Unmet Needs for Persons with HIV/
HCV Coinfection
Shruti H. Mehta, PhD MPH
Associate Professor, Johns Hopkins Bloomberg School of Public Health
July 2, 2013
www.ias2013.org
Kuala Lumpur, Malaysia , 30 June - 3 July 2013
Burden of HIV/HCV co-infection
34 million HIV infected
Eastern Europe
Western &
Central Europe & Central Asia
1.4 million
900 000
North America
1.4 million
~280 000
Caribbean
230 000
4-5 million co-infected with HCV*
~500 000
~180 000
~166 000
Middle East & North Africa
300 000
~60,000
~23 000
Latin America
1.4 million
Sub-Saharan Africa
23.5 million
South & South-East Asia
4 million
~1.8 million
~140 000
East Asia
830 000
~900 000
Oceania
53 000
~10 600
HCV coinfected
HIV only
MSM
Heterosexual
IDUs
0%
20%
40%
60%
80%
100%
Rockstroh JID 2005; Sulkowski Ann Intern Med 2003; Alter Hepatology 2006; Rotman J Virol 2009; Aceijas Sex Trans Inf 2006; Aceijas Int J Drug
Policy 2007; *Where data was not available, # of HIV/HCV co-infected estimated based on distribution of HIV infections by risk group
HIV/HCV co-infected patients are unique in
some ways…
Higher HCV RNA levels1
More rapid disease progression2
Impaired treatment response (to Peg/RBV)3
1Thomas
JID 1996; 2Goedert Blood 2002; 3 Adapted from Sulkowski New Paradigm of HCV Treatment 2013; Torriani N Engl J Med 2004; Chung N
Engl J Med 2004; Carrat R JAMA 2004; Nunez AIDS Res Human Retrovir 2007; Rodriguez-Torre HIV Clin Trials 2012; Laguno Hepatology 2009
HIV/HCV co-infected patients are unique in
some ways…
56
4
0
678
0
5
1
3
1
2
Multi-morbid clinical conditions among
HIV/HCV co-infected IDUs in Baltimore
(n=362)
Multimorbid conditions included diabetes (HbA1c and medication
use), obstructive lung disease (Ratio of FEV to forced vital capacity),
anemia (hemoglobin), obesity (BMI), kidney dysfunction (urine
protein-creatinine, GFR), Hypertension (blood pressure and
medication use), liver cirrhosis (Fibroscan)
Salter M et al, CID 2011
4
3
2
Stability factors among HIV/HCV coinfected IDUs in Baltimore (n=560)
Daily injection drug use, noninjection drug use, alcohol
abuse, >1 mental health condition, suicidal ideation,
incarceration, income < 5000 per year, lack of health
insurance, no primary care
…and not unique in others
900
845
800
Number of persons
700
600
500
400
277
300
185
200
125
69
100
29
0
In regular HIV
care
Mehta et al, AIDS 2006
Referred
Keeps
appointment
Pre-treatment
evaluation
Treatment
eligible
Treatment
initiated
6
Sustained
virologic
response
The hepatitis C care continuum
100
At least 50% of
infected persons
are unaware of
their status
90
Percent of persons
80
70
60
50
1. Referral to a
specialist/someone who
can treat (from a primary
care doctor, HIV clinic,
opiate substitution clinic,
needle exchange program)
2. Attending an
appointment
40
30
1. Receive pre-treatment
work-up
2. Meet eligibility criteria
3. Agree to initiate
treatment
20
1. Efficacious regimen
2. Treatment adherence
10
0
Chronic HCV
infection
HCV
diagnosis
Linkage to
care
Retention
Treatment
initiation
Viral
clearance
Retention
Adeyemi 2004, Cachay 2013, Cacoub 2006, Falck-Ytter 2002, Fishbein 2004, Fleming 2003, Gheorghe 2010, Grebely 2009, Groom 2008, Hall
2004, Hallinan 2007, Jowett 2001, Mehta 2006, Morrill 2005, Restrepo 2005, Rocca 2004, Schackman 2007; Stoove 2005, Mehta 2008, Reiberger
2011, Scott 2009, Vellozi 2011
Patient
Provider
Structural
There are multiple layered barriers : Patient
General barriers
• General health care access ( primary care provider, insurance,
health literacy, patient provider-relationship, stigma)
• Competing health priorities (mental health, comorbidities)
• Stability factors (substance use, employment, income, housing,
drug treatment, social support
Chronic HCV
infection
HCV
diagnosis
Linkage to
care
HCV-specific barriers
• Poor knowledge
• Lack of symptoms
• Fears about treatment
Treatment
initiation
Viral
clearance
Bova 2010, Cacoub 2006, Delwaide 2005, Denniston 2012, Evon 2007, Evon 2010, Gidding 2011, Grebely 2008, Grebely 2011, Hall 2004, Kar-Lung Yan 2010, Khaw 2007, Lally
2008, McLaren 2008, McNally 2006, Mehta 2008, Mendes-Correa 2010, Morrill 2005, Munoz-Plaza 2006, Neale 2007, Ong 2005, Rhodes 2007, Salmon-Ceron 2012, Strauss
2007, Swan 2010
Provider
Structural
There are multiple layered barriers: Provider
Primary care provider barriers
Specialist barriers
• Knowledge (misconceptions about who to
• Knowledge (some providers may have limited
screen, progression risk and treatment)
• Perceptions (may only refer good candidates
who they perceive to need treatment)
Patient
HCV treatment experience)
• Perceptions (concerns about non-adherence,
drug use, relapse, risk of re-infection)
General barriers
• General health care access ( primary care provider, insurance,
health literacy, patient provider-relationship)
• Competing health priorities (mental health, comorbidities)
• Stability factors (substance use, employment, income housing,
drug treatment, social support
Chronic HCV
infection
HCV
diagnosis
Linkage to
care
HCV-specific barriers
• Poor knowledge
• Lack of symptoms
• Fears about treatment
Treatment
initiation
Viral
clearance
Cacoub 2006, Grebely 2011, Fishbein 2004, Hallinan 2007, McGowan 2012; Mehta 2008, Morrill 2005, Rocca 2004, Salmon-Ceron 2012, Scott
2009, Stoove 204, Strauss 2007, Talal 2013, Wagner 2009, Zickmund 2007
Provider
Structural
There are multiple layered barriers: Structural
Health care system issues
•
•
•
•
•
•
Accessibility of HCV antivirals & care locations
Overburdened health systems
Cost / insurance
Segregated service delivery
Criminalization of drug use
Accessibility to drug use-related services
• Inconsistent screening/treatment guidelines
• Insufficient number of providers who can treat
HCV
• Insufficient resources for case managers,
navigators, social workers
Primary care provider barriers
Specialist barriers
• Knowledge (misconceptions about who to
• Knowledge (some providers may have limited
screen, progression risk and treatment)
HCV treatment experience)
• Perceptions (may only refer good candidates
who they perceive to need treatment)
Patient
Workforce issues
• Perceptions (concerns about non-adherence,
drug use, relapse, risk of re-infection)
General barriers
• General health care access ( primary care provider, insurance,
health literacy, patient provider-relationship)
• Competing health priorities (mental health, comorbidities)
• Stability factors (substance use, employment, income housing,
drug treatment, social support
Chronic HCV
infection
HCV
diagnosis
Gidding 2012, Mehta 2006, Mehta 2008, Morrill 2005, Strauss 2007
Linkage to
care
HCV-specific barriers
• Poor knowledge
• Lack of symptoms
• Fears about treatment
Treatment
initiation
Viral
clearance
Provider
Structural
There are multiple layered barriers
Health care system issues
•
•
•
•
•
•
Accessibility of HCV antivirals & care locations
Overburdened health systems
Cost / insurance
Segregated service delivery
Criminalization of drug use
Accessibility to drug use services
• Inconsistent screening/treatment guidelines
• Insufficient number of providers who can treat
HCV
• Insufficient resources for case managers,
navigators, social workers
Primary care provider barriers
Specialist barriers
• Knowledge (misconceptions about who to
• Knowledge (some providers may have limited
screen, progression risk and treatment)
HCV treatment experience)
• Perceptions (may only refer good candidates
who they perceive to need treatment)
Patient
Workforce issues
• Perceptions (concerns about non-adherence,
drug use, relapse, risk of re-infection)
General barriers
• General health care access ( primary care provider, insurance,
health literacy, patient provider-relationship, stigma)
• Competing health priorities (mental health, comorbidities)
• Stability factors (substance use, employment, income, housing,
drug treatment, social support
Chronic HCV
infection
HCV
diagnosis
Linkage to
care
HCV-specific barriers
• Poor knowledge
• Lack of symptoms
• Fears about treatment
Treatment
initiation
Viral
clearance
Mean Likert Score (out of 10)
0= not a barrier; 10=large barrier
Do patient, provider or structural barriers predominate?
10
9
8
7
6
5
4
3
2
1
0
US
Canada
Patient
McGowan Hepatology 2012
Latin Western Central / Nordic
America Europe Eastern
Europe
Provider
Government
Payer
Asia /
Pacific
Middle
East /
Africa
Provider
Structural
Impact of all oral (interferon-free) therapies?
Health care system issues
•
•
•
•
•
•
Accessibility of HCV antivirals & care locations
Overburdened health systems
Cost / insurance
Segregated service delivery
Criminalization of drug use
Accessibility to drug use services
• Inconsistent screening/treatment guidelines
• Insufficient number of providers who can treat
HCV
• Insufficient resources for case managers,
navigators, social workers
Primary care provider barriers
Specialist barriers
• Knowledge (misconceptions about who to
• Knowledge (some providers may have limited
screen, progression risk and treatment)
HCV treatment experience)
• Perceptions (may only refer good candidates
who they perceive to need treatment)
Patient
Workforce issues
• Perceptions (concerns about non-adherence,
drug use, relapse, risk of re-infection)
General barriers
• General health care access ( primary care provider, insurance,
health literacy, patient provider-relationship, stigma)
• Competing health priorities (mental health, comorbidities)
• Stability factors (substance use, employment, income, housing,
drug treatment, social support
Chronic HCV
infection
HCV
diagnosis
Linkage to
care
HCV-specific barriers
• Poor knowledge
• Lack of symptoms
• Fears about treatment
Treatment
initiation
Viral
clearance
Patient
Provider
Structural
Interventions can target all levels
Health Care System
Non-invasive disease staging
Integrated services
HIV & HCV1
HCV & primary care2
HCV and opiate substitution3
Primary Care & Specialist
Education at all levels (specialists, ID physicians, HIV providers, Primary care)
Sensitization to substance use and related comorbidities
General barriers
Directly observed therapy6
Peer Navigation7
Case-management8
Incentives
Brief interventions (e.g., for alcohol use)
Chronic HCV
infection
1
Workforce challenges
Standard screening/treatment guidelines
Multidisciplinary team care4
Telemedicine5
HCV
diagnosis
Linkage to
care
HCV specific barriers
Education & counseling
Peer support
Treatment
initiation
Viral
clearance
PREVENT
Cachay 2013; 2 Evon 2011; 3 Belfori 2007, Krook 2007, Harris 2010, Litwn 2005, Martinez 2012, Mauss 2004, Schaefer 2003 2007, Sylvestre
2002 2005, Treloar 2010; 4 Evon 2011, Sylvestre 2007, Knott 2006, Moussalli 2010; 5 Arora 2010, Hill CROI 2013; 6 Grebely 2007; 7 http:/
13
www.testhepc.com; 8 Evon 2011
What is the best way to move forward?
 Need combination strategies that address all levels (patient,
provider, structural)
 Will shorter duration of treatment change the model needed?
– Public health strategy vs. a more holistic approach
– From a specialist model to a primary care model
 Apply the HIV test & treat concept to HCV: with HCV, the
model is Seek, Test, Treat and Cure
 Treatment as prevention? (who is prioritized for treatment?)
 What about resource-limited settings?
HCV care continuum in the developing world
100
Estimates from multiple studies in developed country settings
90
Estimates from a sample of 7,092 injection drug users in 10 sites
in India
Percent of persons
80
70
60
50
40
•
10% had ever been tested for hepatitis C
•
50% said they had not been tested because they
had never heard of hepatitis C
30
20
10
0
Chronic HCV
infection
HCV
diagnosis
Linkage to
care
Retention
Treatment
initiation
Viral
clearance
Retention
15
Lessons from HIV
Challenge
Lessons from HIV
Action points for HCV
Decrease cost of care
• Mechanism for overcoming patent barriers and
increasing market competition
• Mechanism for monitoring quality of generics
• Prioritize policies to reduce prices of drugs
• Establish quality assurance program to monitor
quality of drugs
Simplify model of care
•
•
•
•
•
•
•
•
Task shifting
(maximize resources)
• WHO guidelines on task shifting to
nonphysician clinicians
• Operational resource to assess effectiveness
• Decentralized HCV care (e.g., telemedicine) to
provide care at the community level
• Ongoing operational research for monitoring
Service integration
• HIV integrated into other services (TB, STIs,
antenatal care)
• Decentralization to primary care
• Integrate HCV care into other services (HIV,
prison health, NEP, OST)
• Models for integrating with primary care
Surveillance, evaluation
& research
• Epidemiologic data available globally
• Monitoring integrated into national programs
• Collect epidemiologic data at the outset
• Integrate monitoring into existing systems
Patient & community
engagement
• Treatment literacy integrated into programs
• Community health workers
• Build treatment literacy materials
• Engage community health workers to promote
engagement and retention in care
Human rights
(vulnerable groups)
• Monitoring of outcomes in vulnerable groups
• Dedicated funding to fulnerable groups
• Ensure reporting among vulnerable groups
• Encourage funding from AIDS donors (e.g.,
GFATM)
Financial & political
commitment
• New funding mechanisms for funding HIV/AIDS
in resource limited settings
• Political & financial support at national level
• New funding to kick start HCV treatment
programs
• Political commitment from governments
Ford N, Clin Infect Dis 2012
Frequently updated treatment guidelines
Fixed dose combinations
Point-of-care laboratory testing
Monitoring integrated into national program
International guidelines
Fixed-dose combinations
POC lab tests
Non-invasive disease strategies
Cannot wait 10 years for HCV treatment to get
to the developing world
On therapy (in millions)1
8
Rilpilvirine
7
Lopinavir/Ritonavir
Etravirine
Raltegravir
Amprenavir
6
Abacavir
Maraviroc
Efavirenz
Darunavir
5
Delaviridine
Tipranavir
Nelfinavir
4
Fosamprenavir
Nevirapine
3
Emtricitabine
Indinavir
Ritonavir
Enfurvirtide
2
Saquinavir
Tenofivir
1
0
Percent2
100
90
80
70
60
50
40
30
20
10
0
1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012
Daclatasvir
Ledipasvir
Simeprevir
Faldaprevir
2011 2012 2013 2014 2015 2016 2017 2018 2019 2020 2021 2022 2023 2024 2025 2026 2027
Population SVR
Individual SVR
1 - UNAIDS Global HIV/AIDS Report 2013; 2 - Adapted from Thomas et al J Int AIDS Soc 2011
Acknowledgements
• Collaborators
– Johns Hopkins Bloomberg School of Public Health
• David Celentano
• Gregory Kirk
– Johns Hopkins School of Medicine
•
•
•
•
•
Gregory Lucas
Richard Moore
Sunil Solomon
Mark Sulkowski
David Thomas
– YR Gaitonde Centre for AIDS Research and Education
• M Suresh Kumar
• Suniti Solomon
• AK Srikrishnan
• Funding
– National Institute on Drug Abuse
www.ias2013.org
Kuala Lumpur, Malaysia , 30 June - 3 July 2013