EDITORIAL COMMENTARY • CID 2006:42 (1 March) • 673
E D I T O R I A L C O M M E N TA R Y
Injection Drug Users: The Overlooked Core
of the Hepatitis C Epidemic
Brian R. Edlin and Michael R. Carden
Center for the Study of Hepatitis C, Weill Medical College of Cornell University and Center for the Study of Hepatitis C, Weill Medical College of Cornell University,
New York, New York
(See the article by Hagan et al. on pages 669–72)
Received 26 October 2005; accepted 28 October 2005;
electronically published 20 January 2006.
Reprints or correspondence: Dr. Brian R. Edlin, Weill
Medical College of Cornell University, 411 E. 69th St., Rm.
KB-218, New York, NY 10021 (firstname.lastname@example.org).
Clinical Infectious Diseases
? 2006 by the Infectious Diseases Society of America. All
Injection drug users (IDUs) constitutethe
core of the hepatitis C epidemic in the
developed world. Four times more prev-
alent than HIV infection, hepatitis C virus
(HCV) has been acquired by at least 5
million Americans and an estimated 170
million people worldwide. In developed
countries, people who use illegal drugs by
injection are the largest group of persons
with HCV infection and the groupamong
whom most new infections occur. Viral
with incidence rates ranging from 16%–
42% per year [1–4], and yet, our efforts
to control this pandemic have largely ig-
nored the population in whom its biology
and epidemiology are being played out
with the most devastating effects.
Disease control depends on epidemi-
ology, basic science, treatment, and pre-
vention. In each of these spheres, workon
HCV has focused on convenient popu-
lations—patients who come to our clinics
and offices of their own accord—rather
than the more challenged and stigmatized
populations in whom the epidemic con-
tinues to rage out of control. The ubiq-
uitously quoted estimate of thenumberof
Americans infected with HCV—4 mil-
lion—was derived from the National
Health and Nutrition Examination Survey,
a study of the housed, noninstitution-
alized, civilian population of the United
States . But the populations most se-
verely affected by HCV are poorly cap-
tured by this study. Disproportionately
low response rates can be expected in
government surveys from persons en-
gaged in illegal activities, disclosure of
which could result in incarceration or
deportation. In addition, the National
Health and Nutrition Examination Sur-
vey sampling frame, by design, explicitly
excluded several large groups known to
have high prevalences of injection drug
use and HCV infection: people who are
homeless, incarcerated, hospitalized, or
institutionalized. Available estimates of
the sizes and HCV prevalences of these
populations suggest that at least a million
more Americans have been infected with
HCV than estimated by the National
Health and Nutrition Examination Sur-
vey data .
New HCV infections in persons who
inject illicit drugs are probably not well-
represented in official estimates of HCV
incidence in the United States, either. Na-
tional estimates of the number of new
infection reported to health departments
in the 4 US counties (recently expanded
Study of Acute Viral Hepatitis . The
calculations rely on the estimate that 1 in
6 new infections come to medical atten-
tion. HCV infections in IDUs, however,
come to medical attention and are diag-
nosed [8, 9]. Thus, the true incidence of
HCV infection among IDUs may be even
less accurately ascertained by our surveil-
lance system than the prevalence. The of-
ficial estimates of these numbers tell us
about infections in those of us who are
stably housed, have nothing to fear from
the criminal justice system, and go to the
doctor when sick, but tell us little about
those at the core of the epidemic.
If epidemiologists overlook IDUs when
studying HCV, it is little wonder thatbasic
scientists and treatmentresearchersdothe
same. Critical lessons about effective hu-
man immune responses to HCV infection
can be learned from persons whoclearthe
virus during the acute phase of infection.
But although tens of thousands of IDUs
year, most of our insights about the bi-
ology of acute HCV infection have come
from less representative but more acces-
sible sources—rare cases of symptomatic
acute HCV infection that come to medi-
674 • CID 2006:42 (1 March) • EDITORIAL COMMENTARY
cal attention and occupationally exposed
health care workers [10, 11]. And even as
considerable progress has been achieved
in developing new effective antiviral reg-
imens for HCV infection, persons who
inject illegal drugs, even former IDUs
receiving methadone maintenance treat-
ment, are routinely excluded from clinical
trials of new HCV therapies.
HCV transmission in developed countries
occurs through the use of contaminated
injection equipment during illicit drugin-
jection, one might expect that prevention
efforts would, of necessity, focus on stop-
ping transmission among IDUs, even if
other clinical or scientific efforts focused
on more accessible populations. Most of-
ficial publications on the prevention and
control of HCV infection [12–14], how-
ever, have avoided directlyrecommending
borne disease transmission among IDUs:
accessible substance abuse treatment, sy-
ringe exchange programs, removal of the
legal barriers to syringe access and pos-
session, community-based outreach, and
HCV testing and treatment programs for
IDUs and incarcerated persons . Pris-
ons offer an unparalleled opportunity for
HCV prevention and treatment , be-
cause an estimated 29%–43% of HCV-
infected persons in the United States pass
through the corrections system annually
, but the opportunity is almost uni-
trality in the epidemic, IDUs all too often
seem invisible to epidemiologists,basicsci-
entists, clinicians, and public health au-
One official document that illuminated
this blind spot was the 2002 National In-
stitutes of Health consensus statement on
the management of HCV . Departing
from previous guidelines, this document
recommended that drug users be consid-
ered for HCV treatment on a case-by-case
use in and of itself not be considered a
contraindication. This change was based
on the recognition that data did not exist
to support the previous recommendation,
made in 1997 , that drug users not be
treated for HCV infection until they had
abstained from all illicit drug use for at
least 6 months . Nonetheless,fewdata
ing active drug users for HCV infection
outside of special targeted programs [22–
38], and most hepatologists still adhere to
sequence, despite the new guidelines, very
few drug users have access to treatment
for HCV infection .
Current treatment regimens for HCV
infection appear to eradicate the virus
from 50% of patients , averting the
risk of liver failure or liver cancer .
When restrictive criteria are applied to
substance users with HCVinfection,how-
ever, the proportion that remains eligible
for antiviral therapy quickly evaporates,as
reported by Hagan and her colleagues in
this issue of Clinical Infectious Diseases
. Four-hundred four IDUs weredrawn
from the more than1 millionactiveIDUs
in the United States with HCV infection.
Of these 404, only 4% would be offered
moderate-to-severe depression, or recent
injection drug use are considered ineli-
gible. If this is the best we can do—if the
“incredible shrinking” pool of patients
depicted in their figure is all we can hope
to treat—we will forever remain con-
signed to treating patients at the periph-
eries of the epidemic, and the burden of
liver disease will continue to rise.
But can patients withtheseproblemsbe
treated for HCV infection? A growing
number of studies suggest that they can.
Reports from Munich [22–24], Oakland
, Chicago , Rhode Island ,
New York , Vancouver , England
, France , Italy,Belgium,
Dusseldorf , Switzerland , Austria
, Norway , and Australia , re-
viewed elsewhere [43–45], have suggested
that drug users treated for HCV infection
can achieve sustained virologic response
even if they have psychiatric comorbidity,
and even if they continue to use drugs
while receiving treatment, although more
frequent drug use may be associated with
less success . Many of these stud-
ies, however, reported on small, diverse
groups of sometimes highly selected pa-
tings with differing strategies. Data are
sparse on the characteristics that distin-
and the programmatic elements that are
critical for success. Larger studies that
carefully characterize patient and pro-
gram characteristics and outcomes are
needed to provide this information. The
need for such research is urgent, in view
of the overwhelming prevalence of HCV
infection in this population [46, 47], the
increasing morbidity and mortalityofthe
disease , and the limited access that
IDUs have to liver transplantation .
In the meantime, these same consider-
ations demand that we use what weknow
already to expand and replicate existing
programs that have been successful .
Cultural and behavioral barriers en-
cumber work with IDUs, whether in re-
search, clinical care, disease prevention,or
continue to spread unabated, and mor-
bidity and mortality fromliverdiseasewill
continue to rise. Fortunately, experience
working effectively with IDUs is available
from a relatively large community of pro-
fessionals serving substance-using popu-
lations, including those working in sub-
stance abuse treatment, HIV prevention,
harm reduction, HIV care, primary med-
ical care, social services, and other areas.
Knowledge and experience with HCV in-
fection and its treatment, however, are
needed in these circles. Dialogue and col-
laboration between experts in HCV treat-
ment and practitioners who have experi-
ence with IDUs will be needed to bring
the unseen core of the HCVepidemicinto
view, so that progress can be madetoward
effective prevention of infection and ef-
fective treatment and care of those with
EDITORIAL COMMENTARY • CID 2006:42 (1 March) • 675
The Ryan White CARE Act has provid-
ed resources for productive collaboration
among providers serving patients with
HIV infection. Advocacy for the needs of
persons with HCV infection may be re-
quired to get needed resources allocated
to support similar work on HCV. The all-
too-frequently overlooked core of the ep-
idemic is the battleground on which ef-
forts to control HCV infection in the
developed world will be won or lost.
Health (grants R01-DA-09532, R01-DA-13245,
Potential conflicts of interest.
M.R.C.: no conflicts.
National Institutes of
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