Renal and Bone Outcome After Switching Tenofovir to Different Antiretroviral Strategies (TDFOUT)

A Prospective, Cohort Study of Renal and Bone Outcome After Changing Tenofovir in Patients With Renal Toxicity According to Antiretroviral Strategy

Renal outcome could be different after switching tenofovir to different antiretroviral strategies, in case of renal toxicity. Therefore, it is necessary to evaluate the importance of renal evolution in these patients, in terms of grade and time to renal improvement, according to the different options after interrupting tenofovir. The aim of this study was to explore the renal outcome after tenofovir according to new antiretroviral regimen.

Study Overview

• Status: Completed
• Conditions: Renal Disease
• Intervention / Treatment: Other: Tenofovir switch

Detailed Description

Renal toxicity has become an important issue in a large number of HIV infected patients receiving a tenofovir-containing regimen. However, there are no data about the best antiretroviral regimen in patients switching tenofovir because of renal toxicity, in time, grade or persistence of renal improvement. Thus, patients with renal toxicity on tenofovir, defined as:

• a progressive decrease of at least 25% of estimated glomerular filtration rate (GFR, by chronic kidney disease-epi equation), or
• confirmed value of GFR below 60 ml/min in two successive determinations, or
• proximal tubular renal dysfunction, as indicated by the presence of at least 3 of the following parameters: proteinuria> 150 mg/g; excretion fractional of phosphorus in urine > 20%; glucosuria > 150 mg; or/and tubular proteinuria/albuminuria ratio above 0.4.

who changed to the combination of abacavir plus a third drug, or to a nucleoside analogues-free antiretroviral combination (dual therapy, monotherapy) will be followed for 1 year to establish the time and grade of improvement (defined as the lack of above criteria).

• Study Type: Observational
• Enrollment (Actual): 245

Contacts and Locations

Study Locations

• Spain
  • Madrid, Spain, 28034
    • Hospital Ramon y Cajal

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

HIV-infected patients in regular clinical and analytical follow up, receiving a tenofovir-containing regimen

Description

Inclusion Criteria:

• HIV-infected patients
• Older than 18 years
• Receiving a Tenofovir-containing regimen, and with criteria of renal toxicity (see above)
• Switching the antiretroviral regimen

Exclusion Criteria:

• Pregnancy
• Patients receiving prolonged therapy with other nephrotoxic drugs
• Patients not receiving or interrupting antiretroviral regimen

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Tenofovir switch; Patients switched tenofovir to different antiretroviral regimen according to physicians decision	Other: Tenofovir switch; Patients switched tenofovir to different antiretroviral regimen according to physicians decision

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Renal outcome	Evolution of renal parameters after switching tenofovir according to antiretroviral drug or regimen used, in terms of GFR (glomerular filtration rate by Chronic Kidney Disease-epidemiological collaboration equation) improvement, increase in excretion fractional of phosphorus in urine, decrease in proteinuria, and in glycosuria. As control group, renal outcome will be evaluated in patients continuing TDF-based therapy	48 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Antiviral efficacy	Number of patients without virological failure, defined as an HIV RNA level above 37 copies/ml, 48 weeks after the change of tenofovir	48 weeks
Bone mineral density (BMD) changes	Changes in BMD in the subgroup of patients with two successive BMD measurements, before and after TDF switch, according to baseline risk factors for BMD change (age, body mass index, hypovitaminosis D, secondary hyperparathyroidism), in comparison with patients continuing TDF	48 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Antiviral safety	Number (and percentage) and degree of adverse events, and percentage of therapy withdrawal, according to antiretroviral strategy after the change of tenofovir	48 weeks

Collaborators and Investigators

• Sponsor: Asociacion para el Estudio de las Enfermedades Infecciosas
• Investigators: Principal Investigator: Jose L Casado, MD, Asociacion para el Estudio de las Enfermedades Infecciosas

Study record dates

Study Major Dates

• Study Start: July 1, 2014
• Primary Completion (Actual): December 1, 2015
• Study Completion (Actual): December 1, 2015

Study Registration Dates

• First Submitted: August 2, 2014
• First Submitted That Met QC Criteria: August 5, 2014
• First Posted (Estimate): August 6, 2014

Study Record Updates

• Last Update Posted (Estimate): December 30, 2015
• Last Update Submitted That Met QC Criteria: December 28, 2015
• Last Verified: December 1, 2015

More Information

Terms related to this study

• Keywords: renal toxicity, HIV, antiretroviral, outcome
• Additional Relevant MeSH Terms: Urologic Diseases; Kidney Diseases; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Tenofovir
• Other Study ID Numbers: TDFOUT; 218/12 revised (Other Identifier: CEIC)