Transcript How Can We Safely Maintain Low Viral Loads?

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
Sensitivity
Prometheus AUROC
Prometheus Index
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
Specificity
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%)
42.6%
(n=61)
83.3%
89.6%
30.0%
rs8099917 TT and total nuclear-STAT1
(<5%) (n=22)
71.9%
44.8%
82.0%
59.0%
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
iPhone Screenshot from iTunes Store
• HIV iChart
– iPhone & Android app
available on iTunes and the
Android Market
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
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
GT4
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