Clinical Trials

MainTitle

Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide as Maintenance Treatment for HIV/HBV-coinfection

This study is ongoing, but not recruiting participants.
Sponsor
National Taiwan University Hospital

Collaborator
National Taiwan University Hospital Hsin-Chu Branch
National Taiwan University Hospital, Yun-Lin Branch
Far Eastern Memorial Hospital
Taoyuan General Hospital
Mackay Memorial Hospital
Chung Shan Medical University
Taichung Veterans General Hospital
National Cheng-Kung University Hospital
Changhua Christian Hospital
Chi Mei Medical Hospital
Kaohsiung Veterans General Hospital.
Kaohsiung Medical University Chung-Ho Memorial Hospital
Chang Gung Memorial Hospital
E-DA Hospital
Lotung Poh-Ai Hospital

Information provided by (Responsible Party)
National Taiwan University Hospital
ClinicalTrials.gov Identifier
NCT03425994

First received: January 11, 2018
Last updated: August 25, 2019
Last Verified: August 2019
History of Changes
Purpose

Purpose

Tenofovir alafenamide (TAF), active against both HIV and HBV, demonstrates similar antiviral efficacy but improved renal and bone safety compared to tenofovir disoproxil fumarate (TDF) in HIV-1-infected patients. HIV-1-infected patients whose estimated glomerular filtration rate (eGFR) between 30-69 mL/min were shown to have minimal change in eGFR and improved proteinuria, albuminuria, and bone mineral density after switching to a single-tablet regimen containing Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (EVG/cob/FTC/TAF). For treatment of chronic HBV infection, a similar proportion of HBV-monoinfected patients who received TAF and those who received TDF achieved undetectable HBV DNA at 48 weeks of therapy. Although TAF is effective for HIV and HBV suppression, data on efficacy of TAF are limited among patients co-infected with both viruses. Currently, only one open-label, single-arm study had investigated the efficacy and safety of TAF in HIV/HBV-coinfected patients. In this study, 72 HIV/HBV-coinfected patients switching to EVG/cob/FTC/TAF were enrolled, and 91.7% of them maintained or achieved virologic suppression for both HIV and HBV at 48 weeks of therapy. Seroconversion occurred in 2.9% of HBsAg-positive participants and in 3.3% of HBeAg-positive participants. Improvements in eGFR and declines in markers of bone turnover of the participants were observed. The limitations of the above study are the small sample size. Taiwan is a country hyperendemic for HBV infection, with 19.8% of HIV-positive patients who were born before the implementation of nationwide neonatal vaccination in 1986 had concurrent chronic HBV infection. To further the understanding of the difference between TAF- and TDF-containing combination antiretroviral therapy among HIV/HBV-coinfected patients, the investigators plan to conduct an observational study to evaluate the efficacy and safety of EVG/cob/FTC/TAF as maintenance treatment of HIV/HBV-coinfected patients.

Condition Intervention
Chronic Hepatitis B in HIV Patient
Kidney Injury
Bone Diseases

Drug : Elvitegravir/Cobicistat/Emtricitabine

Study Type: Observational [Patient Registry]
Study Design:
Official Title: Efficacy and Safety of Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (Genvoya) as Maintenance Treatment of HIV-1/Hepatitis B Virus (HBV)-Coinfected Patients: an Observational Study

Further study details as provided by National Taiwan University Hospital:

Primary Outcome Measures

  • Proportion of patients with undetectable plasma HBV DNA load [ Time Frame: 48 weeks ]
    Proportion of patients achieving undetectable plasma HBV DNA load (defined as <128 copies/mL)
Secondary Outcome Measures:
  • Decreases of plasma HBV DNA load [ Time Frame: 48 weeks ]
    Decreases of plasma HBV DNA load (in log10 copies/mL)
  • Proportion of patients with plasma HIV RNA load <50 copies/mL [ Time Frame: 48 weeks ]
    Proportion of patients achieving plasma HIV RNA load <50 copies/mL
  • Liver function [ Time Frame: 48 weeks ]
    Change of serum aspartate aminotransferase (AST) and alanine transaminase (ALT)
  • Number of patients with change of HBV serology markers [ Time Frame: 48 weeks ]
    Number of patients with HBsAg loss, hepatitis B e-antigen (HBeAg) loss, or appearance of anti-HBs and anti-HBe
  • Serum creatinine [ Time Frame: 48 weeks ]
    Changes of serum creatinine from baseline
  • Number of patients with an increase of serum creatinine [ Time Frame: 48 weeks ]
    Number of patients with an increase of serum creatinine by ≥0.3 mg/dL or ≥50% from baseline
  • Estimated glomerular filtration rate [ Time Frame: 48 weeks ]
    Changes of serum estimated glomerular filtration rate (eGFR, [mL/min per 1.73m2], calculated by Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] equation) from baseline
  • Number of patients with a decline of estimated glomerular filtration rate [ Time Frame: 48 weeks ]
    Number of patients with a decline of estimated glomerular filtration rate (eGFR, calculated by Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] equation) by 15 mL/min per 1.73m2 or 20% from baseline
  • Urine protein-creatinine ratio [ Time Frame: 48 weeks ]
    Change of urine protein-creatinine ratio (UPCR) from baseline
  • Urine albumin-creatinine ratio [ Time Frame: 48 weeks ]
    Change of urine albumin-creatinine ratio (UACR) from baseline
  • Urine β-2 microglobulin [ Time Frame: 48 weeks ]
    Change of β-2 microglobulin from baseline
  • Bone disease [ Time Frame: 48 weeks ]
    Change of bone mineral density
  • Adverse drug reaction [ Time Frame: 48 weeks ]
    Number and types of adverse drug reaction related to Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide

Biospecimen Retention: Samples With DNA
blood samples

Enrollment: 275
Study Start Date: February 6, 2018
Estimated Study Completion Date: October 11, 2019
Estimated Primary Completion Date: February 22, 2019 (Final data collection date for primary outcome measure)

Arms Assigned Interventions
Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide
Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (Genvoya) tablet by mouth, once daily for 48 weeks
Drug: Elvitegravir/Cobicistat/Emtricitabine

Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide 150mg/150mg/200mg/10mg (Genvoya) film coated tablet

Other Name: Genvoya
Eligibility

Eligibility

Ages Eligible for Study: 20 Years and older  
Sexes Eligible for Study: All  
Accepts Healthy Volunteers: No  
Sampling Method: Non-Probability Sample  

Study Population

HIV/HBV-coinfected patients

Criteria

Inclusion Criteria:

  • Aged ≥ 20 years
  • Diagnosed with HIV and HBV-coinfection. HBV infection is defined as positive HBsAg for 6 months or longer before enrollment of the study
  • Serum HBV DNA load <9 log10 IU/mL
  • On Tenofovir Disoproxil Fumarate/Emtricitabine (TDF/FTC) or TDF plus lamivudine (3TC) as backbone plus a 3rd agent for HIV infection for 6 months or longer
  • Plasma HIV RNA load <50 copies/mL twice over the past 12 months
  • No known resistance mutations to Integrase strand transfer inhibitors (InSTIs), and no previous history of HIV treatment failure under InSTIs-containing combination antiretroviral therapy (cART). HIV treatment failure is defined as a plasma HIV RNA load >400 copies/mL after 6 months of InSTIs-containing cART.
  • No known resistance mutations to TDF, 3TC, or FTC, and no previous history of HIV treatment failure while on TDF, 3TC, or FTC-containing cART. HIV treatment failure is defined as a plasma HIV RNA load >400 copies/mL after 6 months of TDF, 3TC, or FTC-containing cART.
  • Baseline eGFR (estimated glomerular filtration rate) ≥30 mL/min per 1.73m2 (calculated by CKD-EPI equation)
  • AST and ALT ≤2-fold the upper limit of normal
  • Able to sign the written informed consent


Exclusion Criteria:
  • Active opportunistic illness
  • On treatment of tuberculosis
  • Pregnancy or lactation
  • Hepatic decompensation (Child-Pugh C)
  • Allergic to TDF, TAF, 3TC, FTC, or InSTIs
  • Intolerance of InSTIs
  • Hepatitis C virus (HCV)-coinfection and plan to start treatment with direct-acting antiviral agents or interferon/ribavirin within 48 weeks
  • Concurrent use of rifamycins, phenytoin, and other drugs that are contraindicated with
EVG/cob/FTC/TAF

contacts and locations

Contacts and Locations

Choosing to participate in a study is an important personal decision.Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT03425994

Locations

Taiwan
National Taiwan University Hospital
Taipei, Taiwan, 100

Sponsors and Collaborators

National Taiwan University Hospital
National Taiwan University Hospital Hsin-Chu Branch
National Taiwan University Hospital, Yun-Lin Branch
Far Eastern Memorial Hospital
Taoyuan General Hospital
Mackay Memorial Hospital
Chung Shan Medical University
Taichung Veterans General Hospital
National Cheng-Kung University Hospital
Changhua Christian Hospital
Chi Mei Medical Hospital
Kaohsiung Veterans General Hospital.
Kaohsiung Medical University Chung-Ho Memorial Hospital
Chang Gung Memorial Hospital
E-DA Hospital
Lotung Poh-Ai Hospital

Investigators

Principal Investigator: Chien-Ching Hung National Taiwan University Hospital
More Information

More Information


Responsible Party: National Taiwan University Hospital  
ClinicalTrials.gov Identifier: NCT03425994   History of Changes  
Other Study ID Numbers: 201710056RIPB  
Study First Received: January 11, 2018  
Last Updated: August 25, 2019  
Individual Participant Data    
Plan to Share IPD: No  

Studies a U.S. FDA-regulated Drug Product: No  
Studies a U.S. FDA-regulated Device Product: No  

Additional relevant MeSH terms:
Hepatitis B
Hepatitis B, Chronic
Bone Diseases
Hepatitis
Emtricitabine
Cobicistat
Genvoya

ClinicalTrials.gov processed this data on June 02, 2020
This information is provided by ClinicalTrials.gov.