- The document summarizes research on HCV infection in young injection drug users (IDUs) aged 18-29 in the United States. It finds that over 200,000 are estimated to be infected with HCV, with an incidence of 8-27 new infections per 100 person-years of injection drug use for those injecting for less than 2 years. Several studies of young IDUs in San Francisco are described that examine prevalence, incidence, risk factors, partnerships, testing strategies, and spontaneous clearance of HCV. Prevention approaches discussed include increasing HCV treatment rates, developing vaccines, and providing counseling to reduce high-risk behaviors and reinfection.

1. Technical Consultation on HCV Infection
in Young IDUs; February 2013
What we know that
can inform prevention
Kimberly Page, PH.D., MPH
Professor in Residence
Injection drug use and HCV in young adults

2. HCV in young IDU in the U.S.
§ 590,000 in U.S ‘ever’ IDU age 18-29 in the U.S.1
§ ~18,287 HIV infected (3% prevalence)2
§ >200,000 HCV infected (35%-45% prevalence)
§ HCV incidence is highest among new injectors:
§ 8-27 HCV infections/100 py IDU < 2 years3
§ HCV has declined from the past 20 years, but in
the last 10 appears stable
§ Reinfection occurs after HCV clearance
1. Armstrong 2007; 2. MMWR 2012; 3. Hagan et al, 2001, 2008;

3. The UFO Studies:
community-based epidemiology of
HCV infection in young adult injectors
in San Francisco
NIH R01 DA016017

4. UFO Studies
UFO-1
Baseline screening for anti-HCV
and HCV RNA
UFO-3a
Prospective cohort of HCV uninfected
(HCV RNA negative)
Acute UFO
Prospective cohort of young IDU
with incident HCV infection
Acute or seroconversion

5. Testing strategies
UFO study questions
UFO-3a
Prospective cohort of HCV uninfected
(HCV RNA negative)
UFO-1
Baseline screening for anti-HCV
and HCV RNA
Acute UFO
Prospective cohort of young IDU
with incident HCV infection
Acute or seroconversion
Acute Treatment Candidacy
Transmission in IDU
partnerships
Immune correlates
of infection
Epidemiology and
Natural history
Vaccine readiness
Differences:
Males vs. females
Genetic factors;
Especially assoc.
With lipids
Prevalence
Incidence

6. UFO IDU
n Median age: 22 (IQR 20, 25)
n Under half (45.9%) had completed high-
school
n Two-thirds (65.2%) male
n Most (76.8%) are white
n Median number of years injecting was 3.7
(IQR 1.3, 6.0)
n Median number of days injected in the
past month was 20 (IQR 7,30)

7. HIV and HCV infection by years injecting
among young IDU in San Francisco
0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
0-1 2-3 4-5 6-7 8-9 >=10
Years injecting
Prevalence
HIV
HCV
Hahn et al, 2002; Page-Shafer et al 2004

8. 0.000.250.500.751.00
Survival
0 2 4 6 8 10
Time (years)
Female Male
HCV Incidence by Sex
Kaplan-Meier Survival Curve
Overall: 23.0 (19.6, 26.7)
Female: 27.8 (21.6, 35.0)
Male: 20.9 (17.2, 25.3)
HCV incidence by Sex (/100 pyo (95% CI))

9. Characteristics of young IDU with incident
HCV infection compared to HCV negative
Incident HCV (n=164)
N (%) or median (IQR)
HCV negative (n=388)
N (%) or median (IQR)
Age 22 (20-25)* 23 (20-26)*
Male 104 (63.4) 265 (69.0)
Years injecting 3.7 (1.8-6.9) 3.8 (1.5, 7.0)
No. of daily injections 3.0 (2.0-4.0)# 2.0 (2.0-3.5)#
Used dirty needle
with cooker (last 3
mo.)
73 (44.5)# 115 (29.8)#
Incarcerated last 3
mo.
51 (31.3) 101 (26.3)
* ≤ 0.05; # ≤ 0.01

10. MULTIPLE
RISK
FACTORS

11. 0.000.250.500.751.00
Survival
0 2 4 6 8 10
Time (years)
RNS = No RNS = Yes
*RNS: Receptive needle/syringe sharing
HCV Incidence by RNS
Kaplan-Meier Survival Curve
RNS no: 17.3 (14.0, 21.4)
RNS yes: 35.8 (28.7, 44.6)
HR: 1.9 (1.4, 2.6)
HCV incidence by RNS (/100 pyo (95% CI))

12. Exposure Pooled RR
Shared syringes (injected with a previously
used syringe)
1.97 (1.57, 2.49)
Shared combinations of drug preparation
equipment other than syringes
2.24 (1.28, 3.93)
Shared drug preparation container (cooker) 2.42 (1.89, 3.10)
Shared drug preparation filter (cotton) 2.61 (1.91, 3.56)
Shared drug preparation rinse water 1.98 (1.54, 2.56)
Backloading 1.86 (1.14, 2.44)
Meta-analysis of HCV seroconversion risk in relation to shared
syringes and drug preparation equipment. – Pouget et al, 2012

13. 0.000.250.500.751.00
Survival
0 2 4 6 8 10
Time (years)
Heroin/Mix Meth/Cocaine/Crack
HCV Incidence by Drug Used Most Days Last Month
Kaplan-Meier Survival Curve
Heroin: 29.6 (24.7, 35.4)
Stimulants: 16.8 (12.6, 22.5)
HR: 1.7 (1.2, 2.4)
HCV incidence by Drug used most days in the
past month (/100 pyo (95% CI))

14. 0
50
100
150
200
250
FY0607 FY0708 FY0809 FY0910 FY1011 FY1112
Non-­‐Prescription
Methadone Other
Opiates OxyCodone/OxyContin
San Francisco Treatment Service Episode by
Primary Drug Problem : FY0607 through FY1112
(Source: CBHS BIS Admission Data)
0
1000
2000
3000
4000
5000
FY0607 FY0708 FY0809 FY0910 FY1011 FY1112
Heroin Alcohol Methamphetamines
Cocaine Marijuana Non-­‐Rx
Pills
Courtesy: A. Gleghorn, SFDPH

15. Opioid OD Deaths in SF County
0
60
120
180
1995 2000 2005 2010
Heroin
Opiate Analgesic
Source: Tabulated from SF ME Annual
Reports COFFIN SFDPH

16. Cumulative HCV seroincidence among IDUs in
Montreal by prescription opioid (PO) injection use
Interaction: p = 0.06 -
0.0
0.2
0.4
0.6
0.8
1.0
0
1
2
3
4
5
6
Propor%on
seroconverted
Time
since
enrolment
(year)
and
number
of
par%cipants
at
each
period
No
injec2on
PO
Injec2on
PO
and
no
injec2on
heroin
Injec2on
PO
and
Injec2on
Heroin
N=2
46
N=
96
N=14
4
N=
60
N=
23
N=
1
*: adjusted for age, gender, cocaine
injection, sharing, incarceration, recruitment
scheme, nb. injection
Bruneau, J, et al 2012

17. SPECIAL
RELATIONSHIPS

18. Partnerships and HCV transmission
n Some “social” risk factors for incident HCV:1
n Pooling money with another IDU to buy drugs
n Engaging in receptive needle sharing with a main sex partner who
was perceived to be HCV+
n Risk among IDU who reported partnerships:
n IDU who perceived that their IDU partner was HCV positive had
lower odds of RNS compared to those who thought their partner
was HCV-neg
n Odds of AES were lower among IDU who said they didn’t know the
HCV status of their injecting partner (vs. knowing partner was
HCV-negative), among non-sexual partnerships
1. Hahn et al, 2002; 2. Hahn et al, 2010

19. Incidence of HCV in young IDU by sex, and IDU sexual partnership —
UFO Study , San Francisco 2000–2011
female, main sex partner IDU= NO - - - - - - female, main sex partner IDU= Yes
---- - ---- male, main se partner IDU = NO --- --- --- male, main sex partner IDU= Yes
Days

20. Variable Adjusted OR (95% CI)
Perceived HCV status of partner (versus Negative)
Positive
Unknown
0.46 (0.21-1.01)
0.86 (0.44-1.67)
Sex of partnerships (versus male/male)
Female respondent / Male partner
Male respondent / Female partner
Female respondent / Female partner
2.70 (1.29-5.65)
1.62 (0.80-3.26)
2.18 (0.84-5.61)
Frequency injected with partner (versus <1 time/week)
Every day/almost every day
3-5 times/week
1-2 times/week
5.75 (2.27-14.57)
3.00 (1.20-7.54)
1.51 (0.58-3.96)
Months respondent knew partner (versus<3)
3-12
>12
1.09 (0.54-2.20)
2.09 (1.10-3.95)
Had sex with injecting partner, prior month 2.44 (1.48-4.02)
Race/Ethnicity=Non-white (versus white) 2.06 (1.01-4.23)
Factors independently associated with receptive needle sharing in
injecting partnerships
Morris et al, 2013 under review

21. HCV TESTING
AND
COUNSELING

22. HCV testing and counseling
n Behaviors after individual HCV+ disclosure1
– No change in injecting behaviors*
– Declines in non-IDU behaviors, alcohol use but
not sustained.
– No increase in depression symptoms
n Knowledge of partners HCV status
– less likely to engage in RNS with partner2
1. Tsui et al, 2009; *also found by Ompad et al,2002, Cox et al, 2009; 2.
Hahn et al, 2010; Morris et al, 2013

23. Acceptability of anti-HCV rapid test
Variable! %!
Main reason for choosing rapid test:!
Wanted fast results"
Rapid test is more convenient"
Rapid test requires less blood"
Rapid test is less stressful"
Other reasons"
"
63.2"
10.5"
10.5"
5.3"
10.4"
Compared to Standard blood draw, getting a
fingerstick was:"
Much less painful"
Less painful"
About the same amount of pain"
More painful"
"
"
36.4"
31.8"
25.0"
6.9"
“I found the fingerstick uncomfortable”"
Disagree"
Strongly disagree"
Agree"
Strongly disagree"
"
40.9"
29.6"
25.0"
4.6"

24. INJECTION
CESSATION

25. Characteristic HR (95% CI)
Drug treatment, last 3 mo. 2.08 1.31–3.29
<30 injection events, last month 2.31 1.45–3.69
History of incarceration 0.48 0.29–0.78
Injected heroin, or heroin mixed with other
drugs, last 3 mo.
0.53 0.33–0.85
Injected someone’s rinse, last 3 mo. 0.40 0.21–0.75
Drank alcohol, last month 0.61 0.41–0.92
Used benzodiazepine pills, last 3 mo. 0.57 0.34–0.94
Adjusted hazard ratios for injection cessation in young
IDU in the UFO Cohort Study, San Francisco, CA, 2000–
2008 (N= 362).

26. CLEARANCE
AND
REINFECTION

27. Spontaneous clearance by sex and
IL28B
Grebeley et al, under review 2013

28. Reinfection after clearance
n Varying rates (1.8%-47%)
– Lower viremia
– A high proportion re-clear, and have shorter duration
of viremia
n No data on how individuals do or don’t change behavior
after clearance of HCV
– Counseling messages needed:
§ Individual level, by sex, and partnerships
– What factors are associated with reinfection?
– Data needed to inform trials and programs of HCV
treatment among IDU

29. What we
know that
can inform
PREVENTION

30. Impact of Duration of Injecting on HIV and HCV Transmission
Kwon J et al.; JAIDS 2009

32. Changing HCV treatment landscape
• Telaprevir/boceprevir +pegIFN/RBV increase SVR for
genotype 1 (from ~45% to ~70%)
• Future IFN-free DAA treatment regimes could substantially
increase impact and feasibility of treatment as prevention:
• Enhanced efficacy (>90%)
• Once-daily oral-only dosing
• Reduced toxicity
• Shortened treatment duration (~12 weeks)
• May lead to:
• Higher uptake/adherance/completion
• More treatment capacity
• ISSUES: affordability, drug using population; acute Rx?

33. Antiviral Therapy Might Be Used to Reduce
HCV Prevalence Among Injecting Drug Users
§ Annually treating 10 HCV
infections per 1000 IDU and
achieve SVR of 62.5%
§ Projected to result in a relative
decrease in HCV prevalence over
10 years of 31%, 13%, or 7% for
prevalences of 20%, 40%, or 60%,
respectively
§ Can the HIV model of “Treatment
as Prevention” be applied to HCV?
Martin et al. Journal of Hepatology 2011
Courtesy J. Ward CDC

34. Potential Impact of HCV Vaccination on Incidence
Among IDU
n Model of a three dose vaccine to prevent chronic HCV
(VEi)
– Target population: HCV – IDUs
– Best case - 80% efficacy, 1% vaccinated per month
§ From 13.5% HCV incidence at baseline
– 4.3% at 5 years
– 3.2% at 10 yrs
– Success dependent on efficacy, vaccine coverage
– Greater declines with addition of other strategies (safe
equipment)
Hahn JA, et al Epidemics 2009

35. VIP Vaccine Trial
A Staged Phase I/II Study, to Assess
Safety, Efficacy and Immunogenicity of
a New Hepatitis C Prophylactic
Vaccine
Kimberly Page, Ph.D., MPHAndrea Cox, M.D., PhD. NIAID
Clinicaltrial.gov ID: NCT01436357

36. Discussion points: young IDU and HCV
n Highly efficient transmission
• Not just needles:
n Rapidly acquired after initiation
– The ‘window’ of prevention opportunity is small
n Incidence has declined, but plateaued:
– How to get further declines?
n Socio-behavioral factors
– Sex differences; Injecting partnerships; Serosorting
n PO use is associated with HCV
n Engaging young IDU
– Testing, programs, health care……

37. UFO Presents! a CDC funded
replication project

38. What’s in the ‘tool box’ for HCV
prevention for IDU?
Before exposure
Point of
transmission
After exposure
• Change in injecting
behavior (reducing,
not sharing)
• Clean injecting
equipment
• Needles
• Ancillary equip
• Alcohol, bleach
• Safe injecting rooms
• Biocide
l Acute HCV Rx
l HCV treatment
• HCV testing &
counselling
• Drug treatment
• Reducing
transmission
from positive
partners
• Drug treatment
• Preventive
vaccines
• Health care
contact

39. Conclusions
n Interventions need to be early and we
need more
n Young IDU can be reached
n Young IDU will engage and participate in
– Using clean equipment, NEP, pharmacy
– Drug treatment
– HCV testing
– Health care
– Research
– And Prevention

40. Acknowledgements
§ The UFO team at UCSF
§ Judith Hahn, Ph.D; Paula Lum, M.D, Jennifer Evans
M.S.; Michael Busch, M.D., Ph.D; Alya Briceno, Alice
Asher, CNS; Kelsey Maher, Caycee Cullen, Jenni Jain,
Meghan Morris; Ph.D.
§ Holly Hagan, Ph.D., New York University
§ Julie Bruneau, M.D., Univ. of Montreal
§ Alice Gleghorn, Ph.D.; Phil Coffin, M.D., SFDPH
§ John Ward, M.D., CDC
§ Jason Grebeley, Ph.D., University of New South Wales
§ Funding: NIDA R01 DA016017, R01 DA031056, NIAID
HHSN2662040074C ; CDC U54 PS001264
§ THANK YOU!