Phase 3
Completed N=511
Tenofovir Disoproxil Fumarate/Emtricitabine/Efavirenz Versus Combivir/Efavirenz in Antiretroviral-Naive HIV-1 Infected Subjects
HIV Infections
Source: ClinicalTrials.gov NCT00112047 ↗
Enrolled (actual)
511
Serious AEs
10.7%
Results posted
Oct 2010
Primary outcomePrimary: 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 — 84.4; 72.8 Percentage of participants — p=0.002
Summary
The purpose of Study GS-01-934 was to assess the efficacy and safety of two simplified antiretroviral treatment (ART) regimens in ART-naive, human immunodeficiency virus, type 1 (HIV-1) infected participants. The primary objective of the study was to assess noninferiority of emtricitabine (FTC) and tenofovir disoproxil fumarate (tenofovir DF; TDF) in combination with efavirenz (EFV) relative to Combivir (CBV) in combination with EFV in the treatment of HIV-1 infected ART-naive participants, determined by the achievement and maintenance of confirmed HIV-1 ribonucleic acid (RNA) < 400 copies/mL (c/mL) through Week 48, as defined by the United States (US) Food and Drug Administration (FDA) time-to-loss-of-virologic-response (TLOVR) algorithm.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| 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 |
84.4; 72.8 | 0.002 sig |
| SECONDARY Percentage of Participants With Confirmed Plasma HIV-1 RNA < 50 c/mL at Week 48 (Defined by FDA TLOVR Algorithm) |
79.5; 70.4 | 0.021 sig |
| SECONDARY Percentage of Participants With Plasma HIV-1 RNA < 400 c/mL at Week 48. |
80.4; 69.3 | 0.004 sig |
| SECONDARY Percentage of Participants With HIV-1 RNA < 50 c/mL at Week 48 |
74.5; 66.9 | 0.058 |
| SECONDARY Percentage of Participants With Loss of Virologic Response (HIV-1 RNA < 400 c/mL) at Week 48 |
19; 30 | 0.003 sig |
| SECONDARY Percentage of Participants With Loss of Virologic Response (HIV-1 RNA < 50 c/mL) at Week 48 |
23; 32 | 0.046 sig |
| SECONDARY Percentage of Participants With Pure Virologic Failure (HIV-1 RNA < 400 c/mL) at Week 48 |
9; 16 | 0.026 sig |
| SECONDARY Percentage of Participants With Pure Virologic Failure (HIV-1 RNA < 50 c/mL) at Week 48 |
16; 24 | 0.063 |
| SECONDARY Change From Study Baseline in HIV-1 RNA (Log10 c/mL) at Week 48 |
-3.31; -3.26 | 0.31 |
| SECONDARY Change From Study Baseline in CD4 Cell Count (Cells/mm^3) at Week 48 |
190; 158 | 0.002 sig |
| SECONDARY Percentage of Participants With Confirmed Plasma HIV-1 RNA < 400 c/mL at Week 96 (Defined by FDA TLOVR Algorithm) |
74.6; 61.9 | 0.004 sig |
| SECONDARY Percentage of Participants With Confirmed Plasma HIV-1 RNA < 50 c/mL at Week 96 (Defined by FDA TLOVR Algorithm) |
67.2; 60.9 | 0.158 |
| SECONDARY Percentage of Participants With Loss of Virologic Response (HIV-1 RNA < 400 c/mL) at Week 96 |
25; 37 | 0.003 sig |
| SECONDARY Percentage of Participants With Loss of Virologic Response (HIV-1 RNA < 50 c/mL) at Week 96 |
32; 38 | 0.124 |
| SECONDARY Percentage of Participants With Pure Virologic Failure (HIV-1 RNA < 400 c/mL) at Week 96 |
9; 17 | 0.025 sig |
| SECONDARY Percentage of Participants With Pure Virologic Failure (HIV-1 RNA < 50 c/mL) at Week 96 |
20; 23 | 0.41 |
| SECONDARY Change From Study Baseline in HIV-1 RNA (Log10 c/mL) at Week 96 |
-3.30; -3.25 | 0.45 |
| SECONDARY Change From Study Baseline in CD4 Cell Count (Cells/mm^3) at Week 96 |
270; 237 | 0.036 sig |
| SECONDARY Change in Limb Fat (kg) From Week 48 to Week 96 |
0.74; -0.77 | <0.001 sig |
| SECONDARY Change in Trunk Fat (kg) From Week 48 to Week 96 |
0.94; -0.04 | 0.025 sig |
| SECONDARY Change in Total Body Fat (kg) From Week 48 to Week 96 |
1.69; -0.82 | <0.001 sig |
| SECONDARY Percentage of Participants With Confirmed Plasma HIV-1 RNA < 400 c/mL at Week 144 (Defined by FDA TLOVR Algorithm) |
70.9; 58.1 | 0.004 sig |
| SECONDARY Percentage of Participants With Confirmed Plasma HIV-1 RNA < 50 c/mL at Week 144 (Defined by FDA TLOVR Algorithm) |
64.3; 56.3 | 0.082 |
| SECONDARY Percentage of Participants With Plasma HIV-1 RNA < 400 c/mL at Week 144 |
63.1; 51.6 | 0.009 sig |
| SECONDARY Percentage of Participants With Plasma HIV-1 RNA < 50 c/mL at Week 144 |
60.8; 50.4 | 0.019 sig |
| SECONDARY Percentage of Participants With Loss of Virologic Response (HIV-1 RNA < 400 c/mL) at Week 144 |
28; 41 | 0.003 sig |
| SECONDARY Percentage of Participants With Loss of Virologic Response (HIV-1 RNA < 50 c/mL) at Week 144 |
34; 43 | 0.056 |
| SECONDARY Percentage of Participants With Pure Virological Failure (HIV-1 RNA < 400 c/mL) at Week 144 |
11; 17 | 0.066 |
| SECONDARY Percentage of Participants With Pure Virological Failure (HIV-1 RNA < 50 c/mL) at Week 144 |
21; 25 | 0.30 |
| SECONDARY Change From Study Baseline in HIV-1 RNA (Log10 c/mL) at Week 144 |
-3.32; -3.30 | 0.39 |
| SECONDARY Change From Study Baseline in CD4 Cell Count (Cells/mm^3) at Week 144 |
312; 271 | 0.089 |
| SECONDARY Change in Limb Fat (kg) From Week 48 to Week 144 |
1.13; -1.09 | 0.001 sig |
| SECONDARY Change in Trunk Fat (kg) From Week 48 to Week 144 |
1.30; -0.10 | 0.011 sig |
| SECONDARY Change in Total Body Fat (kg) From Week 48 to Week 144 |
2.47; -1.18 | <0.001 sig |
| 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 |
87 | — |
| 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 |
85 | — |
| SECONDARY Percentage of Participants With Plasma HIV-1 RNA < 400 c/mL at Week 240 (Atripla Week 96) |
87; 85 | — |
| SECONDARY Percentage of Participants With Plasma HIV-1 RNA < 50 c/mL at Week 240 (Atripla Week 96) |
84; 82 | — |
| 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) |
13 | — |
| 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) |
15 | — |
| SECONDARY Percentage of Participants With Pure Virological Failure (HIV-1 RNA < 400 c/mL) Through Week 240 (Atripla Week 96) |
11; 2 | — |
| SECONDARY Percentage of Participants With Pure Virological Failure (HIV-1 RNA < 50 c/mL) Through Week 240 (Atripla Week 96) |
22; 4 | — |
| SECONDARY Change From Baseline in CD4 Cell Count (Cells/mm^3) at Week 240 (Atripla Week 96) |
346; 42 | — |
| SECONDARY Change in Limb Fat (kg) From Week 144 (Atripla Baseline) to Week 240 (Atripla Week 96) |
0.12 | 0.16 |
| SECONDARY Change in Trunk Fat (kg) From Week 144 (Atripla Baseline) to Week 240 (Atripla Week 96) |
0.27 | 0.049 sig |
| SECONDARY Change in Total Body Fat (kg) From Week 144 (Atripla Baseline) to Week 240 (Atripla Week 96) |
0.37 | 0.055 |
| 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. |
182; 6; 8; 29 | <0.001 sig |
| 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. |
192; 8; 9; 17 | 0.12 |
| 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. |
166; 21; 13; 26 | 0.037 sig |
| SECONDARY Treatment Satisfaction Questionnaire (General Satisfaction With Current Treatment Regimen): Change From Week 144 to Week 240 in the Category Shift From Atripla Baseline. |
180; 10; 9; 23 | 0.013 sig |
| 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. |
41; 126; 31; 28 | 0.70 |
| SECONDARY Quality of Life (SF-12v2 Health Survey: Physical Component Summary) Change From Week 144 (Atripla Baseline) to Week 240 (Atripla Week 96) |
0.0 | 0.95 |
| SECONDARY Quality of Life (SF-12v2 Health Survey: Mental Component Summary) Change From Week 144 (Atripla Baseline) to Week 240 (Atripla Week 96) |
0.9 | 0.23 |
Eligibility Criteria
Inclusion Criteria: Participants must have met all inclusion criteria within 28 days prior to randomization unless specified otherwise including:
- Plasma HIV-1 RNA levels greater than 10,000 c/mL using Roche Amplicor HIV-1 Monitor Test Version 1.5 Standard
- Adequate renal function: Calculated creatinine clearance greater than or equal to 50 mL/min according to the Cockcroft-Gault Formula.
- Hepatic transaminases (aspartate aminotransferase [AST] and alanine aminotransferase [ALT]) 3 x upper limit of normal (ULN).
- Total bilirubin less than or equal to 1.5 mg/dL.
- Adequate hematologic function (absolute neutrophil count greater than or equal to 1,000/mm^3; platelets greater than or equal to 50,000/mm^3; hemoglobin greater than or equal to 8.0 g/dL).
- Serum amylase less than or equal to 1.5 x ULN.
- Serum phosphorus greater than or equal to 2.2 mg/dL.
- Willingness to use effective contraception by both males and females while on study treatment and for 30 days following study drug completion.
- Life expectancy greater than or equal to 1 year
- The ability to understand and sign written informed consent form obtained prior to initiation of study procedures.
Exclusion Criteria: Participants were not eligible for entry to the study if any of the following were met:
- Prior treatment with any non-nucleoside reverse transcriptase inhibitor (NNRTI), nucleoside reverse transcriptase inhibitor (NRTI), or protease inhibitor (PI).
- A new AIDS-defining condition diagnosed (exception CD4 criteria) within 30 days of baseline.
- Receiving ongoing therapy with any of the following: nephrotoxic agents, probenecid, systemic chemotherapeutic agents, systemic corticosteroids, interleukin-2, drugs that interact with efavirenz. Administration of any of the above medications must be discontinued at least 30 days prior to baseline visit and for duration of study.
- Pregnant or lactating participants.
- Malignancy other than cutaneous Kaposi's sarcoma (KS) or basal cell carcinoma. Participants with biopsy-confirmed KS were eligible but must not have received any systemic therapy for KS within 30 days of baseline and not anticipated starting systemic therapy during the study.
- Prior history of renal or bone disease.
- Any other clinical condition prior to therapy that would make the participant unsuitable for the study or unable to comply with the dosing requirements in the opinion of the investigator.
Data sourced from ClinicalTrials.gov (NCT00112047). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.