management of patients co- infected with hcv and hiv: a close look at the role for daas susanna...
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Management of Patients Co-infected with HCV and HIV: A
Close Look at the Role for DAAs
Susanna Naggie, MDAssistant Professor of Medicine
Division of Infectious Diseases
Disclosures
• Research: Vertex, Anandys, Synexis, Gilead, Merck, BMS
• Advisory Board: Vertex, Boehringer Ingelheim, Janssen
• Speaker: None
HIV & HCV
• 10 million people worldwide
• 30% of US patients with HIV have HCVHIV
40 million
Hepatitis C180 million
Staples CT. Clin Infect Dis 1999
D:A:D Study: Liver-Related Deaths in Persons with HIV
DAD Arch Intern Med;2006;166:1632
14.5%
DAD Study Group, Arch Intern Med 2006Thein et al. AIDS 2008; 22:1979
Treatment
• Goal of treatment:– Clinical trial definition– Sustained virologic response
– What we tell patients…
Cure!
Who to Treat?
• Prior response?• Risk stratification
– Liver Biopsy– Fibroscan/non-invasive testing
• Adherence• Other baseline factors
– Race/ethnicity– Genotype 1 subtype
PK Interactions: Telaprevir & ARTART Effects on ART Effects on TVR Recommendations
AUC Cmin AUC Cmin
Efavirenz No change 26% 47% telaprevir dose to 1,125mg q8h
Atazanavir/r - 85% 20% 15% Use standard doses
Darunavir/r 40% 42% 35% 32% Do Not Co-Administer
FPV/r 47% 56% 32% 30% Do Not Co-Administer
Lopinavir/r 34% 43% 54% 52% Do Not Co-Administer
Maraviroc No PK Data, Interaction Possible Do Not Co-Administer
Raltegravir 31% - No significant changes
Use standard doses
Van Heeswijk et al. CROI 2011 Abstract 119and ICAAC 2011 Abstract A1-1738a
Part A: no ART
Follow-upPR48
(control) PR
SVRPbo + PR
T/PR TVR + PR Follow-upSVR
PR
Follow-upPR48
(control) PR
SVRPbo + PR
T/PR TVR + PR Follow-upSVR
PR
Part B: ART (EFV/TDF/FTC or ATV/r + TDF + FTC or 3TC)
Study 110 Design: Randomized, Double-blind, Placebo-controlled Trial of Telaprevir
240 48 72Weeks 12 36 60
SVR12
SVR12
SVR12
SVR121:1
2:1
Dieterich et al. CROI 2012 Abstract 46Barritt and Fried. Gastro 2012; 142:1314
Stopping/Futility Rules
% o
f P
atie
nts
with
Und
etec
tabl
e H
CV
RN
A
n/N= 5/7 11/16 12/15 28/38 2/6 4/8 4/8 10/22
Dieterich et al. CROI 2012 Abstract 46
Study 110: SVR-12 Interim Analysis
PK Interactions: Boceprevir & ARTART Effects on ART Effects on BOC Recommendations
AUC Cmin AUC Cmin
Efavirenz 20% - 19% 44% Do Not Co-Administer
ETR, RPV No PK Data, Interaction Possible Do Not Co-Administer
Atazanavir/r 35% 49% No change Do Not Co-Administer
Darunavir/r 44% 59% 29% 35% Do Not Co-Administer
Lopinavir/r 34% 43% 44% 35% Do Not Co-Administer
FPV/r, TPV/r No PK Data, Interaction Possible Do Not Co-Administer
Maraviroc No PK Data, Interaction Possible Do Not Co-Administer
Raltegravir No significant changes Use standard doses
Kasserra et al. 18th CROI 2011 Abstract 118; Hulskotte et al. 19th CROI 2012 Abstract 771LB
14
Randomized, double blind, placebo controlled trial of Boceprevir
• Two-arm study, double-blinded for BOC, open-label for PEG2b/RBV– 2:1 randomization (experimental: control)– Boceprevir dose 800 mg TID
• 4-week lead-in with PEG2b/RBV for all patients– PEG-2b 1.5 µg/kg QW; RBV 600-1400 mg/day divided BID
Weeks 12 24 28 48 72
PEG2b+RBV 4 wk
Placebo + PEG2b + RBV44 wk
Boceprevir + PEG2b + RBV44 wk
Follow-upSVR-24 wk
Follow-upSVR-24 wk
PEG2b+RBV 4 wk
Arm 1
Arm 2
Futility Rules
Stopping/Futility Rules
Sulkowski et al. CROI 2012 Abstract 47Barritt and Fried. Gastro 2012; 142:1314
% o
f P
atie
nts
with
Und
etec
tabl
e H
CV
RN
A
n/N= 3/34 3/64 5/34 27/64 8/34 38/64 11/34 47/64 10/34 42/64 9/34 37/61
Treatment Week
SVR-12 Interim Analysis
Sulkowski et al. CROI 2012 Abstract 47
Adverse Events
Jacobson IM, et al. NEJM, 2011. Poordad F, et al. NEJM, 2011
Adverse Event, %TVR-Containing Arms
Mono-infection(N=727) Co-infection (N=38)
PegIFN/RBV Arms
(n = 383)
Pruritus 45-50 39 9-36
Nausea 40-43 34 23-31
Rash 35-37 34 23-24
Anemia 37-39 18 18-19
Diarrhea 28-32 24 18-22
Adverse Event, %BOC-Containing Arms
Mono-infection (N=734) Co-infection (N=64)
PegIFN/RBV Arms
(N=397)
Anemia 49 41 26-29
Dysgeusia 37-43 28 15-18
Telaprevir (TVR)
Boceprevir (BOC)
Other Considerations…
Characteristic Good Response Poor Response
HCV GT 1 subtype 1b 1a
Fibrosis 0-2>3 4
Race European/Asian African-descent
Prior treatment Relapse>Partial Null
IFN responsiveness >1log10 decline <1log10 decline
IL28B CC>CT TT
Phase II/III Studies
Drug Class Tx Inclusion RGT Antiretrovirals
TMC-435
NCT01479868
NS3/4A Naive and experienced
Y RPV, Ralt, MVC,T20, TDF, FTC,3TC, ABC*
BI-201335
NCT01399619
NS3/4A Naive and relapsers
Y DRV/r, ATV/r, Ralt, TDF, FTC, EFV, ABC, 3TC, MVC
BMS-790052
NCT01471574
NS5A Naive Y All except PI + NNRTI combo
*Ouwerkerk-Mahadevain 19th CROI Abstract 49