Chris Fraser, MDMedical Director,Cool Aid Community Health CentreClinical Faculty,UBC Faculty of Medicine

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.

“ 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

“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

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

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

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

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

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 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 =

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

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.

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

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

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.

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)

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