Tenofovir Disoproxil Fumarate/Emtricitabine/Efavirenz Versus Combivir/Efavirenz in Antiretroviral-Naive HIV-1 Infected Subjects

This study has been completed.
Sponsor:
Information provided by:
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT00112047
First received: May 27, 2005
Last updated: October 11, 2010
Last verified: October 2010
Results First Received: June 22, 2010  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: HIV Infections
Interventions: Drug: Emtricitabine (FTC)
Drug: Tenofovir Disoproxil Fumarate (TDF)
Drug: Efavirenz (EFV)
Drug: FTC/TDF
Drug: FTC/TDF/EFV
Drug: Lamivudine/zidovudine

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Participants were enrolled at 70 study sites in the United States and Europe. The first participant was screened on 29 July 2003; the last participant was randomized on 16 January 2004; the last participant observation for the primary endpoint analysis was 11 February 2005; the last participant last visit for end of study analysis was 10 June 2009.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Of the 517 enrolled participants, 6 received no study drug (the safety analysis set was therefore 511 participants: 257 [efavirenz+emtricitabine+tenofovir disoproxil fumarate group] and 254 [efavirenz+combivir group], respectively).

Reporting Groups
  Description
EFV+FTC+TDF

Participants in this group received 3 component drugs: efavirenz (EFV) 600 mg + emtricitabine (FTC) 200 mg + tenofovir disoproxil fumarate (tenofovir DF; TDF) 300 mg, each once daily, from the start of the study. At 96 weeks Truvada ([TVD] the fixed-dose combination pill containing FTC/TDF (200 mg/300 mg) replaced FTC + TDF; participants continued to receive EFV as before. Nevirapine 200 mg twice daily could replace EFV in the event of efavirenz-associated central nervous system (CNS) toxicity.

At Week 144 all participants who opted to roll over into the further 96-week study extension received Atripla ([ATR]; the fixed dose combination pill containing EFV/FTC/TDF, 600 mg/200 mg/300 mg) until the end of the study (Week 240). At sites in France, the study was extended by a further 48 weeks or until ATR became commercially available (whichever happened first); once ATR became commercially available in France participants were not required to complete the full 288 weeks of the study.

CBV+EFV

Participants in this group received EFV 600 mg once daily + Combivir ([CBV]; the fixed dose combination pill containing lamivudine + zidovudine [150 mg/300 mg]) twice daily from the start of the study until Week 144. Nevirapine 200 mg twice daily could replace EFV in the event of efavirenz-associated CNS toxicity.

At Week 144 all participants who opted to roll over into the additional 96-week study extension received ATR until the end of the study (Week 240). At sites in France, the study was extended by a further 48 weeks or until ATR became commercially available (whichever happened first); once ATR became commercially available in France participants were not required to complete the full 288 weeks of the study.


Participant Flow for 2 periods

Period 1:   Randomized Phase
    EFV+FTC+TDF     CBV+EFV  
STARTED     257 [1]   254 [2]
COMPLETED     187     166  
NOT COMPLETED     70     88  
Lost to Follow-up                 26                 33  
Adverse Event                 10                 10  
Withrawal of consent                 10                 18  
Sub-optimal virological response                 3                 13  
Noncompliance                 8                 4  
Protocol Violation                 2                 0  
Pregnancy                 3                 1  
Death                 1                 3  
Hepatitis C treatment contraindicated                 0                 1  
Inability to swallow pills                 0                 1  
Incarceration                 3                 2  
Moved out of State                 0                 1  
Baseline NNRTI resistance mutations                 4                 0  
High Hepatitis B DNA                 0                 1  
[1] Intention to treat (ITT) population N=255 (2 participants had received prior antiretroviral therapy)
[2] ITT analysis population

Period 2:   Atripla Phase
    EFV+FTC+TDF     CBV+EFV  
STARTED     160 [1]   126 [1]
COMPLETED     142     106  
NOT COMPLETED     18     20  
Adverse Event                 2                 1  
Lost to Follow-up                 5                 7  
Pregnancy                 0                 1  
Death                 0                 2  
Withdrew consent                 7                 7  
Sub-optimal virological response                 0                 1  
Non-compliance                 1                 0  
Not specified                 3                 1  
[1] Number of participants who completed randomized phase and opted to roll over to Atripla at Week 144



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
EFV+FTC+TDF

Participants in this group received 3 component drugs: efavirenz (EFV) 600 mg + emtricitabine (FTC) 200 mg + tenofovir disoproxil fumarate (tenofovir DF; TDF) 300 mg, each once daily, from the start of the study. At 96 weeks Truvada ([TVD] the fixed-dose combination pill containing FTC/TDF (200 mg/300 mg) replaced FTC + TDF; participants continued to receive EFV as before. Nevirapine 200 mg twice daily could replace EFV in the event of efavirenz-associated central nervous system (CNS) toxicity.

At Week 144 all participants who opted to roll over into the further 96-week study extension received Atripla ([ATR]; the fixed dose combination pill containing EFV/FTC/TDF, 600 mg/200 mg/300 mg) until the end of the study (Week 240). At sites in France, the study was extended by a further 48 weeks or until ATR became commercially available (whichever happened first); once ATR became commercially available in France participants were not required to complete the full 288 weeks of the study.

CBV+EFV

Participants in this group received EFV 600 mg once daily + Combivir ([CBV]; the fixed dose combination pill containing lamivudine + zidovudine [150 mg/300 mg]) twice daily from the start of the study until Week 144. Nevirapine 200 mg twice daily could replace EFV in the event of efavirenz-associated CNS toxicity.

At Week 144 all participants who opted to roll over into the additional 96-week study extension received ATR until the end of the study (Week 240). At sites in France, the study was extended by a further 48 weeks or until ATR became commercially available (whichever happened first); once ATR became commercially available in France participants were not required to complete the full 288 weeks of the study.

Total Total of all reporting groups

Baseline Measures
    EFV+FTC+TDF     CBV+EFV     Total  
Number of Participants  
[units: participants]
  255     254     509  
Age  
[units: years]
Mean ± Standard Deviation
  38  ± 9.9     38  ± 9.0     38  ± 9.5  
Gender  
[units: participants]
     
Female     36     33     69  
Male     219     221     440  
Race/Ethnicity, Customized  
[units: Participants]
     
White     142     156     298  
Black     65     51     116  
Hispanic     39     40     79  
Asian     3     3     6  
Not allowed to report     0     1     1  
Other     6     3     9  
HIV Status  
[units: Participants]
     
Asymptomatic     33     26     59  
Symptomatic HIV Infection     117     127     244  
AIDS     105     101     206  
CD4 cell count  
[units: Cells/mm^3]
Mean ± Standard Deviation
  246  ± 171.9     245  ± 156.6     245  ± 164.2  
HIV-1 RNA  
[units: Log10┬ác/mL]
Mean ± Standard Deviation
  5.03  ± 0.54     5.00  ± 0.51     5.01  ± 0.52  



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Percentage of Participants With Confirmed Plasma HIV-1 RNA < 400 c/mL at Week 48 (Defined by the Food and Drug Administration [FDA] Time-to-Loss-of Virologic Response [TLOVR] Algorithm   [ Time Frame: 48 weeks ]

2.  Secondary:   Percentage of Participants With Confirmed Plasma HIV-1 RNA < 50 c/mL at Week 48 (Defined by FDA TLOVR Algorithm)   [ Time Frame: Week 48 ]

3.  Secondary:   Percentage of Participants With Plasma HIV-1 RNA < 400 c/mL at Week 48.   [ Time Frame: 48 weeks ]

4.  Secondary:   Percentage of Participants With HIV-1 RNA < 50 c/mL at Week 48   [ Time Frame: 48 Weeks ]

5.  Secondary:   Percentage of Participants With Loss of Virologic Response (HIV-1 RNA < 400 c/mL) at Week 48   [ Time Frame: Baseline to 48 weeks ]

6.  Secondary:   Percentage of Participants With Loss of Virologic Response (HIV-1 RNA < 50 c/mL) at Week 48   [ Time Frame: Baseline to 48 Weeks ]

7.  Secondary:   Percentage of Participants With Pure Virologic Failure (HIV-1 RNA < 400 c/mL) at Week 48   [ Time Frame: Baseline to 48 Weeks ]

8.  Secondary:   Percentage of Participants With Pure Virologic Failure (HIV-1 RNA < 50 c/mL) at Week 48   [ Time Frame: Baseline to 48 Weeks ]

9.  Secondary:   Change From Study Baseline in HIV-1 RNA (Log10 c/mL) at Week 48   [ Time Frame: Study baseline to Week 48 ]

10.  Secondary:   Change From Study Baseline in CD4 Cell Count (Cells/mm^3) at Week 48   [ Time Frame: Study baseline to Week 48 ]

11.  Secondary:   Percentage of Participants With Confirmed Plasma HIV-1 RNA < 400 c/mL at Week 96 (Defined by FDA TLOVR Algorithm)   [ Time Frame: 96 Weeks ]

12.  Secondary:   Percentage of Participants With Confirmed Plasma HIV-1 RNA < 50 c/mL at Week 96 (Defined by FDA TLOVR Algorithm)   [ Time Frame: Week 96 ]

13.  Secondary:   Percentage of Participants With Loss of Virologic Response (HIV-1 RNA < 400 c/mL) at Week 96   [ Time Frame: Week 96 ]

14.  Secondary:   Percentage of Participants With Loss of Virologic Response (HIV-1 RNA < 50 c/mL) at Week 96   [ Time Frame: Week 96 ]

15.  Secondary:   Percentage of Participants With Pure Virologic Failure (HIV-1 RNA < 400 c/mL) at Week 96   [ Time Frame: Week 96 ]

16.  Secondary:   Percentage of Participants With Pure Virologic Failure (HIV-1 RNA < 50 c/mL) at Week 96   [ Time Frame: Week 96 ]

17.  Secondary:   Change From Study Baseline in HIV-1 RNA (Log10 c/mL) at Week 96   [ Time Frame: Study baseline to Week 96 ]

18.  Secondary:   Change From Study Baseline in CD4 Cell Count (Cells/mm^3) at Week 96   [ Time Frame: Baseline to Week 96 ]

19.  Secondary:   Change in Limb Fat (kg) From Week 48 to Week 96   [ Time Frame: Week 48 to Week 96 ]

20.  Secondary:   Change in Trunk Fat (kg) From Week 48 to Week 96   [ Time Frame: Week 48 to Week 96 ]

21.  Secondary:   Change in Total Body Fat (kg) From Week 48 to Week 96   [ Time Frame: 48 weeks to 96 weeks ]

22.  Secondary:   Percentage of Participants With Confirmed Plasma HIV-1 RNA < 400 c/mL at Week 144 (Defined by FDA TLOVR Algorithm)   [ Time Frame: 144 weeks ]

23.  Secondary:   Percentage of Participants With Confirmed Plasma HIV-1 RNA < 50 c/mL at Week 144 (Defined by FDA TLOVR Algorithm)   [ Time Frame: Week 144 ]

24.  Secondary:   Percentage of Participants With Plasma HIV-1 RNA < 400 c/mL at Week 144   [ Time Frame: Week 144 ]

25.  Secondary:   Percentage of Participants With Plasma HIV-1 RNA < 50 c/mL at Week 144   [ Time Frame: Week 144 ]

26.  Secondary:   Percentage of Participants With Loss of Virologic Response (HIV-1 RNA < 400 c/mL) at Week 144   [ Time Frame: Week 144 ]

27.  Secondary:   Percentage of Participants With Loss of Virologic Response (HIV-1 RNA < 50 c/mL) at Week 144   [ Time Frame: Week 144 ]

28.  Secondary:   Percentage of Participants With Pure Virological Failure (HIV-1 RNA < 400 c/mL) at Week 144   [ Time Frame: Week 144 ]

29.  Secondary:   Percentage of Participants With Pure Virological Failure (HIV-1 RNA < 50 c/mL) at Week 144   [ Time Frame: Week 144 ]

30.  Secondary:   Change From Study Baseline in HIV-1 RNA (Log10 c/mL) at Week 144   [ Time Frame: Study baseline to Week 144 ]

31.  Secondary:   Change From Study Baseline in CD4 Cell Count (Cells/mm^3) at Week 144   [ Time Frame: Baseline to Week 144 ]

32.  Secondary:   Change in Limb Fat (kg) From Week 48 to Week 144   [ Time Frame: Week 48 to Week 144 ]

33.  Secondary:   Change in Trunk Fat (kg) From Week 48 to Week 144   [ Time Frame: Week 48 to Week 144 ]

34.  Secondary:   Change in Total Body Fat (kg) From Week 48 to Week 144   [ Time Frame: Week 48 to Week 144 ]

35.  Secondary:   Percentage of Participants With Confirmed Plasma HIV-1 RNA < 400 c/mL at Week 240 (Atripla Week 96) Defined by the FDA TLOVR Algorithm   [ Time Frame: Week 144 (Atripla baseline) to Week 240 (Atripla Week 96) ]

36.  Secondary:   Percentage of Participants With Confirmed Plasma HIV-1 RNA < 50 c/mL at Week 240 (Atripla Week 96) Defined by the FDA TLOVR Algorithm   [ Time Frame: Week 144 (Atripla baseline) to Week 240 (Atripla Week 96) ]

37.  Secondary:   Percentage of Participants With Plasma HIV-1 RNA < 400 c/mL at Week 240 (Atripla Week 96)   [ Time Frame: Week 240 (Atripla Week 96) ]

38.  Secondary:   Percentage of Participants With Plasma HIV-1 RNA < 50 c/mL at Week 240 (Atripla Week 96)   [ Time Frame: Week 240 (Atripla Week 96) ]

39.  Secondary:   Percentage of Participants With Loss of Virologic Response (HIV-1 RNA < 400 c/mL) From Week 144 (Atripla Baseline) Through Week 240 (Atripla Week 96)   [ Time Frame: Week 144 (Atripla Baseline) to Week 240 (Atripla Week 96) ]

40.  Secondary:   Percentage of Participants With Loss of Virologic Response (HIV-1 RNA < 50 c/mL) From Week 144 (Atripla Baseline) Through Week 240 (Atripla Week 96)   [ Time Frame: Week 144 (Atripla Baseline) to Week 240 (Atripla Week 96) ]

41.  Secondary:   Percentage of Participants With Pure Virological Failure (HIV-1 RNA < 400 c/mL) Through Week 240 (Atripla Week 96)   [ Time Frame: Week 240 (Atripla Week 96) ]

42.  Secondary:   Percentage of Participants With Pure Virological Failure (HIV-1 RNA < 50 c/mL) Through Week 240 (Atripla Week 96)   [ Time Frame: Week 240 (Atripla Week 96) ]

43.  Secondary:   Change From Baseline in CD4 Cell Count (Cells/mm^3) at Week 240 (Atripla Week 96)   [ Time Frame: Study/Atripla baseline to Week 240 (Atripla Week 96) ]

44.  Secondary:   Change in Limb Fat (kg) From Week 144 (Atripla Baseline) to Week 240 (Atripla Week 96)   [ Time Frame: Week 144 (Atripla Baseline) to Week 240 (Atripla Week 96) ]

45.  Secondary:   Change in Trunk Fat (kg) From Week 144 (Atripla Baseline) to Week 240 (Atripla Week 96)   [ Time Frame: Week 144 (Atripla Baseline) to Week 240 (Atripla Week 96) ]

46.  Secondary:   Change in Total Body Fat (kg) From Week 144 (Atripla Baseline) to Week 240 (Atripla Week 96)   [ Time Frame: Week 144 (Atripla Baseline) to Week 240 (Atripla Week 96) ]

47.  Secondary:   Treatment Satisfaction Questionnaire (Satisfaction With Convenience and Simplicity of Current Treatment Regimen): Change From Week 144 to Week 240 in the Category Shift From Atripla Baseline.   [ Time Frame: Week 144 ([W 144]; Atripla baseline) to Week 240 ([W 240]; Atripla Week 96) ]

48.  Secondary:   Treatment Satisfaction Questionnaire (Satisfaction With Current Treatment Regimen to Control HIV): Change From Week 144 to Week 240 in the Category Shift From Atripla Baseline.   [ Time Frame: Week 144 ([W 144]; Atripla baseline) to Week 240 ([W 240]; Atripla Week 96) ]

49.  Secondary:   Treatment Satisfaction Questionnaire (Satisfaction With Tolerability of Current Treatment Regimen) Change From Week 144 to Week 240 in the Category Shift From Atripla Baseline.   [ Time Frame: Week 144 ([W 144]; Atripla baseline) to Week 240 ([W 240]; Atripla Week 96) ]

50.  Secondary:   Treatment Satisfaction Questionnaire (General Satisfaction With Current Treatment Regimen): Change From Week 144 to Week 240 in the Category Shift From Atripla Baseline.   [ Time Frame: Week 144 ([W 144]; Atripla baseline) to Week 240 ([W 240]; Atripla Week 96) ]

51.  Secondary:   Treatment Satisfaction Questionnaire (Bothered With the Side Effects of Current Treatment Regimen): Change From Week 144 to Week 240 in the Category Shift From Atripla Baseline.   [ Time Frame: Week 144 ([W 144]; Atripla baseline) to Week 240 ([W 240]; Atripla Week 96) ]

52.  Secondary:   Quality of Life (SF-12v2 Health Survey: Physical Component Summary) Change From Week 144 (Atripla Baseline) to Week 240 (Atripla Week 96)   [ Time Frame: Week 144 (Atripla Baseline) to Week 240 (Atripla Week 96) ]

53.  Secondary:   Quality of Life (SF-12v2 Health Survey: Mental Component Summary) Change From Week 144 (Atripla Baseline) to Week 240 (Atripla Week 96)   [ Time Frame: Week 144 (Atripla Baseline) to Week 240 (Atripla Week 96) ]


  Serious Adverse Events


  Other Adverse Events


  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Limitations and Caveats
Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.  


Results Point of Contact:  
Name/Title: Dara Wambach MA, Associate Director, Regulatory Affairs
Organization: Gilead Sciences
phone: 650-522-5163
e-mail: dara.wambach@gilead.com


Publications of Results:

Responsible Party: Steven Chuck MD, Vice President, HIV Therapeutics, Clinical Research, Gilead Sciences, Inc
ClinicalTrials.gov Identifier: NCT00112047     History of Changes
Other Study ID Numbers: GS-01-934
Study First Received: May 27, 2005
Results First Received: June 22, 2010
Last Updated: October 11, 2010
Health Authority: United States: Food and Drug Administration