Analysis of the Impact of HCV Treatment by Last Generation Direct Antiviral Agents (DAA) on Antiviral Immunity and HIV DNA Reservoir in Coinfected HIV-HCV Patients (HCURE)

Spontaneous recovery of patients infected with HCV is related to the development of a cytotoxic immune response that is executed by specialized white blood cells, the CD8+ T cells, which develop a virus-specific response. In addition, the natural killer (NK) cells provide a first-line innate cytotoxic response, which is pivotal for the spontaneous clearing of HCV. In patients where HCV infection settles chronically, CD8+ T lymphocytes and NK cells fall into a state of anergy induced by chronic viral challenge. This anergic state is also found in the case of HIV infection and exacerbated by HIV-HCV coinfection. The first therapeutic strategies against HCV were based on a treatment with interferon alpha, which had an antiviral but also immunosuppressive effect. In fact, this therapeutic strategy was unable to help the recovery of the patient's immune system that would be expected after HCV cure. However, interferon-free therapeutic strategies combining first generation direct antiviral agents (DAA) showed a positive effect on HCV antiviral immunity, by enhancing the proliferative response of CD8+ T cells and the cytotoxic and proinflammatory responses of NK cells in HCV monoinfected patients (4, 5). Since HCV-targeted therapies based on combinations of the latest generation of DAA have nearly 100% cure rates and enable faster viral suppression over shorter treatment times, a positive impact of these regimens on antiviral immunity is plausible. This possibility would be particularly interesting in HIV-HCV co-infected patients, where reactivation of the innate antiviral immunity may contribute to immune defenses against both viruses. Moreover, it has been previously reported a moderate but significant and sustained decline of HIV-1 DNA in CD4 T cells from HIV-1/hepatitis C virus-coinfected patients receiving highly active antiretroviral therapy and treated with IFN alpha/ribavirin.

To date, the real impact on antiviral immunity of treatment as well as on HIV reservoir with the latest generation of DAA was not measured in HIV-HCV co-infected patients.

The aim of this study is to analyze the impact of the cure of hepatitis C on the HIV DNA reservoir and antiviral function of CD8+ and NK cells in a subgroup of patients receiving the latest generation DAAs for treatment of HCV infection, as part of a program for a reduction of the prevalence of chronic hepatitis C patients co-infected HIV-HCV set up within the Immuno-Hematology Service of the Sainte Marguerite Hospital (Research in routine care-Ethics committee Approval Sud- Méditerranée I ID RCB 2015-A01913-46/ Principal Investigator: Dr I Poizot-Martin).

The analysis of HIV DNA, NK and CD8+ T lymphocyte antiviral immune response prior, during and after anti-HCV treatment will need the collection of a biobank. Indeed, 25 mL peripheral blood will be collected at treatment initiation, during an interim assessment, at the end of treatment and six months post-treatment, for a total of 100 ml of additional blood collection. These analyzes will be performed by Dr C Tamalet for HIV DNA IHU-Méditerranée Infection, and the team of Prof. E Vivier, DHU- Marseille Immunopole for NK and CD8+ T lymphocyte antiviral immune response.

Study Overview

• Status: Unknown
• Conditions: HIV Associated HCV
• Intervention / Treatment: Other: blood draw

• Study Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Isabelle POIZOT-MARTIN, MD; Phone Number: +33491746163; Email: isabelle.poizot@ap-hm.fr

Study Locations

• France
  • Marseille, France, 13273
    • Recruiting
    • Assistance Publique Hopitaux de Marseille
    • Contact: Isabelle POIZOT-MARTIN, MD; Phone Number: +33491746163; Email: isabelle.poizot@ap-hm.fr

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• HIV1 infected patient
• HCV positive serologie and RNA-HCV positive
• Starting an anti-HCV traitment with direct antiviral agent
• With an hepatic fibrosis score < 12,5KPa measured through elastometry or with a score < F4 from liver biopsy

Exclusion Criteria:

• HIV2 infected patients par le VIH2
• Positive for HBsAg,
• Cirrohtic patient (elastométry >12,5kPa or métavir score F4)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Co infected HIV and HCV patients	Other: blood draw; 4 blood draws of 25 mls of blood will be performed at 4 differents time points (before treatment, 4 weeks later, at the end of the treatment and 6 months after the end of the treatment)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
number of CD8+ at each time point of the treatment	24 months
number of NK cells at each time point of the treatment	24 month

Collaborators and Investigators

• Sponsor: Assistance Publique Hopitaux De Marseille
• Investigators: Study Director: Urielle DESALBRES, AP-HM

Study record dates

Study Major Dates

• Study Start (Actual): August 31, 2016
• Primary Completion (Anticipated): August 31, 2018
• Study Completion (Anticipated): February 28, 2019

Study Registration Dates

• First Submitted: August 7, 2017
• First Submitted That Met QC Criteria: August 7, 2017
• First Posted (Actual): August 9, 2017

Study Record Updates

• Last Update Posted (Actual): August 9, 2017
• Last Update Submitted That Met QC Criteria: August 7, 2017
• Last Verified: August 1, 2017

More Information

Terms related to this study

• Other Study ID Numbers: 2016-31; 2016-A01028-43 (Other Identifier: IDRCB)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No