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

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

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.

Study Overview

• Status: Unknown
• Conditions: Bone Diseases; Kidney Injury; Chronic Hepatitis B in HIV Patient
• Intervention / Treatment: Drug: Elvitegravir/Cobicistat/Emtricitabine

• Study Type: Observational
• Enrollment (Actual): 275

Contacts and Locations

Study Locations

• Taiwan
  • Taipei, Taiwan, 100
    • National Taiwan University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

HIV/HBV-coinfected patients

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

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 Names: Genvoya

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Decreases of plasma HBV DNA load	Decreases of plasma HBV DNA load (in log10 copies/mL)	48 weeks
Proportion of patients with plasma HIV RNA load <50 copies/mL	Proportion of patients achieving plasma HIV RNA load <50 copies/mL	48 weeks
Liver function	Change of serum aspartate aminotransferase (AST) and alanine transaminase (ALT)	48 weeks
Number of patients with change of HBV serology markers	Number of patients with HBsAg loss, hepatitis B e-antigen (HBeAg) loss, or appearance of anti-HBs and anti-HBe	48 weeks
Serum creatinine	Changes of serum creatinine from baseline	48 weeks
Number of patients with an increase of serum creatinine	Number of patients with an increase of serum creatinine by ≥0.3 mg/dL or ≥50% from baseline	48 weeks
Estimated glomerular filtration rate	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	48 weeks
Number of patients with a decline of estimated glomerular filtration rate	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	48 weeks
Urine protein-creatinine ratio	Change of urine protein-creatinine ratio (UPCR) from baseline	48 weeks
Urine albumin-creatinine ratio	Change of urine albumin-creatinine ratio (UACR) from baseline	48 weeks
Urine β-2 microglobulin	Change of β-2 microglobulin from baseline	48 weeks
Bone disease	Change of bone mineral density	48 weeks
Adverse drug reaction	Number and types of adverse drug reaction related to Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide	48 weeks

Collaborators and Investigators

• Sponsor: National Taiwan University Hospital
• Collaborators: Mackay Memorial Hospital; Chang Gung Memorial Hospital; Kaohsiung Medical University Chung-Ho Memorial Hospital; National Cheng-Kung University Hospital; Far Eastern Memorial Hospital; Changhua Christian Hospital; Taichung Veterans General Hospital; Lotung Poh-Ai Hospital; E-DA Hospital; Kaohsiung Veterans General Hospital.; Chi Mei Medical Hospital; Chung Shan Medical University; National Taiwan University Hospital Hsin-Chu Branch; Taoyuan General Hospital; National Taiwan University Hospital, Yun-Lin Branch
• Investigators: Principal Investigator: Chien-Ching Hung, National Taiwan University Hospital

Publications and helpful links

General Publications

• 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. Erratum In: Lancet Gastroenterol Hepatol. 2016 Nov;1(3):e2.
• 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.
• 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. Erratum In: Lancet Gastroenterol Hepatol. 2016 Nov;1(3):e2.
• 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. Erratum In: Lancet. 2016 Apr 30;387(10030):1816.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): February 6, 2018
• Primary Completion (Actual): February 22, 2019
• Study Completion (Anticipated): October 11, 2019

Study Registration Dates

• First Submitted: January 11, 2018
• First Submitted That Met QC Criteria: February 1, 2018
• First Posted (Actual): February 8, 2018

Study Record Updates

• Last Update Posted (Actual): August 28, 2019
• Last Update Submitted That Met QC Criteria: August 25, 2019
• Last Verified: August 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Musculoskeletal Diseases; Hepatitis, Viral, Human; Hepadnaviridae Infections; DNA Virus Infections; Hepatitis, Chronic; Hepatitis B; Hepatitis; Hepatitis B, Chronic; Bone Diseases; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Integrase Inhibitors; Emtricitabine; Cobicistat; Elvitegravir
• Other Study ID Numbers: 201710056RIPB

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No