CROI 2011 UPDATE Kenneth E. Sherman, MD, PhD Gould Professor of Medicine Director, Division of Digestive Diseases Univ. of Cincinnati College of Medicine
Areas of Interest HCV Epidemiology, Natural History HCV Treatment Monoinfected Coinfected HBV Epidemiology and Prevention
ACUTE HCV EPIDEMIOLOGY Phylogenetic analysis of acute HCV in MSM from New York, SF, Philadelphia, LA, San Diego N=73 Limited mixing either between cities or between U.S. and Europe Fierer D et al, CROI 2011 Abs 112
SPONTANEOUS CLEARANCE OF ACUTE HCV IN HCV/HIV- Role of IL28b 80 Patients with Acute HCV CC n=38 Non-CC n= 42 Spontaneous Clearance Could be assessed in 38 (others started treatment too early) 8/38 had spontaneous clearance 5 CC (CC was present in 47.5% of population) 3 CT/TT Neukam K et al, CROI 2011, Abs 945
FOUNDER VIRUS HCV Single genome amplification and sequencing Viral sequences from acutely infected subjects showed 1 or more low-diversity lineages (<0.2% diversity) 1-12 (median 3) founder genomes could be found in every subject examined No evidence of recombination, selection or hypermutation Hui et al., CROI 2011
Liver Fibrosis in African-Americans N=105 Subjects enrolled in DC Partnership for HIV Median duration of HCV estimated to be 30 years 92% of subjects A-A Median CD4 503 Fishbein D, et al. CROI, 2011 100 90 80 70 60 50 30 20 10 0 Non-Cirrhotic Cirrhotic
ITPA Gene Variants in HCV/HIV ITPA Gene Encodes enzyme that catalyzes Inosine Triphosphate Two relevant SNPs Prospective study in Barcelona N=173 HCV/HIV Baseline Hgb 14.5 Hgb decrease Guardiola J et al, CROI 2011, Abs 480
EVR % HIGH DOSE RIBAVIRIN INDUCTION PERICO STUDY PegIFN + RBV 1000-1200 vs PegIFN + RBV 2000 mg/day 4 weeks then standard dosing N= 326 EVR Rate Evaluated 100 90 80 70 60 50 30 20 10 P=0.07 0 Standard dose High Dose Labarga P et al, CROI 2011, Abs 962
% SVR LDL RECEPTOR AND HCV TREATMENT RESPONSE IN HCV/HIV LDL Receptor is Utilized by HCV for Entry LDLR SNP 14158 Analyzed N=184 treated with SOC SVR Geno 1-4 48% Geno 2-3 90% 100 90 80 70 60 50 30 20 10 CC TT/TC Pineda et al, CROI 2011, Abs 481 0 Geno 1,4 Geno 2,3
% SVR Phase 3 Randomized, Placebo controlled trial HCV Genotype 1 Treatment naïve subjects in 2 cohorts Non-Black (Blue bars) Black (Red bars) BOC 800 mg q8h; pegifn alfa-2b 1.5 µg/kg/wk; weight-based RBV 600-10 mg/day with lead-in Response guided therapy vs. 48 week Sulkowski et al., CROI 2011 Abs 115 Boceprevir SPRINT-2 100 90 80 70 60 50 30 20 10 0 67 68 42 53 RGT 48 week 23 PR48
% SVR BOCEPREVIR RESPOND-2 Phase 3 Randomized, Controlled Trial in Nonresponder subjects N= 3 Prior Null responders excluded Partial: >2 log drop at 12 weeks Three arms RGT (32 vs. 48) BPR48 PR48 100 90 80 70 60 50 30 20 10 0 69 52 75 7 29 NR Relapsers Gordon et al. CROI 2011, Abs 116
TELAPREVIR Pooled Analysis ADVANCE/ILLUMINATE N= 903 Early response and SVR examined All subject in T12PR arm vs. PR control arm from ADVANCE Week 1 to 4 data by interval and RVR/SVR cumulative. Week 3 not shown 80 70 60 % 50 30 20 10 0 T12/PR PR Sherman et al., CROI 2011, Abs 957
Effect of Telaprevir on HIV PIs van Heeswijk et al., CROI 2011, Abs 119
Effect of HIV PI s on Telaprevir van Heeswijk et al., CROI 2011
Boceprevir Metabolism and DDI s Substrate of aldoketoreductase primary pathway Substrate of CYP3A4/5 Coadministration of EFV (CYP3A4/5 inducer) decreased BOC mean exposure (AUC) 19% to 44% and increased efavirenz mean exposure 11% to 20% Not boosted by RTV Strong CYP3A4 inhibitor without evidence of induction Midazolam AUC markedly increased Substrate for the efflux inhibitor P-glycoprotein (P-gp) No interactions with tenofovir Kasserra C et al. CROI 2011
HBV MORTALITY IN MACS HCV 1 Relative Risk 95% CI P-value HBV vs. HCV 2.17 1-4.6 0.047 Age> vs. < 1.8.8-4.1 0.156 HBV Active ARV- TDF vs. non.6.2-2.3.5 Falade-Nwulia et al, CROI 2011, Abs 968
HBV VACCINATION IN HIV n= 163 ug dose recombinant HBV given IM Time 0, 1, 2, 6 months Low CD (<350 cells/mm) associated with poorer response rates in multivariate analysis Potsch D et al, CROI 2011, Abs 971 100 90 80 70 60 50 30 20 10 0 3rd Dose 4th Dose