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

Study of Once-Daily Abacavir/Lamivudine Versus Tenofovir/Emtricitabine, Administered With Efavirenz in Antiretroviral-Naive, HIV-1 Infected Adult Subjects

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.

Study Overview

• Status: Completed
• Conditions: HIV Infection; Infection, Human Immunodeficiency Virus I
• Intervention / Treatment: Drug: Abacavir/lamivudine and efavirenz; 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.

• Study Type: Interventional
• Enrollment (Actual): 392
• Phase: Phase 4

Contacts and Locations

Study Locations

• Austria
  • Innsbruck, Austria, A-6020
    • GSK Investigational Site
  • Salzburg, Austria, A-5020
    • GSK Investigational Site
  • Vienna, Austria, A-1090
    • GSK Investigational Site
  • Vienna, Austria, A-1140
    • GSK Investigational Site
• Belgium
  • Brugge, Belgium, 8000
    • GSK Investigational Site
  • Bruxelles, Belgium, 1000
    • GSK Investigational Site
  • Charleroi, Belgium, 6000
    • GSK Investigational Site
  • Gent, Belgium, 9000
    • GSK Investigational Site
  • Leuven, Belgium, 3000
    • GSK Investigational Site
• Denmark
  • Aalborg, Denmark, DK-9000
    • GSK Investigational Site
  • Aarhus N, Denmark, 8200
    • GSK Investigational Site
  • Hvidovre, Denmark, DK-2650
    • GSK Investigational Site
  • Koebenhavn, Denmark, DK-2100
    • GSK Investigational Site
  • Odense C, Denmark, 5000
    • GSK Investigational Site
• France
  • Garches, France, 92380
    • GSK Investigational Site
  • Levallois-Perret, France, 92300
    • GSK Investigational Site
  • Saint Denis Cedex 01, France, 93205
    • GSK Investigational Site
• Germany
  • Berlin, Germany, 13353
    • GSK Investigational Site
  • Hamburg, Germany, 20246
    • GSK Investigational Site
  • Hamburg, Germany, 20146
    • GSK Investigational Site
  • Baden-Wuerttemberg
    • Heidelberg, Baden-Wuerttemberg, Germany, 69115
      • GSK Investigational Site
  • Bayern
    • Muenchen, Bayern, Germany, 80335
      • GSK Investigational Site
  • Niedersachsen
    • Hannover, Niedersachsen, Germany, 30159
      • GSK Investigational Site
    • Hannover, Niedersachsen, Germany, 30625
      • GSK Investigational Site
  • Nordrhein-Westfalen
    • Duesseldorf, Nordrhein-Westfalen, Germany, 40237
      • GSK Investigational Site
    • Essen, Nordrhein-Westfalen, Germany, 45122
      • GSK Investigational Site
  • Sachsen
    • Leipzig, Sachsen, Germany, 04170
      • GSK Investigational Site
• Ireland
  • Dublin, Ireland, 8
    • GSK Investigational Site
  • Dublin, Ireland, 7
    • GSK Investigational Site
• Italy
  • Emilia-Romagna
    • Ferrara, Emilia-Romagna, Italy, 44100
      • GSK Investigational Site
    • Modena, Emilia-Romagna, Italy, 41100
      • GSK Investigational Site
    • Rimini, Emilia-Romagna, Italy, 47900
      • GSK Investigational Site
  • Lazio
    • Roma, Lazio, Italy, 00149
      • GSK Investigational Site
  • Lombardia
    • Legnano (MI, Lombardia, Italy, 20025
      • GSK Investigational Site
    • Milano, Lombardia, Italy, 20127
      • GSK Investigational Site
    • Milano, Lombardia, Italy, 20142
      • GSK Investigational Site
  • Piemonte
    • Torino, Piemonte, Italy, 10149
      • GSK Investigational Site
• Latvia
  • Riga, Latvia, LV 1006
    • GSK Investigational Site
• Netherlands
  • Alkmaar, Netherlands, 1815 JD
    • GSK Investigational Site
  • Den Haag, Netherlands, 2512 VA
    • GSK Investigational Site
  • Groningen, Netherlands, 9713 GZ
    • GSK Investigational Site
  • Rotterdam, Netherlands, 3078 HT
    • GSK Investigational Site
  • Utrecht, Netherlands, 3584 CX
    • GSK Investigational Site
• Portugal
  • Amadora, Portugal, 2720-276
    • GSK Investigational Site
• Spain
  • Madrid, Spain, 28034
    • GSK Investigational Site
  • Valencia, Spain, 46015
    • GSK Investigational Site
• Switzerland
  • Basel, Switzerland, 4031
    • GSK Investigational Site
  • Bern, Switzerland, 3010
    • GSK Investigational Site
  • Lausanne, Switzerland, 1011
    • GSK Investigational Site
  • St Gallen, Switzerland, 9007
    • GSK Investigational Site
  • Zuerich, Switzerland, 8091
    • GSK Investigational Site
  • Zurich, Switzerland, 8038
    • GSK Investigational Site
• United Kingdom
  • Birmingham, United Kingdom, B4 6DH
    • GSK Investigational Site
  • Birmingham, United Kingdom, WS2 9PS
    • GSK Investigational Site
  • Farnworth, Bolton, United Kingdom, BL4 0JR
    • GSK Investigational Site
  • Gloucester, United Kingdom, GL1 3NN
    • GSK Investigational Site
  • Leicester, United Kingdom, LE1 5WW
    • GSK Investigational Site
  • London, United Kingdom, E1 1BB
    • GSK Investigational Site
  • London, United Kingdom, SW10 9TH
    • GSK Investigational Site
  • London, United Kingdom, NW3 2QG
    • GSK Investigational Site
  • London, United Kingdom, SW17 0QT
    • GSK Investigational Site
  • London, United Kingdom, N18 1QX
    • GSK Investigational Site
  • Middlesborough, United Kingdom, TS4 3BW
    • GSK Investigational Site
  • Sheffield, United Kingdom, S10 2JF
    • GSK Investigational Site
  • Lancashire
    • Manchester, Lancashire, United Kingdom, M8 5RB
      • GSK Investigational Site
  • London
    • Woolwich, London, London, United Kingdom, SE18 4QH
      • GSK Investigational Site
  • Midlothian
    • Edinburgh, Midlothian, United Kingdom, EH4 2XU
      • GSK Investigational Site
  • Sussex East
    • Brighton, Sussex East, United Kingdom, BN2 1ES
      • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ABC/3TC + EFV	Drug: Abacavir/lamivudine and efavirenz
Active Comparator: TDF/FTC + EFV	Drug: Tenofovir/Emtricitabine and efavirenz

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Change From Baseline in Estimated Glomerular Filtration Rate (GFR), Calculated by Modification of Diet in Renal Disease (MDRD) Equation, at Week 48	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.	Baseline, Week 48

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Change From Baseline in Estimated Glomerular Filtration Rate (GFR), Calculated by Modification of Diet in Renal Disease (MDRD) Equation, at Week 24	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.	Baseline, Week 24
Mean Change From Baseline in Estimated Glomerular Filtration Rate (GFR), Calculated by Modification of Diet in Renal Disease (MDRD) Equation, at Week 96	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.	Baseline, Week 96
Mean Change From Baseline in Estimated GFR, Calculated by Cockcroft-Gault Equation, at Week 24	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.	Baseline, Week 24
Mean Change From Baseline in Estimated GFR, Calculated by Cockcroft-Gault Equation, at Week 48	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.	Baseline, Week 48
Mean Change From Baseline in Estimated GFR, Calculated by Cockcroft-Gault Equation, at Week 96	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.	Baseline, Week 96
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	mL, milliliter; min, minute; m^2, meters squared	Baseline, Week 24
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	mL, milliliter; min, minute; m^2, meters squared	Baseline, Week 48
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	mL, milliliter; min, minute; m^2, meters squared	Baseline, Week 96
Number of Participants With National Kidney Foundation Chronic Kidney Disease Stage 1, 2, 3, 4, or 5 Categories of Renal Function at Week 24	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.	Baseline, Week 24
Number of Participants With National Kidney Foundation Chronic Kidney Disease Stage 1, 2, 3, 4, or 5 Categories of Renal Function at Week 48	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.	Baseline, Week 48
Number of Participants With National Kidney Foundation Chronic Kidney Disease Stage 1, 2, 3, 4, or 5 Categories of Renal Function at Week 96	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.	Baseline, Week 96
Percent Change From Baseline in Lumbar Spine Bone Mineral Density (BMD), Measured by Dual-energy X-ray Absorptiometry (DXA), at Week 24	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.	Baseline, Week 24
Percent Change From Baseline in Hip Bone Mineral Density (BMD), Measured by Dual-energy X-ray Absorptiometry (DXA), at Week 24	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.	Baseline, Week 24
Percent Change From Baseline in Lumbar Spine Bone Mineral Density (BMD), Measured by Dual-energy X-ray Absorptiometry (DXA), at Week 48	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.	Baseline, Week 48
Percent Change From Baseline in Hip Bone Mineral Density (BMD), Measured by Dual-energy X-ray Absorptiometry (DXA), at Week 48	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.	Baseline, Week 48
Percent Change From Baseline in Lumbar Spine Bone Mineral Density (BMD), Measured by Dual-energy X-ray Absorptiometry (DXA), at Week 96	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.	Baseline, Week 96
Percent Change From Baseline in Hip Bone Mineral Density (BMD), Measured by Dual-energy X-ray Absorptiometry (DXA), at Week 96	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.	Baseline, Week 96
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	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.	Baseline, Week 24
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	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.	Baseline, Week 48
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	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.	Baseline, Week 96
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	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.	Week 24
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	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.	Week 48
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	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.	Week 96
Number of Participants Experiencing an Adverse Event (AE) Leading to Discontinuation by Week 24	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.	Baseline to Week 24
Number of Participants Experiencing an Adverse Event (AE) Leading to Discontinuation by Week 48	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.	Baseline to Week 48
Number of Participants Experiencing an Adverse Event (AE) Leading to Discontinuation by Week 96	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.	Baseline to Week 96
Number of Participants With the Indicated Change From Baseline in National Cholesterol Education Program (NCEP) Thresholds for Fasting Total Cholesterol at Week 24	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.	Baseline, Week 24
Number of Participants With the Indicated Change From Baseline in National Cholesterol Education Program (NCEP) Thresholds for Fasting Total Cholesterol at Week 48	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.	Baseline, Week 48
Number of Participants With the Indicated Change From Baseline in National Cholesterol Education Program (NCEP) Thresholds for Fasting Total Cholesterol at Week 96	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.	Baseline, Week 96
Number of Participants With the Indicated Change From Baseline in National Cholesterol Education Program (NCEP) Thresholds for Low-density Lipoprotein (LDL) at Week 24	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.	Baseline, Week 24
Number of Participants With the Indicated Change From Baseline in National Cholesterol Education Program (NCEP) Thresholds for Low-density Lipoprotein (LDL) at Week 48	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.	Baseline, Week 48
Number of Participants With the Indicated Change From Baseline in National Cholesterol Education Program (NCEP) Thresholds for Low-density Lipoprotein (LDL) at Week 96	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.	Baseline, Week 96
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	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.	Baseline, Week 24
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	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.	Baseline, Week 48
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	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.	Baseline, Week 96
Number of Participants With the Indicated Change From Baseline in National Cholesterol Education Program (NCEP) Thresholds for Fasting Triglycerides at Week 24	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.	Baseline, Week 24
Number of Participants With the Indicated Change From Baseline in National Cholesterol Education Program (NCEP) Thresholds for Fasting Triglycerides at Week 48	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.	Baseline, Week 48
Number of Participants With the Indicated Change From Baseline in National Cholesterol Education Program (NCEP) Thresholds for Fasting Triglycerides at Week 96	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.	Baseline, Week 96
Number of Participants With the Indicated Treatment-emergent Division of AIDS (DAIDS) Toxicities at Week 24	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.	Week 24
Number of Participants With the Indicated Treatment-emergent Division of AIDS (DAIDS) Toxicities at Week 48	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.	Week 48
Number of Participants With the Indicated Treatment-emergent Division of AIDS (DAIDS) Toxicities at Week 96	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.	Week 96
Number of Participants With HIV-1 RNA <50 Copies/Milliliter (c/mL) and 400 c/mL at Week 24	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.	Week 24
Number of Participants With HIV-1 RNA <50 Copies/Milliliter (c/mL) and 400 c/mL at Week 48	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.	Week 48
Number of Participants With HIV-1 RNA <50 Copies/Milliliter (c/mL) and 400 c/mL at Week 96	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.	Week 96
Change From Baseline in Cluster Difference 4 (CD4+) Cell Count at Week 24	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.	Baseline, Week 24
Change From Baseline in Cluster Difference 4 (CD4+) Cell Count at Week 48	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.	Baseline, Week 48
Change From Baseline in Cluster Difference 4 (CD4+) Cell Count at Week 96	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.	Baseline, Week 96
Number of Participants Classified as Protocol-defined Failures With Treatment-emergent Resistance to Study Drug in the Indicated Viruses at Week 96	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.	Week 96
Number of Participants Who Indicated "Yes" or "No" to the Question of Whether Unplanned Healthcare Resources Were Utilized	Participants were asked at each visit whether or not they utilized unplanned healthcare resources.	Baseline to Week 96

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Exploratory Analysis of Change From Baseline in Albumin as a Ratio to Urine Creatinine at Week 96	Renal biomarkers were analyzed using urine samples collected from participants at baseline and Week 96. Renal biomarkers may be an indicator of various aspects of kidney function. The ratio was calculated by dividing the change from baseline albumin value by the urine creatinine value. Albumin is measured in milligrams per millimole (mg/mmol).	Baseline, Week 96
Exploratory Analysis of Change From Baseline in Beta 2 Microglobulin (B2M) as a Ratio to Urine Creatinine at Week 96	Renal biomarkers were analyzed using urine samples collected from participants at baseline and Week 96. Renal biomarkers may be an indicator of various aspects of kidney function. The ratio was calculated by dividing the change from baseline B2M value by the urine creatinine value. B2M, beta 2 microglobulin (measured in mg/mmol).	Baseline, Week 96
Exploratory Analysis of Change From Baseline in N-acetyl-B-glucosaminidase (NAG) as a Ratio to Urine Creatinine at Week 96	Renal biomarkers were analyzed using urine samples collected from participants at baseline and Week 96. Renal biomarkers may be an indicator of various aspects of kidney function. The ratio was calculated by dividing the change from baseline NAG value by the urine creatinine value. NAG, N-acetyl-B-glucosaminidase (measured in micromoles per hour per millimole [umol/h/mmol]).	Baseline, Week 96
Exploratory Analysis of Change From Baseline in Retinol Binding Protein (RBP) as a Ratio to Urine Creatinine at Week 96	Renal biomarkers were analyzed using urine samples collected from participants at baseline and Week 96. Renal biomarkers may be an indicator of various aspects of kidney function. The ratio was calculated by dividing the change from baseline RBP value by the urine creatinine value. RBP, retinol binding protein (measured in micrograms per millimole [ug/mmol]).	Baseline, Week 96
Exploratory Analysis of Change From Baseline in Procollagen Type 1 Amino-terminal Propeptide (P1NP) at Week 96	P1NP is a bone biomarker that was analyzed using blood samples collected from participants at baseline and Week 96. Bone biomarkers may be an indicator of bone turnover.	Baseline, Week 96
Exploratory Analysis of Change From Baseline in Type 1 Collagen Cross-linked C-telopeptide at Week 96	Bone biomarkers were analyzed using blood samples collected from participants at baseline and Week 96. Bone biomarkers may be an indicator of bone turnover.	Baseline, Week 96
Exploratory Analysis of Change From Baseline in Osteocalcin at Week 96	Bone biomarkers were analyzed using blood samples collected from participants at baseline and Week 96. Bone biomarkers may be an indicator of bone turnover.	Baseline, Week 96
Exploratory Analysis of Change From Baseline in Bone Specific Alkaline Phosphatase (BSAP) at Week 96	Bone biomarkers were analyzed using blood samples collected from participants at baseline and Week 96. Bone biomarkers may be an indicator of bone turnover.	Baseline, Week 96

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

General Publications

• Post FA, Moyle GJ, Stellbrink HJ, Domingo P, Podzamczer D, Fisher M, Norden AG, Cavassini M, Rieger A, Khuong-Josses MA, Branco T, Pearce HC, Givens N, Vavro C, Lim ML. Randomized comparison of renal effects, efficacy, and safety with once-daily abacavir/lamivudine versus tenofovir/emtricitabine, administered with efavirenz, in antiretroviral-naive, HIV-1-infected adults: 48-week results from the ASSERT study. J Acquir Immune Defic Syndr. 2010 Sep;55(1):49-57. doi: 10.1097/QAI.0b013e3181dd911e.

Study record dates

Study Major Dates

• Study Start: June 1, 2007
• Primary Completion (Actual): December 1, 2009
• Study Completion (Actual): December 1, 2009

Study Registration Dates

• First Submitted: October 24, 2007
• First Submitted That Met QC Criteria: October 24, 2007
• First Posted (Estimate): October 25, 2007

Study Record Updates

• Last Update Posted (Estimate): April 12, 2011
• Last Update Submitted That Met QC Criteria: April 7, 2011
• Last Verified: April 1, 2011

More Information

Terms related to this study

• Keywords: renal; HIV; tenofovir; abacavir; efavirenz; lamivudine; emtricitabine; naive
• Additional Relevant MeSH Terms: Pathologic Processes; RNA Virus Infections; Virus Diseases; Blood-Borne Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; Disease Attributes; Slow Virus Diseases; HIV Infections; Infections; Communicable Diseases; Acquired Immunodeficiency Syndrome; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 Enzyme Inducers; Cytochrome P-450 CYP3A Inducers; Cytochrome P-450 CYP2B6 Inducers; Cytochrome P-450 CYP2C9 Inhibitors; Cytochrome P-450 CYP2C19 Inhibitors; Tenofovir; Emtricitabine; Lamivudine; Efavirenz; Abacavir
• Other Study ID Numbers: CNA109586