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

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.

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.

Study Overview

• Status: Completed
• Conditions: HIV Infections
• Intervention / Treatment: Drug: Truvada; Drug: Current HAART regimen

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.

• Study Type: Interventional
• Enrollment (Actual): 92
• Phase: Phase 4

Contacts and Locations

Study Locations

• France
  • Paris, France, 75015
    • Gilead Sciences

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Gilead Sciences
• Investigators: Study Director: Camille Aubron-Olivier, Gilead Sciences

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: September 1, 2005
• Primary Completion (Actual): July 1, 2007
• Study Completion (Actual): March 1, 2008

Study Registration Dates

• First Submitted: May 5, 2006
• First Submitted That Met QC Criteria: May 5, 2006
• First Posted (Estimate): May 9, 2006

Study Record Updates

• Last Update Posted (Estimate): January 20, 2010
• Last Update Submitted That Met QC Criteria: January 13, 2010
• Last Verified: January 1, 2010

More Information

Terms related to this study

• Keywords: HIV 1 Infection
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; HIV Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination
• Other Study ID Numbers: GS-FR-164-0109