Tenofovir Renal Toxicity and Glomerular Filtration Rate (GFR) Validation

Study Overview
=================
Brief Summary
-----------------
To assess and validate equation eGFR in HIV-infected subjects and -uninfected Thai patients

Detailed Description
-----------------
With significant reductions in mortality and risk of progression to AIDS with antiretroviral therapy (ART), complications of long-standing HIV infection and treatment, including renal disease, have become increasingly important. Aging, concomitant metabolic diseases, and use of potentially nephrotoxic ART lead to higher risk for renal disease in HIV-infected persons.WHO encourage TDF as first line ARV regimen. The data on TDF related renal toxicity in Asian population is limited. For this cohort, we plan to look at these topics: proximal tubular dysfunction between TDF and non-TDF user incidence and predictor of TDF related renal toxicity TDF plasma concentrations Pharmacokinetic of TDF when used with boosted DRV, boosted ATV, and boosted LPV in Thai population Bone density and vitamin D in patients with and without hypophosphatemia. Pharmacogenomic of TDF in Thai population

Official Title
-----------------
Incidence and Predictor of TDF Associated Nephrotoxicity and Pharmacokinetic of TDF in HIV-1 Infected Thai Patients: A Sub-study of HIV-NAT 006 Long Term Cohort

Conditions
-----------------
Renal Function, HIV Infection

Intervention / Treatment
-----------------
* Other: Tc99mDTPA renal clearance


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: > 18 years old. HIV RNA < 50 copies/ml (For ART-experienced group only). Exclusion Criteria: a history of Tc-99m DTPA allergy, malnutrition (BMI <18m2), amputation, bed-ridden, currently taking cotrimoxazole or cimetidine, acute deterioration of renal function within the last 3 months, serum creatinine > 1.5 mg/dl, or pregnant/lactating.

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

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

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

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

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| 1<br>ARV experience (TDF based HAART) | Other: Tc99mDTPA renal clearance<br>* Tc99mDTPA renal clearance only for 200 patients Plasma and urine 24 hr for creatinin, glucose, Creatinin clearance, Phosphatemia, uric acid, HCO3, protein, Microalbuminuria, ß2- microglobulinuria serum creatinine prior and during TDF TDF plasma levels ( only TDF use) using a validated high-performance liquid chromatography (HPLC)-mass method and stored PBMC for intracellular TDF levels stored samples (PBMC) for pharmacogenomic study of transporter gene ie Organic Acid Transporter (OAT) serum for cystanin C ( stored sample prior taking ARV and present time) intensive 24 hours pharmacokinetic study of TDF in 20 patients<br>|
| 2<br>ARV experience (non TDF based ART) | Other: Tc99mDTPA renal clearance<br>* Tc99mDTPA renal clearance only for 200 patients Plasma and urine 24 hr for creatinin, glucose, Creatinin clearance, Phosphatemia, uric acid, HCO3, protein, Microalbuminuria, ß2- microglobulinuria serum creatinine prior and during TDF TDF plasma levels ( only TDF use) using a validated high-performance liquid chromatography (HPLC)-mass method and stored PBMC for intracellular TDF levels stored samples (PBMC) for pharmacogenomic study of transporter gene ie Organic Acid Transporter (OAT) serum for cystanin C ( stored sample prior taking ARV and present time) intensive 24 hours pharmacokinetic study of TDF in 20 patients<br>|
| 3<br>ARV Naive | Other: Tc99mDTPA renal clearance<br>* Tc99mDTPA renal clearance only for 200 patients Plasma and urine 24 hr for creatinin, glucose, Creatinin clearance, Phosphatemia, uric acid, HCO3, protein, Microalbuminuria, ß2- microglobulinuria serum creatinine prior and during TDF TDF plasma levels ( only TDF use) using a validated high-performance liquid chromatography (HPLC)-mass method and stored PBMC for intracellular TDF levels stored samples (PBMC) for pharmacogenomic study of transporter gene ie Organic Acid Transporter (OAT) serum for cystanin C ( stored sample prior taking ARV and present time) intensive 24 hours pharmacokinetic study of TDF in 20 patients<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| to validate eGFR Thai equation in HIV-infected adults | Test of diagnostic accuracy | Blood specimens were drawn to assess plasma radioactivity at 5, 10, 20, 30, 60, 90, 120, 180, and 240 minutes post 99mTc-DTPA injection | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
HIV, Chronic kidney disease, Glomerular Filtration Rate (GFR), Tenofovir, Serum creatinine (sCr), 24 hr urine creatinine clearance, Serum Cystatin C[40], Modification of Diet in Renal Disease (MDRD), Cockcroft Gault Equation, Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), 99mTc-diethylenetriaminepentaacetic acid (Tc-99m DTPA) scan, Validate which renal function assessments can accurately detect GFR and assess the effect of TDF concentration on renal function