Induction/Simplification With Atazanavir + Ritonavir + Abacavir/Lamivudine Fixed-Dose Combination In HIV-1 Infection
This study has been completed.
Sponsor:
ViiV Healthcare
Collaborator:
GlaxoSmithKline
Information provided by (Responsible Party):
ViiV Healthcare
ClinicalTrials.gov Identifier:
NCT00440947
First received: February 23, 2007
Last updated: March 15, 2012
Last verified: July 2011
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Results First Received: May 19, 2011
| Study Type: | Interventional |
|---|---|
| Study Design: | Allocation: Randomized; Endpoint Classification: Safety/Efficacy Study; Intervention Model: Parallel Assignment; Masking: Open Label; Primary Purpose: Treatment |
| Conditions: |
Infection, Human Immunodeficiency Virus I HIV Infection |
| Interventions: |
Drug: Abacavir (ABC)/lamivudine (3TC) + atazanavir (ATV) + ritonavir (/r) Drug: Abacavir (ABC)/lamivudine (3TC) + atazanavir (ATV) |
Participant Flow
Recruitment Details
| Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations |
|---|
| Participants (PAR) were recruited at 66 centers in the United States of America and Canada. HIV-RNA, human immunodeficiency virus-ribonucleic acid; ml, milliliters. |
Pre-Assignment Details
| Significant events and approaches for the overall study following participant enrollment, but prior to group assignment |
|---|
| The study had a 36-week Non-randomized Induction Phase, followed by an 84-week Randomized Phase. All PAR completing 84 weeks were eligible to enter an optional 60-week extension phase (EP); some PAR chose not to continue in the EP. PAR whose HIV-RNA wasn't <50 copies/ml before Week 36 weren't allowed to randomize at Week 36 and were withdrawn. |
Reporting Groups
| Description | |
|---|---|
| ABC/3TC + ATV/r: Induction Phase | Abacavir (ABC) 600 milligrams (mg)/lamivudine (3TC) 300 mg fixed-dose combination tablet (FDC) once a day (QD) plus atazanavir (ATV) 300 mg QD + ritonavir (/r) 100 mg QD during the first 36 weeks of the study (planned interim analysis) |
| ABC/3TC + ATV: Randomization Phase | Simplification regimen of the ABC/3TC FDC tablet administered QD for an additional 48 weeks in combination with 400 mg ATV QD |
| ABC/3TC + ATV/r: Randomization Phase | Continuation of ABC/3TC FDC tablet administered QD for an additional 48 weeks in combination with ATV/r QD |
| ABC/3TC + ATV: Extension Phase | Simplification regimen of the ABC/3TC FDC tablet administered QD for an additional 60 weeks in combination with ATV QD |
| ABC/3TC + ATV/r: Extension Phase | Continuation of ABC/3TC FDC tablet administered QD for an additional 60 weeks in combination with ATV/r QD |
Participant Flow for 3 periods
Period 1: 36-Week Induction Phase
| ABC/3TC + ATV/r: Induction Phase | ABC/3TC + ATV: Randomization Phase | ABC/3TC + ATV/r: Randomization Phase | ABC/3TC + ATV: Extension Phase | ABC/3TC + ATV/r: Extension Phase | |
|---|---|---|---|---|---|
| STARTED | 515 | 0 | 0 | 0 | 0 |
| COMPLETED | 442 [1] | 0 | 0 | 0 | 0 |
| NOT COMPLETED | 73 | 0 | 0 | 0 | 0 |
| Adverse Event | 16 | 0 | 0 | 0 | 0 |
| Insufficient Viral Load Response | 11 | 0 | 0 | 0 | 0 |
| Protocol-defined Virologic Failure | 5 | 0 | 0 | 0 | 0 |
| Non-compliance | 10 | 0 | 0 | 0 | 0 |
| Lost to Follow-up | 16 | 0 | 0 | 0 | 0 |
| Withdrawal by Subject | 7 | 0 | 0 | 0 | 0 |
| Kaposi Lesions Requiring Chemotherapy | 1 | 0 | 0 | 0 | 0 |
| Took Exclusionary Medications | 1 | 0 | 0 | 0 | 0 |
| Genotype Had Exclusionary Mutations | 1 | 0 | 0 | 0 | 0 |
| Fleeing Police; Outstanding Warrants | 1 | 0 | 0 | 0 | 0 |
| Incarceration | 3 | 0 | 0 | 0 | 0 |
| Pregnancy | 1 | 0 | 0 | 0 | 0 |
| [1] | 23 PAR without confirmed HIV-RNA<50c/mL prior to Wk 36 couldn’t be randomized but weren’t withdrawn. |
|---|
Period 2: 48-Week Randomization Phase
| ABC/3TC + ATV/r: Induction Phase | ABC/3TC + ATV: Randomization Phase | ABC/3TC + ATV/r: Randomization Phase | ABC/3TC + ATV: Extension Phase | ABC/3TC + ATV/r: Extension Phase | |
|---|---|---|---|---|---|
| STARTED | 0 | 210 | 209 | 0 | 0 |
| COMPLETED | 0 | 194 | 185 | 0 | 0 |
| NOT COMPLETED | 0 | 16 | 24 | 0 | 0 |
| Adverse Event | 0 | 2 | 5 | 0 | 0 |
| Protocol-defined Virologic Failure | 0 | 1 | 1 | 0 | 0 |
| Non-compliance | 0 | 3 | 4 | 0 | 0 |
| Lost to Follow-up | 0 | 2 | 8 | 0 | 0 |
| Protocol Violation | 0 | 0 | 1 | 0 | 0 |
| Withdrawal by Subject | 0 | 2 | 4 | 0 | 0 |
| Pregnancy | 0 | 0 | 1 | 0 | 0 |
| Incarceration | 0 | 3 | 0 | 0 | 0 |
| Trying to Get Pregnant | 0 | 1 | 0 | 0 | 0 |
| Physician Decision | 0 | 2 | 0 | 0 | 0 |
Period 3: Optional 60-Week Extension Phase
| ABC/3TC + ATV/r: Induction Phase | ABC/3TC + ATV: Randomization Phase | ABC/3TC + ATV/r: Randomization Phase | ABC/3TC + ATV: Extension Phase | ABC/3TC + ATV/r: Extension Phase | |
|---|---|---|---|---|---|
| STARTED | 0 | 0 | 0 | 189 | 180 |
| COMPLETED | 0 | 0 | 0 | 160 | 154 |
| NOT COMPLETED | 0 | 0 | 0 | 29 | 26 |
| Adverse Event | 0 | 0 | 0 | 1 | 3 |
| Insufficient Viral Load Response | 0 | 0 | 0 | 1 | 1 |
| Protocol-defined Virologic Failure | 0 | 0 | 0 | 3 | 2 |
| Non-compliance | 0 | 0 | 0 | 1 | 1 |
| Lost to Follow-up | 0 | 0 | 0 | 9 | 9 |
| Protocol Violation | 0 | 0 | 0 | 1 | 0 |
| Withdrawal by Subject | 0 | 0 | 0 | 4 | 3 |
| Pregnancy | 0 | 0 | 0 | 3 | 0 |
| Participant Moved | 0 | 0 | 0 | 1 | 1 |
| Sponsor Request | 0 | 0 | 0 | 1 | 1 |
| Sponsor Terminated Site | 0 | 0 | 0 | 3 | 3 |
| Unknown | 0 | 0 | 0 | 1 | 0 |
| Physician Decision | 0 | 0 | 0 | 0 | 1 |
| Participant Remained in Cuba | 0 | 0 | 0 | 0 | 1 |
Baseline Characteristics
Reporting Groups
| Description | |
|---|---|
| ABC/3TC + ATV/r | All participants starting the Induction Phase: ABC 600 mg/3TC 300 mg FDC tablet QD plus ATV 300 mg QD + /r 100 mg QD during the first 36 weeks of the study (planned interim analysis) |
Baseline Measures
| ABC/3TC + ATV/r | |
|---|---|
|
Number of Participants
[units: participants] |
515 |
|
Age
[units: Years] Mean ± Standard Deviation |
38.3 ± 10.03 |
|
Gender
[units: Participants] |
|
| Female | 86 |
| Male | 429 |
|
Race/Ethnicity, Customized
[units: participants] |
|
| African American/African Heritage | 167 |
| American Indian or Alaskan Native | 9 |
| Asian - Central/South Asian Heritage | 4 |
| Asian - East Asian Heritage | 3 |
| Asian - Japanese Heritage | 1 |
| Asian - South East Asian Heritage | 3 |
| Native Hawaiian or Other Pacific Islander | 1 |
| White - Arabic/North African Heritage | 5 |
| White - White/Caucasian/European Heritage | 316 |
| Mixed Race | 6 |
|
Number of participants with the indicated baseline HIV-RNA level
[1] [units: participants] |
|
| HIV-1 RNA <100,000 | 227 |
| HIV-1 RNA 100,000-<250,000 | 143 |
| HIV-1 RNA 250,000-<500,000 | 73 |
| HIV-1 RNA >=500,000 | 72 |
|
Number of participants with the indicated Baseline CD4+ Cell Count
[2] [units: participants] |
|
| CD4+ cells <50 | 69 |
| CD4+ cells 50-<200 | 190 |
| CD4+ cells >=200 | 256 |
|
Number of participants with the indicated Center for Disease Control (CDC) Classification
[3] [units: participants] |
|
| Asymptomatic HIV Infection | 353 |
| Symptomatic (non-AIDS) condition | 97 |
| AIDS | 65 |
|
Median Baseline CD4+ Cell Count
[units: cells per cubic millimeter] Median ( Full Range ) |
199
( 19 to 754 ) |
|
Median Baseline HIV-1 RNA Level
[units: log10 copies/ml] Median ( Full Range ) |
5.076
( 2.989 to 6.620 ) |
| [1] | HIV-1 RNA, Human Immunodeficiency Virus type 1 Ribonucleic acid. HIV-1 viral load was measured as virus copies per milliliter (ml) at baseline. |
|---|---|
| [2] | A CD4+ cell is a T lymphocyte that carries the CD4 antigen. Immunologic response was assessed by CD4+ counts. |
| [3] | AIDS, Acquired Immunodeficiency Syndrome CDC classifications are Asymptomatic, Symptomatic, or AIDs. |
Outcome Measures
| 1. Primary: | Percentage of Participants (PAR) Who Achieved Plasma HIV-1 RNA <50 Copies (c) /Milliliter (ml) at the Week 84 Visit [ Time Frame: Week 84 ] |
| 2. Secondary: | Mean Age at Baseline of Participants Randomized to Treatment for the 48-Week Randomized Phase [ Time Frame: Baseline of Randomized Phase ] |
| 3. Secondary: | Percentage of Participants Who Achieved Plasma HIV-1 RNA <50 c/ml at the Week 36 Visit [ Time Frame: Week 36 ] |
| 4. Secondary: | Percentage of Participants Who Achieved Plasma HIV-1 RNA <50 c/ml at the Week 84 Visit [ Time Frame: Week 84 ] |
| 5. Secondary: | Percentage of Participants Who Achieved Plasma HIV-1 RNA <50 c/ml at the Week 144 Visit [ Time Frame: Week 144 ] |
| 6. Secondary: | Percentage of Participants Who Achieved Plasma HIV-1 RNA <400 c/ml at the Week 36 Visit [ Time Frame: Week 36 ] |
| 7. Secondary: | Percentage of Participants Who Achieved HIV-1 RNA <400 c/ml at the Week 84 Visit [ Time Frame: Week 84 ] |
| 8. Secondary: | Percentage of Participants Who Achieved HIV-1 RNA <400 c/ml at the Week 144 Visit [ Time Frame: Week 144 ] |
| 9. Secondary: | Number of Participants Who Met the Protocol-defined Virologic Failure (PDVF) Criteria at Week 36 [ Time Frame: Week 36 ] |
| 10. Secondary: | Number of Participants Who Met the PDVF Criteria at Week 84 [ Time Frame: Week 84 ] |
| 11. Secondary: | Number of Participants Who Met the PDVF Criteria at Week 144 [ Time Frame: Week 144 ] |
| 12. Secondary: | Change From Baseline in HIV-1 RNA at Week 36 [ Time Frame: Baseline and Week 36 ] |
| 13. Secondary: | Change From Baseline in HIV-1 RNA at Week 84 [ Time Frame: Baseline and Week 84 ] |
| 14. Secondary: | Change From Baseline in HIV-1 RNA at Week 144 [ Time Frame: Baseline and Week 144 ] |
| 15. Secondary: | Change From Baseline in CD4+ Cell Count at Week 36 [ Time Frame: Baseline and Week 36 ] |
| 16. Secondary: | Change From Baseline in CD4+ Cell Count at Week 84 [ Time Frame: Baseline and Week 84 ] |
| 17. Secondary: | Change From Baseline in CD4+ Cell Count at Week 144 [ Time Frame: Baseline and Week 144 ] |
| 18. Secondary: | Number of Confirmed Virologic Failure Participants With Treatment-emergent HIV Genotypic Resistance in Reverse Transcriptase and Protease From Baseline Through Week 36 [ Time Frame: Baseline through Week 36 ] |
| 19. Secondary: | Number of Confirmed Virologic Failure Participants With Treatment-emergent HIV Genotypic Resistance in Reverse Transcriptase and Protease From Randomization at Week 36 Through Week 84 [ Time Frame: Randomization at Week 36 through Week 84 ] |
| 20. Secondary: | Number of Confirmed Virologic Failure Participants With Treatment-emergent HIV Genotypic Resistance in Reverse Transcriptase and Protease From Week 84 Through Week 144 [ Time Frame: Week 84 through Week 144 ] |
| 21. Secondary: | Number of Confirmed Virologic Failure Participants From Baseline Through Week 36 With Treatment-emergent Reductions in Susceptibility to Abacavir, Lamivudine, Atazanavir, or Ritonavir [ Time Frame: Baseline through Week 36 ] |
| 22. Secondary: | Number of Confirmed Virologic Failure Participants From Randomization at Week 36 Through Week 84 With Treatment-emergent Reductions in HIV Susceptibility to Abacavir, Lamivudine, Atazanavir, or Ritonavir [ Time Frame: Randomization at Week 36 through Week 84 ] |
| 23. Secondary: | Number of Confirmed Virologic Failure Participants From Week 84 Through Week 144 With Treatment-emergent Reductions in HIV Susceptibility to Abacavir, Lamivudine, Atazanavir, or Ritonavir [ Time Frame: Week 84 through Week 144 ] |
| 24. Secondary: | Mean Percent Compliance at Week 36 [ Time Frame: Week 36 ] |
| 25. Secondary: | Mean Percent Compliance at Week 84 [ Time Frame: Week 84 ] |
| 26. Secondary: | Mean Percent Compliance at Week 144 [ Time Frame: Week 144 ] |