Switching From Tenofovir Disoproxil Fumarate to Abacavir or Tenofovir Alafenamide — BACTAF  

Hiv Clinical Trial

Official title: Switching to Tenofovir Alafenamide Fumarate or Abacavir in Patients With Tenofovir Disoproxil Fumarate Associated eGFR Decline. A Randomized Trial.

Status Recruiting

Clinical Trial Summary

Tenofovir disoproxil fumarate (TDF) is one of the most frequently used drugs to treat HIV. Long term use of TDF can induce renal toxicity. Tenofovir alafenamide (TAF) is a new pro-drug of Tenofovir which has not been associated with renal toxicity and may therefore be a good substitute for TDF in patients with TDF induced renal toxicity. Abacavir (ABC) is another drug that can be used for the treatment of HIV and is not associated with renal toxicity.

In this study the investigators will compare the effect on renal function of a switch from TDF to TAF with a switch from TDF to ABC in patients with TDF induced renal insufficiency.

Clinical Trial Description

The majority of HIV-1 infected patients in resource rich countries receive the tenofovir prodrug tenofovir disoproxil fumarate (TDF) as part of their combination antiretroviral therapy (cART). Long-term exposure to TDF can be associated with an accelerated estimated glomerular filtration rate (eGFR) decline and proximal renal tubular dysfunction (PTD, see definition below). The current practice in patients in which TDF related renal toxicity becomes apparent is to substitute abacavir (ABC) for TDF. However, ABC is contraindicated in patients with HLAB57*01 and has been associated with an increased risk of cardiovascular disease in large HIV cohort studies, but not in randomized clinical trials. Recently, a new tenofovir prodrug, tenofovir alafenamide (TAF) was developed by Gilead Sciences and is available in a coformulation with emtricitabine (FTC). Due to the targeted delivery of tenofovir inside the CD4 positive cell by this prodrug, only 25 mg TAF is needed for the same antiviral effect observed in patients taking 250 mg of TDF and this lower TAF dose leads to 90% lower serum levels of tenofovir. In recently completed phase III studies in which patients with a normal kidney function where included, this lower tenofovir exposure in patients on TAF was shown to prevent off-target renal and bone toxicity in comparison with patients taking TDF. However, whether an already established TDF related renal toxicity in a HIV patient can be reversed after a switch to TAF, remains to be shown.

Objective:

To study the renal safety when HIV patients with TDF related renal toxicity switch to TAF compared to the current practice of switching to ABC.

Study design:

96 week open label multicenter randomized non-inferiority clinical trial.

Study population:

HIV-1 infected adults, suppressed HIV-RNA <50c/mL on a TDF containing antiretroviral regimen, with signs of TDF related renal toxicity as indicated by an accelerated eGFR decline.

Intervention:

Replace TDF with TAF (intervention arm) or ABC (control arm).

Main study parameters/endpoints:

Primary endpoint:

Recovery of renal dysfunction in the TAF arm versus the ABC arm at 48 weeks after the switch from TDF to TAF or ABC using the time to the first eGFR within 75% of the eGFR at the time of TDF initiation.

Secondary endpoints:

See below ;

Related Conditions & MeSH terms

• Hiv
• Renal Insufficiency
• Renal Insufficiency, Chronic
• Renal Insufficiency,Chronic
• Therapeutic Agent Toxicity

• NCT number: NCT02957864
• Study type: Interventional
• Source: Erasmus Medical Center
• Contact: Ingeborg Wijting, MD
• Phone: 0031107040704
• Email: i.wijting@erasmusmc.nl
• Status: Recruiting
• Phase: Phase 4
• Start date: October 2016
• Completion date: September 2020