Clinical trial NCT01138241: Tenofovir Renal Toxicity and Glomerular Filtration Rate (GFR) Validation
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
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Renal Function
HIV Infection
Keywords: 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
Lead sponsor: The HIV Netherlands Australia Thailand Research Collaboration
Sponsor class: OTHER
Collaborators: name: Chulalongkorn University
name: Kirby Institute
First posted: 2010-06-07
Enrollment: 700
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: CROSS_SECTIONAL
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

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:

1. proximal tubular dysfunction between TDF and non-TDF user
2. incidence and predictor of TDF related renal toxicity
3. TDF plasma concentrations
4. Pharmacokinetic of TDF when used with boosted DRV, boosted ATV, and boosted LPV in Thai population
5. Bone density and vitamin D in patients with and without hypophosphatemia.
6. Pharmacogenomic of TDF in Thai population

Eligibility criteria: Inclusion Criteria:

1. \> 18 years old.
2. HIV RNA \< 50 copies/ml (For ART-experienced group only).

Exclusion Criteria:

1. a history of Tc-99m DTPA allergy,
2. malnutrition (BMI \<18m2),
3. amputation,
4. bed-ridden,
5. currently taking cotrimoxazole or cimetidine,
6. acute deterioration of renal function within the last 3 months,
7. serum creatinine \> 1.5 mg/dl, or
8. pregnant/lactating.

Primary outcomes:
measure: to validate eGFR Thai equation in HIV-infected adults
timeFrame: Blood specimens were drawn to assess plasma radioactivity at 5, 10, 20, 30, 60, 90, 120, 180, and 240 minutes post 99mTc-DTPA injection
Secondary outcomes:
Other outcomes:
Locations:
city: Bangkok
country: Thailand
facility: HIV-NAT, Thai Red Cross AIDS Research Centre
Study officials:
affiliation: HIV-NAT, Thai Red Cross AIDS Research Centre, Bangkok, Thailand
name: Praphan Phanuphak, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Renal division, Faculty of Medicine, Chulalongkorn University
name: Kearkiat Praditpornsilpa, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.