Switching From Tenofovir Disoproxil Fumarate to Abacavir or Tenofovir Alafenamide

• Status: Recruiting
• Trial end date: 2020-09-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Erasmus Medical Center
• Collaborator: Gilead Sciences
• Treatments: Abacavir; Dideoxynucleosides; Tenofovir

Criteria

Inclusion Criteria:

HIV-positive documented by ELISA or Western Blot or plasma HIV-RNA > 1000 copies/mL.

18 years or older. Stable on TDF/FTC or TDF/3TC for ≥12 months (365 days) in combination with a third antiretroviral agent (NNRTI, INI, or PI) and with an unchanged third agent for at least 1 month.

HIV-1 RNA <50 copies/mL for ≥ 6 months. Patient is negative for the HLA B5701 allele.

Confirmed/probable TDF-related accelerated eGFR decline (one of the following):

1. Accelerated eGFR decline: mean of > 3 mL/min/year since start TDF after ≥5 years of TDF exposure.

2. Confirmed eGFR < 70 mL/min in patients with baseline eGFR > 90 mL/min at start of TDF.

3. eGFR decrease > 25% compared to baseline eGFR at TDF-initiation.

Absence of other causes of eGFR decline:

Diabetic patients with diabetic nephropathy (defined as an eGFR decline and uACR>30mg/mmol with uAPR >/=0.4, or biopsy proven).

Hypertensive patients (defined as the use of antihypertensives or untreated systolic (>=160mmHg) or diastolic (>=95mmHg) hypertension) in combination with hypertensive nephropathy (defined as eGFR decline with uACR>30mg/mmol with uAPR>/=0.4, or biopsy proven).

Nephrotic syndromes/nephrotic range proteinuria (uACR >300mg/mmol and uAPR ≥ 0.4, or total 24hrs proteinuria >3.5g/24hr, or biopsy proven) Nephrotic syndromes including rapid progressive glomerulonephritis and tubular interstitial nephritis (defined as active urine sediment with erythrocyturia and leucocyturia and proteinuria with eGFR decline, with or without the presence of systemic disease, or biopsy proven).

Obvious other renal toxic effects related to lifestyle or medication (e.g. creatin use) suspected by the investigators or biopsy proven.

Concomittantly used medication does not interfere with trial procedures (on investigators' discretion).

Exclusion Criteria:

Likely other cause (as defined above) of the accelerated GFR decline. HLA-B5701 positivity. Active hepatitis C or B. Documented intermediate or high level resistance to ABC. eGFR <30ml/min. Any other disease or medical condition that, in the opinion of the investigators, would interfere with the safety of the participant or the conduct of the trial.