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

Completed

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

• Registration Number: NCT02196064
• Lead Sponsor: Fundación Pública Andaluza Progreso y Salud

Brief Summary

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

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

1. Primary endpoint: Emergence of grade 3-4 TEs/grade 4 TBEs (hepatic toxicity) from baseline to week 48.

2. 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.

Study Timeline

• Study Start: 2014-05
• Study First Submitted: 2014-07-15
• Study First Submitted QC: 2014-07-17
• Study First Posted: 2014-07-21
• Primary Completion: 2015-07
• Study Completion: 2015-07
• Status Verified: 2015-08
• Last Update Submitted: 2015-08-04
• Last Update Posted: 2015-08-05

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 519

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.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Incidence of hepatic events	First 48 weeks of antiretroviral therapy	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.

Secondary Outcome Measures

Name	Time	Method
Viral Kinetics and Immune response	48 weeks of antiretroviral therapy	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
Comparison of hepatic events between exposed and unexposed to Eviplera®	First 48 weeks of antiretroviral therapy	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.

Trial Locations

Locations (1)

Fundación Pública Andaluza Progreso y Salud; 🇪🇸 Sevilla, Spain