Informations générales (source: ClinicalTrials.gov)
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)
Interventional
N/A
Assistance Publique Hopitaux De Marseille (Voir sur ClinicalTrials)
août 2016
février 2019
29 juin 2024
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.
Etablissements
| Les établissements hors Île-de-France dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données | |||||
|---|---|---|---|---|---|
| Assistance Publique Hôpitaux de Marseille - 13273 - Marseille - France | Isabelle POIZOT-MARTIN, MD | Contact (sur clinicalTrials) | |||
Critères
Tous
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
- 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
- HIV2 infected patients par le VIH2
- Positive for HBsAg,
- Cirrohtic patient (elastométry >12,5kPa or métavir score F4)