A Randomised, Open-label Trial to Assess the Safety and Efficacy of Switching to Tenofovir-emtricitabine or Abacavir-lamivudine: The STEAL Study

Study Overview
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Brief Summary
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Combination antiretroviral therapy for the treatment of HIV has a high pill burden. Two dual-tablets, abacavir-lamivudine and tenofovir-emtricitabine, are now licensed in the United States and will be available in Australia in December 2005. Data available suggest that the potency of these tablets are similar in controlling replication of the HIV virus, but not have not been directly compared in regard to clinically significant toxicities. We therefore aim to compare the overall safety and efficacy of the two dual-tablets over a 2 year period in HIV infected adults. We hypothesise that the two dual-NRTI treatments will be similar in efficacy and safety.

Detailed Description
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The aim of this study is to compare the overall safety and efficacy of two dual-NRTI, once daily, tablets over a 2 year period in HIV infected adults. The study is a randomised, multi-centre, 2 year study of two dual NRTI, once daily tablets in subjects with HIV, currently taking two individual NRTIs as part of their therapy. 350 subjects will be randomised in a 1:1 ratio to either: tenofovir (TDF) 300mg + emtricitabine (FTC) 200mg OR abacavir (ABC) 600mg + lamivudine (3TC) 300mg. Subjects will cease their current individual NRTI treatment, commence their randomised dual NRTI tablet, and continue on their current NNRTI or PI therapy. Subjects will be stratified by the type of NRTI they are currently taking (ABC, TDF or other); whether they are currently taking a protease inhibitor (yes or no); and by the site where they are randomised. A study plan is enclosed Subjects will be closely monitored (at 1 month and then every 3 months until week 96) for safety by evaluating the incidence and severity of adverse effects/abnormal laboratory parameters. Study investigations enclosed. It is optional whether subjects also provide plasma, serum and cells (PBMCs) for storage. These samples will be available for analysis for sub-studies agreed to through the IVRN expression of interest network.

Official Title
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A Randomised, Open-label Trial to Assess the Safety and Efficacy of Switching to Tenofovir-emtricitabine or Abacavir-lamivudine: The STEAL Study.

Conditions
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HIV Infections

Intervention / Treatment
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* Drug: Emtricitabine 200mg - Tenofovir 300mg
* Drug: Abacavir 600mg - Lamivudine 300mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: documented HIV infection age at least 18 years stable (≥ to 12 weeks) ART including at least two NRTIs, currently well tolerated, with no plan to change any other component of the ART regimen at or after baseline HIV RNA < 50 copies/mL plasma for the preceding 12 weeks GFR ≥ 70 mL/min/1.73m2 (estimated by the abbreviated MDRD equation23 estimated GFR = 186 x ([SCR/88.4]-1.154) x age-0.203 x (0.742 if female) x (1.210 if African-American) provision of written, informed consent Exclusion Criteria: HLA-B*5701 positive at screening OR evidence of previous ABC hypersensitivity OR clinical failure in participants taking abacavir for at least 30 days current therapy comprising triple NRTI therapy alone current use of ABC/3TC FDC (Kivexa) or TDF/FTC FDC (Truvada) history of non-traumatic osteoporotic fracture prior hypersensitivity or intolerance to ABC, 3TC, TDF or FTC prior clinical failure to a regimen containing ABC or TDF prior use of TDF for control of previously active hepatitis B (HBsAg+ or HBV DNA+) in patients likely to be resistant to 3TC/FTC current therapy including unboosted atazanavir concurrent use of aminoglycosides, IV amphotericin B, cidofovir, cisplatin, foscarnet, IV pentamidine, probenecid, adefovir or immunomodulatory agents clinical evidence of cirrhosis (e.g. smooth liver, no features of portal hypertension) creatinine clearance < 50 mL/min (estimated by the Cockcroft-Gault equation)18,19 Male: (140 - age in years) x (wt in kg) = CLCr (mL/min) 0.814 x (serum creatinine in µmol/L) Female:(140 - age in years) x (wt in kg) x 0.85 = CLCr (mL/min) 0.814 x (serum creatinine in µmol/L)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br>Abacavir 600mg/Lamivudine 300mg | Drug: Abacavir 600mg - Lamivudine 300mg<br>* 1 tablet once daily for 96 weeks<br>* Other names: Kivexa;|
| Active Comparator: 2<br>Tenofovir 300mg/emtricitabine 200mg | Drug: Emtricitabine 200mg - Tenofovir 300mg<br>* 1 tablet once daily for 96 weeks<br>* Other names: Truvada;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| virological failure defined by HIV RNA>400copies/mL plasma on 2 consecutive occasions ³4 wks apart(Roche Amplicor v1.5, LLD 50 copies/mL) |  | Week 48 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| plasma HIV RNA<50copies/mL; time to virological failure (VF); virological resistance in those with VF; all SAEs; use of concomitant meds for toxicity; adherence; QoL; CD4+lymphocyte count; full blood count; biochemistry; lipid parameters |  | Week 48 and 96 | 
| glycaemic parameters; DEXA parameters; resolution of AEs; progression to AIDS; death; discontinuation of ART. |  | Week 48 and 96 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV, Antiretroviral therapy, nucleoside analogue reverse transcriptase, fixed dose combination, Treatment Experienced