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

Kidney Injury Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03425994
• Other study ID #: 201710056RIPB
• Status: Active, not recruiting
• Start date: February 6, 2018
• Est. completion date: October 11, 2019

Study information

• Verified date: August 2019
• Source: National Taiwan University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 275
• Est. completion date: October 11, 2019
• Est. primary completion date: February 22, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Bone Diseases
• Chronic Hepatitis B in HIV Patient
• Hepatitis
• Hepatitis B
• Hepatitis B, Chronic
• Kidney Injury

Intervention

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

Locations

Country	Name	City	State
Taiwan	National Taiwan University Hospital	Taipei

Sponsors (16)

Lead Sponsor

Collaborator

National Taiwan University Hospital

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

Country where clinical trial is conducted

Taiwan, 

References & Publications (5)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Decreases of plasma HBV DNA load	Decreases of plasma HBV DNA load (in log10 copies/mL)	48 weeks
Secondary	Proportion of patients with plasma HIV RNA load <50 copies/mL	Proportion of patients achieving plasma HIV RNA load <50 copies/mL	48 weeks
Secondary	Liver function	Change of serum aspartate aminotransferase (AST) and alanine transaminase (ALT)	48 weeks
Secondary	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
Secondary	Serum creatinine	Changes of serum creatinine from baseline	48 weeks
Secondary	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
Secondary	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
Secondary	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
Secondary	Urine protein-creatinine ratio	Change of urine protein-creatinine ratio (UPCR) from baseline	48 weeks
Secondary	Urine albumin-creatinine ratio	Change of urine albumin-creatinine ratio (UACR) from baseline	48 weeks
Secondary	Urine ß-2 microglobulin	Change of ß-2 microglobulin from baseline	48 weeks
Secondary	Bone disease	Change of bone mineral density	48 weeks
Secondary	Adverse drug reaction	Number and types of adverse drug reaction related to Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide	48 weeks