HIV/HCV Coinfection News – HCV Protease Inhibitors Juergen Rockstroh, MD Marc Poliquin, MD
Mar 26, 2015
HIV/HCV Coinfection News – HCV Protease Inhibitors
Juergen Rockstroh, MDMarc Poliquin, MD
Efficacy of HCV Protease Inhibitors in Co-Infected Patients
Telaprevir + PegIFN/r• Undetectable HCV RNA
at week 12– 86% TP/r vs 33% placebo
• Undetectable HCV RNA at week 24– 74% TP/4 vs 55% placebo
Boceprevir+ PegIFN/r• Undetectable HCV RNA
at week 12– 59.4% BOC+ P/r vs.
23.5% P/r• Undetectable HCV RNA
at week 24– 73.4% BOC+ P/r vs.
32.4% P/r
Dieterich D et al. Telaprevir in Combination with Pegylated Interferon--2a+RBV in HCV/HIV-co-infected Patients: A 24-Week Treatment Interim Analysis. CROI 2012 Paper #46Sulkowski M et al. Boceprevir + Pegylated Interferon + Ribavirin for the Treatment ofHCV/HIV-co-infected Patients: End of Treatment (Week-48) Interim Results. CROI 2012 Paper #47
Drug-Drug Interactions with Boceprevir (BOC)
Kasserra C. et al. Clinical Pharmacology of BOC: Metabolism, Excretion, andDrug-Drug Interactions . CROI 2011 Paper #118
Tenofovir Efavirenz RitonavirDrug Effect on BOC
None slight reduction in AUC(0-8h) and Cmax (19% and 8%, respectively)44% decrease in Cmin
decreased AUCt by 19%
BOC Effect on Drug
No notable effect on AUC or renal clearance, but increased Cmax by 32%.
slightly increased AUC(0-24h) & Cmax (20% & 11%, respectively)
Rivero-Juarez A. et al. IL28B and the LDLr Have a Synergistic Effect on HCV Early Viral Kinetics duringthe First Weeks of Treatment with Pegylated Interferon + Ribavirin in HIV/HCV-co-infected Patients.CROI 2012 Paper #765
IL-28B Genotype and Treatment Response to PegIFN-RBV
Predictors of Non-Response to Therapy with PegIFN-RBV
Medrano J. et al. Baseline Prediction of Response to Pegylated Interferon + Ribavirin in ChronicHCV Using the Prometheus Score. CROI 2012 Paper #761
Available at:www.fundacionies.comiTunes App StoreAndroid Market
Prometheus Index
Prometheus AUROC
Specificity
IL28B Genotype and HCV Viral Load
Miyamura T, et al. Hepatic STAT1-nuclear translocation and interleukin 28B polymorphismspredict treatment outcomes in hepatitis C virus genotype 1-infected patients.PLoS One. 2011;6(12):e28617. Epub 2011 Dec 12.
Predictive values for SVR in patients infected with HCV genotype 1 (n=79).
Nuclear-STAT1, STAT1-nuclear translocation; PPV, positive predictive value; NPV, negative predictive value.
Electronic Tools for Assessing Drug-Drug Interactions in HIV Infected Patients
• Online drug interaction charts www.hiv-druginteractions.org/interactioncharts.aspx
• HIV iChart– iPhone & Android app available on iTunes and the Android Market
iPhone Screenshot from iTunes Store
Incidence of HCV in the Swiss HIV Cohort Study, by Transmission Group
Wandeler G.. et al. HCV Incidence in the SHCS: A Changing Epidemic . CROI 2012 Paper #743
2011 Treatment Guidelines
AIDS 2011 Feb 20;25(4):399-409.Acute hepatitis C in HIV-infected individuals:
recommendations from the European AIDS Treatment Network (NEAT) consensus conference.
European AIDS Treatment Network (NEAT) Acute Hepatitis C Infection Consensus Panel.
The Role of Ribavirin in Treating HCV in Co-infected MSM
• In group 2, – Sustained virological response (SVR) rates were significantly higher for
peg-IFN+RBV (31 of 33) peg-IFN mono-therapy (6 of 10) (94% vs 60%, respectively; p = 0.02).
– SVR was significantly associated with Peg-IFN+RBV combination therapy (p = 0.037) and rapid virological response (p ≤0.0001)
• In group 1– SVR was only significantly associated with rapid virological response (p
≤0.0001)
Boesecke C. et al. Ribavirin Is Needed in Addition to Pegylated Interferon for OptimalTreatment Responses in the Treatment of Acute HCV Genotype 2 and 3 Infection I HIV-co-infected Individuals . CROI 2012 Paper #50
Repeated Co-Infection With HCV in HIV Positive MSM
Outcome of acute HCV according to episode number, pending patients on treatment
Ingiliz P. et al. Prior HCV Infection Does Not Protect from Sexually Transmitted HCVReinfection in HIV+ MSM. CROI 2012 Paper #752