Distinct hepatitis C virus kinetics in HIV- infected patients treated with ribavirin plus either pegylated interferon α-2a or α-2b Eugenia Vispo, Pablo.

Slides:

Advertisements

Similar presentations

Hepatitis C & HIV in 2011 Vincent Soriano Infectious Diseases Department Hospital Carlos III, Madrid, Spain.

Advertisements

Optimal therapy in genotype 2 and 3 patients Antonio Craxì Liver & GI Unit, Di.Bi.M.I.S., University of Palermo, Italy

Hepatitis web study Hepatitis web study Sofosbuvir + Ribavirin in HCV-HIV Coinfection: HCV GT 1,2,3,4 PHOTON-2 Trial Phase 3 Molina JM, et al. IAC. 2014;

Hepatitis web study Hepatitis web study Peginterferon alfa-2b + RBV versus Interferon alfa-2b RIBAVIC STUDY Phase 3 Treatment Naïve, Chronic HCV and HIV.

Hepatitis web study Hepatitis web study PEG alfa-2a + RBV versus PEG alfa-2a versus INF + RBV APRICOT STUDY Phase 3 Treatment Naïve, Chronic HCV and HIV.

Hepatitis web study Hepatitis web study Peginterferon alfa-2b + RBV vs. Peginterferon alfa-2a + RBV IDEAL STUDY Phase 3, Treatment Naïve Treatment Naïve,

Hepatitis web study Hepatitis web study Sofosbuvir + Ribavirin in HCV Recurrence Following Liver Transplantation Phase 2 Charlton M, et al. Gastroenterology.

Hepatitis web study Hepatitis web study Sofosbuvir + Ribavirin in HCV GT 4 Egyptian Ancestry Trial Phase 2 Ruane PJ, et al. J Hepatol. 2015;62:

Norma I. Rallón 1, José Medrano 1, Salvador Resino 2, Clara Restrepo 1, Vincent Soriano 1 and José M. Benito 1 1 Department of Infectious Diseases, Hospital.

Mixed HCV Genotype Infection and Response to anti-HCV treatment in HIV/HCV Co-Infected Patients Lucy Porrino, Sabrina Bagaglio, Giulia Morsica, Giulia.

Persisting long term benefit of genotypic guided treatment in HIV infected patients failing HAART and Importance of Protease Inhibitor plasma levels. Viradapt.

Abstract Results Objectives Results Conclusions Background Methods V-1637 Background-At the CORE center in Chicago, despite an on-site hepatitis clinic.

Treatment of Chronic Hepatitis C in HCV-HIV Infected Patients J Mallolas Infectious Diseases Service Hospital Clínic Barcelona.

Liver fibrosis regression after anti HCV therapy and the rate of death, liver-related death, liver- related complications, and hospital.

Peginterferon Alfa-2a plus Ribavirin vs Peginterferon Alfa-2b plus Ribavirin for Chronic Hepatitis C Virus Infection in HIV- Infected Patients J Berenguer.

HEPATITIS C VIRUS REINFECTION IN PEOPLE WHO INJECT DRUG (PWID) PREVIOUSLY SUCCESFULY TREATED G. Ntetskas, V. Papastergiou, L. Skorda, A. Katsili, E. Anastasiou,

ATOMIC  Design  Objective –SVR 24 by ITT-analysis, detection of a 30% or 25% difference between two treatment groups, 2-sided significance level of 5%,

ELECTRON  Design SOF + RBV Randomisation* 1 : 1 : 1 : 1 Open-label ELECTRON Study: SOF-based therapy for genotypes 1, 2 and 3 W8W4W12 ≥ 19 years Chronic.

OBV/PTV/r + DSV + RBV Placebo Randomisation** 3 : 1 Double blind years Chronic HCV genotype 1 HCV RNA ≥ 10,000 IU/ml Failure to pre-treatment with.

Triglycerides,LDL cholesterol and HOMA score predict the virological response in HIV/HCV co-infected patients treated with Pegylated interferon alpha 2a.

OBV/PTV/r + DSV + RBV OBV/PTV/r + DSV Randomisation* 1 : 1 Open label years Chronic HCV infection Genotype 1b Prior failure to PEG-IFN + RBV HCV.

No prior therapy with PI

Twice Weekly Peg-IFN-alpha-2a with Ribavirin Improves Early Viral Kinetics over Standard Therapy Among HIV/HCV Co-Infected African American Patients Alison.

COSMOS SOF + SMV + RBV SOF + SMV Randomisation 2 : 1 : 2 : 1* Open-label * Randomisation was stratified on genotype (1a or 1b) in both cohorts, IL28B in.

SMV + PEG-IFN + RBV Open-label W12 W24* or W48* N = years Chronic HCV infection Genotype 4 Treatment-naïve or experienced with relapse or partial.

HBV related complications in HIV positive patients during HAART therapy Irina Magdalena Dumitru*, E. Dumitru*, S. Rugina*, Roxana Carmen Cernat**, Simona.

Randomisation* 2 : 1 Double blind *Randomisation was stratified on genotype (1a or 1b or other) and IL28B genotype (CC, CT or TT) N = 133 N = 260 W24W48.

Simplification from Protease Inhibitors to Once or Twice Daily Raltegravir: the ODIS trial Eugenia Vispo, Pablo Barreiro, Francisco Blanco, Sonia Rodríguez-Novoa*,

FISSION  Design  Objective –Non inferiority of SOF + RBV : SVR 12 (2-sided significance level of 5%, lower margin of the 95% CI for the difference =

No HBV or HIV co-infection

SMV SOF 400 Open-label OPTIMIST-2 Study: SMV + SOF for genotype 1 and cirrhosis W12  Objective –Superiority of SVR 12 (HCV RNA historical control.

SMV 150 mg QD + SOF 400 mg QD Randomisation 1 : years HCV genotype 1 Naïve or pre-treated with IFN-based regimen No cirrhosis HCV RNA ≥

OBV/PTV/r + DSV + RBV OBV/PTV/r + DSV + placebo Randomisation* Partial blind years Chronic HCV infection Genotype 1 Treatment-naïve HCV RNA > 10,000.

Reddy KR. Lancet Infect Dis. 2015;15:27-35 ATTAIN SMV + TVR placebo + PEG-IFN + RBV TVR + SMV placebo + PEG-IFN + RBV Randomisation* 1 : 1 Double-blind.

Progressive histological liver improvement after sustained virological response to therapy in HCV / HIV coinfected patients. Jose L. Casado,

Placebo + PR W48 Placebo + PR Yes Hezode C. Gut 2015;64: COMMAND-1 COMMAND-1 Study: daclatasvir + PEG-IFN + RBV for genotype 1 or 4 DCV60 + PEG-IFN.

SIRIUS Placebo LDV/SOF + placebo Randomisation* 1 : 1 Double-blind SIRIUS Study: LDV/SOF ± RBV for genotype 1 and cirrhosis with non response to prior.

ION-1  Design LDV/SOF LDV/SOF + RBV Randomisation* 1 : 1 : 1 : 1 Open-label ION-1 Study: LDV/SOF + RBV for genotype 1 W24W12 ≥ 18 years Chronic HCV infection.

W24 ≥ 18 years Chronic HCV infection Genotype 1 Treatment naïve Early fibrosis to compensated cirrhosis No HBV or HIV co-infection N = 10 SOF + weight-based.

SOLAR-2 LDV/SOF + RBV Randomisation of the 7 groups 1 : 1 Open-label SOLAR-2 Study: LDV/SOF + RBV in decompensated and post-liver transplant with genotype.

SOLAR-1 LDV/SOF + RBV Randomisation* of the 7 groups 1 : 1 Open-label SOLAR-1 Study: LDV/SOF + RBV in advanced liver disease  Design W12W24 ≥ 18 years.

TURQUOISE-I OBV/PTV/r + DSV + RBV Randomisation* 1 : 1 Open-label years HCV genotype 1 HCV RNA ≥ 10,000 IU/ml Naïve or pre-treated with PEG-IFN +

 Treatment regimens –Co-formulated ombitasvir (OBV)/paritaprevir (PTV)/rironavir (r) : 25/150/100 mg QD = 2 tablets –Dasabuvir (DSV) : 250 mg BID –RBV.

Evolution of the Functional Profile of HIV-Specific CD8+ T cells in a Cohort of Long Term Nonprogressors M López, N Rallón, A Peris, M Salgado, B Rodés,

> 18 years Chronic HCV infection Genotype 1 Failure (relapse) to 4, 6 or 8 weeks of GZR/EBR + SOF in C-SWIFT Part A Compensated cirrhosis assessed by liver.

SOF/VEL 400/100 mg qd N = 250 W24 SOF + RBV W12 * Randomisation was stratified on prior treatment (naïve or experienced) and cirrhosis (yes or no) ** Metavir.

Sulkowski M. Lancet 2015;385: C-WORTHY  Design Randomisation* Open-label > 18 years HCV genotype 1, treatment naïve HCV RNA ≥ 10,000 IU/ml No cirrhosis.

Switch to RAL-containing regimen  Canadian Study  CHEER  Montreal Study  EASIER  SWITCHMRK  SPIRAL  Switch ER.

Asselah T. AASLD 2015, Abs OSIRIS  Design SMV + PEG-IFN + RBV Open label Chronic HCV infection Genotype 4 Treatment-naïve Mild to moderate fibrosis.

 Objective –SVR 12 (HCV RNA < 25 IU/ml), with 95% CI, next observation carried backward DCV + SOF + RBV Randomised* 1:1 Open-label ALLY-3+ study: DCV.

SAPPHIRE-I Feld JJ. NEJM 2014;370: SAPPHIRE-I Study: ombitasvir/paritaprevir/ritonavir + dasabuvir + ribavirin for genotype 1  Treatment regimens.

Open-label W24 ≥ 18 years Chronic HCV infection All genotypes HCV RNA ≥ 10,000 IU/ml Liver transplantation months earlier Child Pugh ≤ 7 and MELD.

SOF/VEL 400/100 mg qd N = 120 W12 SOF + RBV > 18 years Chronic HCV infection Genotype 2 Naïve or pre-treatment with IFN-based regimen Compensated cirrhosis.

Placebo + PR W24 DCV + PR Placebo + PR Yes Dore GJ. Gastroenterology 2015;148: COMMAND GT2/3 COMMAND GT2/3 Study: daclatasvir + PEG-IFN + RBV for.

 Design Randomisation* 2 : 1 Double blind *Randomisation was stratified on genotype (1a vs 1b) and ILB28 genotype (CC or non-CC) N = 134 N = 257 W24W48.

Poordad F. NEJM 2014;368: D Phase IIa  Design  Treatment regimens – Paritaprevir/rironavir (PTV/r) : PTV 250 or 150 mg qd/ritonavir 100 mg qd (2.

 Design Open-label years Chronic HCV infection Genotype 1 HCV RNA > 10,000 IU/mL HIV co-infection Stable ART* with HIV RNA < 50 c/mL ≥ 24 weeks.

Weekly Alendronate Safe and Effective at Increasing Bone Mineral Density in HIV-Infected Persons on Antiretroviral Therapy Slideset on: McComsey GA, Kendall.

Trends in Treatment of Recurrent Hepatitis C After Liver Transplantation Kate Forgan-Smith KA Stuart 1,4, C Tallis 1,4 GA Macdonald 1,3,4, J Fawcett 2,3.

Hadziyannis SJ et al. EASL Peginterferon alfa-2a (40KD) (PEGASYS ® ) in combination with ribavirin (RBV): efficacy and safety results from a phase.

Previous SVR With Interferon-Based Therapy for HCV Lowers Risk of Hepatotoxicity in HIV/HCV-Coinfected Individuals on Antiretroviral Therapy Slideset on:

Maria Buti,1 Yoav Lurie,2 Natalia G. Zakharova,3 Natalia P. Blokhina,4 Andrzej Horban,5 Gerlinde Teuber,6 Christoph Sarrazin,6 Ligita Balciuniene,7 Saya.

Journal Conference Hepatology 2009;50: Background.

SOF + RBV GT2 Japanese SOF + RBV Open-label Japanese SOF + RBV Study: SOF + RBV in genotype 2  Design W12 Japanese patients ≥ 20 years Chronic HCV infection.

Adefovir Suppresses HBV DNA Levels in Lamivudine-Resistant HIV/HBV Patients Slideset on: Benhamou Y, Thibault V, Vig P, et al. Safety and efficacy of adefovir.

Genotype 1 HCV infection Stable immunosuppressive therapy

A. Stepanov, A. Kruk, N. Polovinkina, A. Vinogradova

Simeprevir in HIV Coinfection, GT-1 C212 Trial

Ombitasvir + Paritaprevir + Ritonavir +/- Ribavirin in HCV GT4 PEARL-I

Presentation transcript:

Distinct hepatitis C virus kinetics in HIV- infected patients treated with ribavirin plus either pegylated interferon α-2a or α-2b Eugenia Vispo, Pablo Barreiro, Sonia Rodríguez-Nóvoa, Judit Morello, Pablo Labarga, Luz Martín-Carbonero, Ivana Maida, Pilar Garcia-Gascó and Vincent Soriano Infectious Diseases Department Hospital Carlos III, Madrid, Spain

BACKGROUND Pegylated interferon alpha -2a and -2b differ in their molecular weight and consequently in their pharmacokinetic properties might impact on their respective antiviral effects could be more pronounced in HIV-infected individuals, in whom response to hepatitis C virus treatment is impaired

PURPOSE OF THE STUDY Assess and compare the kinetics of serum HCV-RNA during the first 24 weeks of therapy with pegIFNα-2a or -2b in a relatively large group of HIV-HCV coinfected patients

PATIENTS AND METHODS All HCV/HIV patients included in PRESCO and EXTENT trials recruited at one referral centre were retrospectively analysed Ribavirin at doses of mg/day was prescribed along with standard doses of pegIFNα-2a or -2b The attainment of serum HCV-RNA <10 IU/mL at weeks 4, 12 and 24 was assessed On-treatment analyses were made to estimate the intrinsic potency of pegIFNα-2a versus -2b after adjusting for other variables

Main characteristics of the study population PegIFN  -2aPegIFN  -2b p No. of patients13880 Male gender (%) Mean age (years) 45  844  Mean body weight (kg)69±1167± Mean CD4 count (cells/  L)549   Mean serum HIV-RNA (log copies/mL) 2.1   Plasma HIV-RNA <50 copies/mL (%) Concomitan antiretroviral therapy (%) Mean serum HCV-RNA (log IU/mL) 6.06   Baseline HCV-RNA >800,000 IU/mL (%) HCV genotypes 1 or 4 (%) Mean liver elasticity (Kpa) 10.9   Advanced liver fibrosis (Metavir F3-F4) (%)

RESULTS (1) Proportion (%) of patients with serum HCV-RNA <10 IU/mL (on treatment analysis) PegIFN  -2a (n=138) PegIFN  -2b (n=80) P Week 4 All patients Genotypes 2/ Genotypes 1/ Week 12 All patients Genotypes 2/ Genotypes 1/ Week 24 All patients Genotypes 2/ Genotypes 1/

Univariate analysisMultivariate analysis OR [95 % CI] pOR [95 % IC] p Age (per year)0.96 [ ] Mean body weight (per kg)0.92 [ ] CD4 count (per cells/  L) 1 [ ] Advanced liver fibrosis (>9.5 kPa)0.89 [ ] Mean baseline serum HCV-RNA (per log IU/mL)0.63 [ ] [ ] 0.09 HCV genotypes 2/3 vs 1/49.09 [ ] < [ ] <0.001 RBV plasma trough levels (per  g/mL) 1.48 [ ] Concomitant antiretroviral therapy0.59 [ ] Zidovudine use0.36 [ ] [ ] 0.02 Abacavir use0.71 [ ] PegIFN α-2a vs α-2b2.56 [ ] [ ] 0.04 RESULTS (2) Predictors of serum HCV-RNA suppression <10 IU/mL at week 24

RESULTS (4) Evolution of mean serum HCV-RNA levels according to pegylated interferon treatment modality and HCV genotype (on-treatment analysis) HCV genotypes 1 or pegIFN alpha-2a pegIFN alpha-2b p=0.88 p=0.20 p=0.01 p=0.06 Weeks Serum HCV-RNA (log IU/mL)

RESULTS (5) Evolution of mean serum HCV-RNA levels according to pegylated interferon treatment modality and HCV genotype (on-treatment analysis) HCV genotypes 2 or p= pegIFN alpha-2a pegIFN alpha-2b p=0.38 p=0.01 p=0.07 Weeks Serum HCV-RNA (log IU/mL)

RESULTS (5) Adverse events leading to premature interruption of pegylated interferon plus ribavirin therapy PegIFN  -2a (n=159) PegIFN  -2b (n=83) p Overall21 (13.2%)3 (3.6%)0.018 Flu-like symptoms12 (7.5%)1 (1.2%)0.038 Weight loss 2 (1.3%)00.4 Psychiatric disorders4 (2.5%)2 (2.4%)0.6 Others3 (1.9%)00.3

DISCUSSION SUPRESSION OF HCV-RNA: more pronounced with pegIFNα-2a Genotypes 2/3: limited to week 4 and lost thereafter Genotypes 1/4: mainly noticed at week 24 ADVERSE EVENTS: incidence was significantly lower using pegIFNα-2b than -2a, which could account for more similar responses using ITT analysis. EXPLANATION: a greater and more durable drug exposure to pegIFNα- 2a than to -2b due to longer half-life of the former Limitations: retrospective study slight differences in baseline characteristics of study populations, although not significant.

CONCLUSION In HIV patients with chronic hepatitis C, in whom the antiviral effect of IFNα may be impaired, a greater efficacy of pegIFNα-2a than -2b could be recognised An insufficient sustained antiviral effect at the end of weekly interval administration of pegIFNα-2b due to its shorter half-life could explain this observation

LaboratoryClinical AreaPharmacology unit Antonio MadejónPablo BarreiroJudith Morello Marcelle BottechiaLuz Martín-Carbonero Sonia Rodríguez-Novoa José Miguel Benito Pablo LabargaInmaculada Jiménez Norma RallonFrancisco Blanco Mariola LópezPaula Tuma José Medrano Ivana Maida Dolores Herrero Pablo Rivas Vicente Soriano José Vicente Fernández Juan González-Lahoz Acknowledgments