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Chris Fraser, MDMedical Director,Cool Aid Community Health CentreClinical Faculty,UBC Faculty of Medicine
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HIV / Hepatitis C CoInfection HIV infection as a roadmap for HCV
and Coinfection HIV/ Hep C Coinfection overview Coinfection guidelines Coinfection trial outcomes Future coinfection regimens Pharmacology of ART/ DAA
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“ Working with drug addicts brings out some of health care providers’ worst fears, prejudices, and feelings of powerlessness.”
“ It is arrogant for a doctor (nurse) to presume - yet we do it all the time - that we can suddenly put a stop to a patient’s drug addiction, which by the time we first see the patient has become a powerful, biologically reinforced behaviour that has lasted for years if not decades.”
“ Our role as care providers is to be there, to bear witness, to be willing to accompany patients through their illness, and to refrain from passing judgment. Neither can we save them nor do we have the right to condemn them.”
Peter A. Selwyn, Surviving the Fall:The personal journey of an AIDS doctor.
“ Working with drug addicts brings out some of health care providers’ worst fears, prejudices, and feelings of powerlessness.”
“ It is arrogant for a doctor (nurse) to presume - yet we do it all the time - that we can suddenly put a stop to a patient’s drug addiction, which by the time we first see the patient has become a powerful, biologically reinforced behaviour that has lasted for years if not decades.”
“ Our role as care providers is to be there, to bear witness, to be willing to accompany patients through their illness, and to refrain from passing judgment. Neither can we save them nor do we have the right to condemn them.”
Peter A. Selwyn, Surviving the Fall:The personal journey of an AIDS doctor.
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“The only non compliant people are physicians (nurses) . If the patient doesn’t get better, it’s your own fault. Fix it.”
Dr. Paul Farmer
Mountains Beyond Mountains: Healing the World: The Quest of
Dr. Paul Farmer
“The only non compliant people are physicians (nurses) . If the patient doesn’t get better, it’s your own fault. Fix it.”
Dr. Paul Farmer
Mountains Beyond Mountains: Healing the World: The Quest of
Dr. Paul Farmer
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Stopping HIV: Giving Pregnant Women Hope
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Stopping HIV:Children free of HIV
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Stopping HIV:Walking long miles to help
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Living with HIV: Winifrida’s smile is bigger
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Living with HIV:Income Generating Projects
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The Challenges:Stop AIDS, TB, ESLD
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HIV impact on Hep C Infection
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HIV/ Hep C CoInfection Overview:
Teamwork THANK YOU CAHN nurses !
Open doors: more room at the inn Increasing clinical and cultural
competence Adherence, adherence , adherence Beyond coinfection treatment as
engagement in life change
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Coinfection Overview
HCV 2013 = HIV 1999 Guidelines: here today … gone tomorrow IFN = child who won’t leave home Leaky cascade: increase treatment Health Infrastructure – merge HIV/ HCV
treatment systems Peer involvement : Navigators /
Facilitators Ways forward: look to Europe / cohorts
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1. Chen EY, et al. AASLD 2012. Abstract 133. 2. Bichoupan K, et al. AASLD 2012. Abstract 1755.
50
40
30
20
10
0
Pati
ents
(%
)
n/N =
18
498 GT1 Patients Evaluated[1]
Started Therapy
2217
1169/407
89/407
43/407
Did Not Start
PatientChoice
Wait forBetter
Therapies
MildDisease
Higher Discontinuation Rates in Real-World Settings Than in Clinical Trials
D/CBeforeWk 12
21
40
30
20
10
0
91/498
D/C TVR < 12 wks
58/174
33[2]
21
36/174
174 GT1 Patients StartedTVR-Based Triple Therapy[2]
Due to AEs
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Inner City Primary Care:Inner City Primary Care:
Untold Clinical Stories:
• 24 year shorter life expectancy
• many patients declining contact with health care system
• large numbers of patients declining treatment after engaged in care
• total drug abstinence NOT required for treatment Mental health, Hepatitis C , HIV
Untold Clinical Stories:
• 24 year shorter life expectancy
• many patients declining contact with health care system
• large numbers of patients declining treatment after engaged in care
• total drug abstinence NOT required for treatment Mental health, Hepatitis C , HIV
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Cool Aid CHC : OverviewCool Aid CHC : Overview
5000 clients served Interdisciplinary: NP, MD , onsite
pharmacy, counselors, psychiatry, nutrition
Multi-site outreach program Concurrent diagnoses the norm:
Mental health, chemical dependency, HIV, Hepatitis C, Chronic pain
5000 clients served Interdisciplinary: NP, MD , onsite
pharmacy, counselors, psychiatry, nutrition
Multi-site outreach program Concurrent diagnoses the norm:
Mental health, chemical dependency, HIV, Hepatitis C, Chronic pain
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Meanwhile in the clinic...Meanwhile in the clinic...
34 yo Male
• polydrug chemical dependency IDU
• HIV+ 2006; HCV+ 2003 ; HBV+ 2002
• Untreated depression
• Unstable housing
• Criminal charges pending
34 yo Male
• polydrug chemical dependency IDU
• HIV+ 2006; HCV+ 2003 ; HBV+ 2002
• Untreated depression
• Unstable housing
• Criminal charges pending
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EACS Guideline Recommendations for Use of PegIFN in HCV/HIV-Coinfected Pts
European AIDS Clinical Society HIV Treatment Guidelines, 2011, Version 6.0.
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Study 110: TVR + PegIFN for Treatment of HCV in HCV/HIV-Coinfected Pts
Dieterich D, et al. CROI 2012. Abstract 46.
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Study 110: SVR24 With TVR + PegIFN/RBV in HCV GT1/HIV-Coinfected Patients Higher SVR24 rate with TVR-
based therapy No significant drug–drug
interactions with TVR and ART TVR plasma levels similar
in patients with or without ART
EFV and ATV/RTV plasma levels similar in patients with or without TVR
No HIV breakthroughs in patients using ART during HCV treatment
Safety and tolerability similar to treatment in patients with HCV monoinfection
Sulkowski MS, et al. AASLD 2012. Abstract 54. Reproduced with permission.
Telaprevir + PRPlacebo + PR
Overa
ll
Popu
latio
nNo
ART
EFV-B
ased
ART
ATV-B
ased
ART
74 71 69
80
45
33
50 50
0
20
40
60
80
100
28/38
10/22
5/ 7
2/6
11/16
4/ 8
12/15
4/ 8
SV
R24 (
%)
n/N =
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Phase II Study of BOC + PegIFN in HCV/HIV-Coinfected Individuals
Sulkowski M, et al. IDSA 2011. Abstract LB-37.
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Higher SVR12 Rates With BOC + P/R vs P/R Alone in HIV/HCV Coinfection Interim efficacy analysis
3 BOC pts had not yet reached SVR12 time point
HIV-1 RNA breakthrough observed in 7 pts BOC + P/R: n = 3/64
Placebo + P/R: n = 4/34
Tolerability similar to that seen in HCV monoinfection Similar rates of total and
serious adverse events in BOC and placebo groups
Higher rates of discontinuation due to toxicity with BOC (20%) vs placebo (9%)
Caution needed with drug-drug interactions
0
20
40
60
80
100
SV
R12 (
%)
P/R
n/N = 9/34
26.5
37/61
60.7*
BOC + P/R
*Reflects presented data; speaker noted verbally that remaining 3 pts have now reached and achieved SVR12
Mallolas J, et al. EASL 2012. Abstract 50.
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Treatment Paradigm With HCV PIs in the HCV/HIV-Coinfection Setting
Telaprevir PI. Boceprevir PI.
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Management of Newly Diagnosed Gt 1 HCV/HIV–Coinfected Pts
Ingiliz P, Rockstroh J. Liver Int. 2012;[E-pub ahead of print].
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Management of Gt 1 HCV/HIV–Coinfected Pts by Fibrosis Stage, Prior Tx Outcome
Ingiliz P, Rockstroh J. Liver Int. 2012;[E-pub ahead of print].
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Toward a Future of Personalized Medicine for HCV Therapy
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Likelihood of SVR With Current Therapies Related to IFN Responsiveness
1. Vierling JM, et al. EASL 2011. Abstract 481. 2. Foster G, et al. EASL 2011. Abstract 6. *Pooled data from RGT and arm 3.
≥ 1 log decline< 1 log decline
0
20
40
60
80
100
SV
R (
%)
33
REALIZE (TVR)[2]
82
158
0
20
40
60
80
100
SV
R (
%)
RESPOND-2* (BOC)[1]
HCV RNA Reduction After 4-Wk Lead-in
33
76
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Daclatasvir and Asunaprevir in GT1 HCV Previous Null Responders AI447-011: randomized, open-label phase IIa study with daclatasvir
(NS5A inhibitor) and asunaprevir (NS3 protease inhibitor)
Lok AS, et al. AASLD 2012. Abstract 79.
Noncirrhotic pts with GT1 HCV and
previous null response to pegIFN/RBV(N = 101)
Daclatasvir 60 mg QD + Asunaprevir 200 mg BID*
(n = 18)
Daclatasvir 60 mg QD + Asunaprevir 200 mg QD*
(n = 20)
Daclatasvir 60 mg QD + Asunaprevir 200 mg BID + PegIFN/RBV
(n = 20)
Daclatasvir 60 mg QD + Asunaprevir 200 mg QD + PegIFN/RBV
(n = 21)
Daclatasvir 60 mg QD + Asunaprevir 200 mg BID + RBV
(n = 22)
Wk 24Wk 24
*Only pts with GT1b HCV included in dual-therapy arms.
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Outcomes With Daclatasvir + Asunaprevir ± PegIFN or RBV in Null Responders High response rates with 4-drug regimen of
DCV + ASV + pegIFN/RBV Lower response rates with 2-drug regimen (all
GT1b pts) Better response with ASV 200 mg BID vs ASV
200 mg QD
SVR data from 3-drug arm not reported due to high rate of virologic breakthrough in GT1a but not in GT1b 10 GT1a pts with virologic breakthrough All triple-therapy pts offered pegIFN No virologic breakthrough with addition of
pegIFN
Virologic breakthrough in 8 pts in 2-drug arms but none in 4-drug arm
3 relapses 1 with DCV + ASV QD 2 with DCV + ASV + PR
All regimens generally well tolerated, with no discontinuations due to toxicity
Lok AS, et al. AASLD 2012. Abstract 79.
9095
HC
V R
NA
< L
LOQ
(%
)
100 100
21/21
EOT0
20
40
60
80
100
SVR24 EOT SVR12
89
7078
65
20/20
18/20
20/21
16/18
14/20
14/18
13/20
n/N =
DCV + ASV (BID) + PRDCV + ASV (QD) + PRDCV + ASV (BID)DCV + ASV (QD)
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Drug–Drug Interaction Resource
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Summary of Boceprevir Drug–Drug Interactions With Antiretrovirals
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DHHS Recommendations on Use of BOC or TVR in Gt 1 HCV/HIV–Coinfected
DHHS Guidelines March 2012. .
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HIV / Hepatitis C CoInfection HIV infection as a roadmap for HCV
and Coinfection HIV/ Hep C Coinfection overview Coinfection guidelines Coinfection trial outcomes Future coinfection regimens Pharmacology of ART/ DAA