Low Dose Atazanavir/r Versus Standard Dose Atazanavir/r (LASA)

Study Overview
=================
Brief Summary
-----------------
This study will compare the efficacy and safety of ATV/r at either 200/100 mg or 300/100mg given daily in Thai patients in combination with 2NRTIs.

Detailed Description
-----------------
To demonstrate non-inferiority of treatment with atazanavir/ritonavir (ATV/r) 200/100 mg once daily (OD) compared to the control group (ATV/r 300/100 mg OD) in regards to the proportion of virologic responders (plasma HIV RNA < 200 copies/mL) at 48 weeks in ARV-experienced HIV-1 infected subjects.

Official Title
-----------------
A Multicenter Randomized Study to Compare the Efficacy and Safety of Lower Dose Atazanavir /Ritonavir (ATV/r 200/100 OD) Versus Standard Dose (ATV/r 300/100 mg OD) in Combination With 2NRTIs in Well Virology Suppressed HIV-infected Adults

Conditions
-----------------
HIV Infections

Intervention / Treatment
-----------------
* Drug: ATV/r


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: HIV infected adults aged more than or equal to 18 years Received ritonavir boosted PI-based HAART for >3 months prior screening visit History of HIV RNA < 50 copies/ml within 12 months prior to screening visit HIV-RNA < 50 copies/ml at screening visit Signed written informed consent Exclusion Criteria: Active AIDS-defining disease or active opportunistic infection History of virological failure (plasma HIV-RNA ≥1,000 copies/ml) while using any ritonavir boosted PI-based HAART Pregnancy or lactation at screening visit Relevant history or current conditions or illnesses that might interfere with drug absorption, distribution, metabolism or excretion e.g. chronic diarrhea, malabsorption Use of concomitant medication that may interfere with the pharmacokinetics of the study drugs e.g. rifampicin, proton pump inhibitor History of sensitivity/idiosyncrasy to the drug or chemically related compounds which may be employed in the study ALT ≥200 IU/L at screening visit Creatinine clearance < 60 c.c. per min by Cockroft-Gault formula at screening visit

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>ATV/r 200 mg/100 mg OD | Drug: ATV/r<br>* All participants will be randomized to take ATV/r 200 mg/100 mg OD or ATV/r 300/100 mg OD. NRTIs background regimens will remain unchanged if possible. NRTIs background may include zidovudine/lamivudine, zidovudine plus ddI, ddI plus lamivudine, tenofovir plus lamivudine, tenofovir/emtricitabine, zidovudine plus tenofovir. NRTI backbone could be switched or modified due to toxicity or intolerance<br>|
| Experimental: 2<br>ATV/r 300 mg/100 mg OD | Drug: ATV/r<br>* All participants will be randomized to take ATV/r 200 mg/100 mg OD or ATV/r 300/100 mg OD. NRTIs background regimens will remain unchanged if possible. NRTIs background may include zidovudine/lamivudine, zidovudine plus ddI, ddI plus lamivudine, tenofovir plus lamivudine, tenofovir/emtricitabine, zidovudine plus tenofovir. NRTI backbone could be switched or modified due to toxicity or intolerance<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| noninferiority | ATV/r 200/100 mg will be judged to be non-inferior to ATV 300/100mg if the lower limit of the 95% confidence interval for the difference in proportion of patients with virological response between the two groups does not exceed -10% | Dec. 2013 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| viral load | A secondary efficacy analysis will explore the impact of changing the lower limit of detection of viral load to <50 copies/mL | DEc. 2013 | 
| serious adverse events | Changes in HDL, LDL, cholesterol, triglycerides and bilirubin, or having grade 3 and 4 laboratory adverse events | Dec. 2013 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
atazanavir / ritonavir, low dose, noninferiority, safety and efficacy, efficacy and safety of lower dose atazanavir/ritonavir in suppressed HIV-infected adults