Coinfezione HIV-HCV. Raffaele Bruno, MD. Department of Infectious Diseases, University of Pavia Fondazione IRCCS Policlinico San Matteo, Pavia, Italy

Transcription

1 Coinfezione HIV-HCV Raffaele Bruno, MD This program is supported by educational grants from Department of Infectious Diseases, University of Pavia Fondazione IRCCS Policlinico San Matteo, Pavia, Italy

2 Raffaele Bruno Università degli Studi di Pavia Il sottoscritto dichiara di aver avuto negli ultimi 12 mesi conflitto d interesse in relazione a questa presentazione Gilead Sciences, Janssen, MSD, Roche. e che la presentazione contiene discussione di farmaci in studio o ad uso off-label Telaprevir, Boceprevir

3 General recommendations for therapy of hepatitis C in HIV coinfection HCV treatment offers the possibility of eradicating HCV within a defined treatment period. This is potentially advantageous for the subsequent management of the patient with HIV, and every coinfected patient should therefore be considered for treatment when the benefits of therapy outweigh the risks. This also needs to be seen in the context of faster liver fibrosis progression in HIV/ HCV coinfection and with better HCV treatment outcome with the use of direct acting antivirals (DAAs) in these patients.

4

5

6 HCV-Treatment-related variables Information on liver fibrosis staging is important for making therapeutic decisions in coinfected patients. liverbiopsyisno longermandatoryfor consideringtreatment of chronichcv. Currenttherapyisparticularlyrecommendedin patientswith a high likelihood of achieving sustained virological response (SVR) suchasgenotypes2 or 3 or genotype1 patientswith an IL28B CC genotypeor GT 1 patientswith a previousrelapse under dualtherapywhichnowcan be retreatedwith triple therapy

7 HIV -Treatment-related variables If chronic hepatitis C is detected early in the course of HIV infection (before the initiation of ART is necessary), treatment for chronic HCV is advised. For patients with a CD4-count < 500/µL, early ART initiation is recommended to optimize HCV treatment outcome. However, if a coinfected patient has significant immunodeficiency (CD4 count < 350 cells/µl), the CD4-count should be improved using ART prior to commencing anti-hcv treatment. Patients with a CD4 relative percentage > 25% are more likely to achieve SVR than those with a lower CD4 percentage.

8 HCV- Treatment-related variables Based on 4 baseline variables (serum HCV-RNA, HCV genotype, liver fibrosis staging using elastometry, and IL28B genotyping), the Prometheus index has recently been developed and can optionally be used as a risk calculator for predicting the likelihood of SVR using Peg- IFNribavirin therapy in HIV-HCV coinfected patients. It is freely available on the web ( prometheusindex.php ).

9 Management of newly diagnosed HIV/HCV coinfected genotype 1 patients

10 Management of HIV-HCV coinfected genotype-1 patients according to fibrosis stage and prior treatment outcome* ii Monitor fibrosis stage annually, preferably with two established methods. Treat with triple therapy, if rapid progression EACS Guidelines Version 6.1 November 2012 AISF Position Paper 2013

11

12 Management of HIV-HCV coinfected patients according to HCV genotype and HCV-RNA viral decay The combination of Peg-IFN alpha and ribavirin(rbv) remains the treatment of choice for HCV genotype 2, 3 and 4 infection. The standard dose for Peg-IFN 2a is 180 μg once weekly, and for Peg-IFN 2b it is 1.5 μg/kg bodyweight once weekly. An initial weight-adapted dose of RBV of 1000 (wt 75kg) (wt > 75kg) mg/day(administered BID) is recommended for all HCV genotypes in the HIV setting. EACS Guidelines Version 6.1 November 2012

13 Classification of and interventions for HCV genotype 2, 3 or 4 HIV-coinfected non-responders/relapsers to prior interferon-based therapies CATEGORY SUBGROUP SUGGESTED INTERVENTION Suboptimal treatment Suboptimal schedule Interferon (monotherapy or with ribavirin) Low ribavirin dose Short length of therapy Limiting toxicities& poor adherence Re-treatment using combination therapy with Peg-IFN plus weightbased ribavirin dosing Optimal support(ssri, paracetamol/nsaid, adherence support, use of haematopoietic growth factors) Optimal treatment with virological failure Relapse (HCV-RNA negative at the end of treatment) For Genotypes 2, 3 and 4 for patients with mildfibrosis, waitand monitor. If rapid progression or > moderate fibrosis, re-treatment using combination therapy with Peg-IFN plus weightbased ribavirin dosing (consider longer treatment duration) Non response(no undetectable HCV-RNA during treatment) In patientswithout a 2 log decreaseof HCV-RNA or without data on HCV-RNA, decrease in the previous treatment cycle triple therapy is recommended if there is a HCV-RNA decreaseof 1 log aftera 4-week leadin phasewith pegylated interferon and ribavirin For others, monitor carefully and wait until new antivirals become available through clinical trials or are licensed. Modified from EACS Guidelines Version 6.1 November 2012

14 Algorithm for management of acute HCV in HIV-infected individuals Identification of patients with acute hepatitis C is important since treatment in the acute phase leads to higher SVR rates than for treatment of chronic HCV infection. In patients with acute HCV infection, HCV-RNA should be measured at initial presentation and 4 weeks later. Treatment should be offered in patients without a decrease of 2 log10 of HCV-RNA at 4 weeks compared with initial HCV RNA and to patients with persistent serum HCV -RNA 12 weeks after diagnosis of acute HCV.