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CompletedNCT00323492TOTEMUpdated Jan 20, 2010Results posted

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

A Phase 4 interventional study of Truvada and Current HAART regimen in HIV Infections, sponsored by Gilead Sciences. Completed at 1 site in France. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2010-01-20.

Sponsored by Gilead Sciences · Phase 4, Interventional, and Treatment

Phase
Phase 4
Study type
Interventional
Enrollment
92
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study 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.

Read the 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.

02

Conditions studied

  • HIV Infections

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Keywords

  • HIV 1 Infection
03

In context

HIV Infections

4,258 studies on the registry are indexed under HIV Infections; 240 are open to participants now.

This study's enrollment of 92 is above the median of 83 across 3,251 interventional studies indexed under HIV Infections.

Browse HIV Infections studies →

Lead sponsor

Gilead Sciences is the lead sponsor of 680 studies on the registry; 24 are open to participants now.

Of its 259 completed or terminated interventional studies of FDA-regulated products, 249 (96%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Eligibility criteria

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
05

Study design

Phase
Phase 4
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
92 participants (actual)

Study arms

  • Experimental
    Truvada

    Truvada once daily with continuation of the current NNRTI or PI at randomization

    Drug: Truvada

  • Active comparator
    Maintain Baseline Regimen

    Maintain baseline regimen

    Drug: Current HAART 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

  • 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

Interventions

  • DrugTruvada

    Truvada + NNRTI or PI.

  • DrugCurrent HAART regimen

    Maintain baseline regimen

06

What researchers measure

Primary outcomes

  1. 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

  2. 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

Secondary outcomes

  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

  6. Percentage of Participants With Fasting Plasma Triglycerides > 10 g/L (> 11.29 mmol/L) at Week 12

    Centralized laboratory assessment

    Time frame: 12 weeks

  7. 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

  8. Change From Baseline to Week 48 in CD4 Cell Count

    Change = Week 48 value minus baseline value.

    Time frame: Baseline to Week 48

  9. Percentage of Participants With Virologic Control (Plasma HIV-1 Ribonucleic Acid [RNA] < 400 Copies/mL) at Week 12

    Time frame: 12 weeks

  10. Percentage of Participants With Plasma HIV-1 RNA Greater Than or Equal to 400 Copies/mL at Week 12

    Time frame: 12 weeks

  11. Percentage of Participants With Plasma HIV-1 RNA < 400 Copies/mL at Week 48

    Time frame: 48 weeks

07

Results

Posted Dec 23, 2009
Limitations and caveats
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.

Participant flow

Study Phase 1
Participant flow — Study Phase 1
MilestoneTruvadaMaintain Baseline RegimenDelayed Truvada
Started47450
Intent-to-treat (itt) analysis set46450
Completed45450
Not completed200
Withdrew: Adverse event200
Study Phase 2
Participant flow — Study Phase 2
MilestoneTruvadaMaintain Baseline RegimenDelayed Truvada
Started441825
Completed401724
Not completed411
Withdrew: Adverse event100
Withdrew: Physician decision100
Withdrew: Lost to follow-up100
Withdrew: Withdrawal by subject010
Withdrew: Noncompliance with study schedule001
Withdrew: Protocol violation100

Outcome measures

PrimaryChange From Baseline to Week 12 in Fasting Triglycerides

Centralized laboratory assessment. Change = Week 12 value minus baseline value.

Time frame:
Baseline to Week 12
Reported as:
Median · mmol/L
Change From Baseline to Week 12 in Fasting Triglycerides
mmol/LTruvadaMaintain Baseline Regimen
Change From Baseline to Week 12 in Fasting Triglycerides-0.5 (-1.2 to 0.0)-0.1 (-0.8 to 0.3)
Statistical analysis
  • Truvada vs Maintain Baseline Regimen · Wilcoxon Rank Sum test · p = 0.034 (No adjustments for multiple comparisons were made.) · Median difference (net): -0.42 · 95% CI -0.86 to -0.03Difference is for Truvada minus Maintain Baseline Regimen. The non-parametric estimate of the difference between groups (Hodges-Lehmann) and its 95% confidence intervals (Moses) are provided.
PrimaryChange 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
Reported as:
Median · mmol/L
Change From Baseline to Week 12 in Fasting Low-density Lipoprotein Cholesterol (LDL-CHO)
mmol/LTruvadaMaintain Baseline Regimen
Change From Baseline to Week 12 in Fasting Low-density Lipoprotein Cholesterol (LDL-CHO)-0.4 (-1.0 to 0.1)-0.1 (-0.5 to 0.4)
Statistical analysis
  • Truvada vs Maintain Baseline Regimen · Wilcoxon Rank Sum text · p = 0.031 (No adjustments for multiple comparisons were made.) · Median difference (net): -0.36 · 95% CI -0.67 to -0.03Difference is for Truvada minus Maintain Baseline Regimen. The non-parametric estimate of the difference between groups (Hodges-Lehmann) and its 95% confidence intervals (Moses) are provided.
SecondaryChange 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
Reported as:
Median · mmol/L
Change From Baseline to Week 12 in Fasting High-density Lipoprotein Cholesterol (HDL-CHO)
mmol/LTruvadaMaintain Baseline Regimen
Change From Baseline to Week 12 in Fasting High-density Lipoprotein Cholesterol (HDL-CHO)-0.1 (-0.2 to 0.1)0.0 (0.0 to 0.1)
Statistical analysis
  • Truvada vs Maintain Baseline Regimen · Wilcoxon Rank Sum test · p = 0.009 (No adjustments for multiple comparisons were made.) · Median difference (net): -0.10 · 95% CI -0.18 to -0.02Difference is for Truvada minus Maintain Baseline Regimen. The non-parametric estimate of the difference between groups (Hodges-Lehmann) and its 95% confidence intervals (Moses) are provided.
SecondaryChange 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
Reported as:
Median · mmol/L
Change From Baseline to Week 12 in Fasting Total Cholesterol (T-CHO)
mmol/LTruvadaMaintain Baseline Regimen
Change From Baseline to Week 12 in Fasting Total Cholesterol (T-CHO)-0.8 (-1.3 to -0.1)-0.1 (-0.7 to 0.5)
Statistical analysis
  • Truvada vs Maintain Baseline Regimen · Wicoxon Rank Sum test · p = < 0.001 (No adjustments for multiple comparisons were made.) · Median difference (net): -0.64 · 95% CI -1.01 to -0.27Difference is for Truvada minus Maintain Baseline Regimen. The non-parametric estimate of the difference between groups (Hodges-Lehmann) and its 95% confidence intervals (Moses) are provided.
SecondaryChange 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
Reported as:
Median · Ratio
Change From Baseline to Week 12 in Fasting T-CHO/HDL-CHO
RatioTruvadaMaintain Baseline Regimen
Change From Baseline to Week 12 in Fasting T-CHO/HDL-CHO-0.5 (-0.7 to 0.2)-0.1 (-0.8 to 0.3)
Statistical analysis
  • Truvada vs Maintain Baseline Regimen · Wilcoxon Rank Sum test · p = 0.51 (No adjustments for multiple comparisons were made.) · Median difference (net): -0.10 · 95% CI -0.44 to 0.19Difference is for Truvada minus Maintain Baseline Regimen. The non-parametric estimate of the difference between groups (Hodges-Lehmann) and its 95% confidence intervals (Moses) are provided.
SecondaryChange 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
Reported as:
Median · Ratio
Change From Baseline to Week 12 in Fasting HDL-CHO/LDL-CHO
RatioTruvadaMaintain Baseline Regimen
Change From Baseline to Week 12 in Fasting HDL-CHO/LDL-CHO0.0 (0.0 to 0.0)0.0 (0.0 to 0.1)
Statistical analysis
  • Truvada vs Maintain Baseline Regimen · Wilcoxon Rank Sum test · p = 0.79 (No adjustments for multiple comparisons were made.) · Median difference (net): 0.0 · 95% CI -0.03 to 0.02Difference is for Truvada minus Maintain Baseline Regimen. The non-parametric estimate of the difference between groups (Hodges-Lehmann) and its 95% confidence intervals (Moses) are provided.
SecondaryChange 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
Reported as:
Median · mg/L
Change From Baseline to Week 12 in Fasting Ultra-sensitive C-reactive Protein (Us-CRP)
mg/LTruvadaMaintain Baseline Regimen
Change From Baseline to Week 12 in Fasting Ultra-sensitive C-reactive Protein (Us-CRP)0.4 (-0.5 to 0.9)0.7 (-3.2 to 2.5)
Statistical analysis
  • Truvada vs Maintain Baseline Regimen · Wilcoxon Rank Sum test · p = 0.86 (No adjustments for multiple comparisons were made.)No adjustments were made.
SecondaryPercentage of Participants With Fasting Plasma Triglycerides > 10 g/L (> 11.29 mmol/L) at Week 12

Centralized laboratory assessment

Time frame:
12 weeks
Reported as:
Number · Percentage of participants
Percentage of Participants With Fasting Plasma Triglycerides > 10 g/L (> 11.29 mmol/L) at Week 12
Percentage of participantsTruvadaMaintain Baseline Regimen
Percentage of Participants With Fasting Plasma Triglycerides > 10 g/L (> 11.29 mmol/L) at Week 1200
SecondaryChange 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
Reported as:
Median · cells/mm^3
Change From Baseline to Week 12 in Cluster Determinant 4 (CD4) Cell Count
cells/mm^3TruvadaMaintain Baseline Regimen
Change From Baseline to Week 12 in Cluster Determinant 4 (CD4) Cell Count17.5 (-36.0 to 63.5)16.0 (-31.0 to 92.0)
Statistical analysis
  • Truvada vs Maintain Baseline Regimen · Wilcoxon Rank Sum test · p = 0.65 (No adjustments for multiple comparisons were made.)No adjustments were made.
SecondaryChange From Baseline to Week 48 in CD4 Cell Count

Change = Week 48 value minus baseline value.

Time frame:
Baseline to Week 48
Reported as:
Median · cells/mm^3
Change From Baseline to Week 48 in CD4 Cell Count
cells/mm^3TruvadaMaintain Baseline Regimen
Change From Baseline to Week 48 in CD4 Cell Count35.0 (-37.0 to 116.0)40.0 (-41.5 to 79.5)
Statistical analysis
  • Truvada · Wilcoxon Signed Rank test · p = 0.11 (No adjustments were made.)No adjustments were made.
  • Maintain Baseline Regimen · Wilcoxon Signed Rank test · p = 0.34 (No adjustments were made.)No adjustments were made.
SecondaryPercentage of Participants With Virologic Control (Plasma HIV-1 Ribonucleic Acid [RNA] < 400 Copies/mL) at Week 12
Time frame:
12 weeks
Reported as:
Number · Percentage of participants
Percentage of Participants With Virologic Control (Plasma HIV-1 Ribonucleic Acid [RNA] < 400 Copies/mL) at Week 12
Percentage of participantsTruvadaMaintain Baseline Regimen
Percentage of Participants With Virologic Control (Plasma HIV-1 Ribonucleic Acid [RNA] < 400 Copies/mL) at Week 129698
Statistical analysis
  • Truvada vs Maintain Baseline Regimen · Fisher Exact · p = 1.00 (No adjustments were made.)No adjustments were made.
SecondaryPercentage of Participants With Plasma HIV-1 RNA Greater Than or Equal to 400 Copies/mL at Week 12
Time frame:
12 weeks
Reported as:
Number · Percentage of participants
Percentage of Participants With Plasma HIV-1 RNA Greater Than or Equal to 400 Copies/mL at Week 12
Percentage of participantsTruvadaMaintain Baseline Regimen
Percentage of Participants With Plasma HIV-1 RNA Greater Than or Equal to 400 Copies/mL at Week 1200
SecondaryPercentage of Participants With Plasma HIV-1 RNA < 400 Copies/mL at Week 48
Time frame:
48 weeks
Reported as:
Number · Percentage of participants
Percentage of Participants With Plasma HIV-1 RNA < 400 Copies/mL at Week 48
Percentage of participantsTruvadaMaintain Baseline Regimen
Percentage of Participants With Plasma HIV-1 RNA < 400 Copies/mL at Week 488080

Adverse events

Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Truvada—7/47 (14.9%)15/47 (31.9%)
Maintain Baseline Regimen—3/45 (6.7%)6/45 (13.3%)
All Truvada—7/72 (9.7%)16/72 (22.2%)
Most frequent serious events
Most frequent serious events
EventTruvadaMaintain Baseline RegimenAll Truvada
Renal failureRenal and urinary disorders2/470/452/72
Intestinal ObstructionGastrointestinal disorders1/471/451/72
Lung disorderRespiratory, thoracic and mediastinal disorders0/471/450/72
SciaticaNervous system disorders0/471/450/72
NephrolithiasisRenal and urinary disorders1/470/451/72
Renal impairmentRenal and urinary disorders1/470/451/72
Tubulointerstitial NephritisRenal and urinary disorders1/470/451/72
AsthmaRespiratory, thoracic and mediastinal disorders1/470/451/72
Prostatic adenomaNeoplasms benign, malignant and unspecified (incl cysts and polyps)1/470/451/72
Most frequent other events
Most frequent other events
EventTruvadaMaintain Baseline RegimenAll Truvada
DiarrhoeaGastrointestinal disorders6/472/457/72
BronchitisInfections and infestations3/472/453/72
Herpes simplexInfections and infestations3/470/453/72
NasopharyngitisInfections and infestations3/470/453/72
Abdominal painGastrointestinal disorders3/471/453/72
TendonitisMusculoskeletal and connective tissue disorders3/471/453/72
PollakiuriaRenal and urinary disorders3/470/453/72

Baseline characteristics

Age Continuous
Age Continuous(years)TruvadaMaintain Baseline RegimenTotal
Median49.0 ± 10.743.0 ± 7.747.0 ± 9.8
Sex: Female, Male
Sex: Female, Male(Participants)TruvadaMaintain Baseline RegimenTotal
Female8412
Male394180
Region of Enrollment
Region of Enrollment(participants)TruvadaMaintain Baseline RegimenTotal
France474592
Participants with plasma HIV-1 RNA < 400 copies/mL
Participants with plasma HIV-1 RNA < 400 copies/mL(participants)TruvadaMaintain Baseline RegimenTotal
Number474592
Cluster determinant 4 (CD4) cell count
Cluster determinant 4 (CD4) cell count(cells/mm^3)TruvadaMaintain Baseline RegimenTotal
Median467 (314 to 698)559 (337 to 714)528 (318 to 709)
Low density lipoprotein cholesterol (LDL-CHO)
Low density lipoprotein cholesterol (LDL-CHO)(mmol/L)TruvadaMaintain Baseline RegimenTotal
Median4.0 (3.2 to 4.7)4.0 (3.6 to 4.8)4.0 (3.4 to 4.7)
Triglycerides
Triglycerides(mmol/L)TruvadaMaintain Baseline RegimenTotal
Median2.3 (1.9 to 4.0)2.7 (1.9 to 3.6)2.4 (1.9 to 3.7)
08

Study locations

1 site
  • Gilead Sciences
    Paris, 75015, France
09

References and documents

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. PubMed 20053692 ↗
10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Jan 20, 2010, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT00323492
Lead sponsor
Gilead Sciences
First posted
May 9, 2006
Start date
Sep 2005
Primary completion
Jul 2007
Completion
Mar 2008
Results posted
Dec 23, 2009
Last update
Jan 20, 2010

Study contacts

Camille Aubron-Olivier
study director · Gilead Sciences

Oversight

Data monitoring committee
No
View the source record on ClinicalTrials.gov ↗

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