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

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

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.  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) ]