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

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ClinicalTrials.gov Identifier: NCT03425994
Recruitment Status : Not yet recruiting
First Posted : February 8, 2018
Last Update Posted : February 8, 2018
Sponsor:
Collaborators:
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

Brief Summary:
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 or disease Intervention/treatment
Chronic Hepatitis B in HIV Patient Kidney Injury Bone Diseases Drug: Elvitegravir/Cobicistat/Emtricitabine

Study Type : Observational [Patient Registry]
Estimated Enrollment : 200 participants
Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration: 48 Weeks
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
Estimated Study Start Date : April 2018
Estimated Primary Completion Date : October 2019
Estimated Study Completion Date : January 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS
U.S. FDA Resources

Group/Cohort Intervention/treatment
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



Primary Outcome Measures :
  1. 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 :
  1. Decreases of plasma HBV DNA load [ Time Frame: 48 weeks ]
    Decreases of plasma HBV DNA load (in log10 copies/mL)

  2. 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

  3. Liver function [ Time Frame: 48 weeks ]
    Change of serum aspartate aminotransferase (AST) and alanine transaminase (ALT)

  4. 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

  5. Serum creatinine [ Time Frame: 48 weeks ]
    Changes of serum creatinine from baseline

  6. 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

  7. 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

  8. 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

  9. Urine protein-creatinine ratio [ Time Frame: 48 weeks ]
    Change of urine protein-creatinine ratio (UPCR) from baseline

  10. Urine albumin-creatinine ratio [ Time Frame: 48 weeks ]
    Change of urine albumin-creatinine ratio (UACR) from baseline

  11. Urine β-2 microglobulin [ Time Frame: 48 weeks ]
    Change of β-2 microglobulin from baseline

  12. Bone disease [ Time Frame: 48 weeks ]
    Change of bone mineral density

  13. 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


Information from the National Library of Medicine

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Ages Eligible for Study:   20 Years and older   (Adult, Senior)
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03425994


Contacts
Contact: Chien-Ching Hung +886-2-23123456 ext 67552 hcc0401@ntu.edu.tw
Contact: Yu-Shan Huang +886-3-5326151 ext 32026 b101091021@gmail.com

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

Publications:

Responsible Party: National Taiwan University Hospital
ClinicalTrials.gov Identifier: NCT03425994     History of Changes
Other Study ID Numbers: 201710056RIPB
First Posted: February 8, 2018    Key Record Dates
Last Update Posted: February 8, 2018
Last Verified: January 2018
Individual Participant Data (IPD) Sharing Statement:
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
Hepatitis, Chronic
Hepatitis B
Hepatitis B, Chronic
Bone Diseases
Liver Diseases
Digestive System Diseases
Hepadnaviridae Infections
DNA Virus Infections
Virus Diseases
Hepatitis, Viral, Human
Musculoskeletal Diseases
Tenofovir
Emtricitabine
Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination
Cobicistat
Antiviral Agents
Anti-Infective Agents
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Retroviral Agents
Anti-HIV Agents
Cytochrome P-450 CYP3A Inhibitors
Cytochrome P-450 Enzyme Inhibitors