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

Study Overview
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Brief Summary
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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.

Official Title
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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

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

Intervention / Treatment
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* Drug: Elvitegravir/Cobicistat/Emtricitabine


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide<br>Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (Genvoya) tablet by mouth, once daily for 48 weeks | Drug: Elvitegravir/Cobicistat/Emtricitabine<br>* Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide 150mg/150mg/200mg/10mg (Genvoya) film coated tablet<br>* Other names: Genvoya;|

What is the study measuring?
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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 |