Tenofovir Renal Toxicity and Glomerular Filtration Rate (GFR) Validation - Full Text View

Purpose

To assess and validate equation eGFR in HIV-infected subjects and -uninfected Thai patients

Condition	Intervention
Renal Function HIV Infection	Other: Tc99mDTPA renal clearance


Study Type:	Observational
Study Design:	Observational Model: Cohort Time Perspective: Cross-Sectional
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

Resource links provided by NLM:

MedlinePlus related topics: HIV/AIDS

Drug Information available for: Tenofovir

U.S. FDA Resources

Further study details as provided by The HIV Netherlands Australia Thailand Research Collaboration:

Primary Outcome Measures:

to validate eGFR Thai equation in HIV-infected adults [ Time Frame: Blood specimens were drawn to assess plasma radioactivity at 5, 10, 20, 30, 60, 90, 120, 180, and 240 minutes post 99mTc-DTPA injection ] [ Designated as safety issue: No ]
Test of diagnostic accuracy

Biospecimen Retention: Samples With DNA

PBMC collection


Estimated Enrollment:	700
Study Start Date:	March 2010
Estimated Study Completion Date:	June 2030
Estimated Primary Completion Date:	June 2030 (Final data collection date for primary outcome measure)

Groups/Cohorts	Assigned Interventions
1 ARV experience (TDF based HAART)	Other: Tc99mDTPA renal clearance 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
2 ARV experience (non TDF based ART)	Other: Tc99mDTPA renal clearance 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
3 ARV Naive	Other: Tc99mDTPA renal clearance 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

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

Eligibility


Ages Eligible for Study:	18 Years and older (Adult, Senior)
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No
Sampling Method:	Non-Probability Sample

Study Population

HIV-NAT 006 participants (TDF +non TDF)and ARV naive population

For TDF group, on TDF > 3 months HIV/HBV co-infected patients from COLD (Liver disease and HIV/HBV coinfection in the era of HAART) and TDF surveillance study

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.

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01138241

Locations


Thailand
HIV-NAT, Thai Red Cross AIDS Research Centre
Bangkok, Thailand, 10330

Sponsors and Collaborators

The HIV Netherlands Australia Thailand Research Collaboration

Chulalongkorn University

Kirby Institute

Investigators


Principal Investigator:	Praphan Phanuphak, MD, PhD	HIV-NAT, Thai Red Cross AIDS Research Centre, Bangkok, Thailand
Principal Investigator:	Kearkiat Praditpornsilpa, MD	Renal division, Faculty of Medicine, Chulalongkorn University

More Information

Additional Information:

HIV Netherlands Australia Thailand Research Collaboration (HIV-NAT) This link exits the ClinicalTrials.gov site

Publications:

Praditpornsilpa K, Avihingsanon A, Chaiwatanarat T, Chaiyahong P, Wongsabut J, Ubolyam S, Chulakadabba A, Avihingsanon Y, Ruxrungtham K, Tunsanga K, Eiam-Ong S, Phanuphak P. Comparisons between validated estimated glomerular filtration rate equations and isotopic glomerular filtration rate in HIV patients. AIDS. 2012 Sep 10;26(14):1781-8. doi: 10.1097/QAD.0b013e328356480d. Erratum in: AIDS. 2013 Mar 13;27(5):853.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Avihingsanon A, Kerr SJ, Ramautarsing RA, Praditpornsilpa K, Sophonphan J, Ubolyam S, Avihingsanon Y, Khovidhunkit W, Hiransuthikul N, Ruxrungtham K. The Association of Gender, Age, Efavirenz Use, and Hypovitaminosis D Among HIV-Infected Adults Living in the Tropics. AIDS Res Hum Retroviruses. 2016 Apr;32(4):317-24. doi: 10.1089/AID.2015.0069. Epub 2015 Oct 15.

Punyawudho B, Thammajaruk N, Thongpeang P, Matthews G, Lewin SR, Burger D, Ruxrungtham K, Avihingsanon A. Population pharmacokinetics of tenofovir in HIV/HBV co-infected patients. Int J Clin Pharmacol Ther. 2015 Nov;53(11):947-54. doi: 10.5414/CP202386.

Rungtivasuwan K, Avihingsanon A, Thammajaruk N, Mitruk S, Burger DM, Ruxrungtham K, Punyawudho B, Pengsuparp T. Influence of ABCC2 and ABCC4 polymorphisms on tenofovir plasma concentrations in Thai HIV-infected patients. Antimicrob Agents Chemother. 2015;59(6):3240-5. doi: 10.1128/AAC.04930-14. Epub 2015 Mar 23.

Avihingsanon A, Jitmitraparp S, Tangkijvanich P, Ramautarsing RA, Apornpong T, Jirajariyavej S, Putcharoen O, Treeprasertsuk S, Akkarathamrongsin S, Poovorawan Y, Matthews GV, Lange JM, Ruxrungtham K; HIV-NAT125 study team. Advanced liver fibrosis by transient elastography, fibrosis 4, and alanine aminotransferase/platelet ratio index among Asian hepatitis C with and without human immunodeficiency virus infection: role of vitamin D levels. J Gastroenterol Hepatol. 2014 Sep;29(9):1706-14. doi: 10.1111/jgh.12613.

Avihingsanon A, Apornpong T, Ramautarsing RA, Ubolyam S, Tangkijvanich P, Ananworanich J, Lange JM, Matthews G, Lewin SR, Ruxrungtham K; HIV-NAT 105 study team. Decline in serum 25 hydroxyvitamin D levels in HIV-HBV-coinfected patients after long-term antiretroviral therapy. Antivir Ther. 2014;19(1):41-9. doi: 10.3851/IMP2673. Epub 2013 Aug 23.


Responsible Party:	The HIV Netherlands Australia Thailand Research Collaboration
ClinicalTrials.gov Identifier:	NCT01138241 History of Changes
Other Study ID Numbers:	HIV-NAT 114
Study First Received:	June 4, 2010
Last Updated:	June 1, 2016
Health Authority:	Thailand: Ethical Committee

Keywords provided by The HIV Netherlands Australia Thailand Research Collaboration:


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

Additional relevant MeSH terms:


HIV Infections Lentivirus Infections Retroviridae Infections RNA Virus Infections Virus Diseases Sexually Transmitted Diseases, Viral Sexually Transmitted Diseases Immunologic Deficiency Syndromes Immune System Diseases	Tenofovir Antiviral Agents Anti-Infective Agents Reverse Transcriptase Inhibitors Nucleic Acid Synthesis Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Anti-Retroviral Agents Anti-HIV Agents

ClinicalTrials.gov processed this record on September 30, 2016