Clinical trial NCT03425994: Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide as Maintenance Treatment for HIV/HBV-coinfection
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
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Chronic Hepatitis B in HIV Patient
Kidney Injury
Bone Diseases
Lead sponsor: National Taiwan University Hospital
Sponsor class: OTHER
Collaborators: name: National Taiwan University Hospital Hsin-Chu Branch
name: National Taiwan University Hospital, Yun-Lin Branch
name: Far Eastern Memorial Hospital
name: Taoyuan General Hospital
name: Mackay Memorial Hospital
name: Chung Shan Medical University
name: Taichung Veterans General Hospital
name: National Cheng-Kung University Hospital
name: Changhua Christian Hospital
name: Chi Mei Medical Hospital
name: Kaohsiung Veterans General Hospital.
name: Kaohsiung Medical University Chung-Ho Memorial Hospital
name: Chang Gung Memorial Hospital
name: E-DA Hospital
name: Lotung Poh-Ai Hospital
First posted: 2018-02-08
Enrollment: 275
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: HIV/HBV-coinfected patients

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.


Eligibility 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

Primary outcomes:
measure: Proportion of patients with undetectable plasma HBV DNA load
timeFrame: 48 weeks
Secondary outcomes:
measure: Decreases of plasma HBV DNA load
timeFrame: 48 weeks
measure: Proportion of patients with plasma HIV RNA load <50 copies/mL
timeFrame: 48 weeks
measure: Liver function
timeFrame: 48 weeks
measure: Number of patients with change of HBV serology markers
timeFrame: 48 weeks
measure: Serum creatinine
timeFrame: 48 weeks
measure: Number of patients with an increase of serum creatinine
timeFrame: 48 weeks
measure: Estimated glomerular filtration rate
timeFrame: 48 weeks
measure: Number of patients with a decline of estimated glomerular filtration rate
timeFrame: 48 weeks
measure: Urine protein-creatinine ratio
timeFrame: 48 weeks
measure: Urine albumin-creatinine ratio
timeFrame: 48 weeks
measure: Urine β-2 microglobulin
timeFrame: 48 weeks
measure: Bone disease
timeFrame: 48 weeks
measure: Adverse drug reaction
timeFrame: 48 weeks
Other outcomes:
Locations:
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
Study officials:
affiliation: National Taiwan University Hospital
name: Chien-Ching Hung
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
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.
citation: 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.
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. doi: 10.1097/QAI.0000000000001069.
citation: 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.