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
Reprints or correspondence: Dr. Brian R. Edlin, Weill Medical
College of Cornell University, 411 E. 69th St., Rm. KB-218, New
York, NY 10021 (Email: firstname.lastname@example.org ).
The publisher's final edited version of this article is
available at Clin Infect Dis
See other articles in PMC that cite the published article.
Injection drug users (IDUs) constitute the core of the hepatitis
C epidemic in the developed world. Four times more prevalent
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 group among whom most new infections occur. Viral
transmission is uncontrolled among IDUs, with incidence rates
ranging from 16%–42% per year [1–4], and yet, our efforts to
control this pandemic have largely ignored the population in
whom its biology and epidemiology are being played out with the
most devastating effects.
Disease control depends on epidemiology, basic science,
treatment, and prevention. In each of these spheres, work on HCV
has focused on convenient populations—patients who come to our
clinics and offices of their own accord—rather than the more
challenged and stigmatized populations in whom the epidemic
continues to rage out of control. The ubiquitously quoted
estimate of the number of Americans infected with HCV—4
million—was derived from the National Health and Nutrition
Examination Survey, a study of the housed, noninstitutionalized,
civilian population of the United States . But the
populations most severely affected by HCV are poorly captured by
this study. Disproportionately low response rates can be
expected in government surveys from persons engaged in illegal
activities, disclosure of which could result in incarceration or
deportation. In addition, the National Health and Nutrition
Examination Survey 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 Survey 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. National estimates of
the number of new HCV infections—about 30,000 per year—are based
on data from cases of acute HCV infection reported to health
departments in the 4 US counties (recently expanded to 6)
participating in the Sentinel Counties Study of Acute Viral
Hepatitis . The calculations rely on the estimate that 1 in 6
new infections come to medical attention. HCV infections in IDUs,
however, are rarely symptomatic, and probably<1% come to medical
attention and are diagnosed [8, 9]. Thus, the true incidence of
HCV infection among IDUs may be even less accurately ascertained
by our surveillance system than the prevalence. The official
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 that basic scientists and treatment researchers do the
same. Critical lessons about effective human immune responses to
HCV infection can be learned from persons who clear the virus
during the acute phase of infection. But although tens of
thousands of IDUs in the United States become infected every
year, most of our insights about the biology of acute HCV
infection have come from less representative but more accessible
sources—rare cases of symptomatic acute HCV infection that come
to medical attention and occupationally exposed health care
workers [10, 11]. And even as considerable progress has been
achieved in developing new effective antiviral regimens for HCV
infection, persons who inject illegal drugs, even former IDUs
receiving methadone maintenance treatment, are routinely
excluded from clinical trials of new HCV therapies.
Because, even by official estimates, most HCV transmission in
developed countries occurs through the use of contaminated
injection equipment during illicit drug injection, one might
expect that prevention efforts would, of necessity, focus on
stopping transmission among IDUs, even if other clinical or
scientific efforts focused on more accessible populations. Most
official publications on the prevention and control of HCV
infection [12–14], however, have avoided directly recommending
the central strategies for preventing blood-borne disease
transmission among IDUs: accessible substance abuse treatment,
syringe exchange programs, removal of the legal barriers to
syringe access and possession, community-based outreach, and HCV
testing and treatment programs for IDUs and incarcerated persons
. Prisons offer an unparalleled opportunity for HCV
prevention and treatment , because an estimated 29%–43% of
HCV-infected persons in the United States pass through the
corrections system annually , but the opportunity is almost
universally squandered . Despite their centrality in the
epidemic, IDUs all too often seem invisible to epidemiologists,
basic scientists, clinicians, and public health authorities
One official document that illuminated this blind spot was the
2002 National Institutes of Health consensus statement on the
management of HCV . Departing from previous guidelines, this
document recommended that drug users be considered for HCV
treatment on a case-by-case basis, just like other patients, and
that drug 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, few data exist to guide physicians
considering treating active drug users for HCV infection outside
of special targeted programs [22–38], and most hepatologists
still adhere to the old guidelines on this matter. As a
consequence, 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 HCV infection, however, 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 were drawn from the more than 1 million active IDUs in the
United States with HCV infection. Of these 404, only 4% would be
offered treatment if those with problem drinking,
moderate-to-severe depression, or recent injection drug use are
considered ineligible. 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 consigned to
treating patients at the peripheries of the epidemic, and the
burden of liver disease will continue to rise.
But can patients with these problems be 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 , reviewed
elsewhere [43–45], have suggested that drug users treated for
HCV infection can achieve sustained virologic response rates
similar to those in other populations, 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 studies,
however, reported on small, diverse groups of sometimes highly
selected patients recruited and treated in different settings
with differing strategies. Data are sparse on the
characteristics that distinguish those who can be successfully
treated and the programmatic elements that are critical for
success. Larger studies that carefully characterize patient and
program 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 mortality of the disease
, and the limited access that IDUs have to liver
transplantation . In the meantime, these same considerations
demand that we use what we know already to expand and replicate
existing programs that have been successful .
Cultural and behavioral barriers encumber work with IDUs,
whether in research, clinical care, disease prevention, or
public health. Nonetheless, until these barriers are overcome,
the HCV epidemic will continue to spread unabated, and morbidity
and mortality from liver disease will continue to rise.
Fortunately, experience working effectively with IDUs is
available from a relatively large community of professionals
serving substance-using populations, including those working in
substance abuse treatment, HIV prevention, harm reduction, HIV
care, primary medical care, social services, and other areas.
Knowledge and experience with HCV infection and its treatment,
however, are needed in these circles. Dialogue and collaboration
between experts in HCV treatment and practitioners who have
experience with IDUs will be needed to bring the unseen core of
the HCV epidemic into view, so that progress can be made toward
effective prevention of infection and effective treatment and
care of those with HCV infection at the core of the epidemic.
The Ryan White CARE Act has provided resources for productive
collaboration among providers serving patients with HIV
infection. Advocacy for the needs of persons with HCV infection
may be required to get needed resources allocated to support
similar work on HCV. The all-too-frequently overlooked core of
the epidemic is the battleground on which efforts to control HCV
infection in the developed world will be won or lost.
Financial support. National Institutes of Health (grants
R01-DA-09532, R01-DA-13245, and R01-DA-16159).
Potential conflicts of interest. B.R.E. and M.R.C.: no
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