TOTEM: Switch From Other Nucleoside Reverse Transcriptase Inhibitors (NRTIs) to Once Daily Truvada

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Open-label Randomized Multicenter Trial to Evaluate the Impact on the Lipid Profile of the Substitution of the NRTIs of a HAART Regimen by a Once Daily Fixed Dose Combination Tablet of Emtricitabine and Tenofovir DF Versus Maintained Treatment in HIV Infected Controlled Patients.

Conditions
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HIV Infections

Intervention / Treatment
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* Drug: Truvada
* Drug: Current HAART regimen


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Truvada<br>Truvada once daily with continuation of the current NNRTI or PI at randomization | Drug: Truvada<br>* Truvada + NNRTI or PI.<br>|
| Active Comparator: Maintain Baseline Regimen<br>Maintain baseline regimen | Drug: Current HAART regimen<br>* Maintain baseline regimen<br>|
| Experimental: Delayed Truvada<br>Truvada once daily with NNRTI or PI (participants from the comparator group who switched to Truvada during Study Phase 2) | Drug: Truvada<br>* Truvada + NNRTI or PI.<br>|
| Experimental: All Truvada<br>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) | Drug: Truvada<br>* Truvada + NNRTI or PI.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | 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 | 

Secondary Outcome Measures

| Outcome Measure | 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) | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV 1 Infection