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

Phase 4

Completed

Conditions: HIV Infections

Interventions: Drug: Truvada
Drug: Current HAART regimen

Registration Number: NCT00323492

Lead Sponsor: Gilead Sciences

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 92

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

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
All Truvada	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)
Truvada	Truvada	Truvada once daily with continuation of the current NNRTI or PI at randomization
Maintain Baseline Regimen	Current HAART regimen	Maintain baseline regimen
Delayed Truvada	Truvada	Truvada once daily with NNRTI or PI (participants from the comparator group who switched to Truvada during Study Phase 2)

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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.
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.
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 48 in CD4 Cell Count	Baseline to Week 48	Change = Week 48 value minus baseline value.
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