HIV Infections
Conditions
Brief summary
This 2 arm study will evaluate the efficacy, safety and tolerability of saquinavir/ritonavir or lopinavir/ritonavir in combination with emtricitabine/tenofovir in patients with human immunodeficiency virus type 1 (HIV-1) infection who have received no prior HIV treatment. Patients will be randomized to receive either saquinavir/ritonavir 1000/100mg oral (po) twice daily (bid) + emtricitabine/tenofovir 200/300mg po once daily (qd), or lopinavir/ritonavir 400/100mg po bid + emtricitabine/tenofovir 200/300mg po qd. The anticipated time on study treatment is 3-12 months, and the target sample size is 100-500 individuals.
Interventions
1000 milligram (mg) Oral (po) twice daily (bid)
DRUGLopinavir/ritonavir
Lopinavir/ritonavir 400/100 mg po bid
DRUGEmtricitabine/tenofovir disoproxil fumarate
Emtricitabine/tenofovir disoproxil fumarate 200/300 mg po qd
DRUGRitonavir
100 mg po bid
Sponsors
Hoffmann-La Roche
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* adult patients \>=18 years of age; * chronic HIV-1 infection; * treatment-naive; * HIV-1 RNA viral load \>=10,000copies/mL; * women of childbearing potential must have a negative pregnancy test, and must use reliable contraception for the duration of the study and for 90 days after the last dose of study medication.
Exclusion criteria
* females who are pregnant or breastfeeding; * active hepatitis B infection; * previous treatment with antiretroviral medication; * patients who have received an investigational drug within the last 4 weeks.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients With Human Immunodeficiency Virus Type 1 (HIV-1) Ribonucleic Acid (RNA) Viral Load <50 Copies/mL | Week 48 | The primary objective of this study was to evaluate the efficacy of saquinavir/ritonavir BID plus emtricitabine/tenofovir QD versus lopinavir/ritonavir BID plus emtricitabine/tenofovir QD in treatment-naïve HIV-1 infected adults. Blood samples for HIV-1 RNA viral load measurement were collected at the Week 48 clinic visit. The number of participants with HIV-1 RNA results \<50 copies/mL is reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in HIV-1 RNA Viral Load | Baseline to Week 48 | Descriptive statistics for change from baseline in log10 transformed plasma HIV-1 RNA load (copies/mL) were presented by treatment arm. Logarithmic transformation (base 10) was applied to HIV-1 RNA viral load at baseline and at each study visit. Change from baseline in plasma HIV-1 RNA was derived as follows: Change from baseline = Log10 (HIV-1 RNA at week x) - Log10 (HIV-1 RNA at baseline) |
| Number of Patients With HIV-1 RNA Viral Load <50 and <400 Copies/mL | Week 48 | The secondary objectives of the study were to evaluate the safety, adherence, and tolerability of saquinavir/ritonavir BID plus emtricitabine/tenofovir QD versus lopinavir/ritonavir BID plus emtricitabine/tenofovir QD in treatment-naïve HIV-1 infected adults. Blood samples for HIV-1 RNA viral load measurement were collected at the Week 48 clinic visit. The number of participants with HIV-1 RNA results \<50 copies/mL and the number of participants with HIV-1 RNA results \<400 copies/mL are reported. |
| Change From Baseline in Cluster Differentiation Antigen 4 Positive (CD4+) Lymphocyte Count | Baseline to Week 48 | Summary statistics for change from baseline in CD4+ lymphocyte count were presented by treatment arm. Change from baseline in CD4+ lymphocyte count was derived as follows: Change from baseline = (CD4+ count at week x) - (CD4+ count at baseline). |
| Number of Participants Assessed for Adverse Events (AEs) | reported up to 28 days after the last dose of study treatment. (Up to 52 weeks) | Detailed information for Adverse Events and Serious Adverse Events will be represented in the SAE/AE section of PRS. |
| Number of Patients Who Discontinued Treatment Due to Abnormal Laboratory Parameters | baseline and all study visits (Up to Week 52) | Routine clinical testing, including hematology and standard chemistry panel was performed at all study visits. Laboratory tests for a fasting lipid profile and fasting insulin determination were obtained at baseline, weeks 24 and 48, and the 4-week follow-up visit. The number of participants who discontinued treatment due to an abnormal laboratory result at any visit is reported. |
Countries
Canada, France, Puerto Rico, Thailand, United States
Participant flow
Recruitment details
This study was conducted between 28 April 2005 and 24 August 2007 at 38 study centers in the United States, Canada, France and Thailand. Patients were randomized to receive saquinavir/ritonavir 1000/100 mg PO BID plus emtricitabine/tenofovir 200/300 mg PO QD or lopinavir/ritonavir 400/100 mg PO BID plus emtricitabine/tenofovir 200/300 mg PO QD .
Participants by arm
| Arm | Count |
|---|---|
| Saquinavir/Ritonavir saquinavir mesylate 1000 mg twice daily (BID) + ritonavir 100 mg BID + emtricitabine/tenofovir disoproxil fumarate 200/300 mg orally every day for 48 weeks. | 167 |
| Lopinavir/Ritonavir lopinavir/ritonavir 400/100 mg BID + emtricitabine/tenofovir disoproxil fumarate 200/300 mg orally every day for 48 weeks. | 170 |
| Total | 337 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 5 | 12 |
| Overall Study | Death | 3 | 1 |
| Overall Study | Lack of Efficacy | 9 | 3 |
| Overall Study | Lost to Follow-up | 12 | 12 |
| Overall Study | Other | 3 | 1 |
| Overall Study | Protocol Violation | 1 | 0 |
| Overall Study | Refused treatment | 6 | 4 |
| Overall Study | Violation of selection criteria at entry | 0 | 2 |
Baseline characteristics
| Characteristic | Saquinavir/Ritonavir | Lopinavir/Ritonavir | Total |
|---|---|---|---|
| Age Continuous | 38.3 years STANDARD_DEVIATION 9.31 | 37.9 years STANDARD_DEVIATION 9.6 | 38.1 years STANDARD_DEVIATION 9.45 |
| Sex: Female, Male Female | 31 Participants | 39 Participants | 70 Participants |
| Sex: Female, Male Male | 136 Participants | 131 Participants | 267 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 76 / 163 | 92 / 168 |
| serious Total, serious adverse events | 24 / 163 | 19 / 168 |
Outcome results
Primary
Number of Patients With Human Immunodeficiency Virus Type 1 (HIV-1) Ribonucleic Acid (RNA) Viral Load <50 Copies/mL
The primary objective of this study was to evaluate the efficacy of saquinavir/ritonavir BID plus emtricitabine/tenofovir QD versus lopinavir/ritonavir BID plus emtricitabine/tenofovir QD in treatment-naïve HIV-1 infected adults. Blood samples for HIV-1 RNA viral load measurement were collected at the Week 48 clinic visit. The number of participants with HIV-1 RNA results \<50 copies/mL is reported.
Time frame: Week 48
Population: intent-to-treat (ITT) Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Saquinavir/Ritonavir | Number of Patients With Human Immunodeficiency Virus Type 1 (HIV-1) Ribonucleic Acid (RNA) Viral Load <50 Copies/mL | Pts. with HIV-1 RNA Viral Load <50 copies/mL - YES | 108 participants |
| Saquinavir/Ritonavir | Number of Patients With Human Immunodeficiency Virus Type 1 (HIV-1) Ribonucleic Acid (RNA) Viral Load <50 Copies/mL | Pts. with HIV-1 RNA Viral Load <50 copies/mL - NO | 59 participants |
| Lopinavir/Ritonavir | Number of Patients With Human Immunodeficiency Virus Type 1 (HIV-1) Ribonucleic Acid (RNA) Viral Load <50 Copies/mL | Pts. with HIV-1 RNA Viral Load <50 copies/mL - YES | 108 participants |
| Lopinavir/Ritonavir | Number of Patients With Human Immunodeficiency Virus Type 1 (HIV-1) Ribonucleic Acid (RNA) Viral Load <50 Copies/mL | Pts. with HIV-1 RNA Viral Load <50 copies/mL - NO | 62 participants |
Secondary
Change From Baseline in Cluster Differentiation Antigen 4 Positive (CD4+) Lymphocyte Count
Summary statistics for change from baseline in CD4+ lymphocyte count were presented by treatment arm. Change from baseline in CD4+ lymphocyte count was derived as follows: Change from baseline = (CD4+ count at week x) - (CD4+ count at baseline).
Time frame: Baseline to Week 48
Population: ITT Population. (n) in each of the categories is the number of participants from the ITT population who had data available at that time point.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Saquinavir/Ritonavir | Change From Baseline in Cluster Differentiation Antigen 4 Positive (CD4+) Lymphocyte Count | Baseline (n=166,169) | 141.5 cells/mm^3 |
| Saquinavir/Ritonavir | Change From Baseline in Cluster Differentiation Antigen 4 Positive (CD4+) Lymphocyte Count | Week 48 (n=122,131) | 319.0 cells/mm^3 |
| Saquinavir/Ritonavir | Change From Baseline in Cluster Differentiation Antigen 4 Positive (CD4+) Lymphocyte Count | Change from Baseline to Week 48 (n=121,130) | 178.0 cells/mm^3 |
| Lopinavir/Ritonavir | Change From Baseline in Cluster Differentiation Antigen 4 Positive (CD4+) Lymphocyte Count | Baseline (n=166,169) | 142.0 cells/mm^3 |
| Lopinavir/Ritonavir | Change From Baseline in Cluster Differentiation Antigen 4 Positive (CD4+) Lymphocyte Count | Week 48 (n=122,131) | 348.0 cells/mm^3 |
| Lopinavir/Ritonavir | Change From Baseline in Cluster Differentiation Antigen 4 Positive (CD4+) Lymphocyte Count | Change from Baseline to Week 48 (n=121,130) | 204.0 cells/mm^3 |
Secondary
Change From Baseline in HIV-1 RNA Viral Load
Descriptive statistics for change from baseline in log10 transformed plasma HIV-1 RNA load (copies/mL) were presented by treatment arm. Logarithmic transformation (base 10) was applied to HIV-1 RNA viral load at baseline and at each study visit. Change from baseline in plasma HIV-1 RNA was derived as follows: Change from baseline = Log10 (HIV-1 RNA at week x) - Log10 (HIV-1 RNA at baseline)
Time frame: Baseline to Week 48
Population: ITT Population. (n) in each of the categories is the number of participants from the ITT population who had data available at that time point.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Saquinavir/Ritonavir | Change From Baseline in HIV-1 RNA Viral Load | Baseline | 5.20 copies/mL |
| Saquinavir/Ritonavir | Change From Baseline in HIV-1 RNA Viral Load | Week 48 (n=126,133) | 1.80 copies/mL |
| Saquinavir/Ritonavir | Change From Baseline in HIV-1 RNA Viral Load | Change from Baseline to Week 48 (n=126,133) | -3.39 copies/mL |
| Lopinavir/Ritonavir | Change From Baseline in HIV-1 RNA Viral Load | Baseline | 5.17 copies/mL |
| Lopinavir/Ritonavir | Change From Baseline in HIV-1 RNA Viral Load | Week 48 (n=126,133) | 1.83 copies/mL |
| Lopinavir/Ritonavir | Change From Baseline in HIV-1 RNA Viral Load | Change from Baseline to Week 48 (n=126,133) | -3.36 copies/mL |
Secondary
Number of Participants Assessed for Adverse Events (AEs)
Detailed information for Adverse Events and Serious Adverse Events will be represented in the SAE/AE section of PRS.
Time frame: reported up to 28 days after the last dose of study treatment. (Up to 52 weeks)
Population: Safety population included all randomized patients who received at least one dose of study medication
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Saquinavir/Ritonavir | Number of Participants Assessed for Adverse Events (AEs) | 163 participants |
| Lopinavir/Ritonavir | Number of Participants Assessed for Adverse Events (AEs) | 168 participants |
Secondary
Number of Patients Who Discontinued Treatment Due to Abnormal Laboratory Parameters
Routine clinical testing, including hematology and standard chemistry panel was performed at all study visits. Laboratory tests for a fasting lipid profile and fasting insulin determination were obtained at baseline, weeks 24 and 48, and the 4-week follow-up visit. The number of participants who discontinued treatment due to an abnormal laboratory result at any visit is reported.
Time frame: baseline and all study visits (Up to Week 52)
Population: Safety population included all randomized patients who received at least one dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Saquinavir/Ritonavir | Number of Patients Who Discontinued Treatment Due to Abnormal Laboratory Parameters | 0 participants |
| Lopinavir/Ritonavir | Number of Patients Who Discontinued Treatment Due to Abnormal Laboratory Parameters | 0 participants |
Secondary
Number of Patients With HIV-1 RNA Viral Load <50 and <400 Copies/mL
The secondary objectives of the study were to evaluate the safety, adherence, and tolerability of saquinavir/ritonavir BID plus emtricitabine/tenofovir QD versus lopinavir/ritonavir BID plus emtricitabine/tenofovir QD in treatment-naïve HIV-1 infected adults. Blood samples for HIV-1 RNA viral load measurement were collected at the Week 48 clinic visit. The number of participants with HIV-1 RNA results \<50 copies/mL and the number of participants with HIV-1 RNA results \<400 copies/mL are reported.
Time frame: Week 48
Population: Intent-to-Treat Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Saquinavir/Ritonavir | Number of Patients With HIV-1 RNA Viral Load <50 and <400 Copies/mL | Patients with <50 Copies/mL | 108 participants |
| Saquinavir/Ritonavir | Number of Patients With HIV-1 RNA Viral Load <50 and <400 Copies/mL | Patients with <400 Copies/mL | 121 participants |
| Lopinavir/Ritonavir | Number of Patients With HIV-1 RNA Viral Load <50 and <400 Copies/mL | Patients with <50 Copies/mL | 108 participants |
| Lopinavir/Ritonavir | Number of Patients With HIV-1 RNA Viral Load <50 and <400 Copies/mL | Patients with <400 Copies/mL | 127 participants |