Clinical trial NCT02196064: Hepatic Safety of Eviplera® in HIV/Hepatitis C (HCV)-Coinfected Patients Without HCV Treatment in the "The HEPAVIR HEPATIC SAFETY Cohort."
Official title: Hepatic Safety of Eviplera® in HIV/Hepatitis C (HCV)-Coinfected Patients Without HCV Treatment in the "The HEPAVIR HEPATIC SAFETY Cohort." hEPAtic Study.
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Human Immunodeficiency Virus (HIV) Hepatitis C Virus (HCV) Coinfected Subjects
Keywords: HIV HCV antiretroviral
Lead sponsor: Andalusian Network for Design and Translation of Advanced Therapies
Sponsor class: OTHER
Collaborators: name: Gilead Sciences
First posted: 2014-07-21
Enrollment: 519
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Incidence of hepatic events
timeFrame: First 48 weeks of antiretroviral therapy
Secondary outcomes:
measure: Comparison of hepatic events between exposed and unexposed to Eviplera®
timeFrame: First 48 weeks of antiretroviral therapy
measure: Viral Kinetics and Immune response
timeFrame: 48 weeks of antiretroviral therapy
Other outcomes:
Locations:
city: Sevilla
country: Spain
facility: Fundación Pública Andaluza Progreso y Salud
Study officials:
affiliation: Hospital Universitario Virgen de Valme
name: Juan Antonio Pineda Vergara
role: STUDY_CHAIR
affiliation: Hospital Universitario Reina Sofía
name: Antonio Rivero Román
role: STUDY_CHAIR
affiliation: Complejo Hospitalario de Especialidades Juan Ramón Jimenez
name: Dolores Merino Muñoz
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital Universitario Virgen Macarena
name: María José Rios Villega
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital La Línea de la Concepción
name: Francisco Téllez Pérez
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital de Poniente
name: Inés Pérez Camacho
role: PRINCIPAL_INVESTIGATOR
affiliation: Complejo Hospitario Torrecárdenas
name: Antonio Collado Romacho
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital Universitario Virgen de la Victoria
name: Josefa Ruiz Morales
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital Regional de Malaga
name: Marcial Delgado Fernández
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital Universitario San Cecilio
name: Leopoldo Muñoz Medina
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital Santa María de Rosell
name: Francisco Vera Méndez
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospitales Universitarios Virgen del Rocío
name: Nuria Espinosa Aguilera
role: PRINCIPAL_INVESTIGATOR
affiliation: Fundación de Investigación Biomédica - Hospital Universitario de La Princesa
name: Iganacio Santos Gil
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital Universitario La Paz
name: Juan González García
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital Universitario de Puerto Real
name: Antonio Vergara de Campos
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital Universitario Gregorio Marañón
name: Juan Berenguer Berenguer
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital 12 de Octubre
name: Federico Pulido Ortega
role: PRINCIPAL_INVESTIGATOR
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