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

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

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.

Study Overview

• Status: Completed
• Conditions: 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 Type: Observational
• Enrollment (Actual): 519

Contacts and Locations

Study Locations

• Spain
  • Sevilla, Spain, 41092
    • Fundacion Publica Andaluza Progreso Y Salud

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

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.

Description

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 Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Safety of the three-drug combination TDF/FTC/RPV; 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?

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

Collaborators and Investigators

• Sponsor: Fundación Pública Andaluza Progreso y Salud
• Collaborators: Gilead Sciences
• Investigators: Study Chair: Juan Antonio Pineda Vergara, Hospital Universitario Virgen de Valme; Study Chair: Antonio Rivero Román, Hospital Universitario Reina Sofía; Principal Investigator: Dolores Merino Muñoz, Complejo Hospitalario de Especialidades Juan Ramón Jiménez; Principal Investigator: María José Rios Villega, Hospital Universitario Virgen Macarena; Principal Investigator: Francisco Téllez Pérez, Hospital La Linea de la Concepción; Principal Investigator: Inés Pérez Camacho, Hospital de Poniente; Principal Investigator: Antonio Collado Romacho, Complejo Hospitario Torrecardenas; Principal Investigator: Josefa Ruiz Morales, Hospital Universitario Virgen de la Victoria; Principal Investigator: Marcial Delgado Fernández, Hospital Regional de Malaga; Principal Investigator: Leopoldo Muñoz Medina, Hospital Universitario San Cecilio; Principal Investigator: Francisco Vera Méndez, Hospital Santa María de Rosell; Principal Investigator: Nuria Espinosa Aguilera, Hospitales Universitarios Virgen del Rocío; Principal Investigator: Iganacio Santos Gil, Fundación de Investigación Biomédica - Hospital Universitario de La Princesa; Principal Investigator: Juan González García, Hospital Universitario La Paz; Principal Investigator: Antonio Vergara de Campos, Hospital Universitario de Puerto Real; Principal Investigator: Juan Berenguer Berenguer, Hospital Universitario Gregorio Maranon; Principal Investigator: Federico Pulido Ortega, Hospital 12 de Octubre

Study record dates

Study Major Dates

• Study Start: May 1, 2014
• Primary Completion (Actual): July 1, 2015
• Study Completion (Actual): July 1, 2015

Study Registration Dates

• First Submitted: July 15, 2014
• First Submitted That Met QC Criteria: July 17, 2014
• First Posted (Estimate): July 21, 2014

Study Record Updates

• Last Update Posted (Estimate): August 5, 2015
• Last Update Submitted That Met QC Criteria: August 4, 2015
• Last Verified: August 1, 2015

More Information

Terms related to this study

• Keywords: HIV HCV antiretroviral
• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; Liver Diseases; Flaviviridae Infections; Hepatitis, Viral, Human; Enterovirus Infections; Picornaviridae Infections; Slow Virus Diseases; HIV Infections; Hepatitis; Hepatitis A; Hepatitis C; Acquired Immunodeficiency Syndrome
• Other Study ID Numbers: hEPAtic