HIV Infections
Conditions
Keywords
HIV 1 Infection
Brief summary
This study looked at lipid changes in human immunodeficiency virus type 1 (HIV-1) infected patients when the nucleoside reverse transcriptase inhibitors (NRTIs) in their existing highly active antiretroviral therapy (HAART) regimen were switched to Truvada® (a fixed dose combination tablet of emtricitabine/tenofovir disoproxil fumarate 200 mg/300 mg \[FTC/TDF\]). Subjects continued their nonnucleoside reverse transcriptase inhibitor (NNRTI) or protease inhibitor (PI) at the same dose.
Detailed description
This was a Phase IV, multicenter (in France), open label study. The study was conducted in two phases: a comparative randomized phase, which served the primary objective of the study, and a follow-up phase. Study Phase 1, Day -14 to Week 12: patients were randomized on a 1:1 basis to one of two groups: * A. Truvada (substitution of their current NRTIs by Truvada \[FTC/TDF\] with continuation of their current NNRTI or PI at the same dose) * B. Maintain Baseline Regimen (continuation of previous HAART regimen, i.e., maintained baseline regimen). This phase of the study served the primary objective of the study. Study Phase 2, roll-over follow-up, Week 12 to Week 48: Patients in the Truvada group continued with Truvada + an NNRTI or PI. Patients in the control group could switch their NRTIs to Truvada in this phase of the study (Delayed Truvada group). Patients were assessed for efficacy and safety during both phases of the study.
Interventions
DRUGTruvada
Truvada + NNRTI or PI.
DRUGCurrent HAART regimen
Maintain baseline regimen
Sponsors
Gilead Sciences
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
* Patients displaying abnormal fasted triglycerides (\> 2 g/L \[2.26 mmol/L\] and less than or equal to 10 g/L \[11.29 mmol/L\]) and/or fasted low density lipoprotein cholesterol (LDL-CHO; \> 1.6 g/L \[4.15 mmol/L\]) * Patients on stable HAART with 2 NRTIs + 1 NNRTI or 1 PI for at least 3 months prior to screening, and with plasma viral load \< 400 copies/mL for at least 6 months prior to screening
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Week 12 in Fasting Triglycerides | Baseline to Week 12 | Centralized laboratory assessment. Change = Week 12 value minus baseline value. |
| Change From Baseline to Week 12 in Fasting Low-density Lipoprotein Cholesterol (LDL-CHO) | Baseline to Week 12 | Centralized laboratory assessment. Change = Week 12 value minus baseline value. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Plasma HIV-1 RNA Greater Than or Equal to 400 Copies/mL at Week 12 | 12 weeks | — |
| Change From Baseline to Week 48 in CD4 Cell Count | Baseline to Week 48 | Change = Week 48 value minus baseline value. |
| Change From Baseline to Week 12 in Fasting High-density Lipoprotein Cholesterol (HDL-CHO) | Baseline to Week 12 | Centralized laboratory assessment. Change = Week 12 value minus baseline value. |
| Change From Baseline to Week 12 in Fasting Total Cholesterol (T-CHO) | Baseline to Week 12 | Centralized laboratory assessment. Change = Week 12 value minus baseline value. |
| Percentage of Participants With Plasma HIV-1 RNA < 400 Copies/mL at Week 48 | 48 weeks | — |
| Change From Baseline to Week 12 in Fasting HDL-CHO/LDL-CHO | Baseline to Week 12 | Centralized laboratory assessment. Change = Week 12 value minus baseline value. |
| Change From Baseline to Week 12 in Fasting Ultra-sensitive C-reactive Protein (Us-CRP) | Baseline to Week 12 | Local laboratory assessment. Change = Week 12 value minus baseline value. |
| Percentage of Participants With Fasting Plasma Triglycerides > 10 g/L (> 11.29 mmol/L) at Week 12 | 12 weeks | Centralized laboratory assessment |
| Change From Baseline to Week 12 in Cluster Determinant 4 (CD4) Cell Count | Baseline to Week 12 | Change = Week 12 value minus baseline value. |
| Change From Baseline to Week 12 in Fasting T-CHO/HDL-CHO | Baseline to Week 12 | Centralized laboratory assessment. Change = Week 12 value minus baseline value. |
| Percentage of Participants With Virologic Control (Plasma HIV-1 Ribonucleic Acid [RNA] < 400 Copies/mL) at Week 12 | 12 weeks | — |
Countries
France
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Truvada Truvada + NNRTI or PI. | 47 |
| Maintain Baseline Regimen Maintain baseline regimen. | 45 |
| Total | 92 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Study Phase 1 | Adverse Event | 2 | 0 | 0 |
| Study Phase 2 | Adverse Event | 1 | 0 | 0 |
| Study Phase 2 | Lost to Follow-up | 1 | 0 | 0 |
| Study Phase 2 | Noncompliance with study schedule | 0 | 0 | 1 |
| Study Phase 2 | Physician Decision | 1 | 0 | 0 |
| Study Phase 2 | Protocol Violation | 1 | 0 | 0 |
| Study Phase 2 | Withdrawal by Subject | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Truvada | Maintain Baseline Regimen | Total |
|---|---|---|---|
| Age Continuous | 49.0 years INTER_QUARTILE_RANGE 10.7 | 43.0 years INTER_QUARTILE_RANGE 7.7 | 47.0 years INTER_QUARTILE_RANGE 9.8 |
| Cluster determinant 4 (CD4) cell count | 467 cells/mm^3 | 559 cells/mm^3 | 528 cells/mm^3 |
| Low density lipoprotein cholesterol (LDL-CHO) | 4.0 mmol/L | 4.0 mmol/L | 4.0 mmol/L |
| Participants with plasma HIV-1 RNA < 400 copies/mL | 47 participants | 45 participants | 92 participants |
| Region of Enrollment France | 47 participants | 45 participants | 92 participants |
| Sex: Female, Male Female | 8 Participants | 4 Participants | 12 Participants |
| Sex: Female, Male Male | 39 Participants | 41 Participants | 80 Participants |
| Triglycerides | 2.3 mmol/L | 2.7 mmol/L | 2.4 mmol/L |
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 | 15 / 47 | 6 / 45 | 16 / 72 |
| serious Total, serious adverse events | 7 / 47 | 3 / 45 | 7 / 72 |
Outcome results
Primary
Change From Baseline to Week 12 in Fasting Low-density Lipoprotein Cholesterol (LDL-CHO)
Centralized laboratory assessment. Change = Week 12 value minus baseline value.
Time frame: Baseline to Week 12
Population: ITT. LOCF method was used for the analysis if the Week 12 value was missing. A missing datum were replaced by the last post-baseline value.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Truvada | Change From Baseline to Week 12 in Fasting Low-density Lipoprotein Cholesterol (LDL-CHO) | -0.4 mmol/L |
| Maintain Baseline Regimen | Change From Baseline to Week 12 in Fasting Low-density Lipoprotein Cholesterol (LDL-CHO) | -0.1 mmol/L |
Comparison: Null Hypothesis: changes from baseline in the two treatment groups are equal. Alternative Hypothesis: changes from baseline in the two treatment groups are different (two sided).p-value: 0.03195% CI: [-0.67, -0.03]Wilcoxon Rank Sum text
Primary
Change From Baseline to Week 12 in Fasting Triglycerides
Centralized laboratory assessment. Change = Week 12 value minus baseline value.
Time frame: Baseline to Week 12
Population: ITT. Last post-baseline observation carried forward (LOCF) method was used for the analysis if the Week 12 value was missing. A missing datum were replaced by the last post-baseline value.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Truvada | Change From Baseline to Week 12 in Fasting Triglycerides | -0.5 mmol/L |
| Maintain Baseline Regimen | Change From Baseline to Week 12 in Fasting Triglycerides | -0.1 mmol/L |
Comparison: Null Hypothesis: changes from baseline in the two treatment groups are equal. Alternative Hypothesis: changes from baseline in the two treatment groups are different (two sided).p-value: 0.03495% CI: [-0.86, -0.03]Wilcoxon Rank Sum test
Secondary
Change From Baseline to Week 12 in Cluster Determinant 4 (CD4) Cell Count
Change = Week 12 value minus baseline value.
Time frame: Baseline to Week 12
Population: ITT. Missing values were excluded.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Truvada | Change From Baseline to Week 12 in Cluster Determinant 4 (CD4) Cell Count | 17.5 cells/mm^3 |
| Maintain Baseline Regimen | Change From Baseline to Week 12 in Cluster Determinant 4 (CD4) Cell Count | 16.0 cells/mm^3 |
Comparison: Null Hypothesis: changes from baseline in the two treatment groups are equal. Alternative Hypothesis: changes from baseline in the two treatment groups are different (two sided).p-value: 0.65Wilcoxon Rank Sum test
Secondary
Change From Baseline to Week 12 in Fasting HDL-CHO/LDL-CHO
Centralized laboratory assessment. Change = Week 12 value minus baseline value.
Time frame: Baseline to Week 12
Population: ITT. Missing values were excluded.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Truvada | Change From Baseline to Week 12 in Fasting HDL-CHO/LDL-CHO | 0.0 Ratio |
| Maintain Baseline Regimen | Change From Baseline to Week 12 in Fasting HDL-CHO/LDL-CHO | 0.0 Ratio |
Comparison: Null Hypothesis: changes from baseline in the two treatment groups are equal. Alternative Hypothesis: changes from baseline in the two treatment groups are different (two sided).p-value: 0.7995% CI: [-0.03, 0.02]Wilcoxon Rank Sum test
Secondary
Change From Baseline to Week 12 in Fasting High-density Lipoprotein Cholesterol (HDL-CHO)
Centralized laboratory assessment. Change = Week 12 value minus baseline value.
Time frame: Baseline to Week 12
Population: ITT. Missing values were excluded.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Truvada | Change From Baseline to Week 12 in Fasting High-density Lipoprotein Cholesterol (HDL-CHO) | -0.1 mmol/L |
| Maintain Baseline Regimen | Change From Baseline to Week 12 in Fasting High-density Lipoprotein Cholesterol (HDL-CHO) | 0.0 mmol/L |
Comparison: Null Hypothesis: changes from baseline in the two treatment groups are equal. Alternative Hypothesis: changes from baseline in the two treatment groups are different (two sided).p-value: 0.00995% CI: [-0.18, -0.02]Wilcoxon Rank Sum test
Secondary
Change From Baseline to Week 12 in Fasting T-CHO/HDL-CHO
Centralized laboratory assessment. Change = Week 12 value minus baseline value.
Time frame: Baseline to Week 12
Population: ITT. Missing values were excluded.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Truvada | Change From Baseline to Week 12 in Fasting T-CHO/HDL-CHO | -0.5 Ratio |
| Maintain Baseline Regimen | Change From Baseline to Week 12 in Fasting T-CHO/HDL-CHO | -0.1 Ratio |
Comparison: Null Hypothesis: changes from baseline in the two treatment groups are equal. Alternative Hypothesis: changes from baseline in the two treatment groups are different (two sided).p-value: 0.5195% CI: [-0.44, 0.19]Wilcoxon Rank Sum test
Secondary
Change From Baseline to Week 12 in Fasting Total Cholesterol (T-CHO)
Centralized laboratory assessment. Change = Week 12 value minus baseline value.
Time frame: Baseline to Week 12
Population: ITT. Missing values were excluded.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Truvada | Change From Baseline to Week 12 in Fasting Total Cholesterol (T-CHO) | -0.8 mmol/L |
| Maintain Baseline Regimen | Change From Baseline to Week 12 in Fasting Total Cholesterol (T-CHO) | -0.1 mmol/L |
Comparison: Null Hypothesis: changes from baseline in the two treatment groups are equal. Alternative Hypothesis: changes from baseline in the two treatment groups are different (two sided).p-value: <0.00195% CI: [-1.01, -0.27]Wicoxon Rank Sum test
Secondary
Change From Baseline to Week 12 in Fasting Ultra-sensitive C-reactive Protein (Us-CRP)
Local laboratory assessment. Change = Week 12 value minus baseline value.
Time frame: Baseline to Week 12
Population: ITT. Missing values were excluded. Assessment of us-CRP was added to the study schedule via protocol amendment part way through the study. This resulted in small numbers of subjects having data available for this analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Truvada | Change From Baseline to Week 12 in Fasting Ultra-sensitive C-reactive Protein (Us-CRP) | 0.4 mg/L |
| Maintain Baseline Regimen | Change From Baseline to Week 12 in Fasting Ultra-sensitive C-reactive Protein (Us-CRP) | 0.7 mg/L |
Comparison: Null Hypothesis: changes from baseline in the two treatment groups are equal. Alternative Hypothesis: changes from baseline in the two treatment groups are different (two sided).p-value: 0.86Wilcoxon Rank Sum test
Secondary
Change From Baseline to Week 48 in CD4 Cell Count
Change = Week 48 value minus baseline value.
Time frame: Baseline to Week 48
Population: ITT. Missing values were excluded.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Truvada | Change From Baseline to Week 48 in CD4 Cell Count | 35.0 cells/mm^3 |
| Maintain Baseline Regimen | Change From Baseline to Week 48 in CD4 Cell Count | 40.0 cells/mm^3 |
Comparison: Null Hypothesis: no indication of shift from 0 in distribution of change from baseline. Alternative Hypothesis: shift from 0 is observed in distribution of change from baseline.p-value: 0.11Wilcoxon Signed Rank test
Comparison: Null Hypothesis: no indication of shift from 0 in distribution of change from baseline. Alternative Hypothesis: shift from 0 is observed in distribution of change from baseline.p-value: 0.34Wilcoxon Signed Rank test
Secondary
Percentage of Participants With Fasting Plasma Triglycerides > 10 g/L (> 11.29 mmol/L) at Week 12
Centralized laboratory assessment
Time frame: 12 weeks
Population: ITT. Missing values were excluded.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Truvada | Percentage of Participants With Fasting Plasma Triglycerides > 10 g/L (> 11.29 mmol/L) at Week 12 | 0 Percentage of participants |
| Maintain Baseline Regimen | Percentage of Participants With Fasting Plasma Triglycerides > 10 g/L (> 11.29 mmol/L) at Week 12 | 0 Percentage of participants |
Secondary
Percentage of Participants With Plasma HIV-1 RNA < 400 Copies/mL at Week 48
Time frame: 48 weeks
Population: ITT. Missing values were treated as failure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Truvada | Percentage of Participants With Plasma HIV-1 RNA < 400 Copies/mL at Week 48 | 80 Percentage of participants |
| Maintain Baseline Regimen | Percentage of Participants With Plasma HIV-1 RNA < 400 Copies/mL at Week 48 | 80 Percentage of participants |
Secondary
Percentage of Participants With Plasma HIV-1 RNA Greater Than or Equal to 400 Copies/mL at Week 12
Time frame: 12 weeks
Population: ITT. Missing values were excluded. Any subjects with plasma HIV-1 RNA greater than or equal to 400 copies/mL at Week 12 were to have virologic genotyping performed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Truvada | Percentage of Participants With Plasma HIV-1 RNA Greater Than or Equal to 400 Copies/mL at Week 12 | 0 Percentage of participants |
| Maintain Baseline Regimen | Percentage of Participants With Plasma HIV-1 RNA Greater Than or Equal to 400 Copies/mL at Week 12 | 0 Percentage of participants |
Secondary
Percentage of Participants With Virologic Control (Plasma HIV-1 Ribonucleic Acid [RNA] < 400 Copies/mL) at Week 12
Time frame: 12 weeks
Population: ITT. Missing values were treated as failure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Truvada | Percentage of Participants With Virologic Control (Plasma HIV-1 Ribonucleic Acid [RNA] < 400 Copies/mL) at Week 12 | 96 Percentage of participants |
| Maintain Baseline Regimen | Percentage of Participants With Virologic Control (Plasma HIV-1 Ribonucleic Acid [RNA] < 400 Copies/mL) at Week 12 | 98 Percentage of participants |
Comparison: Null Hypothesis: treatment is not associated with the observed virologic response. Alternative Hypothesis: treatment is associated with the observed virologic responsep-value: 1Fisher Exact