TAF for HIV-HBV With Renal Dysfunction

Study Overview
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Brief Summary
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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
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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.

Official Title
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Prospective Cohort Study to Assess the Safety and Efficacy of Replacing Tenofovir Disoproxil Fumarate by Tenofovir Alafenamide in HIV/HBV-coinfected Patients With Mild or Moderate Renal Dysfunction

Conditions
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HIV and Hepatitis B Coinfection

Intervention / Treatment
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* Drug: Tenofovir Alafenamide


Participation Criteria
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Eligibility Criteria
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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 Exclusion Criteria: Study drug considered by the treating physician not a valid option for the patient Pregnancy Decompensated liver cirrhosis

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Switch<br>Patients are switched from a TDF-containing antiretroviral therapy regimen to a TAF-containing regimen | Drug: Tenofovir Alafenamide<br>* Patients are switched to either Genvoya (TAF/FTC/EVG/COB) or another FTC/TAF-containing ART regimen<br>|

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV, Hepatitis B, Renal dysfunction, tenofovir alafenamide