HIV/HCV Coinfection News – HCV Protease Inhibitors Juergen Rockstroh, MD Marc 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 #46 Sulkowski M et al. Boceprevir + Pegylated Interferon + Ribavirin for the Treatment of HCV/HIV-co-infected Patients: End of Treatment (Week-48) Interim Results. CROI 2012 Paper #47

Drug-Drug Interactions with Boceprevir (BOC) Tenofovir Efavirenz Ritonavir Drug 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) Kasserra C. et al. Clinical Pharmacology of BOC: Metabolism, Excretion, and Drug-Drug Interactions . CROI 2011 Paper #118

IL-28B Genotype and Treatment Response to PegIFN-RBV Rivero-Juarez A. et al. IL28B and the LDLr Have a Synergistic Effect on HCV Early Viral Kinetics during the First Weeks of Treatment with Pegylated Interferon + Ribavirin in HIV/HCV-co-infected Patients. CROI 2012 Paper #765

Predictors of Non-Response to Therapy with PegIFN-RBV Prometheus AUROC Sensitivity Prometheus Index Specificity Available at: www.fundacionies.com iTunes App Store Android Market Medrano J. et al. Baseline Prediction of Response to Pegylated Interferon + Ribavirin in Chronic HCV Using the Prometheus Score. CROI 2012 Paper #761

IL28B Genotype and HCV Viral Load Predictive values for SVR in patients infected with HCV genotype 1 (n=79). PPV NPV Sensitivity Specificity rs8099917 TT (n=53) 45.2% 80.7% 82.7% 42.0% Total nuclear-STAT1 (<5%) (n=30) 50.0% 71.4% 51.7% 70.0% rs8099917 TT or total nuclear-STAT1 (<5%) (n=61) 42.6% 83.3% 89.6% 30.0% rs8099917 TT and total nuclear-STAT1 (<5%) (n=22) 59.0% 71.9% 44.8% 82.0% Nuclear-STAT1, STAT1-nuclear translocation; PPV, positive predictive value; NPV, negative predictive value. Miyamura T, et al. Hepatic STAT1-nuclear translocation and interleukin 28B polymorphisms predict treatment outcomes in hepatitis C virus genotype 1-infected patients. PLoS One. 2011;6(12):e28617. Epub 2011 Dec 12.

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) HCV Genotype GT1 GT2 GT3 GT4 Percent infected 68% 4.6% 10.6% 16.9% Boesecke C. et al. Ribavirin Is Needed in Addition to Pegylated Interferon for Optimal Treatment 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 HCV Reinfection in HIV+ MSM. CROI 2012 Paper #752