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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.
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:
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Truvada | Experimental | Truvada once daily with continuation of the current NNRTI or PI at randomization |
|
| Maintain Baseline Regimen | Active Comparator | Maintain baseline regimen |
|
| Delayed Truvada | Experimental | Truvada once daily with NNRTI or PI (participants from the comparator group who switched to Truvada during Study Phase 2) |
|
| All Truvada | Experimental | Truvada once daily with NNRTI or PI (all participants who received Truvada during the study, i.e., participants in the Truvada and Delayed Truvada groups) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Truvada | Drug | Truvada + NNRTI or PI. |
| |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline to Week 12 in Fasting Triglycerides | Centralized laboratory assessment. Change = Week 12 value minus baseline value. | Baseline to Week 12 |
| Change From Baseline to Week 12 in Fasting Low-density Lipoprotein Cholesterol (LDL-CHO) | Centralized laboratory assessment. Change = Week 12 value minus baseline value. | Baseline to Week 12 |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline to Week 12 in Fasting High-density Lipoprotein Cholesterol (HDL-CHO) | Centralized laboratory assessment. Change = Week 12 value minus baseline value. | Baseline to Week 12 |
| Change From Baseline to Week 12 in Fasting Total Cholesterol (T-CHO) |
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Inclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Camille Aubron-Olivier | Gilead Sciences | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Gilead Sciences | Paris | 75015 | France |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 20053692 | Derived | Valantin MA, Bittar R, de Truchis P, Bollens D, Slama L, Giral P, Bonnefont-Rousselot D, Petour P, Aubron-Olivier C, Costagliola D, Katlama C; TOTEM trial group. Switching the nucleoside reverse transcriptase inhibitor backbone to tenofovir disoproxil fumarate + emtricitabine promptly improves triglycerides and low-density lipoprotein cholesterol in dyslipidaemic patients. J Antimicrob Chemother. 2010 Mar;65(3):556-61. doi: 10.1093/jac/dkp462. Epub 2010 Jan 6. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Truvada | Truvada + nonnucleoside reverse transcriptase inhibitor (NNRTI) or protease inhibitor (PI). |
| FG001 | Maintain Baseline Regimen | Maintain baseline regimen. |
| FG002 | Delayed Truvada | Truvada + NNRTI or PI (participants from the control group who switched NRTIs to Truvada during Study Phase 2). |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Study Phase 1 |
|
| |||||||||||||||||||||
| Study Phase 2 |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Truvada | Truvada + NNRTI or PI. |
| BG001 | Maintain Baseline Regimen | Maintain baseline regimen. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age Continuous | Median |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Change From Baseline to Week 12 in Fasting Triglycerides | Centralized laboratory assessment. Change = Week 12 value minus baseline value. | 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. | Posted | Median | Inter-Quartile Range | mmol/L | Baseline to Week 12 |
|
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Truvada | Truvada + NNRTI or PI. The number of participants at risk is the number who started the study by switching to Truvada. Participants in this group were to remain on Truvada for 48 weeks (duration of the study). The number at risk was reduced only by study discontinuation (from 47 at baseline to 40 who completed Study Phase 2). |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Nephrolithiasis | Renal and urinary disorders | MedDRA 9.0 | Non-systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Bronchitis | Infections and infestations | MedDRA 9.0 | Non-systematic Assessment |
Comparison of adverse events between Truvada and maintain baseline regimen groups is inappropriate since numbers at risk (and exposure to study drug) are not balanced, as described in the adverse event treatment group descriptions.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Camille Aubron-Olivier | Gilead Sciences | +33(0)1 42 737130 | camille.aubron-olivier@gilead.com |
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| ID | Term |
|---|---|
| D015658 | HIV Infections |
| ID | Term |
|---|---|
| D000086982 | Blood-Borne Infections |
| D003141 | Communicable Diseases |
| D007239 | Infections |
| D015229 | Sexually Transmitted Diseases, Viral |
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| ID | Term |
|---|---|
| D000069480 | Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination |
| ID | Term |
|---|---|
| D000068698 | Tenofovir |
| D063065 | Organophosphonates |
| D009943 | Organophosphorus Compounds |
| D009930 | Organic Chemicals |
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| Current HAART regimen |
| Drug |
Maintain baseline regimen |
|
Centralized laboratory assessment. Change = Week 12 value minus baseline value. |
| Baseline to Week 12 |
| Change From Baseline to Week 12 in Fasting T-CHO/HDL-CHO | Centralized laboratory assessment. Change = Week 12 value minus baseline value. | Baseline to Week 12 |
| Change From Baseline to Week 12 in Fasting HDL-CHO/LDL-CHO | Centralized laboratory assessment. Change = Week 12 value minus baseline value. | Baseline to Week 12 |
| 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. | Baseline to Week 12 |
| Percentage of Participants With Fasting Plasma Triglycerides > 10 g/L (> 11.29 mmol/L) at Week 12 | Centralized laboratory assessment | 12 weeks |
| Change From Baseline to Week 12 in Cluster Determinant 4 (CD4) Cell Count | Change = Week 12 value minus baseline value. | Baseline to Week 12 |
| Change From Baseline to Week 48 in CD4 Cell Count | Change = Week 48 value minus baseline value. | Baseline to Week 48 |
| Percentage of Participants With Virologic Control (Plasma HIV-1 Ribonucleic Acid [RNA] < 400 Copies/mL) at Week 12 | 12 weeks |
| Percentage of Participants With Plasma HIV-1 RNA Greater Than or Equal to 400 Copies/mL at Week 12 | 12 weeks |
| Percentage of Participants With Plasma HIV-1 RNA < 400 Copies/mL at Week 48 | 48 weeks |
|
| NOT COMPLETED |
|
|
| BG002 |
| Total |
Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Participants with plasma HIV-1 RNA < 400 copies/mL | At screening | Number | participants |
|
| Cluster determinant 4 (CD4) cell count | At screening | Median | Inter-Quartile Range | cells/mm^3 |
|
| Low density lipoprotein cholesterol (LDL-CHO) | Centralized laboratory assessment | Median | Inter-Quartile Range | mmol/L |
|
| Triglycerides | Centralized laboratory assessment | Median | Inter-Quartile Range | mmol/L |
|
| Units | Counts |
|---|---|
| Participants |
|
|
|
| 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. | 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. | Posted | Median | Inter-Quartile Range | mmol/L | Baseline to Week 12 |
|
|
|
|
| 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. | ITT. Missing values were excluded. | Posted | Median | Inter-Quartile Range | mmol/L | Baseline to Week 12 |
|
|
|
|
| Secondary | Change From Baseline to Week 12 in Fasting Total Cholesterol (T-CHO) | Centralized laboratory assessment. Change = Week 12 value minus baseline value. | ITT. Missing values were excluded. | Posted | Median | Inter-Quartile Range | mmol/L | Baseline to Week 12 |
|
|
|
|
| Secondary | Change From Baseline to Week 12 in Fasting T-CHO/HDL-CHO | Centralized laboratory assessment. Change = Week 12 value minus baseline value. | ITT. Missing values were excluded. | Posted | Median | Inter-Quartile Range | Ratio | Baseline to Week 12 |
|
|
|
|
| Secondary | Change From Baseline to Week 12 in Fasting HDL-CHO/LDL-CHO | Centralized laboratory assessment. Change = Week 12 value minus baseline value. | ITT. Missing values were excluded. | Posted | Median | Inter-Quartile Range | Ratio | Baseline to Week 12 |
|
|
|
|
| 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. | 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. | Posted | Median | Inter-Quartile Range | mg/L | Baseline to Week 12 |
|
|
|
|
| Secondary | Percentage of Participants With Fasting Plasma Triglycerides > 10 g/L (> 11.29 mmol/L) at Week 12 | Centralized laboratory assessment | ITT. Missing values were excluded. | Posted | Number | Percentage of participants | 12 weeks |
|
|
|
| Secondary | Change From Baseline to Week 12 in Cluster Determinant 4 (CD4) Cell Count | Change = Week 12 value minus baseline value. | ITT. Missing values were excluded. | Posted | Median | Inter-Quartile Range | cells/mm^3 | Baseline to Week 12 |
|
|
|
|
| Secondary | Change From Baseline to Week 48 in CD4 Cell Count | Change = Week 48 value minus baseline value. | ITT. Missing values were excluded. | Posted | Median | Inter-Quartile Range | cells/mm^3 | Baseline to Week 48 |
|
|
|
|
| Secondary | Percentage of Participants With Virologic Control (Plasma HIV-1 Ribonucleic Acid [RNA] < 400 Copies/mL) at Week 12 | ITT. Missing values were treated as failure. | Posted | Number | Percentage of participants | 12 weeks |
|
|
|
|
| Secondary | Percentage of Participants With Plasma HIV-1 RNA Greater Than or Equal to 400 Copies/mL at Week 12 | 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. | Posted | Number | Percentage of participants | 12 weeks |
|
|
|
| Secondary | Percentage of Participants With Plasma HIV-1 RNA < 400 Copies/mL at Week 48 | ITT. Missing values were treated as failure. | Posted | Number | Percentage of participants | 48 weeks |
|
|
|
| 7 |
| 47 |
| 15 |
| 47 |
| EG001 | Maintain Baseline Regimen | Maintain baseline regimen. The number of participants at risk is the number who started the study by maintaining their baseline regimen. Per protocol, participants in this group were allowed to switch to Truvada after Week 12 (Delayed TVD group), therefore the number of participants at risk declines over time (from 45 at baseline to 17 who completed Study Phase 2; with most participants switching to Truvada at Week 12). | 3 | 45 | 6 | 45 |
| EG002 | All Truvada | Truvada + NNRTI or PI (all participants who received Truvada during the study, i.e., participants in the Truvada and Delayed Truvada groups). The number of participants at risk is the number who started the study by switching to Truvada (Truvada group), plus those who started the study by maintaining their baseline regimen but who switched to Truvada during the study (Delayed Truvada group). The number of participants at risk increases over time (from 47 at baseline to 72 when the last switch to Truvada took place; 25 participants switched to Truvada from the "maintain baseline regimen" group in Study Phase 2). | 7 | 72 | 16 | 72 |
| Renal failure | Renal and urinary disorders | MedDRA 9.0 | Non-systematic Assessment |
|
| Renal impairment | Renal and urinary disorders | Non-systematic Assessment |
|
| Tubulointerstitial Nephritis | Renal and urinary disorders | Non-systematic Assessment |
|
| Intestinal Obstruction | Gastrointestinal disorders | Non-systematic Assessment |
|
| Asthma | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
|
| Lung disorder | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
|
| Prostatic adenoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | Non-systematic Assessment |
|
| Sciatica | Nervous system disorders | Non-systematic Assessment |
|
| Herpes simplex | Infections and infestations | Non-systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | Non-systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | Non-systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | Non-systematic Assessment |
|
| Tendonitis | Musculoskeletal and connective tissue disorders | Non-systematic Assessment |
|
| Pollakiuria | Renal and urinary disorders | Non-systematic Assessment |
|
After conclusion of the study and without prior written approval from Gilead Sciences, investigators in this study may communicate, orally present, or publish in scientific journals or other scholarly media only after the following conditions have been met: results of the study in their entirety have been publicly disclosed by or with the consent of Gilead Sciences in an abstract, manuscript, or presentation form; or study has been completed at all study sites for at least 2 years.
| D012749 | Sexually Transmitted Diseases |
| D016180 | Lentivirus Infections |
| D012192 | Retroviridae Infections |
| D012327 | RNA Virus Infections |
| D014777 | Virus Diseases |
| D000091662 | Genital Diseases |
| D000091642 | Urogenital Diseases |
| D007153 | Immunologic Deficiency Syndromes |
| D007154 | Immune System Diseases |
| D000068679 |
| Emtricitabine |
| D003841 | Deoxycytidine |
| D003562 | Cytidine |
| D011741 | Pyrimidine Nucleosides |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D000225 | Adenine |
| D011687 | Purines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D003853 | Deoxyribonucleosides |
| D009705 | Nucleosides |
| D009706 | Nucleic Acids, Nucleotides, and Nucleosides |
| D004338 | Drug Combinations |
| D004364 | Pharmaceutical Preparations |
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. |
| Wilcoxon Signed Rank test |
No adjustments were made. |
| 0.34 |
No adjustments were made. |
| 95 |
| No |
| Superiority or Other |