HIV Infections
Conditions
Brief summary
The purpose of this study is to learn how well atazanavir (ATV) works in combination with ritonavir (RTV) or saquinavir (SQV) with tenofovir (TDF) and a nucleoside to reduce the viral load of treatment experienced subjects with human immunodeficiency virus (HIV). There is a comparison arm with lopinavir (LPV)/RTV and TDF and a nucleoside.
Interventions
DRUGAtazanavir + ritonavir + tenofovir + nucleoside
Active Comparator, Capsules, tablets, Oral
DRUGAtazanavir + saquinavir + tenofovir + nucleoside
Active Comparator, Capsules, tablets, Oral
DRUGLopinavir/ritonavir + tenofovir + nucleoside
Active Comparator, Capsules, tablets, Oral
Sponsors
Bristol-Myers Squibb
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
16 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Virologic failure to 2 or more highly active antiretroviral therapy (HAART) regimens that, in total, have included at least one drug from all approved classes protease inhibitors, non-nucleoside reverse transcriptase inhibitors, nucleoside reverse transcriptase inhibitors (PI, NNRTI, NRTI): 1. Currently on a failing HAART regimen with 2 qualifying plasma viral load measurements (hospital/clinic value within 4 weeks of screening with viral load equivalent to =\>1,000 c/mL on the Roche Amplicor\[TM\] and central lab measurements of =\>1,000 c/mL (Roche Amplicor\[TM\]) within 4 weeks of randomization 2. Cluster of Differentiation 4 (CD4) cell count =\>50 cells/mm3 obtained within 4 weeks prior to randomization * =\>16 years of age (or minimum age as determined by local regulations or as legal requirements dictate); * History of prior virologic response to at least one HAART regimen, defined as a 1.0 log10 decline or a decline in viral load to \<400 c/mL by Roche Amplicor or \<500 c/mL by Chiron Quantiplex branched DNA (bDNA) assay * Both females of child bearing potential and males must utilize effective barrier contraception to reduce transmission of sexually transmitted disease, including human immunodeficiency virus (HIV). Other contraception in addition to barrier methods is permitted; interaction between atazanavir and oral contraceptives has not been studied. * Subjects must be able to provide written informed consent; * Subjects should be available for follow-up for a period of at least 48 weeks * Baseline laboratory values measured within 2 weeks prior to initiating study drugs as follows: 1. serum creatine \<1.5 times the upper limit of normal (ULN) 2. total serum lipase \<1.4 times the ULN 3. liver enzymes alanine aminotransferase (AST), aspartate aminotransferase (ALT) \<3 times the ULN 4. total serum bilirubin \<1.5 times the ULN
Exclusion criteria
* Prior use (=\>3 days) of atazanavir, TVF or LPV/RTV; if history of SQV, then must be phenotypically sensitive * the current failing antiretroviral regimen must have been administered for at least eight weeks at he initiation of screening and must not include both a PI and NNRTI * Presence of a newly diagnosed HIV-related opportunistic infection or any medical requiring acute therapy at the time of enrollment * Proven or suspected acute hepatitis in the 30 days prior to study entry. Subjects with chronic hepatitis are eligible provided that their liver function enzymes (ALT/AST) are \<3 x ULN * Previous therapy with agents with significant systemic myelosuppressive, neurotoxic, pancreatoxic, hepatoxic or cytotoxic potential within 3 months of study start or the expected need for such therapy at the time of enrollment of therapy with methadone or ribavirin/interferons or treatment with neurotoxic drugs or drugs that affect Cytochrome P450 3A4 (CYP3A4). * Active alcohol or substance use sufficient, in the Investigator's opinion, to prevent adequate compliance with study therapy or to increase the risk of developing pancreatitis or chemical hepatitis * Intractable diarrhea (=\> 6 loose stools/day for at least 7 days consecutive days) within 30 days prior to study entry * Pregnancy or breast-feeding * History of hemophilia * Presence of cardiomyopathy * Any one of the following: 1. Heart rate-corrected QT (QTc) interval \>450 msec on the screening electrocardiogram (EKG) 2. Heart rate \<40 beats per minute (bpm) 3. Pause length \>3 seconds seen on EKG 4. Clinical symptoms potentially related to heart block 5. Third degree heart block * History of acute or chronic pancreatitis * If choosing 2'-3' dideoxyinosine (ddI) or 2',3'-didehydro-3'-deoxythymidine (d4T) as the NRTI: History or signs and symptoms of bilateral peripheral neuropathy =\> Grade 2 at the time of screening * Inability to tolerate oral medications * Any other clinical conditions or prior therapy that, in the opinion of the Investigator, would make the subject unsuitable for study or unable to comply with the dosing requirements.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Mean Change From Baseline in HIV Ribonucleic Acid (RNA) at Week 24 | Baseline, Week 24 |
| Mean Change From Baseline in HIV RNA at Week 48 | Baseline, Week 48 |
| Mean Change From Baseline in HIV RNA at Week 96 | Baseline, Week 96 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in CD4 Cell Count at Week 48 | Baseline, Week 48 | — |
| Change From Baseline in CD4 Cell Count at Week 96 | Baseline, Week 96 | — |
| Mean Change From Baseline in HIV RNA at Week 2 | Baseline, Week 2 | — |
| Participants Achieving Virologic Half Log Suppression (Limit of Quantification [LOQ] = 400 c/mL) at Week 24 (Overall and by Protease Inhibitor [PI] Sensitivity) | Baseline, Week 24 | Number of participants with a \>=0.5 log10 decrease in HIV RNA from baseline or HIV RNA \< 400 c/mL at Week 24, by their baseline phenotypic sensitivity to their randomized PI. |
| Participants Achieving Virologic Half Log Suppression (LOQ = 400 c/mL) at Week 48, (Overall and by PI Sensitivity) | Baseline, Week 48 | Number of participants with a \>=0.5 log10 decrease in HIV RNA from baseline or HIV RNA \< 400 c/mL at Week 48, by their baseline phenotypic sensitivity to their randomized PI. |
| Participants Achieving Virologic Half Log Suppression (LOQ = 400 c/mL) at Week 96 | Baseline, Week 96 | Number of participants with a \>=0.5 log10 decrease in HIV RNA from baseline or HIV RNA \< 400 c/mL at Week 96. |
| Participants Achieving Virologic Half Log Suppression (LOQ = 50 c/mL) at Week 24 | Week 24 | — |
| Participants Achieving Virologic Half Log Suppression (LOQ = 50 c/mL) at Week 24, by PI Sensitivity | Baseline, Week 24 | Number of participants with a \>=0.5 log10 decrease in HIV RNA from baseline or HIV RNA \< 50 c/mL at Week 24, by their baseline phenotypic sensitivity to their randomized PI. |
| Participants Achieving Virologic Half Log Suppression (LOQ = 50 c/mL) at Week 48 | Week 48 | — |
| Participants Achieving Virologic Half Log Suppression (LOQ = 50 c/mL) at Week 48, by PI Sensitivity | Baseline, Week 48 | Number of participants with a \>=0.5 log10 decrease in HIV RNA from baseline or HIV RNA \< 50 c/mL at Week 48, by their baseline phenotypic sensitivity to their randomized PI. |
| Participants Achieving Virologic Half Log Suppression (LOQ = 50 c/mL) at Week 96 | Week 96 | — |
| Participants Achieving Treatment Response (LOQ = 400 c/mL) Without Prior Failure at Week 24 | Week 24 | Treatment Response = confirmed suppression to LOQ (400 c/mL). The Algorithm for Treatment Response Without Prior Failure (TRPWF) = participants staying in response at the analysis timepoint without having an intervening, confirmed rebound. |
| Participants Achieving Treatment Response (LOQ = 400 c/mL) Without Prior Failure at Week 48 | Week 48 | Treatment Response = confirmed suppression to LOQ (400 c/mL). The Algorithm for Treatment Response Without Prior Failure (TRPWF) = participants staying in response at the analysis timepoint without having an intervening, confirmed rebound. |
| Participants Achieving Treatment Response (LOQ = 400 c/mL) Without Prior Failure at Week 96 | Week 96 | Treatment Response = confirmed suppression to LOQ (400 c/mL). The Algorithm for Treatment Response Without Prior Failure (TRPWF) = participants staying in response at the analysis timepoint without having an intervening, confirmed rebound. |
| Participants Achieving Treatment Response (LOQ = 50 c/mL) Without Prior Failure at Week 24 | Week 24 | Treatment Response = confirmed suppression to LOQ (50 c/mL). The Algorithm for Treatment Response Without Prior Failure (TRPWF) = participants staying in response at the analysis timepoint without having an intervening, confirmed rebound. |
| Participants Achieving Treatment Response (LOQ = 50 c/mL) Without Prior Failure at Week 48 | Week 48 | Treatment Response = confirmed suppression to LOQ (50 c/mL). The Algorithm for Treatment Response Without Prior Failure (TRPWF) = participants staying in response at the analysis timepoint without having an intervening, confirmed rebound. |
| Participants Achieving Treatment Response (LOQ = 50 c/mL) Without Prior Failure at Week 96 | Week 96 | Treatment Response = confirmed suppression to LOQ (50 c/mL). The Algorithm for Treatment Response Without Prior Failure (TRPWF) = participants staying in response at the analysis timepoint without having an intervening, confirmed rebound. |
| Change From Baseline in CD4 Cell Count at Week 24 | Baseline, Week 24 | — |
| Correlation of ATV Minimum Plasma Concentration (Cmin), Inhibitory Quotient (IQ), and Number of Protease Inhibitor (PI) Mutations at Baseline With HIV RNA Change From Baseline at Week 24 | Baseline, Week 24 | Pearson correlations of the Cmin (trough plasma concentration), IQ (the ratio of Cmin of ATV to HIV IC50), and Number of baseline PI Mutations with HIV RNA change from baseline at Week 24 were explored. |
| Correlation of ATV Minimum Plasma Concentration (Cmin), Inhibitory Quotient (IQ), and Number of Protease Inhibitor (PI) Mutations at Baseline With HIV RNA Change From Baseline at Week 48 | Baseline, Week 48 | Pearson correlations of the Cmin (trough plasma concentration), IQ (the ratio of Cmin of ATV to HIV IC50), and Number of baseline PI Mutations with HIV RNA change from baseline at Week 48 were explored. |
| Correlation of ATV Minimum Plasma Concentration (Cmin) Inhibitory Quotient (IQ), and Number of PI Mutations at Baseline and CD4 Cell Count Change From Baseline at Week 24 | Baseline, Week 24 | Pearson correlations of the Cmin (trough plasma concentration), IQ (the ratio of Cmin of ATV to HIV IC50), and Number of baseline PI Mutations with CD4 cell count change from baseline at Week 24 were explored. |
| Correlation of ATV Minimum Plasma Concentration (Cmin) Inhibitory Quotient (IQ), and Number of PI Mutations at Baseline and CD4 Cell Count Change From Baseline at Week 48 | Baseline, Week 48 | Pearson correlations of the Cmin (trough plasma concentration), IQ (the ratio of Cmin of ATV to HIV IC50), and Number of baseline PI Mutations with CD4 cell count change from baseline at Week 48 were explored. |
| Lipid Mean Percent Change From Baseline at Week 24 | Baseline, Week 24 | Mean percent change in total cholesterol, high density lipoprotein (HDL) cholesterol, fasting low density lipoprotein (LDL) cholesterol, and fasting triglycerides. |
| Lipid Mean Percent Change From Baseline at Week 48 | Week 48 | Mean percent change in total cholesterol, high density lipoprotein (HDL) cholesterol, fasting low density lipoprotein (LDL) cholesterol, and fasting triglycerides. |
| Lipid Mean Percent Change From Baseline at Week 96, Observed Values | Week 96 | Mean percent change in total cholesterol, high density lipoprotein (HDL) cholesterol, fasting low density lipoprotein (LDL) cholesterol, and fasting triglycerides. |
| Deaths, Serious Adverse Events (SAEs), and Adverse Events (AEs) Through Week 48 | From Enrollment through Week 48 | AE=any new untoward medical occurrence/worsening of a pre-existing medical condition regardless of causal relationship. SAE=any untoward medical occurrence at any dose that: results in death; is life-threatening; requires/prolongs inpatient hospitalization; results in persistent/significant disability; is cancer; is congenital anomaly/birth defect; results in drug dependency/abuse; is an important medical event. |
| Most Common AEs and AEs of Interest Through Week 48 | From Enrollment to Week 48 | Prespecified AEs of interest included jaundice, ocular icterus, and hyperbilirubinemia. |
| Fasting Glucose Mean Change From Baseline at Week 24 | Baseline, Week 24 | — |
| Fasting Glucose Mean Change From Baseline at Week 48 | Week 48 | — |
| Grade 3/4 Laboratory Abnormalities Through Week 48 | From Enrollment to Week 48 | Common Terminology Criteria for Adverse Events v3.0 (CTCAE) Grades:1=Mild, 2=Moderate, 3=Severe, 4=Life-threatening/disabling, 5=Death. Abnormal values: absolute neutrophil count: ≥500 to \<750/mm3 (grade 3), \<500/mm3 (grade 4); platelets: 20,000-49,999/mm3 (grade 3), \<20,000/mm3 or diffuse petechiae (grade 4); alanine transaminase (ALT): 5.1-10 x upper limit of normal (ULN; grade 3), \>10 x ULN (grade 4); aspartate transaminase (AST): 5.1-10 x ULN (grade 3), \>10 x ULN (grade 4); bilirubin: 2.6-5 x ULN (grade 3), \>5 x ULN (grade 4). |
| Fridericia-corrected QT (QTcF) Interval and Change From Baseline by Analysis Time Point | Baseline, Week 4 predose, 2-3 hours postdose, 6-12 hours postdose, Week 12, Week 24, Week 48 | The QT interval is a measure of the time between the start of the Q wave and the end of the T wave in the heart's electrical cycle. The QT interval was corrected for heart rate using Fridericia's (QTcF) formula. |
| PR Interval and Change From Baseline by Analysis Time Point | Baseline, Week 4 predose, 2-3 hours postdose, 6-12 hours postdose, Week 12, Week 24, Week 48 | The PR interval is measured from the beginning of the P wave to the beginning of the QRS complex, and reflects the time the electrical impulse takes to travel from the sinus node through the atrioventricular (AV) node and entering the ventricles. The PR interval is therefore a good estimate of AV node function. |
| Adherence to Regimen Though Week 48 Based on MACS the Multicenter AIDS Cohort Study (MACS) Adherence Questionnaire | Baseline, Week 24, Week 48 | The MACS adherence questionnaire asks patients how many medication doses they missed during the previous day, 2 days, 3 days and 4 days. Drug-specific questions included adherence with dose and frequency. Adherence was defined as taking all doses and numbers of pills as prescribed for each medication. This strict adherence cut-off was based on the guidelines stating that anything less than excellent adherence may result in a virus breakthrough and development of resistance. |
| Mean Score of European Quality of Life-5 Dimensions (EQ-5D) Health Index Score at Baseline, Mid-Study (Week 24), and Final (Week 48) | Baseline, Week 24, Week 48 | The EQ-5D is a 5-item questionnaire to assess health-related quality of life in 5 health dimensions (mobility, self-care, usual activity, pain/discomfort, anxiety/depression) are scored on a 3-level scale: no problems (1), some problems (2), extreme problems (3). Using a standard algorithm, responses are summarized into a single score, the EQ-5D Health Index Score (HIS), which ranges between 1 (representing perfect health) and 0 (representing the worst imaginable health state or death). The smallest coefficient of change is 0.03. |
| Mean Score of European Quality of Life-5 Dimensions (EQ-5D) Visual Analog Scale (VAS) at Baseline, Mid-Study (Week 24), and Final (Week 48) | Baseline, Week 24, Week 48 | The EQ-5D has a Visual Analog Scale (VAS), which is a feeling thermometer-like scale with a range between 0 and 100. Patients are required to draw a line from a box on the VAS scale to an actual mark on the thermometer-like scale that corresponds with a number that reflects their self-assessed health status at the time they are completing the questionnaire. Higher VAS scores indicate better overall health. There is no minimum clinically important difference reported in the literature for VAS. |
| Number of Participants Utilizing Resources for Managing Lipid Elevation | Baseline, Week 24, Week 48 | Participants' overall resource utilization for managing lipid elevation that includes the management of side effects of lipid lowering medications, such as those due to drug interactions. |
| Mean ATV, RTV and SQV Minimum Concentration (Cmin) Values | collected at the pre-dose time point after receiving atazanavir for at least four weeks | The minimum or trough concentration (Cmin) of a drug observed after its administration and just prior to the administration of a subsequent dose. |
| HIV IC50 at Week 24 | Week 24 | IC50: inhibitory concentration of drug required to reduce viral replication by 50%. |
| Inhibitory Quotient at Week 24 | Baseline, Week 24 | Inhibitory quotient is a measure of drug exposure and susceptibility in an individual. The IQ is typically calculated as the ratio of Cmin to HIV IC50. |
| Inhibitory Quotient at Week 48 | Baseline, Week 48 | Inhibitory quotient is a measure of drug exposure and susceptibility in an individual. The IQ is typically calculated as the ratio of Cmin to HIV IC50. |
| HIV RNA Level - Treated Subjects With Evaluable Cmins at Week 24 | Baseline, Week 24 | Week 24 HIV RNA level and change from baseline were summarized for treated subjects with evaluable Cmins. |
| HIV RNA Level - Treated Subjects With Evaluable Cmins at Week 48 | Baseline, Week 48 | Week 24 HIV RNA level and change from baseline were summarized for treated subjects with evaluable Cmins. |
Countries
United States
Participant flow
Pre-assignment details
571 human immunodeficiency virus (HIV)-infected participants were enrolled; 358 (63%) were randomized to treatment. Of the 213 not randomized, 194 did not meet eligibility criteria; other reasons include duplicate enrollment (4), accrual closed (1), noncompliance (1), serious adverse event (2), patient request (11), missing information (4).
Participants by arm
| Arm | Count |
|---|---|
| ATV 300 mg / RTV ATV 300 mg + RTV 100 mg + TDF 300 mg + nucleoside of choice
ATV , RTV, and TDF once daily, nucleoside per label 48 Weeks and then for as long as subject is in need of therapy through study | 120 |
| ATV 400 mg / SQV ATV 400 mg + SQV 1200 mg + TDF 300 mg + nucleoside of choice
ATV, SQV, and TDF once daily, nucleoside per label 48 Weeks and then for as long as subject is in need of therapy through study | 115 |
| LPV / RTV LPV/RTV 400/100 mg + TDF 300 mg + nucleoside of choice
LPV/RTV twice daily, TDF once daily, nucleoside per label 48 Weeks and then for as long as subject is in need of therapy through study | 123 |
| Total | 358 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 10 | 9 | 9 |
| Overall Study | Death | 0 | 0 | 1 |
| Overall Study | Disease Progression / Relapse | 1 | 1 | 0 |
| Overall Study | Lack of Efficacy | 33 | 33 | 28 |
| Overall Study | Lost to Follow-up | 4 | 4 | 3 |
| Overall Study | Noncompliance | 6 | 7 | 6 |
| Overall Study | Protocol Violation While on Study | 0 | 1 | 2 |
| Overall Study | Study Termination by Sponsor | 1 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 5 | 0 |
Baseline characteristics
| Characteristic | ATV 300 mg / RTV | ATV 400 mg / SQV | LPV / RTV | Total |
|---|---|---|---|---|
| Acquired Immunodeficiency Virus (AIDS) No | 87 participants | 82 participants | 87 participants | 256 participants |
| Acquired Immunodeficiency Virus (AIDS) Yes | 33 participants | 33 participants | 36 participants | 102 participants |
| Age Continuous | 39 years | 41 years | 39 years | 40 years |
| Cluster of Differentiation 4 (CD4) cell count | 317 cells/mm^3 | 286 cells/mm^3 | 283 cells/mm^3 | 297 cells/mm^3 |
| Human Immunodeficiency Virus Ribonucleic Acid (HIV RNA) | 4.44 log10 c/mL | 4.42 log10 c/mL | 4.47 log10 c/mL | 4.45 log10 c/mL |
| Intravenous (IV) Drug Use No | 112 participants | 108 participants | 115 participants | 335 participants |
| Intravenous (IV) Drug Use Yes | 8 participants | 7 participants | 8 participants | 23 participants |
| Race/Ethnicity, Customized Black | 18 participants | 16 participants | 21 participants | 55 participants |
| Race/Ethnicity, Customized Hispanic/Latino | 27 participants | 26 participants | 27 participants | 80 participants |
| Race/Ethnicity, Customized Other | 0 participants | 3 participants | 4 participants | 7 participants |
| Race/Ethnicity, Customized White | 75 participants | 70 participants | 71 participants | 216 participants |
| Region of Enrollment Europe | 25 participants | 22 participants | 22 participants | 69 participants |
| Region of Enrollment North America | 39 participants | 38 participants | 47 participants | 124 participants |
| Region of Enrollment South America | 56 participants | 55 participants | 54 participants | 165 participants |
| Sex: Female, Male Female | 24 Participants | 26 Participants | 27 Participants | 77 Participants |
| Sex: Female, Male Male | 96 Participants | 89 Participants | 96 Participants | 281 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 101 / 119 | 95 / 110 | 104 / 118 |
| serious Total, serious adverse events | 22 / 119 | 22 / 110 | 19 / 118 |
Outcome results
Primary
Mean Change From Baseline in HIV Ribonucleic Acid (RNA) at Week 24
Time frame: Baseline, Week 24
Population: Randomized participants; as-randomized population (refers to the treatment regimen assigned at randomization).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ATV 300 mg / RTV | Mean Change From Baseline in HIV Ribonucleic Acid (RNA) at Week 24 | -1.86 log10 c/mL | Standard Error 0.11 |
| ATV 400 mg / SQV | Mean Change From Baseline in HIV Ribonucleic Acid (RNA) at Week 24 | -1.52 log10 c/mL | Standard Error 0.13 |
| LPV / RTV | Mean Change From Baseline in HIV Ribonucleic Acid (RNA) at Week 24 | -1.89 log10 c/mL | Standard Error 0.11 |
97.5% CI: [-0.09, 0.37]
97.5% CI: [0.07, 0.55]
Primary
Mean Change From Baseline in HIV RNA at Week 48
Time frame: Baseline, Week 48
Population: Randomized participants; as-randomized population (refers to the treatment regimen assigned at randomization).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ATV 300 mg / RTV | Mean Change From Baseline in HIV RNA at Week 48 | -1.93 log10 c/mL | Standard Error 0.12 |
| ATV 400 mg / SQV | Mean Change From Baseline in HIV RNA at Week 48 | -1.55 log10 c/mL | Standard Error 0.14 |
| LPV / RTV | Mean Change From Baseline in HIV RNA at Week 48 | -1.87 log10 c/mL | Standard Error 0.13 |
97.5% CI: [-0.12, 0.39]
97.5% CI: [0.07, 0.6]
Primary
Mean Change From Baseline in HIV RNA at Week 96
Time frame: Baseline, Week 96
Population: Randomized participants while on initial regimen
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ATV 300 mg / RTV | Mean Change From Baseline in HIV RNA at Week 96 | -2.29 log10 c/mL | Standard Error 0.121 |
| ATV 400 mg / SQV | Mean Change From Baseline in HIV RNA at Week 96 | -2.08 log10 c/mL | Standard Error 0.151 |
Comparison: overall97.5% CI: [-0.13, 0.41]
Comparison: last observation carried forward97.5% CI: [-0.16, 0.38]
Secondary
Adherence to Regimen Though Week 48 Based on MACS the Multicenter AIDS Cohort Study (MACS) Adherence Questionnaire
The MACS adherence questionnaire asks patients how many medication doses they missed during the previous day, 2 days, 3 days and 4 days. Drug-specific questions included adherence with dose and frequency. Adherence was defined as taking all doses and numbers of pills as prescribed for each medication. This strict adherence cut-off was based on the guidelines stating that anything less than excellent adherence may result in a virus breakthrough and development of resistance.
Time frame: Baseline, Week 24, Week 48
Population: Number of Participants Analyzed=treated participants; as-randomized population (refers to the treatment regimen assigned at randomization); n=subset of treated participants (Given the language limitation, a subset of the AI424045 population was included in the MACS adherence analysis.)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| ATV 300 mg / RTV | Adherence to Regimen Though Week 48 Based on MACS the Multicenter AIDS Cohort Study (MACS) Adherence Questionnaire | Adherent at Week 48 (n=11, 4, 20) | 8 participants |
| ATV 300 mg / RTV | Adherence to Regimen Though Week 48 Based on MACS the Multicenter AIDS Cohort Study (MACS) Adherence Questionnaire | Adherent at Week 24 (n=18, 11, 25) | 10 participants |
| ATV 300 mg / RTV | Adherence to Regimen Though Week 48 Based on MACS the Multicenter AIDS Cohort Study (MACS) Adherence Questionnaire | Adherent at Baseline (n=27, 25, 33) | 12 participants |
| ATV 400 mg / SQV | Adherence to Regimen Though Week 48 Based on MACS the Multicenter AIDS Cohort Study (MACS) Adherence Questionnaire | Adherent at Week 48 (n=11, 4, 20) | 2 participants |
| ATV 400 mg / SQV | Adherence to Regimen Though Week 48 Based on MACS the Multicenter AIDS Cohort Study (MACS) Adherence Questionnaire | Adherent at Baseline (n=27, 25, 33) | 10 participants |
| ATV 400 mg / SQV | Adherence to Regimen Though Week 48 Based on MACS the Multicenter AIDS Cohort Study (MACS) Adherence Questionnaire | Adherent at Week 24 (n=18, 11, 25) | 5 participants |
| LPV / RTV | Adherence to Regimen Though Week 48 Based on MACS the Multicenter AIDS Cohort Study (MACS) Adherence Questionnaire | Adherent at Week 24 (n=18, 11, 25) | 23 participants |
| LPV / RTV | Adherence to Regimen Though Week 48 Based on MACS the Multicenter AIDS Cohort Study (MACS) Adherence Questionnaire | Adherent at Week 48 (n=11, 4, 20) | 13 participants |
| LPV / RTV | Adherence to Regimen Though Week 48 Based on MACS the Multicenter AIDS Cohort Study (MACS) Adherence Questionnaire | Adherent at Baseline (n=27, 25, 33) | 18 participants |
Secondary
Change From Baseline in CD4 Cell Count at Week 24
Time frame: Baseline, Week 24
Population: Randomized participantsRandomized participants while on initial regimen (completers censored).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ATV 300 mg / RTV | Change From Baseline in CD4 Cell Count at Week 24 | 83 cells/mm3 | Standard Error 14 |
| ATV 400 mg / SQV | Change From Baseline in CD4 Cell Count at Week 24 | 59 cells/mm3 | Standard Error 11.8 |
| LPV / RTV | Change From Baseline in CD4 Cell Count at Week 24 | 90 cells/mm3 | Standard Error 15.3 |
97.5% CI: [-44.3, 7.5]
97.5% CI: [-74.5, -15.3]
Secondary
Change From Baseline in CD4 Cell Count at Week 48
Time frame: Baseline, Week 48
Population: Randomized participants while on initial regimen (completers censored).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ATV 300 mg / RTV | Change From Baseline in CD4 Cell Count at Week 48 | 110 cells/mm3 | Standard Error 22.9 |
| ATV 400 mg / SQV | Change From Baseline in CD4 Cell Count at Week 48 | 72 cells/mm3 | Standard Error 19.7 |
| LPV / RTV | Change From Baseline in CD4 Cell Count at Week 48 | 121 cells/mm3 | Standard Error 20.1 |
97.5% CI: [-45.6, 10.6]
97.5% CI: [-79.2, -16.1]
Secondary
Change From Baseline in CD4 Cell Count at Week 96
Time frame: Baseline, Week 96
Population: Randomized participants (while on initial regimen) with evaluation at time point
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ATV 300 mg / RTV | Change From Baseline in CD4 Cell Count at Week 96 | 122 cells/mm3 | Standard Error 26.3 |
| ATV 400 mg / SQV | Change From Baseline in CD4 Cell Count at Week 96 | 154 cells/mm3 | Standard Error 24.2 |
Secondary
Correlation of ATV Minimum Plasma Concentration (Cmin) Inhibitory Quotient (IQ), and Number of PI Mutations at Baseline and CD4 Cell Count Change From Baseline at Week 24
Pearson correlations of the Cmin (trough plasma concentration), IQ (the ratio of Cmin of ATV to HIV IC50), and Number of baseline PI Mutations with CD4 cell count change from baseline at Week 24 were explored.
Time frame: Baseline, Week 24
Population: Participants with evaluable PK measurements, as-randomized population (refers to the treatment regimen assigned at randomization).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| ATV 300 mg / RTV | Correlation of ATV Minimum Plasma Concentration (Cmin) Inhibitory Quotient (IQ), and Number of PI Mutations at Baseline and CD4 Cell Count Change From Baseline at Week 24 | ATV Cmin | 0.37 Pearson Correlation Coefficient |
| ATV 300 mg / RTV | Correlation of ATV Minimum Plasma Concentration (Cmin) Inhibitory Quotient (IQ), and Number of PI Mutations at Baseline and CD4 Cell Count Change From Baseline at Week 24 | IQ (<10; >=10) | 0.376 Pearson Correlation Coefficient |
| ATV 300 mg / RTV | Correlation of ATV Minimum Plasma Concentration (Cmin) Inhibitory Quotient (IQ), and Number of PI Mutations at Baseline and CD4 Cell Count Change From Baseline at Week 24 | # of PI Mutations at baseline (<4; >=4) | -0.395 Pearson Correlation Coefficient |
| ATV 400 mg / SQV | Correlation of ATV Minimum Plasma Concentration (Cmin) Inhibitory Quotient (IQ), and Number of PI Mutations at Baseline and CD4 Cell Count Change From Baseline at Week 24 | ATV Cmin | -0.21 Pearson Correlation Coefficient |
| ATV 400 mg / SQV | Correlation of ATV Minimum Plasma Concentration (Cmin) Inhibitory Quotient (IQ), and Number of PI Mutations at Baseline and CD4 Cell Count Change From Baseline at Week 24 | IQ (<10; >=10) | 0.105 Pearson Correlation Coefficient |
| ATV 400 mg / SQV | Correlation of ATV Minimum Plasma Concentration (Cmin) Inhibitory Quotient (IQ), and Number of PI Mutations at Baseline and CD4 Cell Count Change From Baseline at Week 24 | # of PI Mutations at baseline (<4; >=4) | -0.227 Pearson Correlation Coefficient |
Comparison: Correlation between ATV Cmin of ATV 300 mg / RTV and CD4 Cell Countp-value: <0.05t-test, 1 sided
Comparison: Correlation between IQ (\<10; \>=10) of ATV 300 mg / RTV and CD4 Cell Countp-value: <0.05t-test, 1 sided
Comparison: Correlation between # of PI Mutations at baseline (\<4; \>=4) of ATV 300 mg / RTV and CD4 Cell Countp-value: <0.05t-test, 1 sided
Secondary
Correlation of ATV Minimum Plasma Concentration (Cmin) Inhibitory Quotient (IQ), and Number of PI Mutations at Baseline and CD4 Cell Count Change From Baseline at Week 48
Pearson correlations of the Cmin (trough plasma concentration), IQ (the ratio of Cmin of ATV to HIV IC50), and Number of baseline PI Mutations with CD4 cell count change from baseline at Week 48 were explored.
Time frame: Baseline, Week 48
Population: Formal population PK/PD analysis was not performed due to difficulties in correlating time of blood sample collection with drug administration, and inability to apply the PK model generated with data obtained from healthy subjects due to newly observed differences in exposure to atazanavir between HIV-infected participants and healthy participants.
Secondary
Correlation of ATV Minimum Plasma Concentration (Cmin), Inhibitory Quotient (IQ), and Number of Protease Inhibitor (PI) Mutations at Baseline With HIV RNA Change From Baseline at Week 24
Pearson correlations of the Cmin (trough plasma concentration), IQ (the ratio of Cmin of ATV to HIV IC50), and Number of baseline PI Mutations with HIV RNA change from baseline at Week 24 were explored.
Time frame: Baseline, Week 24
Population: Week 24: Participants with evaluable PK measurements
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| ATV 300 mg / RTV | Correlation of ATV Minimum Plasma Concentration (Cmin), Inhibitory Quotient (IQ), and Number of Protease Inhibitor (PI) Mutations at Baseline With HIV RNA Change From Baseline at Week 24 | ATV Cmin | -0.056 Pearson Correlation Coefficient |
| ATV 300 mg / RTV | Correlation of ATV Minimum Plasma Concentration (Cmin), Inhibitory Quotient (IQ), and Number of Protease Inhibitor (PI) Mutations at Baseline With HIV RNA Change From Baseline at Week 24 | IQ (<10; >=10) | -0.391 Pearson Correlation Coefficient |
| ATV 300 mg / RTV | Correlation of ATV Minimum Plasma Concentration (Cmin), Inhibitory Quotient (IQ), and Number of Protease Inhibitor (PI) Mutations at Baseline With HIV RNA Change From Baseline at Week 24 | # of PI Mutations at baseline (<4; >=4) | 0.306 Pearson Correlation Coefficient |
| ATV 400 mg / SQV | Correlation of ATV Minimum Plasma Concentration (Cmin), Inhibitory Quotient (IQ), and Number of Protease Inhibitor (PI) Mutations at Baseline With HIV RNA Change From Baseline at Week 24 | # of PI Mutations at baseline (<4; >=4) | 0.437 Pearson Correlation Coefficient |
| ATV 400 mg / SQV | Correlation of ATV Minimum Plasma Concentration (Cmin), Inhibitory Quotient (IQ), and Number of Protease Inhibitor (PI) Mutations at Baseline With HIV RNA Change From Baseline at Week 24 | ATV Cmin | 0.254 Pearson Correlation Coefficient |
| ATV 400 mg / SQV | Correlation of ATV Minimum Plasma Concentration (Cmin), Inhibitory Quotient (IQ), and Number of Protease Inhibitor (PI) Mutations at Baseline With HIV RNA Change From Baseline at Week 24 | IQ (<10; >=10) | -0.081 Pearson Correlation Coefficient |
Comparison: Correlation between IQ (\<10; \>=10) of ATV 300 mg / RTV and HIV RNAp-value: <0.05t-test, 1 sided
Comparison: Correlation between number of PI Mutations at baseline (\<4; \>=4) of ATV 400 mg / SQV and HIV RNAp-value: <0.05t-test, 1 sided
Secondary
Correlation of ATV Minimum Plasma Concentration (Cmin), Inhibitory Quotient (IQ), and Number of Protease Inhibitor (PI) Mutations at Baseline With HIV RNA Change From Baseline at Week 48
Pearson correlations of the Cmin (trough plasma concentration), IQ (the ratio of Cmin of ATV to HIV IC50), and Number of baseline PI Mutations with HIV RNA change from baseline at Week 48 were explored.
Time frame: Baseline, Week 48
Population: Formal population PK/PD analysis was not performed due to difficulties in correlating time of blood sample collection with drug administration, and inability to apply the PK model generated with data obtained from healthy subjects due to newly observed differences in exposure to atazanavir between HIV-infected participants and healthy participants.
Secondary
Deaths, Serious Adverse Events (SAEs), and Adverse Events (AEs) Through Week 48
AE=any new untoward medical occurrence/worsening of a pre-existing medical condition regardless of causal relationship. SAE=any untoward medical occurrence at any dose that: results in death; is life-threatening; requires/prolongs inpatient hospitalization; results in persistent/significant disability; is cancer; is congenital anomaly/birth defect; results in drug dependency/abuse; is an important medical event.
Time frame: From Enrollment through Week 48
Population: Randomized participants for Deaths and SAEs; treated participants for all others; as-randomized population (refers to the treatment regimen assigned at randomization). In addition, of the 213 screen failures (not randomized), there were 4 subjects who had an SAE; these are not included in the table below.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| ATV 300 mg / RTV | Deaths, Serious Adverse Events (SAEs), and Adverse Events (AEs) Through Week 48 | Deaths (n = 120, 115, 123) | 0 participants |
| ATV 300 mg / RTV | Deaths, Serious Adverse Events (SAEs), and Adverse Events (AEs) Through Week 48 | AEs leading to discontinuation (n = 119, 110, 118) | 6 participants |
| ATV 300 mg / RTV | Deaths, Serious Adverse Events (SAEs), and Adverse Events (AEs) Through Week 48 | SAEs (n = 120, 115, 123) | 12 participants |
| ATV 300 mg / RTV | Deaths, Serious Adverse Events (SAEs), and Adverse Events (AEs) Through Week 48 | AEs, grades 1-4 (n = 119, 110, 118) | 97 participants |
| ATV 300 mg / RTV | Deaths, Serious Adverse Events (SAEs), and Adverse Events (AEs) Through Week 48 | AEs, grades 3-4 (n = 119, 110, 118) | 11 participants |
| ATV 400 mg / SQV | Deaths, Serious Adverse Events (SAEs), and Adverse Events (AEs) Through Week 48 | Deaths (n = 120, 115, 123) | 1 participants |
| ATV 400 mg / SQV | Deaths, Serious Adverse Events (SAEs), and Adverse Events (AEs) Through Week 48 | SAEs (n = 120, 115, 123) | 14 participants |
| ATV 400 mg / SQV | Deaths, Serious Adverse Events (SAEs), and Adverse Events (AEs) Through Week 48 | AEs leading to discontinuation (n = 119, 110, 118) | 8 participants |
| ATV 400 mg / SQV | Deaths, Serious Adverse Events (SAEs), and Adverse Events (AEs) Through Week 48 | AEs, grades 1-4 (n = 119, 110, 118) | 93 participants |
| ATV 400 mg / SQV | Deaths, Serious Adverse Events (SAEs), and Adverse Events (AEs) Through Week 48 | AEs, grades 3-4 (n = 119, 110, 118) | 18 participants |
| LPV / RTV | Deaths, Serious Adverse Events (SAEs), and Adverse Events (AEs) Through Week 48 | Deaths (n = 120, 115, 123) | 1 participants |
| LPV / RTV | Deaths, Serious Adverse Events (SAEs), and Adverse Events (AEs) Through Week 48 | AEs, grades 3-4 (n = 119, 110, 118) | 12 participants |
| LPV / RTV | Deaths, Serious Adverse Events (SAEs), and Adverse Events (AEs) Through Week 48 | AEs, grades 1-4 (n = 119, 110, 118) | 103 participants |
| LPV / RTV | Deaths, Serious Adverse Events (SAEs), and Adverse Events (AEs) Through Week 48 | AEs leading to discontinuation (n = 119, 110, 118) | 5 participants |
| LPV / RTV | Deaths, Serious Adverse Events (SAEs), and Adverse Events (AEs) Through Week 48 | SAEs (n = 120, 115, 123) | 11 participants |
Secondary
Fasting Glucose Mean Change From Baseline at Week 24
Time frame: Baseline, Week 24
Population: Treated Participants with evaluation at time point; as-randomized population (refers to the treatment regimen assigned at randomization).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ATV 300 mg / RTV | Fasting Glucose Mean Change From Baseline at Week 24 | 0 mg/dL | Standard Error 1.6 |
| ATV 400 mg / SQV | Fasting Glucose Mean Change From Baseline at Week 24 | -3 mg/dL | Standard Error 1.8 |
| LPV / RTV | Fasting Glucose Mean Change From Baseline at Week 24 | 0 mg/dL | Standard Error 1.4 |
Secondary
Fasting Glucose Mean Change From Baseline at Week 48
Time frame: Week 48
Population: Treated Participants with evaluation at time point; as-randomized population (refers to the treatment regimen assigned at randomization).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ATV 300 mg / RTV | Fasting Glucose Mean Change From Baseline at Week 48 | 4 mg/dL | Standard Error 3.6 |
| ATV 400 mg / SQV | Fasting Glucose Mean Change From Baseline at Week 48 | -1 mg/dL | Standard Error 1.6 |
| LPV / RTV | Fasting Glucose Mean Change From Baseline at Week 48 | 1 mg/dL | Standard Error 1.5 |
Secondary
Fridericia-corrected QT (QTcF) Interval and Change From Baseline by Analysis Time Point
The QT interval is a measure of the time between the start of the Q wave and the end of the T wave in the heart's electrical cycle. The QT interval was corrected for heart rate using Fridericia's (QTcF) formula.
Time frame: Baseline, Week 4 predose, 2-3 hours postdose, 6-12 hours postdose, Week 12, Week 24, Week 48
Population: Treated participants; as-randomized population (refers to the treatment regimen assigned at randomization). n=number of participants evaluated at timepoint
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ATV 300 mg / RTV | Fridericia-corrected QT (QTcF) Interval and Change From Baseline by Analysis Time Point | Mean Change at Week 12 (n=110, 97, 107) | 2 msec | Standard Error 1.6 |
| ATV 300 mg / RTV | Fridericia-corrected QT (QTcF) Interval and Change From Baseline by Analysis Time Point | Mean Change at Week 24 (n=108, 92, 109) | 1 msec | Standard Error 1.8 |
| ATV 300 mg / RTV | Fridericia-corrected QT (QTcF) Interval and Change From Baseline by Analysis Time Point | Mean Change at Week 4 predose (n=117, 104, 110) | -3 msec | Standard Error 1.6 |
| ATV 300 mg / RTV | Fridericia-corrected QT (QTcF) Interval and Change From Baseline by Analysis Time Point | Mean Change at Week 48 (n=89, 75, 97) | -1 msec | Standard Error 1.8 |
| ATV 300 mg / RTV | Fridericia-corrected QT (QTcF) Interval and Change From Baseline by Analysis Time Point | Baseline Mean (n=119, 110, 118) | 390 msec | Standard Error 1.9 |
| ATV 300 mg / RTV | Fridericia-corrected QT (QTcF) Interval and Change From Baseline by Analysis Time Point | Mean Change Wk 4 2-3 hrs postdose (n=113,102,106) | -2 msec | Standard Error 1.6 |
| ATV 300 mg / RTV | Fridericia-corrected QT (QTcF) Interval and Change From Baseline by Analysis Time Point | Mean Change Wk 4 6-12 hrs postdose (n=112,101,105) | -4 msec | Standard Error 1.7 |
| ATV 400 mg / SQV | Fridericia-corrected QT (QTcF) Interval and Change From Baseline by Analysis Time Point | Mean Change at Week 12 (n=110, 97, 107) | 3 msec | Standard Error 2 |
| ATV 400 mg / SQV | Fridericia-corrected QT (QTcF) Interval and Change From Baseline by Analysis Time Point | Mean Change Wk 4 6-12 hrs postdose (n=112,101,105) | -1 msec | Standard Error 1.9 |
| ATV 400 mg / SQV | Fridericia-corrected QT (QTcF) Interval and Change From Baseline by Analysis Time Point | Mean Change at Week 24 (n=108, 92, 109) | 3 msec | Standard Error 2.2 |
| ATV 400 mg / SQV | Fridericia-corrected QT (QTcF) Interval and Change From Baseline by Analysis Time Point | Mean Change Wk 4 2-3 hrs postdose (n=113,102,106) | -3 msec | Standard Error 2 |
| ATV 400 mg / SQV | Fridericia-corrected QT (QTcF) Interval and Change From Baseline by Analysis Time Point | Baseline Mean (n=119, 110, 118) | 387 msec | Standard Error 2.2 |
| ATV 400 mg / SQV | Fridericia-corrected QT (QTcF) Interval and Change From Baseline by Analysis Time Point | Mean Change at Week 48 (n=89, 75, 97) | -1 msec | Standard Error 2.1 |
| ATV 400 mg / SQV | Fridericia-corrected QT (QTcF) Interval and Change From Baseline by Analysis Time Point | Mean Change at Week 4 predose (n=117, 104, 110) | 1 msec | Standard Error 1.9 |
| LPV / RTV | Fridericia-corrected QT (QTcF) Interval and Change From Baseline by Analysis Time Point | Mean Change at Week 48 (n=89, 75, 97) | 0 msec | Standard Error 2 |
| LPV / RTV | Fridericia-corrected QT (QTcF) Interval and Change From Baseline by Analysis Time Point | Baseline Mean (n=119, 110, 118) | 390 msec | Standard Error 1.9 |
| LPV / RTV | Fridericia-corrected QT (QTcF) Interval and Change From Baseline by Analysis Time Point | Mean Change at Week 4 predose (n=117, 104, 110) | -2 msec | Standard Error 1.7 |
| LPV / RTV | Fridericia-corrected QT (QTcF) Interval and Change From Baseline by Analysis Time Point | Mean Change Wk 4 2-3 hrs postdose (n=113,102,106) | -7 msec | Standard Error 1.9 |
| LPV / RTV | Fridericia-corrected QT (QTcF) Interval and Change From Baseline by Analysis Time Point | Mean Change at Week 12 (n=110, 97, 107) | 2 msec | Standard Error 1.6 |
| LPV / RTV | Fridericia-corrected QT (QTcF) Interval and Change From Baseline by Analysis Time Point | Mean Change at Week 24 (n=108, 92, 109) | 2 msec | Standard Error 1.8 |
| LPV / RTV | Fridericia-corrected QT (QTcF) Interval and Change From Baseline by Analysis Time Point | Mean Change Wk 4 6-12 hrs postdose (n=112,101,105) | -8 msec | Standard Error 1.8 |
Secondary
Grade 3/4 Laboratory Abnormalities Through Week 48
Common Terminology Criteria for Adverse Events v3.0 (CTCAE) Grades:1=Mild, 2=Moderate, 3=Severe, 4=Life-threatening/disabling, 5=Death. Abnormal values: absolute neutrophil count: ≥500 to \<750/mm3 (grade 3), \<500/mm3 (grade 4); platelets: 20,000-49,999/mm3 (grade 3), \<20,000/mm3 or diffuse petechiae (grade 4); alanine transaminase (ALT): 5.1-10 x upper limit of normal (ULN; grade 3), \>10 x ULN (grade 4); aspartate transaminase (AST): 5.1-10 x ULN (grade 3), \>10 x ULN (grade 4); bilirubin: 2.6-5 x ULN (grade 3), \>5 x ULN (grade 4).
Time frame: From Enrollment to Week 48
Population: Evaluable treated participants; as-randomized population (refers to the treatment regimen assigned at randomization).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| ATV 300 mg / RTV | Grade 3/4 Laboratory Abnormalities Through Week 48 | Total Bilirubin Elevation | 58 participants |
| ATV 300 mg / RTV | Grade 3/4 Laboratory Abnormalities Through Week 48 | Platelet Reduction | 2 participants |
| ATV 300 mg / RTV | Grade 3/4 Laboratory Abnormalities Through Week 48 | Neutrophil Reduction | 8 participants |
| ATV 300 mg / RTV | Grade 3/4 Laboratory Abnormalities Through Week 48 | ALT Elevation | 5 participants |
| ATV 300 mg / RTV | Grade 3/4 Laboratory Abnormalities Through Week 48 | AST Elevation | 4 participants |
| ATV 400 mg / SQV | Grade 3/4 Laboratory Abnormalities Through Week 48 | ALT Elevation | 4 participants |
| ATV 400 mg / SQV | Grade 3/4 Laboratory Abnormalities Through Week 48 | AST Elevation | 2 participants |
| ATV 400 mg / SQV | Grade 3/4 Laboratory Abnormalities Through Week 48 | Total Bilirubin Elevation | 22 participants |
| ATV 400 mg / SQV | Grade 3/4 Laboratory Abnormalities Through Week 48 | Platelet Reduction | 4 participants |
| ATV 400 mg / SQV | Grade 3/4 Laboratory Abnormalities Through Week 48 | Neutrophil Reduction | 8 participants |
| LPV / RTV | Grade 3/4 Laboratory Abnormalities Through Week 48 | Total Bilirubin Elevation | 1 participants |
| LPV / RTV | Grade 3/4 Laboratory Abnormalities Through Week 48 | ALT Elevation | 4 participants |
| LPV / RTV | Grade 3/4 Laboratory Abnormalities Through Week 48 | AST Elevation | 4 participants |
| LPV / RTV | Grade 3/4 Laboratory Abnormalities Through Week 48 | Neutrophil Reduction | 10 participants |
| LPV / RTV | Grade 3/4 Laboratory Abnormalities Through Week 48 | Platelet Reduction | 3 participants |
Secondary
HIV IC50 at Week 24
IC50: inhibitory concentration of drug required to reduce viral replication by 50%.
Time frame: Week 24
Population: Participants with evaluable IC50 measurements; as-randomized population (refers to the treatment regimen assigned at randomization).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ATV 300 mg / RTV | HIV IC50 at Week 24 | 17.83 ng/mL | Standard Error 4.04 |
| ATV 400 mg / SQV | HIV IC50 at Week 24 | 22.84 ng/mL | Standard Error 11.65 |
Secondary
HIV RNA Level - Treated Subjects With Evaluable Cmins at Week 24
Week 24 HIV RNA level and change from baseline were summarized for treated subjects with evaluable Cmins.
Time frame: Baseline, Week 24
Population: Participants with evaluable Cmins; as-randomized population (refers to the treatment regimen assigned at randomization).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ATV 300 mg / RTV | HIV RNA Level - Treated Subjects With Evaluable Cmins at Week 24 | Baseline Values | 4.53 log10 c/mL | Standard Error 0.13 |
| ATV 300 mg / RTV | HIV RNA Level - Treated Subjects With Evaluable Cmins at Week 24 | Week 24 Values | 2.62 log10 c/mL | Standard Error 0.19 |
| ATV 300 mg / RTV | HIV RNA Level - Treated Subjects With Evaluable Cmins at Week 24 | Change from Baseline at Week 24 | -1.91 log10 c/mL | Standard Error 0.19 |
| ATV 400 mg / SQV | HIV RNA Level - Treated Subjects With Evaluable Cmins at Week 24 | Baseline Values | 4.41 log10 c/mL | Standard Error 0.13 |
| ATV 400 mg / SQV | HIV RNA Level - Treated Subjects With Evaluable Cmins at Week 24 | Week 24 Values | 2.83 log10 c/mL | Standard Error 0.25 |
| ATV 400 mg / SQV | HIV RNA Level - Treated Subjects With Evaluable Cmins at Week 24 | Change from Baseline at Week 24 | -1.57 log10 c/mL | Standard Error 0.29 |
Secondary
HIV RNA Level - Treated Subjects With Evaluable Cmins at Week 48
Week 24 HIV RNA level and change from baseline were summarized for treated subjects with evaluable Cmins.
Time frame: Baseline, Week 48
Population: Formal population PK/PD analysis was not performed due to difficulties in correlating time of blood sample collection with drug administration, and inability to apply the PK model generated with data obtained from healthy subjects due to newly observed differences in exposure to atazanavir between HIV-infected participants and healthy participants.
Secondary
Inhibitory Quotient at Week 24
Inhibitory quotient is a measure of drug exposure and susceptibility in an individual. The IQ is typically calculated as the ratio of Cmin to HIV IC50.
Time frame: Baseline, Week 24
Population: Participants with evaluable IQ measurements (ie, must have both Cmin and IC50 measurements); as-randomized population (refers to the treatment regimen assigned at randomization).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ATV 300 mg / RTV | Inhibitory Quotient at Week 24 | 136.94 ratio | Standard Error 24.33 |
| ATV 400 mg / SQV | Inhibitory Quotient at Week 24 | 25.04 ratio | Standard Error 13.33 |
Secondary
Inhibitory Quotient at Week 48
Inhibitory quotient is a measure of drug exposure and susceptibility in an individual. The IQ is typically calculated as the ratio of Cmin to HIV IC50.
Time frame: Baseline, Week 48
Population: Formal population PK/PD analysis was not performed due to difficulties in correlating time of blood sample collection with drug administration, and inability to apply the PK model generated with data obtained from healthy subjects due to newly observed differences in exposure to atazanavir between HIV-infected participants and healthy participants.
Secondary
Lipid Mean Percent Change From Baseline at Week 24
Mean percent change in total cholesterol, high density lipoprotein (HDL) cholesterol, fasting low density lipoprotein (LDL) cholesterol, and fasting triglycerides.
Time frame: Baseline, Week 24
Population: Treated Participants, Last Observation Carried Forward (LOCF), as-randomized population (refers to the treatment regimen assigned at randomization).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| ATV 300 mg / RTV | Lipid Mean Percent Change From Baseline at Week 24 | Total Cholesterol | -8 percent change |
| ATV 300 mg / RTV | Lipid Mean Percent Change From Baseline at Week 24 | High Density Lipoprotein (HDL) Cholesterol | -7 percent change |
| ATV 300 mg / RTV | Lipid Mean Percent Change From Baseline at Week 24 | Fasting Low Density Lipoprotein (LDL) Cholesterol | -10 percent change |
| ATV 300 mg / RTV | Lipid Mean Percent Change From Baseline at Week 24 | Fasting Triglycerides | -2 percent change |
| ATV 400 mg / SQV | Lipid Mean Percent Change From Baseline at Week 24 | Fasting Triglycerides | -14 percent change |
| ATV 400 mg / SQV | Lipid Mean Percent Change From Baseline at Week 24 | Total Cholesterol | -9 percent change |
| ATV 400 mg / SQV | Lipid Mean Percent Change From Baseline at Week 24 | Fasting Low Density Lipoprotein (LDL) Cholesterol | -11 percent change |
| ATV 400 mg / SQV | Lipid Mean Percent Change From Baseline at Week 24 | High Density Lipoprotein (HDL) Cholesterol | -1 percent change |
| LPV / RTV | Lipid Mean Percent Change From Baseline at Week 24 | Fasting Triglycerides | 31 percent change |
| LPV / RTV | Lipid Mean Percent Change From Baseline at Week 24 | High Density Lipoprotein (HDL) Cholesterol | 0 percent change |
| LPV / RTV | Lipid Mean Percent Change From Baseline at Week 24 | Fasting Low Density Lipoprotein (LDL) Cholesterol | -4 percent change |
| LPV / RTV | Lipid Mean Percent Change From Baseline at Week 24 | Total Cholesterol | 3 percent change |
Comparison: Total Cholesterol95% CI: [-15.5, -6]
Comparison: Total Cholesterol95% CI: [-16.9, -7.6]
Comparison: HDL cholesterol95% CI: [-13.6, 0.7]
Comparison: HDL Cholesterol95% CI: [-9.3, 8.1]
Comparison: Fasting LDL Cholesterol95% CI: [-15.6, 3]
Comparison: Fasting LDL Cholesterol95% CI: [-15.5, 1.8]
Comparison: Fasting Triglycerides95% CI: [-35, -13.2]
Comparison: Fasting Triglycerides95% CI: [-43.4, -23.4]
Secondary
Lipid Mean Percent Change From Baseline at Week 48
Mean percent change in total cholesterol, high density lipoprotein (HDL) cholesterol, fasting low density lipoprotein (LDL) cholesterol, and fasting triglycerides.
Time frame: Week 48
Population: Treated Participants, Last Observation Carried Forward (LOCF); as-randomized population (refers to the treatment regimen assigned at randomization).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| ATV 300 mg / RTV | Lipid Mean Percent Change From Baseline at Week 48 | Fasting LDL Cholesterol | -10 percent change in lipid values |
| ATV 300 mg / RTV | Lipid Mean Percent Change From Baseline at Week 48 | Total Cholesterol | -8 percent change in lipid values |
| ATV 300 mg / RTV | Lipid Mean Percent Change From Baseline at Week 48 | Fasting Triglycerides | -4 percent change in lipid values |
| ATV 300 mg / RTV | Lipid Mean Percent Change From Baseline at Week 48 | HDL Cholesterol | -7 percent change in lipid values |
| ATV 400 mg / SQV | Lipid Mean Percent Change From Baseline at Week 48 | Fasting LDL Cholesterol | -3 percent change in lipid values |
| ATV 400 mg / SQV | Lipid Mean Percent Change From Baseline at Week 48 | HDL Cholesterol | 4 percent change in lipid values |
| ATV 400 mg / SQV | Lipid Mean Percent Change From Baseline at Week 48 | Fasting Triglycerides | -14 percent change in lipid values |
| ATV 400 mg / SQV | Lipid Mean Percent Change From Baseline at Week 48 | Total Cholesterol | -4 percent change in lipid values |
| LPV / RTV | Lipid Mean Percent Change From Baseline at Week 48 | Fasting Triglycerides | 30 percent change in lipid values |
| LPV / RTV | Lipid Mean Percent Change From Baseline at Week 48 | Total Cholesterol | 6 percent change in lipid values |
| LPV / RTV | Lipid Mean Percent Change From Baseline at Week 48 | HDL Cholesterol | 2 percent change in lipid values |
| LPV / RTV | Lipid Mean Percent Change From Baseline at Week 48 | Fasting LDL Cholesterol | 1 percent change in lipid values |
Comparison: Total Cholesterol95% CI: [-17, -7.2]
Comparison: Total Cholesterol95% CI: [-17.4, -6.5]
Comparison: HDL Cholesterol95% CI: [-12.4, 3.5]
Comparison: HDL Cholesterol95% CI: [-11, 9.3]
Comparison: Fasting LDL CHolesterol95% CI: [-19, 1.2]
Comparison: Fasting LDL Cholesterol95% CI: [-17.7, 3]
Comparison: Fasting Triglycerides95% CI: [-41.6, -17.7]
Comparison: Fasting Triglycerides95% CI: [-49.7, -27.1]
Secondary
Lipid Mean Percent Change From Baseline at Week 96, Observed Values
Mean percent change in total cholesterol, high density lipoprotein (HDL) cholesterol, fasting low density lipoprotein (LDL) cholesterol, and fasting triglycerides.
Time frame: Week 96
Population: Treated Participants; as-randomized population (refers to the treatment regimen assigned at randomization).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| ATV 300 mg / RTV | Lipid Mean Percent Change From Baseline at Week 96, Observed Values | Fasting LDL Cholesterol (n=52, 39, 43) | -11 percent change in lipid values |
| ATV 300 mg / RTV | Lipid Mean Percent Change From Baseline at Week 96, Observed Values | Total Cholesterol (n=60, 46, 54) | -7 percent change in lipid values |
| ATV 300 mg / RTV | Lipid Mean Percent Change From Baseline at Week 96, Observed Values | HDL Cholesterol (n=60, 46, 54) | -5 percent change in lipid values |
| ATV 300 mg / RTV | Lipid Mean Percent Change From Baseline at Week 96, Observed Values | Fasting Triglycerides (n=52, 40, 43) | -2 percent change in lipid values |
| ATV 400 mg / SQV | Lipid Mean Percent Change From Baseline at Week 96, Observed Values | Total Cholesterol (n=60, 46, 54) | -1 percent change in lipid values |
| ATV 400 mg / SQV | Lipid Mean Percent Change From Baseline at Week 96, Observed Values | HDL Cholesterol (n=60, 46, 54) | 3 percent change in lipid values |
| ATV 400 mg / SQV | Lipid Mean Percent Change From Baseline at Week 96, Observed Values | Fasting LDL Cholesterol (n=52, 39, 43) | -7 percent change in lipid values |
| ATV 400 mg / SQV | Lipid Mean Percent Change From Baseline at Week 96, Observed Values | Fasting Triglycerides (n=52, 40, 43) | 4 percent change in lipid values |
| LPV / RTV | Lipid Mean Percent Change From Baseline at Week 96, Observed Values | Fasting LDL Cholesterol (n=52, 39, 43) | 1 percent change in lipid values |
| LPV / RTV | Lipid Mean Percent Change From Baseline at Week 96, Observed Values | Total Cholesterol (n=60, 46, 54) | 9 percent change in lipid values |
| LPV / RTV | Lipid Mean Percent Change From Baseline at Week 96, Observed Values | HDL Cholesterol (n=60, 46, 54) | 7 percent change in lipid values |
| LPV / RTV | Lipid Mean Percent Change From Baseline at Week 96, Observed Values | Fasting Triglycerides (n=52, 40, 43) | 30 percent change in lipid values |
Comparison: Observed values, Total Cholesterol95% CI: [-20.1, -8.3]
Comparison: observed values, total cholesterol95% CI: [-16.1, -1.3]
Comparison: observed values, HDL cholesterol95% CI: [-19.9, -1.2]
Comparison: Observed values, HDL cholesterol95% CI: [-14, 7]
Comparison: observed cases, fasting LDL95% CI: [-22.3, -1.8]
Comparison: Observed Cases, Fasting LDL cholesterol95% CI: [-19, 4.8]
Comparison: observed cases, fasting triglycerides95% CI: [-38.6, -8]
Comparison: observed cases, fasting triglycerides95% CI: [-36.5, 1.3]
Secondary
Mean ATV, RTV and SQV Minimum Concentration (Cmin) Values
The minimum or trough concentration (Cmin) of a drug observed after its administration and just prior to the administration of a subsequent dose.
Time frame: collected at the pre-dose time point after receiving atazanavir for at least four weeks
Population: Participants with evaluable Cmins; as-randomized population (refers to the treatment regimen assigned at randomization).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ATV 300 mg / RTV | Mean ATV, RTV and SQV Minimum Concentration (Cmin) Values | ATV (n=40,23) | 719.53 ng/mL | Standard Error 82.81 |
| ATV 300 mg / RTV | Mean ATV, RTV and SQV Minimum Concentration (Cmin) Values | RTV (n=40,0) | 154.83 ng/mL | Standard Error 39.31 |
| ATV 300 mg / RTV | Mean ATV, RTV and SQV Minimum Concentration (Cmin) Values | SQV (n=0,19) | NA ng/mL | — |
| ATV 400 mg / SQV | Mean ATV, RTV and SQV Minimum Concentration (Cmin) Values | ATV (n=40,23) | 312.01 ng/mL | Standard Error 145.31 |
| ATV 400 mg / SQV | Mean ATV, RTV and SQV Minimum Concentration (Cmin) Values | RTV (n=40,0) | NA ng/mL | — |
| ATV 400 mg / SQV | Mean ATV, RTV and SQV Minimum Concentration (Cmin) Values | SQV (n=0,19) | 52.15 ng/mL | Standard Error 16.89 |
Secondary
Mean Change From Baseline in HIV RNA at Week 2
Time frame: Baseline, Week 2
Population: Treated participants, as-randomized (refers to the treatment regimen assigned at randomization).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ATV 300 mg / RTV | Mean Change From Baseline in HIV RNA at Week 2 | -1.18 log10 c/mL | Standard Error 0.06 |
| ATV 400 mg / SQV | Mean Change From Baseline in HIV RNA at Week 2 | -1.14 log10 c/mL | Standard Error 0.07 |
| LPV / RTV | Mean Change From Baseline in HIV RNA at Week 2 | -1.30 log10 c/mL | Standard Error 0.06 |
95% CI: [-0.04, 0.3]
95% CI: [-0.01, 0.35]
Secondary
Mean Score of European Quality of Life-5 Dimensions (EQ-5D) Health Index Score at Baseline, Mid-Study (Week 24), and Final (Week 48)
The EQ-5D is a 5-item questionnaire to assess health-related quality of life in 5 health dimensions (mobility, self-care, usual activity, pain/discomfort, anxiety/depression) are scored on a 3-level scale: no problems (1), some problems (2), extreme problems (3). Using a standard algorithm, responses are summarized into a single score, the EQ-5D Health Index Score (HIS), which ranges between 1 (representing perfect health) and 0 (representing the worst imaginable health state or death). The smallest coefficient of change is 0.03.
Time frame: Baseline, Week 24, Week 48
Population: Treated participants; as-randomized population (refers to the treatment regimen assigned at randomization). n=number of participants evaluated with EQ-5D at given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ATV 300 mg / RTV | Mean Score of European Quality of Life-5 Dimensions (EQ-5D) Health Index Score at Baseline, Mid-Study (Week 24), and Final (Week 48) | Mid-Study (n=103, 83, 95) | 0.87 units on a scale | Standard Error 0.02 |
| ATV 300 mg / RTV | Mean Score of European Quality of Life-5 Dimensions (EQ-5D) Health Index Score at Baseline, Mid-Study (Week 24), and Final (Week 48) | Baseline (n=99, 86, 100) | 0.83 units on a scale | Standard Error 0.02 |
| ATV 300 mg / RTV | Mean Score of European Quality of Life-5 Dimensions (EQ-5D) Health Index Score at Baseline, Mid-Study (Week 24), and Final (Week 48) | Final (n=93, 84, 96) | 0.84 units on a scale | Standard Error 0.02 |
| ATV 400 mg / SQV | Mean Score of European Quality of Life-5 Dimensions (EQ-5D) Health Index Score at Baseline, Mid-Study (Week 24), and Final (Week 48) | Baseline (n=99, 86, 100) | 0.85 units on a scale | Standard Error 0.02 |
| ATV 400 mg / SQV | Mean Score of European Quality of Life-5 Dimensions (EQ-5D) Health Index Score at Baseline, Mid-Study (Week 24), and Final (Week 48) | Mid-Study (n=103, 83, 95) | 0.86 units on a scale | Standard Error 0.02 |
| ATV 400 mg / SQV | Mean Score of European Quality of Life-5 Dimensions (EQ-5D) Health Index Score at Baseline, Mid-Study (Week 24), and Final (Week 48) | Final (n=93, 84, 96) | 0.85 units on a scale | Standard Error 0.03 |
| LPV / RTV | Mean Score of European Quality of Life-5 Dimensions (EQ-5D) Health Index Score at Baseline, Mid-Study (Week 24), and Final (Week 48) | Baseline (n=99, 86, 100) | 0.86 units on a scale | Standard Error 0.02 |
| LPV / RTV | Mean Score of European Quality of Life-5 Dimensions (EQ-5D) Health Index Score at Baseline, Mid-Study (Week 24), and Final (Week 48) | Final (n=93, 84, 96) | 0.88 units on a scale | Standard Error 0.02 |
| LPV / RTV | Mean Score of European Quality of Life-5 Dimensions (EQ-5D) Health Index Score at Baseline, Mid-Study (Week 24), and Final (Week 48) | Mid-Study (n=103, 83, 95) | 0.89 units on a scale | Standard Error 0.01 |
Secondary
Mean Score of European Quality of Life-5 Dimensions (EQ-5D) Visual Analog Scale (VAS) at Baseline, Mid-Study (Week 24), and Final (Week 48)
The EQ-5D has a Visual Analog Scale (VAS), which is a feeling thermometer-like scale with a range between 0 and 100. Patients are required to draw a line from a box on the VAS scale to an actual mark on the thermometer-like scale that corresponds with a number that reflects their self-assessed health status at the time they are completing the questionnaire. Higher VAS scores indicate better overall health. There is no minimum clinically important difference reported in the literature for VAS.
Time frame: Baseline, Week 24, Week 48
Population: Treated participants; as-randomized population (refers to the treatment regimen assigned at randomization). n=number of participants evaluated with EQ-5D at given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ATV 300 mg / RTV | Mean Score of European Quality of Life-5 Dimensions (EQ-5D) Visual Analog Scale (VAS) at Baseline, Mid-Study (Week 24), and Final (Week 48) | Mid-Study (n=102, 83, 97) | 84.89 units on a scale | Standard Error 1.65 |
| ATV 300 mg / RTV | Mean Score of European Quality of Life-5 Dimensions (EQ-5D) Visual Analog Scale (VAS) at Baseline, Mid-Study (Week 24), and Final (Week 48) | Baseline (n=98, 85, 101) | 81.33 units on a scale | Standard Error 1.63 |
| ATV 300 mg / RTV | Mean Score of European Quality of Life-5 Dimensions (EQ-5D) Visual Analog Scale (VAS) at Baseline, Mid-Study (Week 24), and Final (Week 48) | Final (n=95, 81, 96) | 82.77 units on a scale | Standard Error 1.72 |
| ATV 400 mg / SQV | Mean Score of European Quality of Life-5 Dimensions (EQ-5D) Visual Analog Scale (VAS) at Baseline, Mid-Study (Week 24), and Final (Week 48) | Mid-Study (n=102, 83, 97) | 83.34 units on a scale | Standard Error 1.89 |
| ATV 400 mg / SQV | Mean Score of European Quality of Life-5 Dimensions (EQ-5D) Visual Analog Scale (VAS) at Baseline, Mid-Study (Week 24), and Final (Week 48) | Baseline (n=98, 85, 101) | 81.72 units on a scale | Standard Error 1.77 |
| ATV 400 mg / SQV | Mean Score of European Quality of Life-5 Dimensions (EQ-5D) Visual Analog Scale (VAS) at Baseline, Mid-Study (Week 24), and Final (Week 48) | Final (n=95, 81, 96) | 85.80 units on a scale | Standard Error 1.64 |
| LPV / RTV | Mean Score of European Quality of Life-5 Dimensions (EQ-5D) Visual Analog Scale (VAS) at Baseline, Mid-Study (Week 24), and Final (Week 48) | Baseline (n=98, 85, 101) | 81.52 units on a scale | Standard Error 1.53 |
| LPV / RTV | Mean Score of European Quality of Life-5 Dimensions (EQ-5D) Visual Analog Scale (VAS) at Baseline, Mid-Study (Week 24), and Final (Week 48) | Final (n=95, 81, 96) | 86.16 units on a scale | Standard Error 1.36 |
| LPV / RTV | Mean Score of European Quality of Life-5 Dimensions (EQ-5D) Visual Analog Scale (VAS) at Baseline, Mid-Study (Week 24), and Final (Week 48) | Mid-Study (n=102, 83, 97) | 85.09 units on a scale | Standard Error 1.55 |
Secondary
Most Common AEs and AEs of Interest Through Week 48
Prespecified AEs of interest included jaundice, ocular icterus, and hyperbilirubinemia.
Time frame: From Enrollment to Week 48
Population: Treated participants; as-randomized population (refers to the treatment regimen assigned at randomization).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| ATV 300 mg / RTV | Most Common AEs and AEs of Interest Through Week 48 | Diarrhea (Most Common) | 25 participants |
| ATV 300 mg / RTV | Most Common AEs and AEs of Interest Through Week 48 | Headache (Most Common) | 21 participants |
| ATV 300 mg / RTV | Most Common AEs and AEs of Interest Through Week 48 | Nausea (Most Common) | 19 participants |
| ATV 300 mg / RTV | Most Common AEs and AEs of Interest Through Week 48 | Jaundice (AE of Interest) | 19 participants |
| ATV 300 mg / RTV | Most Common AEs and AEs of Interest Through Week 48 | Ocular Icterus (AE of Interest) | 13 participants |
| ATV 300 mg / RTV | Most Common AEs and AEs of Interest Through Week 48 | Hyperbilirubinemia (AE of Interest) | 24 participants |
| ATV 400 mg / SQV | Most Common AEs and AEs of Interest Through Week 48 | Hyperbilirubinemia (AE of Interest) | 8 participants |
| ATV 400 mg / SQV | Most Common AEs and AEs of Interest Through Week 48 | Diarrhea (Most Common) | 29 participants |
| ATV 400 mg / SQV | Most Common AEs and AEs of Interest Through Week 48 | Jaundice (AE of Interest) | 6 participants |
| ATV 400 mg / SQV | Most Common AEs and AEs of Interest Through Week 48 | Ocular Icterus (AE of Interest) | 3 participants |
| ATV 400 mg / SQV | Most Common AEs and AEs of Interest Through Week 48 | Headache (Most Common) | 24 participants |
| ATV 400 mg / SQV | Most Common AEs and AEs of Interest Through Week 48 | Nausea (Most Common) | 24 participants |
| LPV / RTV | Most Common AEs and AEs of Interest Through Week 48 | Headache (Most Common) | 18 participants |
| LPV / RTV | Most Common AEs and AEs of Interest Through Week 48 | Nausea (Most Common) | 15 participants |
| LPV / RTV | Most Common AEs and AEs of Interest Through Week 48 | Hyperbilirubinemia (AE of Interest) | 1 participants |
| LPV / RTV | Most Common AEs and AEs of Interest Through Week 48 | Jaundice (AE of Interest) | 0 participants |
| LPV / RTV | Most Common AEs and AEs of Interest Through Week 48 | Diarrhea (Most Common) | 54 participants |
| LPV / RTV | Most Common AEs and AEs of Interest Through Week 48 | Ocular Icterus (AE of Interest) | 0 participants |
Secondary
Number of Participants Utilizing Resources for Managing Lipid Elevation
Participants' overall resource utilization for managing lipid elevation that includes the management of side effects of lipid lowering medications, such as those due to drug interactions.
Time frame: Baseline, Week 24, Week 48
Population: Although the intent of this planned analysis was to provide a model of economic value for Lipid Management, a different approach was taken to create this model which did not require data from this trial, and thus this analysis was not done.
Secondary
Participants Achieving Treatment Response (LOQ = 400 c/mL) Without Prior Failure at Week 24
Treatment Response = confirmed suppression to LOQ (400 c/mL). The Algorithm for Treatment Response Without Prior Failure (TRPWF) = participants staying in response at the analysis timepoint without having an intervening, confirmed rebound.
Time frame: Week 24
Population: Randomized participants while on initial regimen Randomized participants, (completers censored).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ATV 300 mg / RTV | Participants Achieving Treatment Response (LOQ = 400 c/mL) Without Prior Failure at Week 24 | 76 participants |
| ATV 400 mg / SQV | Participants Achieving Treatment Response (LOQ = 400 c/mL) Without Prior Failure at Week 24 | 50 participants |
| LPV / RTV | Participants Achieving Treatment Response (LOQ = 400 c/mL) Without Prior Failure at Week 24 | 74 participants |
95% CI: [-9.1, 15.4]
95% CI: [-29.4, -4]
Secondary
Participants Achieving Treatment Response (LOQ = 400 c/mL) Without Prior Failure at Week 48
Treatment Response = confirmed suppression to LOQ (400 c/mL). The Algorithm for Treatment Response Without Prior Failure (TRPWF) = participants staying in response at the analysis timepoint without having an intervening, confirmed rebound.
Time frame: Week 48
Population: Randomized participants, as-randomized population (refers to the treatment regimen assigned at randomization).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ATV 300 mg / RTV | Participants Achieving Treatment Response (LOQ = 400 c/mL) Without Prior Failure at Week 48 | 64 participants |
| ATV 400 mg / SQV | Participants Achieving Treatment Response (LOQ = 400 c/mL) Without Prior Failure at Week 48 | 42 participants |
| LPV / RTV | Participants Achieving Treatment Response (LOQ = 400 c/mL) Without Prior Failure at Week 48 | 67 participants |
95% CI: [-13.7, 11.4]
95% CI: [-30.6, -5.3]
Secondary
Participants Achieving Treatment Response (LOQ = 400 c/mL) Without Prior Failure at Week 96
Treatment Response = confirmed suppression to LOQ (400 c/mL). The Algorithm for Treatment Response Without Prior Failure (TRPWF) = participants staying in response at the analysis timepoint without having an intervening, confirmed rebound.
Time frame: Week 96
Population: Randomized participants while on initial regimen (completers censored).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ATV 300 mg / RTV | Participants Achieving Treatment Response (LOQ = 400 c/mL) Without Prior Failure at Week 96 | 52 participants |
| ATV 400 mg / SQV | Participants Achieving Treatment Response (LOQ = 400 c/mL) Without Prior Failure at Week 96 | 53 participants |
95% CI: [-15, 10.3]Chi-squared, Corrected
Secondary
Participants Achieving Treatment Response (LOQ = 50 c/mL) Without Prior Failure at Week 24
Treatment Response = confirmed suppression to LOQ (50 c/mL). The Algorithm for Treatment Response Without Prior Failure (TRPWF) = participants staying in response at the analysis timepoint without having an intervening, confirmed rebound.
Time frame: Week 24
Population: Randomized participants, as-randomized population (refers to the treatment regimen assigned at randomization).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ATV 300 mg / RTV | Participants Achieving Treatment Response (LOQ = 50 c/mL) Without Prior Failure at Week 24 | 46 participants |
| ATV 400 mg / SQV | Participants Achieving Treatment Response (LOQ = 50 c/mL) Without Prior Failure at Week 24 | 25 participants |
| LPV / RTV | Participants Achieving Treatment Response (LOQ = 50 c/mL) Without Prior Failure at Week 24 | 50 participants |
95% CI: [-14.6, 10]
95% CI: [-30.7, -7.1]
Secondary
Participants Achieving Treatment Response (LOQ = 50 c/mL) Without Prior Failure at Week 48
Treatment Response = confirmed suppression to LOQ (50 c/mL). The Algorithm for Treatment Response Without Prior Failure (TRPWF) = participants staying in response at the analysis timepoint without having an intervening, confirmed rebound.
Time frame: Week 48
Population: Randomized participantsRandomized participants while on initial regimen (completers censored).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ATV 300 mg / RTV | Participants Achieving Treatment Response (LOQ = 50 c/mL) Without Prior Failure at Week 48 | 43 participants |
| ATV 400 mg / SQV | Participants Achieving Treatment Response (LOQ = 50 c/mL) Without Prior Failure at Week 48 | 28 participants |
| LPV / RTV | Participants Achieving Treatment Response (LOQ = 50 c/mL) Without Prior Failure at Week 48 | 52 participants |
95% CI: [-18.7, 5.8]
95% CI: [-29.9, -5.9]
Secondary
Participants Achieving Treatment Response (LOQ = 50 c/mL) Without Prior Failure at Week 96
Treatment Response = confirmed suppression to LOQ (50 c/mL). The Algorithm for Treatment Response Without Prior Failure (TRPWF) = participants staying in response at the analysis timepoint without having an intervening, confirmed rebound.
Time frame: Week 96
Population: Randomized participants while on initial regimen (completers censored)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ATV 300 mg / RTV | Participants Achieving Treatment Response (LOQ = 50 c/mL) Without Prior Failure at Week 96 | 38 participants |
| ATV 400 mg / SQV | Participants Achieving Treatment Response (LOQ = 50 c/mL) Without Prior Failure at Week 96 | 41 participants |
Secondary
Participants Achieving Virologic Half Log Suppression (Limit of Quantification [LOQ] = 400 c/mL) at Week 24 (Overall and by Protease Inhibitor [PI] Sensitivity)
Number of participants with a \>=0.5 log10 decrease in HIV RNA from baseline or HIV RNA \< 400 c/mL at Week 24, by their baseline phenotypic sensitivity to their randomized PI.
Time frame: Baseline, Week 24
Population: Number of Participants Analyzed=Randomized participants; as-randomized population (refers to the treatment regimen assigned at randomization); n=number of evaluable (overall, PI sensitive, PI resistant) participants.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| ATV 300 mg / RTV | Participants Achieving Virologic Half Log Suppression (Limit of Quantification [LOQ] = 400 c/mL) at Week 24 (Overall and by Protease Inhibitor [PI] Sensitivity) | PI Sensitive (n=88, 83, 88) | 79 participants |
| ATV 300 mg / RTV | Participants Achieving Virologic Half Log Suppression (Limit of Quantification [LOQ] = 400 c/mL) at Week 24 (Overall and by Protease Inhibitor [PI] Sensitivity) | Overall (n=120, 115, 123) | 95 participants |
| ATV 300 mg / RTV | Participants Achieving Virologic Half Log Suppression (Limit of Quantification [LOQ] = 400 c/mL) at Week 24 (Overall and by Protease Inhibitor [PI] Sensitivity) | PI Resistant (n=32, 30, 33) | 16 participants |
| ATV 400 mg / SQV | Participants Achieving Virologic Half Log Suppression (Limit of Quantification [LOQ] = 400 c/mL) at Week 24 (Overall and by Protease Inhibitor [PI] Sensitivity) | PI Sensitive (n=88, 83, 88) | 58 participants |
| ATV 400 mg / SQV | Participants Achieving Virologic Half Log Suppression (Limit of Quantification [LOQ] = 400 c/mL) at Week 24 (Overall and by Protease Inhibitor [PI] Sensitivity) | Overall (n=120, 115, 123) | 74 participants |
| ATV 400 mg / SQV | Participants Achieving Virologic Half Log Suppression (Limit of Quantification [LOQ] = 400 c/mL) at Week 24 (Overall and by Protease Inhibitor [PI] Sensitivity) | PI Resistant (n=32, 30, 33) | 15 participants |
| LPV / RTV | Participants Achieving Virologic Half Log Suppression (Limit of Quantification [LOQ] = 400 c/mL) at Week 24 (Overall and by Protease Inhibitor [PI] Sensitivity) | Overall (n=120, 115, 123) | 93 participants |
| LPV / RTV | Participants Achieving Virologic Half Log Suppression (Limit of Quantification [LOQ] = 400 c/mL) at Week 24 (Overall and by Protease Inhibitor [PI] Sensitivity) | PI Resistant (n=32, 30, 33) | 19 participants |
| LPV / RTV | Participants Achieving Virologic Half Log Suppression (Limit of Quantification [LOQ] = 400 c/mL) at Week 24 (Overall and by Protease Inhibitor [PI] Sensitivity) | PI Sensitive (n=88, 83, 88) | 72 participants |
Secondary
Participants Achieving Virologic Half Log Suppression (LOQ = 400 c/mL) at Week 48, (Overall and by PI Sensitivity)
Number of participants with a \>=0.5 log10 decrease in HIV RNA from baseline or HIV RNA \< 400 c/mL at Week 48, by their baseline phenotypic sensitivity to their randomized PI.
Time frame: Baseline, Week 48
Population: Number of Participants Analyzed=Randomized participants; as-randomized population (refers to the treatment regimen assigned at randomization).n=number of evaluable (overall, PI sensitive, PI resistant) participants.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| ATV 300 mg / RTV | Participants Achieving Virologic Half Log Suppression (LOQ = 400 c/mL) at Week 48, (Overall and by PI Sensitivity) | PI Sensitive (n=88, 84, 88) | 65 participants |
| ATV 300 mg / RTV | Participants Achieving Virologic Half Log Suppression (LOQ = 400 c/mL) at Week 48, (Overall and by PI Sensitivity) | Overall (n=120, 115, 123) | 77 participants |
| ATV 300 mg / RTV | Participants Achieving Virologic Half Log Suppression (LOQ = 400 c/mL) at Week 48, (Overall and by PI Sensitivity) | PI Resistant (n=32, 30, 33) | 12 participants |
| ATV 400 mg / SQV | Participants Achieving Virologic Half Log Suppression (LOQ = 400 c/mL) at Week 48, (Overall and by PI Sensitivity) | PI Sensitive (n=88, 84, 88) | 52 participants |
| ATV 400 mg / SQV | Participants Achieving Virologic Half Log Suppression (LOQ = 400 c/mL) at Week 48, (Overall and by PI Sensitivity) | Overall (n=120, 115, 123) | 60 participants |
| ATV 400 mg / SQV | Participants Achieving Virologic Half Log Suppression (LOQ = 400 c/mL) at Week 48, (Overall and by PI Sensitivity) | PI Resistant (n=32, 30, 33) | 7 participants |
| LPV / RTV | Participants Achieving Virologic Half Log Suppression (LOQ = 400 c/mL) at Week 48, (Overall and by PI Sensitivity) | Overall (n=120, 115, 123) | 84 participants |
| LPV / RTV | Participants Achieving Virologic Half Log Suppression (LOQ = 400 c/mL) at Week 48, (Overall and by PI Sensitivity) | PI Resistant (n=32, 30, 33) | 16 participants |
| LPV / RTV | Participants Achieving Virologic Half Log Suppression (LOQ = 400 c/mL) at Week 48, (Overall and by PI Sensitivity) | PI Sensitive (n=88, 84, 88) | 67 participants |
Secondary
Participants Achieving Virologic Half Log Suppression (LOQ = 400 c/mL) at Week 96
Number of participants with a \>=0.5 log10 decrease in HIV RNA from baseline or HIV RNA \< 400 c/mL at Week 96.
Time frame: Baseline, Week 96
Population: Observed case analysis: Randomized participants (while on initial regimen--completers censored) with baseline and on-study measurement.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ATV 300 mg / RTV | Participants Achieving Virologic Half Log Suppression (LOQ = 400 c/mL) at Week 96 | 61 participants |
| ATV 400 mg / SQV | Participants Achieving Virologic Half Log Suppression (LOQ = 400 c/mL) at Week 96 | 58 participants |
Comparison: Randomized participants95% CI: [-13.3, 12.3]
Secondary
Participants Achieving Virologic Half Log Suppression (LOQ = 50 c/mL) at Week 24
Time frame: Week 24
Population: Randomized participants; as-randomized population (refers to the treatment regimen assigned at randomization).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ATV 300 mg / RTV | Participants Achieving Virologic Half Log Suppression (LOQ = 50 c/mL) at Week 24 | 95 participants |
| ATV 400 mg / SQV | Participants Achieving Virologic Half Log Suppression (LOQ = 50 c/mL) at Week 24 | 74 participants |
| LPV / RTV | Participants Achieving Virologic Half Log Suppression (LOQ = 50 c/mL) at Week 24 | 93 participants |
95% CI: [-7, 14.1]
95% CI: [-22.9, 0.4]
Secondary
Participants Achieving Virologic Half Log Suppression (LOQ = 50 c/mL) at Week 24, by PI Sensitivity
Number of participants with a \>=0.5 log10 decrease in HIV RNA from baseline or HIV RNA \< 50 c/mL at Week 24, by their baseline phenotypic sensitivity to their randomized PI.
Time frame: Baseline, Week 24
Population: As there were multiple efficacy algorithms run and multiple subsets analyzed, it was decided to only use LOQ \< 50 on the primary endpoint, and to run LOQ\<400 for subsets such as baseline PI sensitivity.
Secondary
Participants Achieving Virologic Half Log Suppression (LOQ = 50 c/mL) at Week 48
Time frame: Week 48
Population: Randomized participants; as-randomized population (refers to the treatment regimen assigned at randomization).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ATV 300 mg / RTV | Participants Achieving Virologic Half Log Suppression (LOQ = 50 c/mL) at Week 48 | 76 Participants |
| ATV 400 mg / SQV | Participants Achieving Virologic Half Log Suppression (LOQ = 50 c/mL) at Week 48 | 60 Participants |
| LPV / RTV | Participants Achieving Virologic Half Log Suppression (LOQ = 50 c/mL) at Week 48 | 84 Participants |
95% CI: [-16.9, 7]
95% CI: [-28.5, -3.7]
Secondary
Participants Achieving Virologic Half Log Suppression (LOQ = 50 c/mL) at Week 48, by PI Sensitivity
Number of participants with a \>=0.5 log10 decrease in HIV RNA from baseline or HIV RNA \< 50 c/mL at Week 48, by their baseline phenotypic sensitivity to their randomized PI.
Time frame: Baseline, Week 48
Population: As there were multiple efficacy algorithms run and multiple subsets analyzed, it was decided to only use LOQ \< 50 on the primary endpoint, and to run LOQ\<400 for subsets such as baseline PI sensitivity.
Secondary
Participants Achieving Virologic Half Log Suppression (LOQ = 50 c/mL) at Week 96
Time frame: Week 96
Population: Randomized participants while on initial regimen (completers censored).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ATV 300 mg / RTV | Participants Achieving Virologic Half Log Suppression (LOQ = 50 c/mL) at Week 96 | 61 Participants |
| ATV 400 mg / SQV | Participants Achieving Virologic Half Log Suppression (LOQ = 50 c/mL) at Week 96 | 57 Participants |
95% CI: [-12.5, 13.2]
Secondary
PR Interval and Change From Baseline by Analysis Time Point
The PR interval is measured from the beginning of the P wave to the beginning of the QRS complex, and reflects the time the electrical impulse takes to travel from the sinus node through the atrioventricular (AV) node and entering the ventricles. The PR interval is therefore a good estimate of AV node function.
Time frame: Baseline, Week 4 predose, 2-3 hours postdose, 6-12 hours postdose, Week 12, Week 24, Week 48
Population: Treated participants; as-randomized population (refers to the treatment regimen assigned at randomization). n=number of participants evaluated at timepoint
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ATV 300 mg / RTV | PR Interval and Change From Baseline by Analysis Time Point | Mean Change at Week 48 (n=89, 75, 97) | 0 msec | Standard Error 1.5 |
| ATV 300 mg / RTV | PR Interval and Change From Baseline by Analysis Time Point | Mean Change Wk 4 2-3 hrs postdose (n=113,102,106) | 1 msec | Standard Error 1.3 |
| ATV 300 mg / RTV | PR Interval and Change From Baseline by Analysis Time Point | Mean Change at Week 24 (n=108, 92, 109) | 2 msec | Standard Error 1.3 |
| ATV 300 mg / RTV | PR Interval and Change From Baseline by Analysis Time Point | Mean Change at Week 4 predose (n=117, 104, 110) | 4 msec | Standard Error 1.2 |
| ATV 300 mg / RTV | PR Interval and Change From Baseline by Analysis Time Point | Mean Change Wk 4 6-12 hrs postdose (n=112,101,105) | 2 msec | Standard Error 1.4 |
| ATV 300 mg / RTV | PR Interval and Change From Baseline by Analysis Time Point | Baseline Mean (n=119, 110, 118) | 153 msec | Standard Error 1.7 |
| ATV 300 mg / RTV | PR Interval and Change From Baseline by Analysis Time Point | Mean Change at Week 12 (n=110, 97, 107) | 5 msec | Standard Error 1.6 |
| ATV 400 mg / SQV | PR Interval and Change From Baseline by Analysis Time Point | Mean Change at Week 4 predose (n=117, 104, 110) | 9 msec | Standard Error 1.6 |
| ATV 400 mg / SQV | PR Interval and Change From Baseline by Analysis Time Point | Mean Change at Week 24 (n=108, 92, 109) | 7 msec | Standard Error 1.7 |
| ATV 400 mg / SQV | PR Interval and Change From Baseline by Analysis Time Point | Mean Change Wk 4 6-12 hrs postdose (n=112,101,105) | 6 msec | Standard Error 1.7 |
| ATV 400 mg / SQV | PR Interval and Change From Baseline by Analysis Time Point | Mean Change at Week 48 (n=89, 75, 97) | 2 msec | Standard Error 1.9 |
| ATV 400 mg / SQV | PR Interval and Change From Baseline by Analysis Time Point | Baseline Mean (n=119, 110, 118) | 155 msec | Standard Error 1.9 |
| ATV 400 mg / SQV | PR Interval and Change From Baseline by Analysis Time Point | Mean Change Wk 4 2-3 hrs postdose (n=113,102,106) | 6 msec | Standard Error 1.6 |
| ATV 400 mg / SQV | PR Interval and Change From Baseline by Analysis Time Point | Mean Change at Week 12 (n=110, 97, 107) | 7 msec | Standard Error 1.7 |
| LPV / RTV | PR Interval and Change From Baseline by Analysis Time Point | Mean Change at Week 48 (n=89, 75, 97) | 4 msec | Standard Error 1.7 |
| LPV / RTV | PR Interval and Change From Baseline by Analysis Time Point | Baseline Mean (n=119, 110, 118) | 154 msec | Standard Error 1.7 |
| LPV / RTV | PR Interval and Change From Baseline by Analysis Time Point | Mean Change Wk 4 2-3 hrs postdose (n=113,102,106) | 1 msec | Standard Error 1.7 |
| LPV / RTV | PR Interval and Change From Baseline by Analysis Time Point | Mean Change Wk 4 6-12 hrs postdose (n=112,101,105) | 2 msec | Standard Error 1.5 |
| LPV / RTV | PR Interval and Change From Baseline by Analysis Time Point | Mean Change at Week 12 (n=110, 97, 107) | 8 msec | Standard Error 1.4 |
| LPV / RTV | PR Interval and Change From Baseline by Analysis Time Point | Mean Change at Week 24 (n=108, 92, 109) | 5 msec | Standard Error 1.6 |
| LPV / RTV | PR Interval and Change From Baseline by Analysis Time Point | Mean Change at Week 4 predose (n=117, 104, 110) | 3 msec | Standard Error 1.4 |