KIVEXA Vs TRUVADA, Both Administered With Efavirenz, In ART-Naive Subjects (ASSERT)

This study has been completed.
Sponsor:
Information provided by:
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00549198
First received: October 24, 2007
Last updated: April 7, 2011
Last verified: April 2011
  Purpose

Recently, the fixed-dose combinations (FDC) KIVEXA™ (abacavir/lamivudine) and TRUVADA (tenofovir disoproxil fumarate/emtricitabine) have facilitated the usage of once-daily regimens. However data from head-to-head randomized trials comparing these two FDCs as part of an initial regimen are not available at present. The long-term toxicity profiles of these regimens are of particular importance, as treatment of HIV is currently life-long and therefore, minimizing long-term toxicity and maximizing adherence and duration of regimen maintenance are critical therapy objectives.

The primary endpoint is estimated glomerular filtration rate (GFR), as measured by the modified diet in renal disease (MDRD) equation, a validated estimate of renal function.


Condition Intervention Phase
Infection, Human Immunodeficiency Virus I
HIV Infection
Drug: Abacavir/lamivudine and efavirenz
Drug: Tenofovir/Emtricitabine and efavirenz
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Study of Once-Daily Abacavir/Lamivudine Versus Tenofovir/Emtricitabine, Administered With Efavirenz in Antiretroviral-Naive, HIV-1 Infected Adult Subjects

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Mean Change From Baseline in Estimated Glomerular Filtration Rate (GFR), Calculated by Modification of Diet in Renal Disease (MDRD) Equation, at Week 48 [ Time Frame: Baseline, Week 48 ] [ Designated as safety issue: No ]
    Change from baseline was calculated as the Week 48 value minus the baseline value. GFR is a measure of the rate at which blood is filtered by the kidney. MDRD is an equation (calculation) used to estimate GFR in participants with impaired renal function based on serum creatinine, age, race, and gender. GFR (mL/min/1.73 m^2) = 175 * (Scr)^-1.154 * (Age)^-0.203 * (0.742 if female) * (1.212 if African American) (conventional units). mL, milliliters; min, minute; m^2, meters squared; Scr, serum creatinine; BMI, body mass index.


Secondary Outcome Measures:
  • Mean Change From Baseline in Estimated Glomerular Filtration Rate (GFR), Calculated by Modification of Diet in Renal Disease (MDRD) Equation, at Week 24 [ Time Frame: Baseline, Week 24 ] [ Designated as safety issue: No ]
    Change from baseline was calculated as the Week 24 value minus the baseline value. GFR is a measure of the rate at which blood is filtered by the kidney. MDRD is an equation (calculation) used to estimate GFR in participants with impaired renal function based on serum creatinine, age, race, and gender. GFR (mL/min/1.73 m^2) = 175 * (Scr)^-1.154 * (Age)^-0.203 * (0.742 if female) * (1.212 if African American) (conventional units). mL, milliliters; min, minute; m^2, meters squared; Scr, serum creatinine.

  • Mean Change From Baseline in Estimated Glomerular Filtration Rate (GFR), Calculated by Modification of Diet in Renal Disease (MDRD) Equation, at Week 96 [ Time Frame: Baseline, Week 96 ] [ Designated as safety issue: No ]
    Change from baseline was calculated as the Week 96 value minus the baseline value. GFR is a measure of the rate at which blood is filtered by the kidney. MDRD is an equation (calculation) used to estimate GFR in participants with impaired renal function based on serum creatinine, age, race, and gender. GFR (mL/min/1.73 m^2) = 175 * (Scr)^-1.154 * (Age)^-0.203 * (0.742 if female) * (1.212 if African American) (conventional units). mL, milliliters; min, minute; m^s, meters squared; Scr, serum creatinine.

  • Mean Change From Baseline in Estimated GFR, Calculated by Cockcroft-Gault Equation, at Week 24 [ Time Frame: Baseline, Week 24 ] [ Designated as safety issue: No ]
    Change from baseline was calculated as the Week 24 value minus the baseline value. Cockcroft-Gault is an equation (calculation) used to estimate GFR based on serum creatinine, weight, and gender. GFR = (140 - age) * (mass in kg) * (0.85 if female) divided by 72 * serum creatinine in mg/dL. mg, milligram; dL, deciliter; kg, kilogram; CG, Cockcroft-Gault.

  • Mean Change From Baseline in Estimated GFR, Calculated by Cockcroft-Gault Equation, at Week 48 [ Time Frame: Baseline, Week 48 ] [ Designated as safety issue: No ]
    Change from baseline was calculated as the Week 48 value minus the baseline value. Cockcroft-Gault is an equation (calculation) used to estimate GFR based on serum creatinine, weight, and gender. GFR = (140 - age) * (mass in kg) * (0.85 if female) divided by 72 * serum creatinine in mg/dL. mg, milligram; dL, deciliter; kg, kilogram.

  • Mean Change From Baseline in Estimated GFR, Calculated by Cockcroft-Gault Equation, at Week 96 [ Time Frame: Baseline, Week 96 ] [ Designated as safety issue: No ]
    Change from baseline was calculated as the Week 96 value minus the baseline value. Cockcroft-Gault is an equation (calculation) used to estimate GFR based on serum creatinine, weight, and gender. GFR = (140 - age) * (mass in kg) * (0.85 if female) divided by 72 * serum creatinine in mg/dL. mg, milligram; dL, deciliter; kg, kilogram.

  • Number of Participants With Decline From Baseline in Estimated GFR, Calculated by MDRD and Cockcroft-Gault Equations, of >=10 mL/Min/1.73 m^2 (mL/Min for Cockcroft-Gault), >=20 mL/Min/1.72 m^2, >=10%, and >=20% at Week 24 [ Time Frame: Baseline, Week 24 ] [ Designated as safety issue: No ]
    mL, milliliter; min, minute; m^2, meters squared

  • Number of Participants With Decline From Baseline in Estimated GFR, Calculated by MDRD and Cockcroft-Gault Equations, of >=10 mL/Min/1.73m^2 (mL/Min for Cockcroft-Gault), >=20 mL/Min/1.72m^2, >=10%, and >=20% at Week 48 [ Time Frame: Baseline, Week 48 ] [ Designated as safety issue: No ]
    mL, milliliter; min, minute; m^2, meters squared

  • Number of Participants With Decline From Baseline in Estimated GFR, Calculated by MDRD and Cockcroft-Gault Equations, of >=10 mL/Min/1.73m^2 (mL/Min for Cockcroft-Gault), >=20 mL/Min/1.72m^2, >=10%, and >=20% at Week 96 [ Time Frame: Baseline, Week 96 ] [ Designated as safety issue: No ]
    mL, milliliter; min, minute; m^2, meters squared

  • Number of Participants With National Kidney Foundation Chronic Kidney Disease Stage 1, 2, 3, 4, or 5 Categories of Renal Function at Week 24 [ Time Frame: Baseline, Week 24 ] [ Designated as safety issue: No ]
    Normal: GFR >=60 mL/min/1.73 m^2 and creatinine ratio <=200 mg/g GFR; Stage 1: GFR >=90 mL/min/1.73 m^2 and creatinine ratio >200 mg/g; Stage 2: GFR >=60-<90 mL/min/1.73 m^2 and creatinine ratio >200 mg/g; Stage 3: GFR >=30-<60 mL/min/1.73 m^2; Stage 4: GFR >=15-<30 mL/min/1.73 m^2; Stage 5: GFR <15 mL/min/1.73 m^2. mL, milliliter; min, minute; m^2, meters squared; mg, milligram; g, gram.

  • Number of Participants With National Kidney Foundation Chronic Kidney Disease Stage 1, 2, 3, 4, or 5 Categories of Renal Function at Week 48 [ Time Frame: Baseline, Week 48 ] [ Designated as safety issue: No ]
    Normal: GFR >=60 mL/min/1.73 m^2 and creatinine ratio <=200 mg/g GFR; Stage 1: GFR >=90 mL/min/1.73 m^2 and creatinine ratio >200 mg/g; Stage 2: GFR >=60-<90 mL/min/1.73 m^2 and creatinine ratio >200 mg/g; Stage 3: GFR >=30-<60 mL/min/1.73 m^2; Stage 4: GFR >=15-<30 mL/min/1.73 m^2; Stage 5: GFR <15 mL/min/1.73 m^2. mL, milliliter; min, minute; m^2, meters squared; mg, milligram; g, gram.

  • Number of Participants With National Kidney Foundation Chronic Kidney Disease Stage 1, 2, 3, 4, or 5 Categories of Renal Function at Week 96 [ Time Frame: Baseline, Week 96 ] [ Designated as safety issue: No ]
    Normal: GFR >=60 mL/min/1.73 m^2 and creatinine ratio <=200 mg/g GFR; Stage 1: GFR >=90 mL/min/1.73 m^2 and creatinine ratio >200 mg/g; Stage 2: GFR >=60-<90 mL/min/1.73 m^2 and creatinine ratio >200 mg/g; Stage 3: GFR >=30-<60 mL/min/1.73 m^2; Stage 4: GFR >=15-<30 mL/min/1.73 m^2; Stage 5: GFR <15 mL/min/1.73 m^2. mL, milliliter; min, minute; m^2, meters squared; mg, milligram; g, gram.

  • Percent Change From Baseline in Lumbar Spine Bone Mineral Density (BMD), Measured by Dual-energy X-ray Absorptiometry (DXA), at Week 24 [ Time Frame: Baseline, Week 24 ] [ Designated as safety issue: No ]
    BMD is a measure (grams [g] per centimeters cubed [cm^3]) of the mineral content of bone in a particular skeletal area. DXA scans use low energy x-rays to measure the density of bones. The standard error (SE) of both treatment groups was based on the model on the log scale.

  • Percent Change From Baseline in Hip Bone Mineral Density (BMD), Measured by Dual-energy X-ray Absorptiometry (DXA), at Week 24 [ Time Frame: Baseline, Week 24 ] [ Designated as safety issue: No ]
    BMD is a measure (grams per cm^3) of the mineral content of bone in a particular skeletal area. DXA scans use low energy x-rays to measure the density of bones. The standard error (SE) of both treatment groups was based on the model on the log scale.

  • Percent Change From Baseline in Lumbar Spine Bone Mineral Density (BMD), Measured by Dual-energy X-ray Absorptiometry (DXA), at Week 48 [ Time Frame: Baseline, Week 48 ] [ Designated as safety issue: No ]
    BMD is a measure (grams per cm^3) of the mineral content of bone in a particular skeletal area. DXA scans use low energy x-rays to measure the density of bones. The standard error (SE) of both treatment groups was based on the model on the log scale.

  • Percent Change From Baseline in Hip Bone Mineral Density (BMD), Measured by Dual-energy X-ray Absorptiometry (DXA), at Week 48 [ Time Frame: Baseline, Week 48 ] [ Designated as safety issue: No ]
    BMD is a measure (grams per cm^3) of the mineral content of bone in a particular skeletal area. DXA scans use low energy x-rays to measure the density of bones. The standard error (SE) of both treatment groups was based on the model on the log scale.

  • Percent Change From Baseline in Lumbar Spine Bone Mineral Density (BMD), Measured by Dual-energy X-ray Absorptiometry (DXA), at Week 96 [ Time Frame: Baseline, Week 96 ] [ Designated as safety issue: No ]
    BMD is a measure (grams per cm^3) of the mineral content of bone in a particular skeletal area. DXA scans use low energy x-rays to measure the density of bones. The standard error (SE) of both treatment groups was based on the model on the log scale.

  • Percent Change From Baseline in Hip Bone Mineral Density (BMD), Measured by Dual-energy X-ray Absorptiometry (DXA), at Week 96 [ Time Frame: Baseline, Week 96 ] [ Designated as safety issue: No ]
    BMD is a measure (grams per cm^3) of the mineral content of bone in a particular skeletal area. DXA scans use low energy x-rays to measure the density of bones. The standard error (SE) of both treatment groups was based on the model on the log scale.

  • Number of Participants With a Decline From Baseline in Lumbar Spine and Hip Bone Mineral Density (BMD) >=2.0% and >=6.0% at Week 24 [ Time Frame: Baseline, Week 24 ] [ Designated as safety issue: No ]
    BMD is a measure of the mineral content of bone in a particular skeletal area. DXA scans use low energy x-rays to measure the density of bones.

  • Number of Participants With a Decline From Baseline in Lumbar Spine and Hip Bone Mineral Density (BMD) >=2.0% and >=6.0% at Week 48 [ Time Frame: Baseline, Week 48 ] [ Designated as safety issue: No ]
    BMD is a measure of the mineral content of bone in a particular skeletal area. DXA scans use low energy x-rays to measure the density of bones.

  • Number of Participants With a Decline From Baseline in Lumbar Spine and Hip Bone Mineral Density (BMD) >=2.0% and >=6.0% at Week 96 [ Time Frame: Baseline, Week 96 ] [ Designated as safety issue: No ]
    BMD is a measure of the mineral content of bone in a particular skeletal area. DXA scans use low energy x-rays to measure the density of bones.

  • Number of Participants Meeting World Health Organization (WHO) Criteria for Osteopenia (T-score of -2.5 to -1.0) and Osteoporosis (T-score of <-2.5) at Week 24 [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    The T-score is a radiographic diagnosis that compares bone mineral density (BMD) to that of a "normal, healthy, 30-year-old female". The lower the T-score, the lower the BMD. A T-score of +1 to -1 is normal. A T-score decrease of -1 indicates a 10%-15% decrease in BMD.

  • Number of Participants Meeting World Health Organization (WHO) Criteria for Osteopenia (T-score of -2.5 to -1.0) and Osteoporosis (T-score of <-2.5) at Week 48 [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
    The T-score is a radiographic diagnosis that compares bone mineral density (BMD) to that of a "normal, healthy, 30-year-old female". The lower the T-score, the lower the BMD. A T-score of +1 to -1 is normal. A T-score decrease of -1 indicates a 10%-15% decrease in BMD.

  • Number of Participants Meeting World Health Organization (WHO) Criteria for Osteopenia (T-score of -2.5 to -1.0) and Osteoporosis (T-score of <-2.5) at Week 96 [ Time Frame: Week 96 ] [ Designated as safety issue: No ]
    The T-score is a radiographic diagnosis that compares bone mineral density (BMD) to that of a "normal, healthy, 30-year-old female". The lower the T-score, the lower the BMD. A T-score of +1 to -1 is normal. A T-score decrease of -1 indicates a 10%-15% decrease in BMD.

  • Number of Participants Experiencing an Adverse Event (AE) Leading to Discontinuation by Week 24 [ Time Frame: Baseline to Week 24 ] [ Designated as safety issue: No ]
    An adverse event was any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Adverse events occurring in two or more participants are presented.

  • Number of Participants Experiencing an Adverse Event (AE) Leading to Discontinuation by Week 48 [ Time Frame: Baseline to Week 48 ] [ Designated as safety issue: No ]
    An adverse event was any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Adverse events occurring in two or more participants are presented.

  • Number of Participants Experiencing an Adverse Event (AE) Leading to Discontinuation by Week 96 [ Time Frame: Baseline to Week 96 ] [ Designated as safety issue: No ]
    An adverse event was any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Adverse events occurring in two or more participants are presented.

  • Number of Participants With the Indicated Change From Baseline in National Cholesterol Education Program (NCEP) Thresholds for Fasting Total Cholesterol at Week 24 [ Time Frame: Baseline, Week 24 ] [ Designated as safety issue: No ]
    Blood samples were collected from participants for analysis of their lipid profile. Data are categorized by the maximum post-baseline threshold reached. <200 mg/dL, desirable; 200-<240 mg/dL, borderline high; >=240 mg/dL, high. mg, milligram; dL, deciliter.

  • Number of Participants With the Indicated Change From Baseline in National Cholesterol Education Program (NCEP) Thresholds for Fasting Total Cholesterol at Week 48 [ Time Frame: Baseline, Week 48 ] [ Designated as safety issue: No ]
    Blood samples were collected from participants for analysis of their lipid profile. Data are categorized by the maximum post-baseline threshold reached. <200 mg/dL, desirable; 200-<240 mg/dL, borderline high; >=240 mg/dL, high. mg, milligram; dL, deciliter.

  • Number of Participants With the Indicated Change From Baseline in National Cholesterol Education Program (NCEP) Thresholds for Fasting Total Cholesterol at Week 96 [ Time Frame: Baseline, Week 96 ] [ Designated as safety issue: No ]
    Blood samples were collected from participants for analysis of their lipid profile. Data are categorized by the maximum post-baseline threshold reached. <200 mg/dL, desirable; 200-<240 mg/dL, borderline high; >=240 mg/dL, high. mg, milligram; dL, deciliter.

  • Number of Participants With the Indicated Change From Baseline in National Cholesterol Education Program (NCEP) Thresholds for Low-density Lipoprotein (LDL) at Week 24 [ Time Frame: Baseline, Week 24 ] [ Designated as safety issue: No ]
    Blood samples were collected from participants for analysis of their lipid profile. Data are categorized by the maximum post-baseline threshold reached. <100 mg/dL, optimal; 100-<130 mg/dL, near/above optimal; 130-<160 mg/dL, borderline high; 160-<190 mg/dL, high; >=190 mg/dL, very high.

  • Number of Participants With the Indicated Change From Baseline in National Cholesterol Education Program (NCEP) Thresholds for Low-density Lipoprotein (LDL) at Week 48 [ Time Frame: Baseline, Week 48 ] [ Designated as safety issue: No ]
    Blood samples were collected from participants for analysis of their lipid profile. Data are categorized by the maximum post-baseline threshold reached. <100 mg/dL, optimal; 100-<130 mg/dL, near/above optimal; 130-<160 mg/dL, borderline high; 160-<190 mg/dL, high; >=190 mg/dL, very high.

  • Number of Participants With the Indicated Change From Baseline in National Cholesterol Education Program (NCEP) Thresholds for Low-density Lipoprotein (LDL) at Week 96 [ Time Frame: Baseline, Week 96 ] [ Designated as safety issue: No ]
    Blood samples were collected from participants for analysis of their lipid profile. Data are categorized by the maximum post-baseline threshold reached. <100 mg/dL, optimal; 100-<130 mg/dL, near/above optimal; 130-<160 mg/dL, borderline high; 160-<190 mg/dL, high; >=190 mg/dL, very high.

  • Number of Participants With the Indicated Change From Baseline in National Cholesterol Education Program (NCEP) Thresholds for Fasting High-density Lipoprotein (HDL) at Week 24 [ Time Frame: Baseline, Week 24 ] [ Designated as safety issue: No ]
    Blood samples were collected from participants for analysis of their lipid profile. Data are categorized by the maximum post-baseline threshold reached. <40 mg/dL, low; 40-<60 mg/dL, normal; >=60 mg/dL, high.

  • Number of Participants With the Indicated Change From Baseline in National Cholesterol Education Program (NCEP) Thresholds for Fasting High-density Lipoprotein (HDL) at Week 48 [ Time Frame: Baseline, Week 48 ] [ Designated as safety issue: No ]
    Blood samples were collected from participants for analysis of their lipid profile. Data are categorized by the maximum post-baseline threshold reached. <40 mg/dL, low; 40-<60 mg/dL, normal; >=60 mg/dL, high.

  • Number of Participants With the Indicated Change From Baseline in National Cholesterol Education Program (NCEP) Thresholds for Fasting High-density Lipoprotein (HDL) at Week 96 [ Time Frame: Baseline, Week 96 ] [ Designated as safety issue: No ]
    Blood samples were collected from participants for analysis of their lipid profile. Data are categorized by the maximum post-baseline threshold reached. <40 mg/dL, low; 40-<60 mg/dL, normal; >=60 mg/dL, high.

  • Number of Participants With the Indicated Change From Baseline in National Cholesterol Education Program (NCEP) Thresholds for Fasting Triglycerides at Week 24 [ Time Frame: Baseline, Week 24 ] [ Designated as safety issue: No ]
    Blood samples were collected from participants for analysis of their lipid profile. Data are categorized by the maximum post-baseline threshold reached. <150 mg/dL, normal; 150-<200 mg/dL, borderline high; 200-<500 mg/dL, high; >=500 mg/dL, very high.

  • Number of Participants With the Indicated Change From Baseline in National Cholesterol Education Program (NCEP) Thresholds for Fasting Triglycerides at Week 48 [ Time Frame: Baseline, Week 48 ] [ Designated as safety issue: No ]
    Blood samples were collected from participants for analysis of their lipid profile. Data are categorized by the maximum post-baseline threshold reached. <150 mg/dL, normal; 150-<200 mg/dL, borderline high; 200-<500 mg/dL, high; >=500 mg/dL, very high.

  • Number of Participants With the Indicated Change From Baseline in National Cholesterol Education Program (NCEP) Thresholds for Fasting Triglycerides at Week 96 [ Time Frame: Baseline, Week 96 ] [ Designated as safety issue: No ]
    Blood samples were collected from participants for analysis of their lipid profile. Data are categorized by the maximum post-baseline threshold reached. <150 mg/dL, normal; 150->200 mg/dL, borderline high; 200-<500 mg/dL, high;>= 500 mg/dL, very high.

  • Number of Participants With the Indicated Treatment-emergent Division of AIDS (DAIDS) Toxicities at Week 24 [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    The DAIDS toxicity table provides descriptive terminology for grading the severity of adult adverse events. Laboratory grades also provide ranges for each parameter. Grade 1: mild, Grade 2: moderate, Grade 3: severe, Grade 4: potentially life-threatening. LDL, low-density lipid; HDL, high-density lipid. Treatment emergent refers to any toxicity that was not present prior to the start of study drug treatment.

  • Number of Participants With the Indicated Treatment-emergent Division of AIDS (DAIDS) Toxicities at Week 48 [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
    The DAIDS toxicity table provides descriptive terminology for grading the severity of adult adverse events. Laboratory grades also provide ranges for each parameter. Grade 1: mild, Grade 2: moderate, Grade 3: severe, Grade 4: potentially life-threatening. LDL, low-density lipid; HDL, high-density lipid. Treatment emergent refers to any toxicity that was not present prior to the start of study drug treatment.

  • Number of Participants With the Indicated Treatment-emergent Division of AIDS (DAIDS) Toxicities at Week 96 [ Time Frame: Week 96 ] [ Designated as safety issue: No ]
    The DAIDS toxicity table provides descriptive terminology for grading the severity of adult adverse events. Laboratory grades also provide ranges for each parameter. Grade 1: mild, Grade 2: moderate, Grade 3: severe, Grade 4: potentially life-threatening. LDL, low-density lipid; HDL, high-density lipid. Treatment emergent refers to any toxicity that was not present prior to the start of study drug therapy.

  • Number of Participants With HIV-1 RNA <50 Copies/Milliliter (c/mL) and 400 c/mL at Week 24 [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    HIV-1 RNA level (viral load) is a strong predictor of the rate of HIV disease progression. It was measured from plasma (participant blood samples) taken at all visits throughout the study. HIV, human immunodeficiency virus; RNA, ribonucleic acid. Viral load is a measure of the severity of the HIV infection.

  • Number of Participants With HIV-1 RNA <50 Copies/Milliliter (c/mL) and 400 c/mL at Week 48 [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
    HIV-1 RNA level (viral load) is a strong predictor of the rate of HIV disease progression. It was measured from plasma (participant blood samples) taken at all visits throughout the study. HIV, human immunodeficiency virus; RNA, ribonucleic acid. Viral load is a measure of the severity of the HIV infection.

  • Number of Participants With HIV-1 RNA <50 Copies/Milliliter (c/mL) and 400 c/mL at Week 96 [ Time Frame: Week 96 ] [ Designated as safety issue: No ]
    HIV-1 RNA level (viral load) is a strong predictor of the rate of HIV disease progression. It was measured from plasma (participant blood samples) taken at all visits throughout the study. HIV, human immunodeficiency virus; RNA, ribonucleic acid. Viral load is a measure of the severity of the HIV infection.

  • Change From Baseline in Cluster Difference 4 (CD4+) Cell Count at Week 24 [ Time Frame: Baseline, Week 24 ] [ Designated as safety issue: No ]
    CD4+ counts are used to monitor the progression of HIV disease and the strength of the immune system. The number of CD4+ cells decreases as HIV disease progresses. Cell counts were measured from participant blood samples taken throughout the study.

  • Change From Baseline in Cluster Difference 4 (CD4+) Cell Count at Week 48 [ Time Frame: Baseline, Week 48 ] [ Designated as safety issue: No ]
    CD4+ counts are used to monitor the progression of HIV disease and the strength of the immune system. The number of CD4+ cells decreases as HIV disease progresses. Cell counts were measured from participant blood samples taken throughout the study.

  • Change From Baseline in Cluster Difference 4 (CD4+) Cell Count at Week 96 [ Time Frame: Baseline, Week 96 ] [ Designated as safety issue: No ]
    CD4+ counts are used to monitor the progression of HIV disease and the strength of the immune system. The number of CD4+ cells decreases as HIV disease progresses. Cell counts were measured from participant blood samples taken throughout the study.

  • Number of Participants Classified as Protocol-defined Failures With Treatment-emergent Resistance to Study Drug in the Indicated Viruses at Week 96 [ Time Frame: Week 96 ] [ Designated as safety issue: No ]
    Viral resistance was measured using blood samples collected from participants throughout the study. NRTI, nucleoside reverse transcriptase inhibitor; NNRTI, non-nucleoside reverse transcriptase inhibitor. Virological failure was defined as any one of: participant does not achieve a 1 log10 copies (cop)/mL decrease in plasma HIV-1 RNA by Week (Wk) 4, or has two consecutive plasma HIV-1 RNA measures >=400 cop/mL separated by at least 2-4 wk after being previously <=400 cop/mL on/after Wk 4, or has two consecutive plasma HIV-1 RNA measures >400 cop/mL separated by at least 2-4 wk on/after Wk 24.

  • Number of Participants Who Indicated "Yes" or "No" to the Question of Whether Unplanned Healthcare Resources Were Utilized [ Time Frame: Baseline to Week 96 ] [ Designated as safety issue: No ]
    Participants were asked at each visit whether or not they utilized unplanned healthcare resources.


Enrollment: 392
Study Start Date: June 2007
Study Completion Date: December 2009
Primary Completion Date: December 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: ABC/3TC + EFV Drug: Abacavir/lamivudine and efavirenz
Active Comparator: TDF/FTC + EFV Drug: Tenofovir/Emtricitabine and efavirenz

Detailed Description:

ViiV Healthcare is the new sponsor of this study, and GlaxoSmithKline is in the process of updating systems to reflect the change in sponsorship.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Subject is at least 18 years of age.
  • Subject is antiretroviral-naïve (defined as having no previous therapy with any NNRTI and 14 days of prior therapy with any other antiretroviral).
  • Subject has plasma HIV-1 RNA 1,000 copies/mL at screening. This test may be repeated once within the 45-day screening window.
  • Subject is willing and able to understand and provide written informed consent prior to participation in this study.
  • A female is eligible to enter and participate in the study if she is of:

    1. Non-childbearing potential (i.e., physiologically incapable of becoming pregnant, including any female who is post-menopausal); or,
    2. Child-bearing potential, has a negative pregnancy test at screen and agrees to one of the following methods of contraception (any contraception method must be used consistently and correctly, i.e., in accordance with both the approved product label and the instructions of a physician):

Complete abstinence from intercourse from 2 weeks prior to administration of the investigational products, throughout the study, and for at least 2 weeks after discontinuation of all study medications Double barrier method (male condom/spermicide, male condom/diaphragm, diaphragm/spermicide). Hormonal contraception will not be considered adequate for inclusion into this study Any intrauterine device (IUD) with published data showing that the expected failure rate is <1% per year.

Sterilization (female subject or male partner of female subject).

  • Prior to randomization, subjects must have been screened and be negative for the HLA-B*5701 allele. Test may be performed by local laboratory and results must be available for source document verification according to local practices.

Exclusion Criteria:

  • Subject is in the initial acute phase of a CDC Clinical Category C infection at Baseline.
  • Subject is enrolled in one or more investigational drug protocols, which may impact HIV RNA suppression.
  • Subject is, in the opinion of the Investigator, unable to complete the study dosing period and protocol evaluations and assessments.
  • Subject is either pregnant or breastfeeding.
  • Subject suffers from a serious medical condition, which in the opinion of the Investigator would compromise the safety of the subject.
  • Subject has a history of inflammatory bowel disease or other gastrointestinal dysfunction.
  • Subject has any acute laboratory abnormality at screening.
  • Subject has an estimated creatinine clearance within the screening period <50mL/min via the Cockcroft-Gault method.
  • Alanine aminotransferase (ALT) >5 times the upper limit of normal.
  • Subjects with a history of thyroid disease, hyperparathyroid disease, chronic hyper or hypocalcemia, vitamin D deficiency, or receiving thyroid hormone or parathyroid hormone replacement within 28 days prior to screening.
  • Subjects with a history of systemic inflammatory arthritis.
  • Subjects who are hepatitis B positive at screening.
  • Subject requires treatment with radiation therapy or cytotoxic chemotherapeutic agents.
  • Subject has received treatment with an HIV-1 immunotherapeutic vaccine or any agents with documented activity against HIV-1 in vitro within 28 days prior to Screening, or an anticipated need during the study.
  • Subjects who require treatment with any of the following medications within 28 days of commencement of investigational product, or an anticipated need during the study:
  • Medications with significant drug-drug interactions with efavirenz:voriconazole, terfenadine, astemizole, cisapride, ergot alkaloids (dihydroergotamine, ergonovine, ergotamine, methylergonovine), midazolam, triazolam, St. John's wort, carbamazepine, phenytoin, phenobarbital, rifampin, pimozide, bepridil
  • Medications which may impact on bone mineral density: oral or systemic corticosteroids, anticonvulsants, heparin, warfarin, cyclosporine, bisphosphonates, calcitonin, parathyroid hormone, Vitamin D supplements and analogues, Calcium supplements, oestrogen or progesterone replacement (oral hormonal contraception permitted), raloxifene, tamoxifen, testosterone or anabolic steroid replacement/supplements.
  • Systemic interleukins or interferons
  • Subject has a history of allergy to any of the protocol-specified medications or any excipients therein.
  • Subject has evidence of genotypic resistance at screening (according to central lab interpretation) or prior documented evidence of genotypic and/or phenotypic (above threshold for reduced susceptibility) resistance to any of the following drugs: efavirenz, abacavir, lamivudine, tenofovir, emtricitabine.
  • Subjects who are unsuitable for DEXA scanning should be excluded, including 1) Less than three vertebra in the range of L1 to L4 that are suitable for BMD measurement by DEXA, or 2) Bilateral hip replacement.
  • The subject has previously participated in an experimental drug and/or vaccine trial(s) within 60 days or 5 half-lives, or twice the duration of the biological effect of the experimental drug or vaccine - whichever is longer, prior to screening for the study.
  • The subject will participate simultaneously in another clinical study.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00549198

  Show 68 Study Locations
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Cheri Hudson; Clinical Disclosure Advisor, GSK Clinical Disclosure
ClinicalTrials.gov Identifier: NCT00549198     History of Changes
Other Study ID Numbers: CNA109586
Study First Received: October 24, 2007
Results First Received: September 23, 2010
Last Updated: April 7, 2011
Health Authority: Austria: Agency for Health and Food Safety
Germany: Federal Institute for Drugs and Medical Devices
Belgium: The Federal Public Service (FPS) Health, Food Chain Safety and Environment

Keywords provided by GlaxoSmithKline:
tenofovir
HIV
efavirenz
naive
lamivudine
abacavir
emtricitabine
renal

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
HIV Infections
Immunologic Deficiency Syndromes
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Slow Virus Diseases
Immune System Diseases
Lamivudine
Tenofovir
Tenofovir disoproxil
Efavirenz
Abacavir
Emtricitabine
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Anti-HIV Agents

ClinicalTrials.gov processed this record on April 15, 2014