Hepatic Safety of Eviplera® in HIV/Hepatitis C (HCV)-Coinfected Patients Without HCV Treatment in the The HEPAVIR HEPATIC SAFETY Cohort.

Study Overview
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Brief Summary
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To evaluate the incidence of grade 3 or 4 transaminase elevations or grade 4 total bilirubin elevations (hepatic toxicity) during the first 48 weeks of antiretroviral therapy with the combination of rilpivirine (25mg), tenofovir (245mg) and emtricitabine (200mg), in a single-tablet regimen (Eviplera®) in human immunodeficiency virus (HIV)/hepatitis C virus (HCV)-coinfected subjects.

Detailed Description
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This is a retrospective analysis of the prospective multicenter, observational HEPAVIR HEPATIC SAFETY Cohort (NCT01908660), in which the hepatic safety of the three-drug combination TDF/FTC/RPV will be assessed. A total of 176 patients will be included in this study, as well as 352 patients naive for RPV who initiated any ART that does not include RPV, who will serve as control group. The main objective is to evaluate the incidence of grade 3 or 4 transaminase elevations or grade 4 total bilirubin elevations (hepatic toxicity) during the first 48 weeks of antiretroviral therapy with the combination of rilpivirine (25mg), tenofovir (245mg) and emtricitabine (200mg), in a single-tablet regimen (Eviplera®) in human immunodeficiency virus (HIV)/hepatitis C virus (HCV)-coinfected subjects. Variables collected within in the cohort: Demographic variable: age, sex. Variables related to hepatitis C virus-infection: infection route, genotype, grade of hepatic fibrosis and method used for its determination, baseline Child-Pugh index in patients with cirrhosis, previous hepatic decompensations. Variables related to HIV-infection: CDC clinical category, HIV viral load, CD4 cell count, previous and new antiretroviral drugs. Blood test: AST, ALT platelets, cholesterol, bilirubin, gamma-glutamyltransferase, alkaline phosphatase, creatinine. Other variables: alcohol intake, self-reported adverse events, abnormal clinical findings. Cause of discontinuing antiviral when applicable. Endpoints Primary endpoint: Emergence of grade 3-4 TEs/grade 4 TBEs (hepatic toxicity) from baseline to week 48. Secondary endpoints Emergence of hepatic adverse events. Drug interruptions due to liver toxicity. Development of hepatic decompensations. CD4 and viral load changes from baseline to week 48.

Official Title
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Hepatic Safety of Eviplera® in HIV/Hepatitis C (HCV)-Coinfected Patients Without HCV Treatment in the The HEPAVIR HEPATIC SAFETY Cohort. hEPAtic Study.

Conditions
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Human Immunodeficiency Virus (HIV) Hepatitis C Virus (HCV) Coinfected Subjects

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ≥ 18 years old. Chronic HIV-1 infection, as diagnosed on the basis of the presence of serum HIV antibodies detected by EIA and western-blot. Chronic HCV infection as proven by detecting HCV antibodies in plasma, as well as detectable plasma HCV-RNA by PCR. To start a new ART regimen during the study period. Exclusion Criteria: Subjects with hepatotoxic events in the 2 months previous to Eviplera® treatment. Acute infections or uncontrolled chronic infection in the two months previous to Eviplera® treatment. Concomitant use of any drug with potential drug-drug interaction with Eviplera®. Documented resistance to study drugs. Concomitant therapy including anti-HCV agents, cytotoxic chemotherapy or immunosuppressors during Eviplera® treatment. Subjects taking part in any other clinical trial using an investigational product, with the exception of studies where the treatment studied have stopped for more than 12 weeks before Eviplera® treatment.

Ages Eligible for Study
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Minimum Age: 18 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 |
| --- | --- |
| Safety of the three-drug combination TDF/FTC/RPV<br>A total of 176 patients will be included in this study, as well as 352 patients naive for RPV who initiated any ART that does not include RPV, who will serve as control group. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of hepatic events | Number of patients with grade 3 or 4 transaminase elevations or grade 4 total bilirubin elevations (hepatic toxicity) during the first 48 weeks of antiretroviral therapy with the combination of rilpivirine (25mg), tenofovir (245mg) and emtricitabine (200mg), in a single-tablet regimen (Eviplera®) in human immunodeficiency virus (HIV)/hepatitis C virus (HCV)-coinfected subjects. | First 48 weeks of antiretroviral therapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparison of hepatic events between exposed and unexposed to Eviplera® | We evaluated the following parameters between subjets exposed and unexposed to Eviplera® Incidence of hepatic toxicity Incidence of hepatic adverse events. Proportion of subjects who interrupt treatment due to liver toxicity according to Eviplera® exposure We will evaluated this parameters taking account the impact of baseline liver fibrosis/cirrhosis on liver toxicity. | First 48 weeks of antiretroviral therapy | 
| Viral Kinetics and Immune response | Viral kinetics.- We compare the viral load between patients exposed and not exposed with Eviplera. Immune response.- We compare number of CD4 cells between patients exposed and not exposed with Eviplera | 48 weeks of antiretroviral therapy | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV HCV antiretroviral