TAF for HIV-HBV With Renal Dysfunction

Phase 2

Completed

• Conditions: HIV and Hepatitis B Coinfection
• Interventions: Drug: Tenofovir Alafenamide

• Registration Number: NCT03115736
• Lead Sponsor: Insel Gruppe AG, University Hospital Bern

Brief Summary

The investigators aim at describing changes in renal glomerular and tubular function with after the switch from TDF to TAF in HIV/HBV-coinfected patients with mild to moderate renal dysfunction and to assess the virological efficacy of TAF on HBV infection.

The study will include HIV/HBV-coinfected participants of the Swiss HIV Cohort Study (SHCS) who are under active care and have been on a stable, TDF-containing ART regimen for at least 6 months. Only patients with an estimated glomerular filtration rate (GFR) between 30 ml/min and 90 ml/min will be included. All individuals who agree to participate will be switched from a TDF-containing ART regimen to a TAF-containing triple ART regimen at week 0 and will be followed for 48 weeks after the treatment change.

Detailed Description

Rationale:

Tenofovir alafenamide (TAF) has been shown to cause less renal complications than tenofovir disoproxil fumarate (TDF) while having the same virological efficacy against HIV and HBV infections. In a recent study from the USA and Japan, over 90% of HIV/HBV-coinfected individuals had a suppressed HBV viral load 48 weeks after TDF was replaced by TAF. Thus, TAF might be a valuable treatment option for HIV/HBV-coinfected individuals with TDF-toxicity, especially in the context of resistance to lamivudine and entecavir. However, the safety and efficacy of TAF has not been evaluated to date in HIV/HBV-coinfected patients with renal dysfunction.

Primary objectives:

* To evaluate changes in glomerular and tubular renal function after switch from TDF to TAF in HIV/HBV coinfected patients with renal dysfunction

* To assess the HBV virological efficacy of TAF in HIV/HBV coinfected patients with renal dysfunction switching from TDF to TAF.

Secondary objectives:

* To assess the percentage of and reasons for treatment interruptions

* To describe toxicity events including liver-related complications

* To evaluate changes in liver fibrosis

Intervention:

In eligible patients willing to participate and who have signed an informed consent TDF will be replaced by TAF on day 1 of the study.

Products:

* Tenofovir alafenamide/emtricitabine (TAF/FTC) Dose: one tbl. once per day in addition to at least one third compound OR

* Elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (EVG/COBI/FTC/TAF) Dose: one tbl. once per day

Study Population: eligible patients from all 7 centers of the Swiss HIV Cohort Study will be considered.

Study Timeline

• Study First Submitted: 2017-04-10
• Study First Submitted QC: 2017-04-10
• Study First Posted: 2017-04-14
• Study Start: 2017-05-23
• Primary Completion: 2019-12-05
• Study Completion: 2019-12-05
• Status Verified: 2020-03
• Last Update Submitted: 2020-03-03
• Last Update Posted: 2020-03-04

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 24

Inclusion Criteria

• HIV/HBV-coinfection
• Suppressed HIV-viremia (<200 cp/ml)
• On TDF-containing ART since at least 6 months
• eGFR > 30 ml/min and <90 ml/min
• Written informed consent

Read More

Exclusion Criteria

• Study drug considered by the treating physician not a valid option for the patient
• Pregnancy
• Decompensated liver cirrhosis

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Switch	Tenofovir Alafenamide	Patients are switched from a TDF-containing antiretroviral therapy regimen to a TAF-containing regimen

Primary Outcome Measures

Name	Time	Method
HBV suppression	48 weeks	Evaluation of HBV virological suppression and HBsAg loss after 12 months of TAF
Change in renal function	48 weeks	Assessment of change in eGFR and tubular markers during the first year of TAF-containing ART

Secondary Outcome Measures

Name	Time	Method
Treatment interruptions	48 weeks	Description of the proportion of patients with treatment changes or interruptions
Adverse events	48 weeks	Evaluation of the proportion of patients with adverse events during therapy, including grade 2 or above transaminases elevations
Liver fibrosis change	48 weeks	Assessment of the proportion of patients with a change in liver fibrosis stage

Trial Locations

Locations (8)

Klinik für Infektiologie und Spitalhygiene, Universitätspital Basel; 🇨🇭 Basel, Switzerland

Inselspital; 🇨🇭 Bern, Switzerland

Cabinet médical Chave-Crottaz-Roggerto; 🇨🇭 Lausanne, Vaud, Switzerland

Kantonsspital St. Gallen; 🇨🇭 St. Gallen, Saint Gallen, Switzerland

Ospedale Regionale di Lugano; 🇨🇭 Lugano, Ticino, Switzerland

Centre hospitalier universitaire vaudois (CHUV); 🇨🇭 Lausanne, Vaude, Switzerland

Department of Infectious Diseases, Hôpitaux Universitaires de Genève; 🇨🇭 Geneva, Switzerland

Klinik für Infektionskrankheiten & Spitalhygiene, Universitätsspital Zürich; 🇨🇭 Zürich, Switzerland