HIV / Hepatitis C Coinfection: From guesswork to Guidelines

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HIV / Hepatitis C CoinfectionFrom guesswork to
Guidelines

• Chris Fraser, MD
• Medical Director,
• Cool Aid Community Health Centre
• Clinical 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 patients 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.

4

• The only non compliant people are physicians
  (nurses) . If the patient doesnt get better,
  its 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 HIVChildren free of HIV
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Stopping HIVWalking long miles to help
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Living with HIV Winifridas smile is bigger
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Living with HIVIncome Generating Projects
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The ChallengesStop 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 wont 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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Higher Discontinuation Rates in Real-World
Settings Than in Clinical Trials
40
30
498 GT1 Patients Evaluated1
174 GT1 Patients StartedTVR-Based Triple
Therapy2
21
50
20
40
332
10
30
21
Patients ()
22
0
18
17
20
D/CBeforeWk 12
11
10
91/ 498
69/ 407
89/ 407
43/ 407
58/ 174
36/ 174
n/N
0
D/C TVR lt 12 wks
Due to AEs
Started Therapy
PatientChoice
Wait forBetterTherapies
MildDisease
Did Not Start
1. Chen EY, et al. AASLD 2012. Abstract 133. 2.
Bichoupan K, et al. AASLD 2012. Abstract 1755.
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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

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Cool 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

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Meanwhile in the clinic...

• 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 drugdrug 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

Telaprevir PR
100
Placebo PR
80
80
74
71
69
60
50
50
SVR24 ()
45
40
33
20
5/ 7
2/ 6
11/ 16
4/ 8
12/ 15
4/ 8
28/ 38
10/ 22
n/N
0
No ART
EFV-Based ART
ATV-Based ART
Overall Population
Sulkowski MS, et al. AASLD 2012. Abstract 54.
Reproduced with permission.
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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

100
80
60.7
60
SVR12 ()
40
26.5
20
n/N
9/34
37/61
0
P/R
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/HIVCoinfected Pts
Ingiliz P, Rockstroh J. Liver Int. 2012E-pub
ahead of print.
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Management of Gt 1 HCV/HIVCoinfected Pts by
Fibrosis Stage, Prior Tx Outcome
Ingiliz P, Rockstroh J. Liver Int. 2012E-pub
ahead of print.
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Toward a Future of Personalized Medicine for HCV
Therapy
Direct-Acting Antivirals
NNI PI RBV
Nuc RBV
PegIFN RBV DAA
Nuc NS5A Inh RBV
Others?
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Likelihood of SVR With Current Therapies Related
to IFN Responsiveness
HCV RNA Reduction After 4-Wk Lead-in
1 log decline
lt 1 log decline
100
100
82
76
80
80
60
60
SVR ()
SVR ()
40
40
33
33
20
20
158
0
0
REALIZE (TVR)2
RESPOND-2 (BOC)1
Pooled data from RGT and arm 3.
1. Vierling JM, et al. EASL 2011. Abstract 481.
2. Foster G, et al. EASL 2011. Abstract 6.
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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)

Wk 24
Daclatasvir 60 mg QD Asunaprevir 200 mg
BID (n 18)
Daclatasvir 60 mg QD Asunaprevir 200 mg QD (n
20)
Noncirrhotic pts with GT1 HCV and previous null
response to pegIFN/RBV(N 101)
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)
Only pts with GT1b HCV included in dual-therapy
arms.
Lok AS, et al. AASLD 2012. Abstract 79.
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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

DCV ASV (BID) PR DCV ASV (QD) PR DCV
ASV (BID) DCV ASV (QD)
100
100
95
100
90
89
78
80
70
65
60
HCV RNA lt LLOQ ()
40
20
21/ 21
20/ 20
18/ 20
20/ 21
16/ 18
14/ 20
14/ 18
13/ 20
n/N
0
EOT
SVR24
EOT
SVR12
Lok AS, et al. AASLD 2012. Abstract 79.
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DrugDrug Interaction Resource
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Summary of Boceprevir DrugDrug Interactions With
Antiretrovirals
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DHHS Recommendations on Use of BOC or TVR in Gt 1
HCV/HIVCoinfected
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