 1 Dosing Interval From Time 0 to 24 Hours Post Observed Dose) (AUC[TAU])of Atazanavir and Ritonavir | AUC(TAU) Ritonavir (n=19, 18, 15) | 20510 ng*h/mL |
| Atazanavir Powder, 250 mg/Ritonavir Oral Solution, 80 mg | Area Under the Concentration Curve (in 1 Dosing Interval From Time 0 to 24 Hours Post Observed Dose) (AUC[TAU])of Atazanavir and Ritonavir | AUC(TAU) Atazanavir | 61485 ng*h/mL |
| Atazanavir Powder, 250 mg/Ritonavir Oral Solution, 80 mg | Area Under the Concentration Curve (in 1 Dosing Interval From Time 0 to 24 Hours Post Observed Dose) (AUC[TAU])of Atazanavir and Ritonavir | AUC(TAU) Ritonavir (n=19, 18, 15) | 13640 ng*h/mL |
Secondary
CD4 Cell Count Changes From Baseline at Week 48 by Prior Antiretroviral (ARV) Treatment Status
Time frame: From Baseline to Week 48
Population: Participants who received at least 1 dose of atazanavir (ATV) and who had CD4 at baseline and Week 48 while taking ATV powder
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Atazanavir Powder, 150 mg/Ritonavir Oral Solution, 80 mg | CD4 Cell Count Changes From Baseline at Week 48 by Prior Antiretroviral (ARV) Treatment Status | 437.9 Cells/mm^3 | Standard Error 253.123 |
| Atazanavir Powder, 200 mg/Ritonavir Oral Solution, 80 mg | CD4 Cell Count Changes From Baseline at Week 48 by Prior Antiretroviral (ARV) Treatment Status | 352.1 Cells/mm^3 | Standard Error 152.6 |
Secondary
CD4 Cell Count Changes From Baseline at Week 48 by Treatment/Weight
Time frame: From Baseline to Week 48
Population: Participants who received at least 1 dose of atazanavir (ATV) and who had CD4 at baseline and Week 48 while taking ATV powder
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Atazanavir Powder, 150 mg/Ritonavir Oral Solution, 80 mg | CD4 Cell Count Changes From Baseline at Week 48 by Treatment/Weight | 550.1 Cells/mm^3 | Standard Error 285.24 |
| Atazanavir Powder, 200 mg/Ritonavir Oral Solution, 80 mg | CD4 Cell Count Changes From Baseline at Week 48 by Treatment/Weight | 225.3 Cells/mm^3 | Standard Error 198.34 |
| Atazanavir Powder, 250 mg/Ritonavir Oral Solution, 80 mg | CD4 Cell Count Changes From Baseline at Week 48 by Treatment/Weight | 373.8 Cells/mm^3 | Standard Error 68.83 |
Secondary
Maximum Observed Concentration (Cmax) and Minimum Observed Concentration (Cmin) of Atazanavir and Ritonavir
Time frame: At Week 2 at Hour 0 predose and at Hours 1.5, 2.5, 4, 6, 8, 12, and 24 postdose
Population: All participants who had received study drug and had adequate pharmacokinetic profiles (n=number evaluable)
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Atazanavir Powder, 150 mg/Ritonavir Oral Solution, 80 mg | Maximum Observed Concentration (Cmax) and Minimum Observed Concentration (Cmin) of Atazanavir and Ritonavir | Atazanavir Cmax | 4131 ng/mL |
| Atazanavir Powder, 150 mg/Ritonavir Oral Solution, 80 mg | Maximum Observed Concentration (Cmax) and Minimum Observed Concentration (Cmin) of Atazanavir and Ritonavir | Atazanavir Cmin | 336 ng/mL |
| Atazanavir Powder, 150 mg/Ritonavir Oral Solution, 80 mg | Maximum Observed Concentration (Cmax) and Minimum Observed Concentration (Cmin) of Atazanavir and Ritonavir | Ritonavir Cmax (n=19, 18, 15) | 2919 ng/mL |
| Atazanavir Powder, 150 mg/Ritonavir Oral Solution, 80 mg | Maximum Observed Concentration (Cmax) and Minimum Observed Concentration (Cmin) of Atazanavir and Ritonavir | Ritonavir Cmin (n=18, 16, 15) | 41.8 ng/mL |
| Atazanavir Powder, 200 mg/Ritonavir Oral Solution, 80 mg | Maximum Observed Concentration (Cmax) and Minimum Observed Concentration (Cmin) of Atazanavir and Ritonavir | Ritonavir Cmin (n=18, 16, 15) | 143 ng/mL |
| Atazanavir Powder, 200 mg/Ritonavir Oral Solution, 80 mg | Maximum Observed Concentration (Cmax) and Minimum Observed Concentration (Cmin) of Atazanavir and Ritonavir | Atazanavir Cmax | 5197 ng/mL |
| Atazanavir Powder, 200 mg/Ritonavir Oral Solution, 80 mg | Maximum Observed Concentration (Cmax) and Minimum Observed Concentration (Cmin) of Atazanavir and Ritonavir | Ritonavir Cmax (n=19, 18, 15) | 2634 ng/mL |
| Atazanavir Powder, 200 mg/Ritonavir Oral Solution, 80 mg | Maximum Observed Concentration (Cmax) and Minimum Observed Concentration (Cmin) of Atazanavir and Ritonavir | Atazanavir Cmin | 572 ng/mL |
| Atazanavir Powder, 250 mg/Ritonavir Oral Solution, 80 mg | Maximum Observed Concentration (Cmax) and Minimum Observed Concentration (Cmin) of Atazanavir and Ritonavir | Ritonavir Cmin (n=18, 16, 15) | 51.0 ng/mL |
| Atazanavir Powder, 250 mg/Ritonavir Oral Solution, 80 mg | Maximum Observed Concentration (Cmax) and Minimum Observed Concentration (Cmin) of Atazanavir and Ritonavir | Atazanavir Cmin | 698 ng/mL |
| Atazanavir Powder, 250 mg/Ritonavir Oral Solution, 80 mg | Maximum Observed Concentration (Cmax) and Minimum Observed Concentration (Cmin) of Atazanavir and Ritonavir | Ritonavir Cmax (n=19, 18, 15) | 1838 ng/mL |
| Atazanavir Powder, 250 mg/Ritonavir Oral Solution, 80 mg | Maximum Observed Concentration (Cmax) and Minimum Observed Concentration (Cmin) of Atazanavir and Ritonavir | Atazanavir Cmax | 6172 ng/mL |
Secondary
Mean CD4 Percent Changes From Baseline at Week 48 by Antiretroviral (ARV) Treatment Status
Time frame: From Baseline to Week 48
Population: Participants who received at least 1 dose of atazanavir (ATV) and who had CD4 percent at baseline and Week 48 while taking ATV powder
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Atazanavir Powder, 150 mg/Ritonavir Oral Solution, 80 mg | Mean CD4 Percent Changes From Baseline at Week 48 by Antiretroviral (ARV) Treatment Status | 4.3 Percentage of lymphocytes | Standard Error 1.316 |
| Atazanavir Powder, 200 mg/Ritonavir Oral Solution, 80 mg | Mean CD4 Percent Changes From Baseline at Week 48 by Antiretroviral (ARV) Treatment Status | 9.8 Percentage of lymphocytes | Standard Error 1.496 |
Secondary
Mean CD4 Percent Changes From Baseline at Week 48 by Treatment/Weight
Time frame: From Baseline to Week 48
Population: Participants who received at least 1 dose of atazanavir (ATV) and who had CD4 percent at baseline and Week 48 while taking ATV powder
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Atazanavir Powder, 150 mg/Ritonavir Oral Solution, 80 mg | Mean CD4 Percent Changes From Baseline at Week 48 by Treatment/Weight | 6.1 Percentage of lymphocytes | Standard Error 1.56 |
| Atazanavir Powder, 200 mg/Ritonavir Oral Solution, 80 mg | Mean CD4 Percent Changes From Baseline at Week 48 by Treatment/Weight | 7.3 Percentage of lymphocytes | Standard Error 2.26 |
| Atazanavir Powder, 250 mg/Ritonavir Oral Solution, 80 mg | Mean CD4 Percent Changes From Baseline at Week 48 by Treatment/Weight | 8.8 Percentage of lymphocytes | Standard Error 1.14 |
Secondary
Mean Change From Baseline in HIV RNA Levels at Week 48 by Prior Antiretroviral (ARV) Treatment Status
Time frame: From Baseline to Week 48
Population: Participants who received at least 1 dose of atazanavir (ATV) and who had an HIV RNA measurement on ATV powder at Week 48
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Atazanavir Powder, 150 mg/Ritonavir Oral Solution, 80 mg | Mean Change From Baseline in HIV RNA Levels at Week 48 by Prior Antiretroviral (ARV) Treatment Status | -2.53 Log10 c/mL | Standard Error 0.2452 |
| Atazanavir Powder, 200 mg/Ritonavir Oral Solution, 80 mg | Mean Change From Baseline in HIV RNA Levels at Week 48 by Prior Antiretroviral (ARV) Treatment Status | -2.81 Log10 c/mL | Standard Error 0.1296 |
Secondary
Mean Change From Baseline in HIV RNA Levels at Week 48 by Treatment/Weight
Participants who received at least 1 dose of atazanavir (ATV) and had an HIV RNA measurement on ATV powder at did not switch to the capsule formulation before Week 48
Time frame: From Baseline to Week 48
Population: Participants who received at least 1 dose of atazanavir and who had HIV RNA while taking atazanavir powder at Week 48
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Atazanavir Powder, 150 mg/Ritonavir Oral Solution, 80 mg | Mean Change From Baseline in HIV RNA Levels at Week 48 by Treatment/Weight | -2.61 Log10 c/mL | Standard Error 0.3111 |
| Atazanavir Powder, 200 mg/Ritonavir Oral Solution, 80 mg | Mean Change From Baseline in HIV RNA Levels at Week 48 by Treatment/Weight | -2.93 Log10 c/mL | Standard Error 0.1678 |
| Atazanavir Powder, 250 mg/Ritonavir Oral Solution, 80 mg | Mean Change From Baseline in HIV RNA Levels at Week 48 by Treatment/Weight | -2.40 Log10 c/mL | Standard Error 0.2412 |
Secondary
Number of Participants Who Acquired Phenotypic Resistance to Atazanavir or Atazanovir/Ritonavir
Criteria for resistance testing= meeting at least 1 of the following: \<1 log10 drop from baseline in HIV RNA level by Week 16 and confirmed by a second HIV RNA level; an HIV RNA level \>200 copies/mL after Week 24, confirmed by a second HIV RNA level; repeated HIV RNA levels ≥50 copies/mL after Week 48; an HIV RNA level ≥400 copies/mL confirmed by a second HIV RNA level of ≥400 copies/mL at any time in a participant who had previously achieved a plasma HIV RNA level \<50 copies/mL; or discontinued due to lack of efficacy. Virologic failure was defined as an incomplete virologic response to therapy or as a viral rebound after the achievement of virologic suppression. The phenotypic resistance to a drug is defined as a fold change (ie, ratio of the 50% inhibitory concentration \[IC50\] of the clinical isolate to the IC50 of the reference strain) greater than the cut-off for reduced susceptibility.
Time frame: After Day 1 to Week 48
Population: Participants who met the criteria for virologic failure
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Atazanavir Powder, 150 mg/Ritonavir Oral Solution, 80 mg | Number of Participants Who Acquired Phenotypic Resistance to Atazanavir or Atazanovir/Ritonavir | Atazanavir | 0 Participants |
| Atazanavir Powder, 150 mg/Ritonavir Oral Solution, 80 mg | Number of Participants Who Acquired Phenotypic Resistance to Atazanavir or Atazanovir/Ritonavir | Ritonavir | 0 Participants |
| Atazanavir Powder, 200 mg/Ritonavir Oral Solution, 80 mg | Number of Participants Who Acquired Phenotypic Resistance to Atazanavir or Atazanovir/Ritonavir | Atazanavir | 0 Participants |
| Atazanavir Powder, 200 mg/Ritonavir Oral Solution, 80 mg | Number of Participants Who Acquired Phenotypic Resistance to Atazanavir or Atazanovir/Ritonavir | Ritonavir | 0 Participants |
Secondary
Percentage of Participants With HIV RNA Levels <50 c/mL and <400 c/mL at Week 48 by Prior Antiretroviral (ARV) Treatment Status
The definition of virologic success included HIV RNA levels \<50 c/mL or \<400 c/mL at the Week 48 analysis.
Time frame: From Day 1 to Week 48
Population: Participants who received at least 1 dose of atazanavir (ATV) and who did not switch to the ATV capsule formulation on or before Week 48
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Atazanavir Powder, 150 mg/Ritonavir Oral Solution, 80 mg | Percentage of Participants With HIV RNA Levels <50 c/mL and <400 c/mL at Week 48 by Prior Antiretroviral (ARV) Treatment Status | HIV RNA levels <50 c/mL | 56.3 Percentage of participants |
| Atazanavir Powder, 150 mg/Ritonavir Oral Solution, 80 mg | Percentage of Participants With HIV RNA Levels <50 c/mL and <400 c/mL at Week 48 by Prior Antiretroviral (ARV) Treatment Status | HIV RNA levels <400 c/mL | 65.6 Percentage of participants |
| Atazanavir Powder, 200 mg/Ritonavir Oral Solution, 80 mg | Percentage of Participants With HIV RNA Levels <50 c/mL and <400 c/mL at Week 48 by Prior Antiretroviral (ARV) Treatment Status | HIV RNA levels <50 c/mL | 68.2 Percentage of participants |
| Atazanavir Powder, 200 mg/Ritonavir Oral Solution, 80 mg | Percentage of Participants With HIV RNA Levels <50 c/mL and <400 c/mL at Week 48 by Prior Antiretroviral (ARV) Treatment Status | HIV RNA levels <400 c/mL | 86.4 Percentage of participants |
Secondary
Percentage of Participants With HIV RNA Levels <50 c/mL and <400 c/mL at Week 48 by Treatment/Weight
The definition of virologic success included HIV RNA levels \<50 c/mL or 400 c/mL at the Week 48 analysis window. .
Time frame: At Week 48
Population: Participants who received at least 1 dose of atazanavir and who did not switch to the capsule formulation at or before Week 48
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Atazanavir Powder, 150 mg/Ritonavir Oral Solution, 80 mg | Percentage of Participants With HIV RNA Levels <50 c/mL and <400 c/mL at Week 48 by Treatment/Weight | HIV RNA levels <400 c/mL | 66.7 Percentage of participants |
| Atazanavir Powder, 150 mg/Ritonavir Oral Solution, 80 mg | Percentage of Participants With HIV RNA Levels <50 c/mL and <400 c/mL at Week 48 by Treatment/Weight | HIV RNA levels <50 c/mL | 47.6 Percentage of participants |
| Atazanavir Powder, 200 mg/Ritonavir Oral Solution, 80 mg | Percentage of Participants With HIV RNA Levels <50 c/mL and <400 c/mL at Week 48 by Treatment/Weight | HIV RNA levels <400 c/mL | 73.7 Percentage of participants |
| Atazanavir Powder, 200 mg/Ritonavir Oral Solution, 80 mg | Percentage of Participants With HIV RNA Levels <50 c/mL and <400 c/mL at Week 48 by Treatment/Weight | HIV RNA levels <50 c/mL | 68.4 Percentage of participants |
| Atazanavir Powder, 250 mg/Ritonavir Oral Solution, 80 mg | Percentage of Participants With HIV RNA Levels <50 c/mL and <400 c/mL at Week 48 by Treatment/Weight | HIV RNA levels <50 c/mL | 71.4 Percentage of participants |
| Atazanavir Powder, 250 mg/Ritonavir Oral Solution, 80 mg | Percentage of Participants With HIV RNA Levels <50 c/mL and <400 c/mL at Week 48 by Treatment/Weight | HIV RNA levels <400 c/mL | 85.7 Percentage of participants |
Secondary
Time to Maximum Observed Concentration (Tmax) of Atazanavir and Ritonavir
Time frame: At Week 2 at Hour 0 predose and at Hours 1.5, 2.5, 4, 6, 8, 12, and 24 postdose
Population: All participants who had received study drug and had adequate pharmacokinetic profiles (n=number evaluable)
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Atazanavir Powder, 150 mg/Ritonavir Oral Solution, 80 mg | Time to Maximum Observed Concentration (Tmax) of Atazanavir and Ritonavir | Tmax Atazanavir | 1.58 Hours |
| Atazanavir Powder, 150 mg/Ritonavir Oral Solution, 80 mg | Time to Maximum Observed Concentration (Tmax) of Atazanavir and Ritonavir | Tmax Ritonavir | 1.8 Hours |
| Atazanavir Powder, 200 mg/Ritonavir Oral Solution, 80 mg | Time to Maximum Observed Concentration (Tmax) of Atazanavir and Ritonavir | Tmax Atazanavir | 1.97 Hours |
| Atazanavir Powder, 200 mg/Ritonavir Oral Solution, 80 mg | Time to Maximum Observed Concentration (Tmax) of Atazanavir and Ritonavir | Tmax Ritonavir | 2.9 Hours |
| Atazanavir Powder, 250 mg/Ritonavir Oral Solution, 80 mg | Time to Maximum Observed Concentration (Tmax) of Atazanavir and Ritonavir | Tmax Atazanavir | 4.0 Hours |
| Atazanavir Powder, 250 mg/Ritonavir Oral Solution, 80 mg | Time to Maximum Observed Concentration (Tmax) of Atazanavir and Ritonavir | Tmax Ritonavir | 4.0 Hours |