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