Transcript Treatment of HIV/HCV Co-infection: Chris Fraser

Chris Fraser, MD
Medical Director,
Cool Aid Community Health Centre
Clinical Faculty,
UBC Faculty of Medicine
HIV / HEPATITIS C COINFECTION:
FROM GUESSWORK TO GUIDELINES
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
“ 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.
“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
Stopping HIV:
Giving Pregnant Women Hope
Stopping HIV:
Children free of HIV
Stopping HIV:
Walking long miles to help
Living with HIV:
Winifrida’s smile is bigger
Living with HIV:
Income Generating Projects
The Challenges:
Stop AIDS, TB, ESLD
HIV impact on Hep C Infection
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
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
Higher Discontinuation Rates in
Real-World Settings Than in Clinical
Trials
40
50
Patients (%)
30
498 GT1 Patients
Evaluated[1]
21
20
40
20
22
18
17
11
10
n/N =
0
33[2]
10
30
69/
407
89/
407
Mild
Disease
Patient
Choice
43/
407
Wait for
Better
Therapies
91/
498
174 GT1 Patients Started
TVR-Based Triple Therapy[2]
21
0
D/C
Before
Wk 12
Started Therapy
58/
174
D/C TVR
< 12 wks
Did Not Start
1. Chen EY, et al. AASLD 2012. Abstract 133. 2. Bichoupan K, et al. AASLD 2012. Abstract 1755.
36/
174
Due to
AEs
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
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
Meanwhile in the clinic...
34 yo Male
• polydrug chemical dependency  IDU
• HIV+ 2006; HCV+ 2003 ; HBV+ 2002
• Untreated depression
• Unstable housing
• Criminal charges pending
EACS Guideline Recommendations for Use of
PegIFN in HCV/HIV-Coinfected Pts
European AIDS Clinical Society HIV Treatment Guidelines, 2011, Version 6.0.
Study 110: TVR + PegIFN for Treatment of
HCV in HCV/HIV-Coinfected Pts
Dieterich D, et al. CROI 2012. Abstract 46.
Study 110: SVR24 With TVR + PegIFN/RBV
in HCV GT1/HIV-Coinfected Patients

Higher SVR24 rate with TVR-based
therapy
SVR24 (%)
71
No HIV breakthroughs in patients
using ART during HCV treatment

Safety and tolerability similar to
treatment in patients with HCV
monoinfection
69
50
45
40
50
33
20
0

80
74
60
n/N =
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
Telaprevir + PR
Placebo + PR
100
80

28/ 10/
38 22
5/
7
2/
6
11/ 4/
16 8
12/ 4/
15 8
Sulkowski MS, et al. AASLD 2012. Abstract 54. Reproduced with permission.
Phase II Study of BOC + PegIFN in
HCV/HIV-Coinfected Individuals
Sulkowski M, et al. IDSA 2011. Abstract LB-37.
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
100

SVR12 (%)
80
60
60.7*
40

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%)
26.5
20
0
HIV-1 RNA breakthrough observed in
7 pts
n/N = 37/61
BOC + P/R
9/34
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.

Caution needed with drug-drug
interactions
Treatment Paradigm With HCV PIs in
the HCV/HIV-Coinfection Setting
Telaprevir PI. Boceprevir PI.
Management of Newly Diagnosed
Gt 1 HCV/HIV–Coinfected Pts
Ingiliz P, Rockstroh J. Liver Int. 2012;[E-pub ahead of print].
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].
Toward a Future of Personalized
Medicine for HCV Therapy
Direct-Acting Antivirals
Nuc + RBV
NNI + PI
± RBV
Nuc + NS5A
Inh ± RBV
PegIFN +
RBV+ DAA
Others?
Likelihood of SVR With Current Therapies
Related to IFN Responsiveness
HCV RNA Reduction After 4-Wk Lead-in
≥ 1 log decline
< 1 log decline
100
100
60
33
80
SVR (%)
SVR (%)
80
40
82
76
60
40
20
20
0
0
RESPOND-2* (BOC)[1]
33
158
REALIZE (TVR)[2]
*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.
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.
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)

100
100 100
90
HCV RNA < LLOQ (%)
DCV + ASV (BID) + PR
DCV + ASV (QD) + PR
DCV + ASV (BID)
DCV + ASV (QD)
95
89
78
70
65
60
40
20
0
20/
20
21/
21
EOT
18/
20
20/
21
SVR24
16/
18
14/
20
EOT
14/
18
13/
20
SVR12
Lok AS, et al. AASLD 2012. Abstract 79.
SVR data from 3-drug arm not reported due to high rate
of virologic breakthrough in GT1a but not in GT1b
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Better response with ASV 200 mg BID vs ASV 200 mg
QD
80
n/N =

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
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3 relapses
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1 with DCV + ASV QD
2 with DCV + ASV + PR
All regimens generally well tolerated, with no
discontinuations due to toxicity
Drug–Drug Interaction Resource
Summary of Boceprevir Drug–Drug
Interactions With Antiretrovirals
DHHS Recommendations on Use of BOC
or TVR in Gt 1 HCV/HIV–Coinfected
DHHS Guidelines March 2012. .
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