Pharmacokinetic Study of 2 Doses of ATV/r OD + 2 NRTIs in Thai HIV-1 Infected Patients

Study Overview
=================
Brief Summary
-----------------
Several studies from HIV-NAT have demonstrated high nevirapine, indinavir, saquinavir and lopinavir/r levels when compared to Caucasian patients. Until now, the pharmacokinetics of atazanavir have not been explored in a Thai population. We postulate that ATV levels, as with other PIs, are higher in Thai people. Therefore, the level of ATV in ATV/RTV 300/100 OD may be higher than the acceptable range and could be associated with ATV related toxicity.

Detailed Description
-----------------
We are interested in once daily ATV/RTV 200/100 mg OD because of the convenience, reduction in ATV doses which may improve adherence while reducing toxicity and cost. There are limited prospective studies evaluating pharmacokinetic and long term efficacy and safety of atazanavir/ritonavir once daily dose in combination of NRTIs in HIV-1 pretreated patients. We believe that the PK parameters of ATV/RTV given at 200/100mg daily in Thai patients will be equivalent to the ATV/RTV 300/100mg once daily dosing in Caucasian patients when combined with 2NRTIs, and that the once daily regimen will have better safety, tolerability profile, and cost saving while maintaining good CD4 and VL outcome. If, the pharmacokinetic profile of ATV/RTV 200/100 mg OD + 2NRTIs is in acceptable range or comparable with standard dose of ATV/RTV 300/100 mg OD, long term efficacy will be explored later.

Official Title
-----------------
The Pharmacokinetics of Atazanavir / Ritonavir 200/100 OD Versus 300/100 mg OD in Combination With 2 NRTIs in HIV Pre-treated Patients

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

Intervention / Treatment
-----------------
* Drug: Atazanavir


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Written informed consent Adults HIV patients currently using ATV/RTV 300/100 mg OD plus 2 NRTIs HIV RNA < 50 copies/ml Exclusion Criteria: Inability to understand the nature and extent of the study and the procedures required. ALT/ AST more than 5x upper limit Relevant history or current condition, illness that might interfere with drug absorption, distribution, metabolism or excretion. Use of concomitant medication that may interfere with the pharmacokinetics of atazanavir, and ritonavir History of sensitivity/idiosyncrasy to the drug or chemically related compounds which may be employed in the study. Active drug abuse or heavy alcoholic drinking History of sensitivity/idiosyncrasy to the drug or chemically related compounds which may be employed in the study. Active drug abuse or heavy alcoholic drinking

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 60 Years

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

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

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

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br>ATV/r 300/100 mg | Drug: Atazanavir<br>* ATV/r 300/100mg OD vs ATV/r 200/100 mg OD<br>|
| Active Comparator: 2<br>ATV/r 200/100 mg OD | Drug: Atazanavir<br>* ATV/r 300/100mg OD vs ATV/r 200/100 mg OD<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| the pharmacokinetics of atazanavir/ritonavir (ATV/RTV) 200/100 mg once daily in a sample of 22 patients experiencing virological success |  | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The pharmacokinetic and pharmacodynamic between these patients and data from Thai cohort treated with ATV/RTV 300/100 mg OD |  | 4 weeks | 
| short term safety, tolerability and efficacy data in these PK participating patients |  | 4 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
atazanavir/ritonavir, pharmacokinetic of ATV/r200/100 OD+2NRTIs