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

NCT03425994 | Unknown

• 1 other identifier: 201710056RIPB
• Study Type: observational
• Target: 275
• Locations: 1 country
• Sites: 1

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.

Conditions

Chronic Hepatitis B in HIV Patient; Kidney Injury; Bone Diseases

Outcome Measures

Primary Outcomes (1)

• Proportion of patients with undetectable plasma HBV DNA load

  Proportion of patients achieving undetectable plasma HBV DNA load (defined as \<128 copies/mL)

  48 weeks

Secondary Outcomes (13)

• Decreases of plasma HBV DNA load

  48 weeks

• Proportion of patients with plasma HIV RNA load <50 copies/mL

  48 weeks

• Liver function

  48 weeks

• Number of patients with change of HBV serology markers

  48 weeks

• Serum creatinine

  48 weeks

Study Arms (1)

Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide

Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (Genvoya) tablet by mouth, once daily for 48 weeks

Drug: Elvitegravir/Cobicistat/Emtricitabine

Interventions

Elvitegravir/Cobicistat/Emtricitabine DRUG

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

Also known as: Genvoya

Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

HIV/HBV-coinfected patients

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

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

Study Sites (1)

National Taiwan University Hospital

Taipei, 100, Taiwan

Location

Related Publications (6)

• Sax PE, Wohl D, Yin MT, Post F, DeJesus E, Saag M, Pozniak A, Thompson M, Podzamczer D, Molina JM, Oka S, Koenig E, Trottier B, Andrade-Villanueva J, Crofoot G, Custodio JM, Plummer A, Zhong L, Cao H, Martin H, Callebaut C, Cheng AK, Fordyce MW, McCallister S; GS-US-292-0104/0111 Study Team. Tenofovir alafenamide versus tenofovir disoproxil fumarate, coformulated with elvitegravir, cobicistat, and emtricitabine, for initial treatment of HIV-1 infection: two randomised, double-blind, phase 3, non-inferiority trials. Lancet. 2015 Jun 27;385(9987):2606-15. doi: 10.1016/S0140-6736(15)60616-X. Epub 2015 Apr 15.

  PMID: 25890673 BACKGROUND

• Pozniak A, Arribas JR, Gathe J, Gupta SK, Post FA, Bloch M, Avihingsanon A, Crofoot G, Benson P, Lichtenstein K, Ramgopal M, Chetchotisakd P, Custodio JM, Abram ME, Wei X, Cheng A, McCallister S, SenGupta D, Fordyce MW; GS-US-292-0112 Study Team. Switching to Tenofovir Alafenamide, Coformulated With Elvitegravir, Cobicistat, and Emtricitabine, in HIV-Infected Patients With Renal Impairment: 48-Week Results From a Single-Arm, Multicenter, Open-Label Phase 3 Study. J Acquir Immune Defic Syndr. 2016 Apr 15;71(5):530-7. doi: 10.1097/QAI.0000000000000908.

  PMID: 26627107 BACKGROUND

• Chan HL, Fung S, Seto WK, Chuang WL, Chen CY, Kim HJ, Hui AJ, Janssen HL, Chowdhury A, Tsang TY, Mehta R, Gane E, Flaherty JF, Massetto B, Gaggar A, Kitrinos KM, Lin L, Subramanian GM, McHutchison JG, Lim YS, Acharya SK, Agarwal K; GS-US-320-0110 Investigators. Tenofovir alafenamide versus tenofovir disoproxil fumarate for the treatment of HBeAg-positive chronic hepatitis B virus infection: a randomised, double-blind, phase 3, non-inferiority trial. Lancet Gastroenterol Hepatol. 2016 Nov;1(3):185-195. doi: 10.1016/S2468-1253(16)30024-3. Epub 2016 Sep 22.

  PMID: 28404091 BACKGROUND

• Buti M, Gane E, Seto WK, Chan HL, Chuang WL, Stepanova T, Hui AJ, Lim YS, Mehta R, Janssen HL, Acharya SK, Flaherty JF, Massetto B, Cathcart AL, Kim K, Gaggar A, Subramanian GM, McHutchison JG, Pan CQ, Brunetto M, Izumi N, Marcellin P; GS-US-320-0108 Investigators. Tenofovir alafenamide versus tenofovir disoproxil fumarate for the treatment of patients with HBeAg-negative chronic hepatitis B virus infection: a randomised, double-blind, phase 3, non-inferiority trial. Lancet Gastroenterol Hepatol. 2016 Nov;1(3):196-206. doi: 10.1016/S2468-1253(16)30107-8. Epub 2016 Sep 22.

  PMID: 28404092 BACKGROUND

• Gallant J, Brunetta J, Crofoot G, Benson P, Mills A, Brinson C, Oka S, Cheng A, Garner W, Fordyce M, Das M, McCallister S; GS-US-292-1249 Study Investigators. Brief Report: Efficacy and Safety of Switching to a Single-Tablet Regimen of Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide in HIV-1/Hepatitis B-Coinfected Adults. J Acquir Immune Defic Syndr. 2016 Nov 1;73(3):294-298. doi: 10.1097/QAI.0000000000001069.

  PMID: 27171740 BACKGROUND

• Huang YS, Cheng CY, Liou BH, Lu PL, Cheng SH, Lee YT, Liu CE, Sun HY, Yang CJ, Tang HJ, Lin SP, Ho MW, Huang SH, Tsai HC, Lee CH, Hung CC; Taiwan HIV Study Group. Efficacy and Safety of Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide as Maintenance Treatment in HIV/HBV-Coinfected Patients. J Acquir Immune Defic Syndr. 2021 Apr 1;86(4):473-481. doi: 10.1097/QAI.0000000000002589.

  PMID: 33273214 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

blood samples

MeSH Terms

Conditions

Bone Diseases

Interventions

elvitegravir; Elvitegravir, Cobicistat, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination

Condition Hierarchy (Ancestors)

Musculoskeletal Diseases

Intervention Hierarchy (Ancestors)

Cobicistat; Carbamates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Tenofovir; Organophosphonates; Organophosphorus Compounds; Thiazoles; Sulfur Compounds; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Emtricitabine; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Drug Combinations; Pharmaceutical Preparations

Study Officials

• Chien-Ching Hung

  National Taiwan University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 48 Weeks
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 11, 2018
• First Posted: February 8, 2018
• Study Start: February 6, 2018
• Primary Completion: February 22, 2019
• Study Completion: October 11, 2019
• Last Updated: August 28, 2019

Record last verified: 2019-08

Data Sharing

• IPD Sharing: Will not share

Locations

TW (1)