C a r e a n d Tr e a t m e n t fo r

HEPATITIS C and HIV COINFECTION

U.S. Department of Health and Human Services, Health Resources and Services Administration,

HIV/AIDS Bureau, April 2006

EXPANDING ACCESS Through the Ryan White C ARE Act

Tr acy Swan, Treatment Action Group
C2

CONTENTS

1. Introduction 3

2. HIV/HCV Coinfection 5

3. HCV Treatment 19

4. Expanding Access to Treatment 29

5. Barriers and Key Issues 37

6. Conclusion 47

7. Resources 51

8. References 55

This publication was produced by Impact Marketing and

Communications for the U.S. Department of Health and Human

Services, Health Resources and Services Administration, under

Contract HHSH231200433002C.
While attending the memorial of a

coinfected patient who had died from

end-stage liver disease, a colleague asked

me why I wasn’t treating my coinfected

patients for hepatitis C. Referring them to

a gastroenterologist wasn’t working. I was

concerned about treating patients with

psychiatric comorbidities and/or ongoing 

substance use. 

My colleague encouraged me to figure

out how, rather than whether, to deliver

care to these patients . . . or we would

continue to attend funerals of patients

dying prematurely from complications of

hepatitis C. Since then, my role has

changed from gloom and doom—

warning patients about side effects—to

one of providing education and support

and encouraging patients to try 

HCV treatment.1

—Lynn E. Taylor, MD

Miriam Hospital, Providence, RI
Prevalence of the hepatitis C virus (HCV) may be as high as 30 percent among people

living with HIV/AIDS (PLWHA) and as high as 90 percent among PLWHA who

contracted HIV infection through injection drug use (IDU). End-stage liver disease

associated with HCV is now a major cause of death among PLWHA.2-4

Today, the standard of care is for all PLWHA to be screened for HCV and for all

coinfected patients to receive comprehensive care services. Evidence suggests that this

is not happening—and for many reasons.

The purpose of this publication is to help Ryan White Comprehensive AIDS Resources

Emergency (CARE) Act planners, administrators, and providers address those reasons,

deal with barriers to care faced by those in need, and construct a response to HIV/HCV

coinfection that reflects the current standard of care. 

This guide comes at a time of intense pressure on the HIV care system arising from such

factors as rising health care costs and growing HIV prevalence among the poor and

uninsured. It reflects that providers must cope with these difficult issues. But this

publication also is full of optimism, reflecting that providers of HIV/AIDS services

already have much of the capacity necessary for providing some services required by

coinfected people—and that the financial barriers to ensuring access to comprehensive

care that includes HCV treatment may not be as significant as may first appear.

Nonetheless, navigating the road that leads to a better system of care for coinfected

patients requires commitment—the same kind of commitment that providers have

shown throughout 25 years of HIV/AIDS. In this publication, the U.S. Department of

Health and Human Services, Health Resources and Services Administration (HRSA)

urges organizations to make that commitment and provides a framework for ensuring

that comprehensive services are extended to all HIV/HCV-coinfected patients. 

3

1. INTRODUCTION
4

HCV antibody status may be a marker for

poorer access to care and competing

problems with addiction that lead to

delays in care and failure to implement

the standard of care. . . . [I]f we are to

improve the health status of patients with

HIV/HCV coinfection, perhaps we should

focus on these issues as well the presence

of the two viruses.5

—Graham and Koziel (2003)
HIV/HCV coinfection in the United States requires that HIV/AIDS service providers,

health planners, and administrators acquire an understanding of how coinfection affects

the health and well-being of their clients, and then build systems of care that respond

to those effects.

But comprehending the consequences of HIV/HCV coinfection is difficult without first

being familiar with the natural history of HCV monoinfection.

HCV 101

HCV is the most common blood-borne infection in the United States: At least 3.8

million people have been infected.6

Previously, the blood supply was a major mode of HCV transmission, but now that the

blood supply is thoroughly screened for the virus, IDU with shared, unsterilized

equipment accounts for 68 percent of new HCV infections.7 HCV is also transmitted

perinatally, from improperly sterilized dialysis equipment, and through unprotected sex

with an infected partner. Cohort studies report that men who have sex with men (MSM)

and people who have other sexually transmitted infections are at greater risk for

contracting HCV from unprotected sex.8-11

Unlike HIV, HCV infections are not always chronic; some people clear the virus

spontaneously (without treatment), usually within a few months after infection. That

said, most people who are infected with HCV—55 to 85 percent—will develop chronic

HCV infection.7,12-16

The course of HCV varies considerably, making it difficult to predict disease progression

(Figures 1 and 2).

5

2 . HIV/HCV COINFECTION
6

Acute HCV Infection

Spontaneous Viral Clearance

20-25 years for monoinfected

and as little as 5 years or

less in co-infected patients

Less than 1 year

• Chronic HCV infection may be asymptomatic, with minimal to no liver disease,

or it may present with mild to moderate liver disease (fibrosis).17-22

• An estimated 20 percent of people with chronic HCV infection will progress to

cirrhosis over a 20- to 50-year interval.20-22 A greater proportion of HIV/HCVcoinfected people may progress to cirrhosis (serious liver scarring), and liver

disease progression is more rapid among those who are coinfected than among

those with HCV alone.23-26

• Alcohol consumption, aging, and duration of HCV infection promote liver disease

progression.

• Each year, 1 to 5 percent of people with HCV-related cirrhosis develop

hepatocellular carcinoma.27,28

• In the United States, liver disease due to chronic HCV infection is the leading

indication for liver transplantation.29

• Annually, at least 8,000 to 12,000 deaths are attributed to complications from

chronic HCV infection.26,30

Transplantation or Death

%

People Infected 0

100

Figure 1. Sequence of Events After Acute HCV Infection

Chronic Infection

Compensated Cirrhosis

Decompensated Cirrhosis

55-85% of Adults 15-45% 

Source: Substance Abuse and Mental Health Services Administration, Unpublished data; 2005.

Time
7

Of all people who contract HCV infection, just 20 percent have acute symptoms, such as fever, fatigue, loss of

appetite, abdominal pain, nausea, vomiting, and jaundice.The absence of early symptoms is one of several reasons

that HCV, like HIV, often goes undetected for some time after seroconversion.

From 15 to 45 percent of monoinfected patients will

clear HCV without treatment, an outcome that is

known as spontaneous viral clearance. Of the

remainder (55 to 85 percent), a portion will clear the

virus after treatment, but most will live with HCV for

the rest of their lives.

In coinfected patients, spontaneous viral clearance

and clearance with treatment occurs less frequently

than among monoinfected patients.

Figure 2. Natural History of HCV and Effects of Coinfection

Chronic HCV Infection

Acute Infection and Early Symptoms

About 80 percent of monoinfected patients with

chronic infection develop fibrosis (mild liver scarring)

or experience symptoms such as depression and

fatigue.

Coinfected patients with chronic infection are more

likely to develop fibrosis or symptoms than

monoinfected patients.

Fibrosis

From 20 to 30 percent of monoinfected patients with

chronic infection develop cirrhosis (serious liver

scarring) from 15 to 50 years after infection.

Coinfected patients are more than twice as likely as

monoinfected patients to develop cirrhosis, and they

may develop it much more rapidly—in as little as 10

years after infection.

Cirrhosis

Every year, from 1 to 5 percent of people with

cirrhosis develop liver cancer. People with cirrhosis are

also at risk for hepatic decompensation.

Coinfected patients may be at greater risk for liver

cancer than are monoinfected patients.Their risk is

six times greater for hepatic decompensation, and

their survival after decompensation develops is

significantly shorter.

Liver Cancer and Hepatic Decompensation 

(Loss of Liver Function)

Monoinfection Coinfection
8

HIV/HCV Coinfection

The prevalence of HCV coinfection is higher than most people realize. In the United

States, HCV prevalence among all PLWHA is estimated to be 15 to 30 percent, and it is

more than three times higher—from 50 to 90 percent—among people who acquired

HIV through IDU.2-4 People who are coinfected with HCV and HIV are more likely than

those with HCV alone to develop end-stage liver disease because HIV accelerates

progression of HCV. Hepatitis C can be treated, even in PLWHA. End-stage liver disease

is preventable in many patients: The first steps are educating patients about HCV,

providing appropriate screening and diagnosis, and assessing the need for HCV

treatment, all in a supportive context.

Table 1. Snapshots: HCV Prevalence Among People Who Are HIV-Positive2,31-35

Sample Total HCV Prevalence in 

Cohort Size Prevalence (%) Subpopulations

Adult AIDS Clinical Trials Group 213 16.1 72.7% among “high-risk” group 

(AACTG) (participants with hemophilia 

or history of injection drug use) 

AIDS Linked to the Intravenous 934 97.6 *

Experience (ALIVE) Cohort

Baltimore, MD

Community Programs for Clinical 2,705 16.6 61.9% among participants with

Research on AIDS (CPCRA) a history of injection drug use 

San Francisco Community 2,859 39.4 *

Health Network

HIV Atlanta Cohort Study (HIVACS) 970 31.6 *

New York City, Cohort of HIV-Positive 557 75.0 *

Current & Former Injection Drug Users

*Data not provided.
9

HCV is an opportunistic infection of HIV disease. In the era of highly active

antiretroviral therapy (HAART), HCV coinfection has become a prominent contributor

to morbidity and mortality among PLWHA. 

Many experts regard HCV infection as a “different animal” in PLWHA, because liver

disease progresses more rapidly in people who are HIV positive. HCV-associated liver

damage appears to be more likely to develop in HIV/HCV-coinfected people than in

those with HCV monoinfection. Coinfected people with <200 CD4 cells/mL are at

greatest risk for end-stage liver disease.36-38

One study evaluated paired liver biopsies from 61 coinfected patients and found that

liver disease progressed by two stages or more in 28 percent (17 of 61 participants) over

an interval of less than 3 years.39 A similar study in people with HCV monoinfection

reported that only 11 percent (23 of 210 participants) progressed by two stages or more

in a similar time period (median of 2.5 years).40

A meta-analysis of eight studies reported that coinfected patients were twice as likely to

develop cirrhosis than patients with HCV alone. They had a sixfold greater risk for

hepatic decompensation (decreased liver function due to damage for which the liver

cannot compensate).41

HCV Diagnostic Testing

Federal guidelines recommend that all PLWHA be tested for HCV.30,42-45 Antibody testing

is not sufficient for diagnosing chronic HCV infection, however, because some people

spontaneously clear the virus without treatment but remain antibody positive. A

hepatitis C viral load (HCV RNA) test is necessary to confirm or rule out chronic HCV

infection (Figure 3). Studies have reported spontaneous viral clearance rates from 15 to

45 percent in HIV-negative persons.7,12-16 Although spontaneous viral clearance is less

likely to occur among people who are HIV positive, some PLWHA, particularly those

with higher CD4 cell counts, do spontaneously clear HCV infection.46-51
10

Figure 3. HCV Testing: Diagnostic Algorithm for HIV-Positive Patients

If RNA is undetectable

Test should be repeated in 6

months to confirm or rule

out chronic HCV infection.

Patients should be provided

prevention counseling and

education and vaccinations

for both hepatitis A and

hepatitis B.

Those with no known risk or

possible exposure to HCV

should receive HCV prevention

counseling.

BUT

HCV RNA (viral load) testing

should be considered for

• PLWHA with CD4 cell count

of <200/mL;

• people with recent exposure

to HCV, acute hepatitis, elevated liver enzymes, or other

signs of hepatitis; and 

• active injection drug users.

If HCV antibody test results are positive

HCV ANTIBODY TESTING

If RNA is detectable

The patient has chronic

HCV infection and should

receive comprehensive HCV

care services that include

vaccinations for hepatitis A

and B; counseling, with an

alcohol and drug use component; treatment education;

and, when appropriate, HCV

treatment.

HCV RNA TESTING

If HCV antibody test results are negative

The patient should be provided with HCV

RNA (viral load) testing.

Federal guidelines recommend that all HIV-positive

individuals be tested for HCV antibodies.
Prior, resolved infection can be distinguished from chronic infection by the presence of

HCV antibodies and the absence of detectable HCV RNA (Table 2). 

• HCV RNA is usually detectable within 2 weeks after infection.52

• HCV antibodies usually develop 6 weeks to 6 months after infection.13 People

who have cleared HCV are no longer infected, although antibodies usually remain

in the bloodstream for years after spontaneous viral clearance.

All positive HCV antibody results should be confirmed by testing for HCV RNA, but the

costs for doing so may be prohibitive in some clinical settings. Thus, to hold down

costs, some providers may delay RNA testing until patients are considering treatment or

require biopsy. HCV antibodies do not always develop in immunocompromised people,

so when HCV infection is suspected or symptoms are present in HCV

antibody–negative patients with a CD4 cell count of less than 200/mL, HCV RNA

testing should be performed to confirm or rule out chronic HCV infection.53,54

Diagnosis Test for HCV Antibodies HCV RNA Alanine Aminotransferase 

Resolved Positive Undetectable; perform a second May be normal, may 

HCV HCV RNA 6 months later to fluctuate, or be elevated 

confirm resolved infection (for other reasons)

Acute Negative; may Detectable; initially very high May be as high as 7 to 10 

HCV seroconvert to positive times the upper limit 

of normal

Chronic Positive (may be negative if CD4 Detectable May be persistently normal,

HCV cell count is <200/mL; if HCV persistently elevated, or 

is suspected, test for HCV RNA) fluctuate

11

Table 2. Diagnosing Hepatitis C
The CARE Act community is already familiar with the consequences of late diagnosis of

HIV disease. Delayed diagnosis of HCV in people who are HIV/HCV coinfected also may

have serious consequences. Unfortunately, clinicians are reporting that coinfected

patients often are evaluated for HCV treatment after they have developed cirrhosis or

end-stage liver disease and may be ineligible for HCV treatment.55-57 Those patients still

require care, however, and cirrhotic patients should be screened for varices and

hepatocellular cancer.

58

Hepatitis A and Hepatitis B Vaccination

Federal guidelines recommend vaccination against hepatitis A (HAV) and hepatitis B

(HBV) for people with chronic HCV, HIV, or both.30,42-45,59 Becoming infected with

another hepatitis virus has serious consequences for people with HIV/HCV coinfection:

• HAV can cause sudden hepatic failure in people with chronic HCV.60,61

• Coinfection with HBV and HCV has been associated with more rapid HCV

disease progression.30,62 

Although vaccinations against HAV and HBV are an important part of care for HIV and

HCV, research indicates that vaccination rates are low. A review of HAV and HBV

screening and vaccination practices at nine HIV Outpatient Study sites reported wide

12

Acute HCV Infection

Acute HCV infections are often undiagnosed because only 20 percent of acutely infected people experience

symptoms, such as fever, fatigue, loss of appetite, nausea, and vomiting.63 Diagnosing acute HCV is

important, because it offers an opportunity for improving treatment outcomes (see Treatment of Acute HCV,

p. 27). 
13

variability among sites. Of 1,071 patients, 57.2 percent (612) were screened for HAV,

and 81.9 percent (877) were screened for HBV, yet only 23.3 percent of those eligible

for vaccination against HAV (167 of 716) received one or more doses of HAV vaccine,

and just 32.4 percent (198 of 612) of eligible patients received one or more doses of

HBV vaccine. In HIV-positive people, vaccination for HAV and HBV is preferable when

CD4 cell counts are higher than 200/mL because the immune response to HAV and

HBV vaccination decreases at lower CD4 cell counts.64-66

Counseling and Support

Successful HCV care programs offer education and counseling, beginning at the initial

screening for HCV antibodies.55-57,67-70 Counseling and education must be an ongoing

part of care, regardless of whether HCV treatment is initiated. In the context of HCV

treatment, these valuable services support adherence to HCV treatment and remain

beneficial after treatment has been completed (see box, Essential Elements of HCV

Education and Support). 

HCV counseling must include an alcohol abuse component, because in some cases,

abstaining from alcohol may be the most important intervention for HCV. A safe amount

of alcohol intake for people with chronic HCV has not been identified.71-72 Thus, it is

particularly important for providers to assess alcohol use in coinfected patients, and

then offer information, resources, and support on reducing or abstaining from alcohol.

Alcohol consumption, particularly more than 50 g per day (approximately four mixed

drinks or glasses of wine or beer) causes and accelerates liver damage in people with

HCV and increases HCV viral load, which may compromise the efficacy of HCV

treatment.23,73-75 Options to help patients reduce or eliminate alcohol intake include

referral to counseling, 12-step programs, alcohol treatment programs, and

pharmacotherapy with naltrexone or acamprosate.76-78

Alameda County Medical Center’s coinfection clinic is an example of a successful program.

One component is a weekly education and support group, which began in February 2002.

Each 2-hour meeting includes lunch and an educational session, which is followed by an

opportunity for members to share experiences and socialize. Initially, mono- and

coinfected patients treated for HCV at other sites were recruited as mentors. After the first

group participant initiated HCV treatment without serious side effects, a “snowball effect”
14

was reported: Within a few months, six participants had started HCV treatment. Although

demographically diverse, the group is quite cohesive. Participants call one another

between meetings, offer each other transportation to medical appointments, and continue

to visit long after they have completed HCV treatment.57-68 

For reasons ranging from the nature of HCV progression to the efficacy of available

treatments, as well as the cost of treatments, most people living with HCV, regardless of HIV

status, will never undergo HCV drug treatment. In fact, the U.S. Department of Veterans

Affairs has identified 270,000 HCV-infected veterans since implementing HCV screening

and testing, yet between 1996 and 2003, just 8 percent were ever treated.79

HIV/HCV Coinfection, Pregnancy, and Perinatal Transmission

People with HIV/HCV coinfection have higher serum HCV viral loads than those with HCV infection alone.80

HCV has been detected in the semen of HIV/HCV-coinfected men81,82 and in the genital tracts of coinfected

women.83 Thus, HIV-positive female partners of men with HCV infection should be tested for HCV and

counseled about the risk of sexual and perinatal transmission of the virus.

Among coinfected women, the risk of perinatal transmission of HCV is approximately 17 percent, or four

to five times greater than that among women with HCV monoinfection.84,85 Although treatment for chronic

HCV infection is contraindicated during pregnancy, coinfected mothers can reduce the risk of vertical

transmission of HIV and HCV with antiretroviral therapy and cesarean delivery. A recent study reported

that either elective or urgent cesarean delivery reduced the rate of perinatal transmission of HCV among

coinfected women from 17.3 to 8.3 percent.86 Because infants may carry maternal antibodies for up to 18

months, HCV viral load testing should be used to diagnose HCV infection in children under 18 months

old.
15

• What is HCV? 

• HCV transmission, reinfection, and risk reduction

• Diagnosis of HCV: acute, chronic, and cleared infection

• Importance of vaccination against hepatitis A and B

• Natural history of HCV in HIV/HCV-coinfected patients

• Reduction or elimination of alcohol intake

• Drug use and risk reduction (counseling to reduce exposure to blood-borne pathogens and infections or

referral to methadone, buprenorphine, counseling, support, or other drug and alcohol treatment programs) 

• Risks and benefits of HCV treatment

• Use of complementary and alternative therapies

• Nutrition

• Possible implications for HIV treatment and other medical therapies

Figure 4. Essential Elements of HCV Education and Support

After Diagnosis

At Screening

• Timeline for new HCV therapies

• Evaluation for treatment (HCV RNA, genotype, biopsy, other tests)

• Strategies for managing side effects

• Effect of HCV treatment on absolute CD4 cell count, relationship of absolute number to CD4 cell percentage

• Making a treatment decision

• Potential interactions among antiretroviral medications, HCV treatment, and other medical therapies

• Development of a treatment plan

• Discussion of mental health, especially history of depression and stabilization as necessary

• Decision about starting prophylactic antidepressant treatment in those with a history of depression

When Considering Treatment

• Strategies for managing side effects

• Monitoring for drug interactions and toxicities 

• Treatment efficacy at Week 12,Week 24,Week 48, and Week 72

• Self-assessment for depression and anxiety and treatment as necessary

When Undergoing Treatment
Table 3. Establishing a Coinfection Clinic 

16

Educate clinic staff by establishing linkages with other sites that have expertise in treating HIV/HCV

coinfection. Arrange visits to learn firsthand about HCV treatment. Hold joint journal club meetings

for HIV clinicians and liver specialists to review current HCV treatment information. Connect with

other treatment providers to talk about their experience and models. Stay informed about HCV

treatment with Internet resources (see Chapter 7).

Don’t reinvent the wheel. Consult with other providers who are treating coinfected patients to see

their protocols, monitoring forms, and checklists.

Arrange space for your coinfection clinic, even if it is only available once a month. Make sure that it

includes space for one-on-one education and counseling sessions.

Collaborate with other specialists to seek their advice when necessary and develop or adopt

interdisciplinary treatment protocols.

Prepare for situations in advance: If you are seeing patients who live in rural areas, contact staff at

their local hospital emergency departments to prepare them for the possibility of patients

experiencing serious adverse events.

Develop linkages with mental health providers if mental health care is not available onsite.

Consider borrowing or buying a portable ultrasound so that biopsies can be performed onsite,

instead of referring patients to another site.

Encourage patients who are having an off-site biopsy by offering to have a nurse or peer escort them.
17

Table 3 (cont’d.) Establishing a Coinfection Clinic 

Design treatment plans according to each patient’s individual situation and needs.

• Comprehensive psychiatric assessment prior to initiation of treatment may not be necessary for all

patients.

• If the patient engages in ongoing opioid misuse, consider prescribing buprenorphine (or facilitating

access to a facility authorized to prescribe it), or provide referral to methadone maintenance or

other substance abuse treatment programs.

• Some clinics do not require that patients undergo biopsy before treatment, while others require it

only for patients with HCV genotype 1. Patients with genotype 1 are less likely than those with

genotypes 2 or 3 to respond to HCV treatment; performing a biopsy for genotype-1 patients can

identify those who need treatment versus those with mild liver damage, who can defer treatment.

When biopsy presents a substantial barrier for otherwise willing patients, some centers offer

treatment without one.

• Some clinicians and patients may be more comfortable with directly observed therapy (DOT) for the

weekly injection of pegylated interferon. DOT also provides an opportunity to monitor clinical and

neuropsychiatric side effects.

Discuss treatment plans during case conferences with mental health providers, clinic staff, and

specialists.

Be creative about finding resources for your patients: Consider referring coinfected patients to a

clinical trial, if appropriate. Some patients may be able to access treatment from pharmaceutical

company–sponsored patient assistance programs or AIDS Drug Assistance Programs (see Access to

HCV Treatment and ADAPs, p. 42). Look into free care programs at local hospitals to cover biopsies.

Hold support group meetings at your clinic regularly.

Support and motivate clinic staff and patients.

Don’t be discouraged. Patients who do not have a virological response to treatment may benefit

nonetheless. HCV treatment may slow progression of liver disease, which in turn may enable some

patients to wait for better treatment.
Support groups are also a powerful

motivational tool, because patients who

are at earlier points in the evaluation

process share in others’ successes as they

pass through milestones in the evaluation

and treatment process. Patients begin to

believe that good outcomes are

attainable. Linking individual recovery to

the notion of fighting back against a

community epidemic produces a

powerful synergy that often results in an

upward spiral of self-esteem.67

—Litwin, Soloway, and Gourevitch 

(2005)
19

Although the medical management of HCV infection is complex, it can result in good

medical outcomes. As with HIV disease, treatment for HCV infection has evolved, as has

management of side effects and adverse events of treatment.

Until 1989, HCV was treated with injections of interferon. Interferon is a synthetic

version of a cytokine (chemical messenger) produced by white blood cells. Response to

interferon monotherapy was dismal. In 1998, treatment outcomes improved significantly

when interferon was combined with ribavirin, a nucleoside analog (a class of drugs used

for HIV treatment). HCV treatment improved again in 2001 with FDA approval of

pegylated interferon. Attaching the polyethylene glycol (PEG) molecule to interferon (a

process called pegylation) keeps the drug in the bloodstream longer and makes it more

effective against HCV. Replacing standard interferon with pegylated interferon has

significantly improved response to HCV treatment and requires a dosing regimen of only

one injection per week (Table 4). Currently, therapy with pegylated interferon plus

ribavirin is the standard treatment of HCV in HIV-positive people and the only FDAapproved treatment for coinfection.

In people with HIV/HCV coinfection, the duration of HCV treatment is usually 48

weeks, regardless of HCV genotype; some clinicians are considering 18 months of

treatment for coinfected people who have HCV genotype 1. The primary endpoint of

HCV therapy is sustained virological response (SVR), defined as no detectable HCV RNA

in the bloodstream 6 months after completion of therapy. SVR is an indication of longterm remission of HCV; some experts consider it a cure. 

Response to HCV Treatment: Prognostic Factors

Because of the limited efficacy and considerable side effects of HCV treatment, clinicians

and their patients need to thoroughly assess and discuss risks and benefits of HCV

treatment. The decision-making process should take into account individual prognostic

factors. 

3 . HCV TREATMENT
20

HCV treatment is less effective for coinfected people than for those with HCV alone. In

three studies (AACTG 5071, APRICOT, and RIBAVIC), however, CD4 cell count was not

associated with response to treatment (Table 4). The sample size of people with CD4 cell

counts of less than 200/mL in each study was small, and most study participants were

taking HAART prior to and during HCV treatment.87-93 The studies did not report an

increased incidence of opportunistic infections among participants who had CD4 cell

counts of less than 200/mL.87-89 

Other factors have a significant effect on response to treatment, regardless of HIV status.

The HCV genotype is a major prognostic factor. At least six different HCV genotypes

have been identified. In the United States, most HCV infections are genotype 1.94

Genotypes 1 and 4 are less sensitive to treatment than are genotypes 2 and 3.87-89,95,96

Although HCV viral load is not strongly associated with disease progression (unlike HIV

viral load), HCV viral load is a prognostic factor for response to therapy, particularly in

genotype 1 and genotype 4 infections. People with a baseline HCV RNA of more than

Pegylated interferon Once-weekly injection An antiviral and immunomodulating 

drug used in combination with ribavirin

Ribavirin 200 mg (tablets, capsules, or liquid) A nucleoside analog that 

taken twice daily increases the efficacy of interferon

Filagrastim/pegfilagrastim* Subcutaneous injection; White blood cell growth factor; used for

dosing varies treatment of interferon-induced neutropenia

Epoetin alfa/darbopoetin alfa* Subcutaneous or intravenous Red blood cell growth factor;

injection; dosing varies treatment for ribavirin-induced anemia

Antidepressants (selective Pills; dosing varies Prevent onset of or treat 

serotonin reuptake inhibitors)* interferon-induced depression

* Use in patients when indicated.

Table 4. Drugs Used for HCV Treatment and Management of Side Effects

Drug Given As Purpose 
21

800,000 per MIU are less likely to respond to HCV treatment than are people with

lower HCV RNA levels.87-89,95,96 HCV RNA levels are usually significantly higher in

coinfected people than in people with HCV monoinfection.97-99

In HCV monoinfection treatment trials, response rates among African-Americans—

among whom both HIV and HCV are disproportionately prevalent—have been

significantly lower than response rates among non-Hispanic whites.6,100-104 The reasons for

this disparity are unclear. Data on response rates to HCV treatment among coinfected

African-Americans are limited; only one pivotal HCV treatment trial in coinfected persons

has been conducted solely in the United States (ACTG 5071), and race and ethnicity were

not predictive of response to HCV treatment in that study.88 HCV genotype was the most

significant predictive factor for response to HCV treatment in the trial; the results could

have masked the effect of race, because genotype 1 infections are more likely among

African-Americans than among people of other ethnicities.94,101,105 The predominance of

HCV 1 genotype among African-Americans has been cited as a factor in decreased

response rates to HCV treatment. 

Data from HCV monoinfection treatment trials suggest that lifetime alcohol consumption

and alcohol intake during HCV treatment are associated with poorer response rates. The

treatment regimen in the studies was standard interferon monotherapy, however, and

SVR, Genotypes 1 SVR, Genotypes 2 

Study SVR, Overall (%) and 4* (%) and 3 (%)

AACTG 5071 27 14 73

APRICOT 40 29 62

RIBAVIC 27 17 44**

*When included.

**Includes genotype 5.

Table 5. Response Rates to HCV Treatment Among Coinfected Trial Participants87-89
22

HCV and Liver Transplantation

Liver transplantation may be the only option for coinfected patients with advanced liver disease. HCV

treatment may cause hepatic decompensation in some cirrhotic patients,117 but access to transplantation

for PLWHA is limited by policies of individual transplant centers. Despite promising rates of

posttransplantation survival, some centers do not perform transplants in PLWHA, and the persistent

shortage of donor organs and reluctance of third-party payers to reimburse contribute to the difficulty as

well, despite promising data on posttransplantation survival of HIV-positive patients, which is similar to

that of HIV-negative patients.119-121 Clinicians and their coinfected patients have another option: A trial

sponsored by the National Institute of Allergy and Infectious Diseases on kidney and liver transplantation

in people with HIV. For more information on study sites and eligibility, go to:

http://spitfire.emmes.com/study/htr/.

information on adherence to HCV therapy was not included.106-109 A more recent study

using standard interferon plus ribavirin reported that alcohol intake prior to or during

treatment did not influence response to HCV treatment.110 Many clinicians withhold HCV

treatment until patients have been abstinent from alcohol for 3 to 6 months, but some

treat on a case-by-case basis.56,111 Because alcohol accelerates HCV disease progression,

clinicians need to work with their patients to help them reduce or eliminate alcohol

consumption as part of HCV care, whether or not the patients are candidates for HCV

treatment.

Liver Biopsy 

Liver biopsy is the diagnostic gold standard for assessment of liver damage and its causes.

However, experts are debating the requirement for a pre-treatment biopsy because of the

rare but serious risks associated with biopsy (puncture of adjoining organs, hemorrhage

and—very rarely—death),112-114 the possibility of sampling error,

115,116 and patient

reluctance. A liver biopsy is most useful for detecting mild to moderate liver damage,
because more severe liver damage, cirrhosis, can be identified with clinical, laboratory,

and radiographic testing. Requiring liver biopsy as a prerequisite for HCV treatment

may create a barrier for some patients. 

Although researchers are working to create a less invasive replacement for liver biopsy

that uses panels of blood tests and imaging techniques, nothing has been validated for

use in coinfected people. Given the limited efficacy and substantial side effects of HCV

treatment, some providers feel that a biopsy is necessary to identify patients who can

defer treatment. Others recommend biopsy for patients with genotype 1 and a high viral

load because they are less likely to respond to treatment; biopsy may not be required

for patients with genotype 2 or 3 because the likelihood that they will achieve an SVR

is significantly greater.30,44,117

Treatment Strategies

Researchers are exploring optimal strategies for treating HIV and HCV in coinfected

patients. Initiating HAART prior to HCV treatment may improve response rates to HCV

treatment.122 Several factors must be considered in making treatment decisions:

• The patient must be willing and ready to treat both HIV and HCV.

• If CD4 cell count is less than 200/mL, HIV treatment should be initiated first.

• If HCV disease is mild, treatment can be delayed. If treatment is indicated

according to current guidelines (Table 6) and there is patient readiness, HCV

should be treated either before initiation of HAART or while the patient is on a

stable antiretroviral drug regimen. Antiretroviral regimens for coinfected people

should be selected carefully to reduce the risk of hepatoxicity and avoid

interactions with HCV treatment. Avoid HAART regimens that contain didanosine

(ddI; Videx), because of a potentially life-threatening interaction with ribavirin123

and potentiation of the risk for hepatic decompensation in coinfected cirrhotic

patients during HCV treatment.118 If possible, zidovudine (AZT; Retrovir) should

be avoided because it increases the risk of anemia from ribavirin124; stavudine

(d4T; Zerit) may increase the risk for lipoatrophy and weight loss during HCV

treatment.96 

23
24

Table 6. HCV Treatment Recommendations for HIV/HCV Coinfected Patients 

Source Treatment Recommendation

American Association for the Study of

Liver Diseases

U.S. Department of Health and Human

Services, Centers for Disease Control

and Prevention, HIV Medical Association 

U.S. Department of Health and Human

Services

Department of Veterans Affairs

Federal Bureau of Prisons

Hepatitis C should be treated in the HIV/HCV coinfected person in whom

the likelihood of serious liver disease and a treatment response are judged

to outweigh the risk of morbidity from the adverse events of therapy.

Because of the scarcity of published experience treating people who are

coinfected with HIV/HCV, practice is dictated largely by principles

established for the treatment of people who are not infected with HIV.

Treatment of HCV is recommended according to standard guidelines, with

preference for those with higher CD4 cell counts (>200 cells/mm3

).

All HIV patients with confirmed, chronic HCV infection should be

evaluated for HCV treatment since (i) HCV treatment can lead to a

sustained virological response (SVR), defined as an undetectable HCV

RNA six months after discontinuing therapy; and (ii) HCV treatment may

slow the progression of hepatic fibrosis and/or delay the onset of clinical

consequences of decompensated cirrhosis.45

HCV-related liver disease has now emerged as a serious concern for many

persons with HIV infection. Antiviral therapy should be considered for

inmates with chronic HCV and HIV coinfection, since HIV may accelerate

the development of fibrosis and subsequent end-stage liver disease.

Diagnosis, Management and Treatment of Hepatitis C (April 2004).

Available at: www.aasld.org/eweb/docs/hepatitisc.pdf

Treating Opportunistic Infections Among HIV-Infected Adults and Adolescents: Recommendations From CDC, the National Institutes of

Health and the HIV Medicine Association/Infectious Diseases Society of America (December 2004).

Available at: www.cdc.gov/mmwr/preview/mmwrhtml/rr5315a1.htm

Management and Treatment of Hepatitis C Virus Infection in HIV Infected Adults: Recommendations From the Veterans Affairs Hepatitis C Resource

Center Program and National Hepatitis C Program Office (September, 2005).

Available at: http://hepatitis.va.gov/vahep?page=tp04-gd-01 

Clinical Practice Guidelines for the Prevention and Treatment of Viral Hepatitis. (February 2003).

Available at: http://nicic.org/Library/016972

Guidelines for the Use of Antiretroviral Agents in HIV-Infected Adults and Adolescents (2005).

Available at: http://aidsinfo.nih.gov/guidelines/default_db2.asp?id=50
25

Often, real-life situations are less clear-cut. Because many people present with both

advanced HIV disease and advanced HCV disease, clinicians often start HAART first, so

that side effects from antiretroviral agents can be identified and managed. Antiretroviral

regimens for coinfected people should be selected carefully to reduce the risk for

hepatotoxicity and avoid interactions with HCV treatment. Some patients who start HIV

treatment with a low CD4 cell count do not achieve a CD4 count of more than 200/mL,

although they have a stable or undetectable HIV RNA; those patients should be evaluated

for HCV treatment on an individual basis. Although it is possible to initiate treatment for

both viruses simultaneously, side effects and toxicities from medications make it difficult

to do so. 

Side Effects and Strategies for Managing Them

Pegylated and standard interferon and ribavirin may cause numerous side effects,

including neuropsychiatric symptoms such as mood swings, anxiety, irritability,

insomnia, and depression. Depression may be severe; but in HCV treatment trials,

suicide or attempted suicide was reported among less than 1 percent of participants.125,126

Hematologic toxicities (anemia, neutropenia, thrombocytopenia); fatigue; weight loss;

and “flulike symptoms” also may occur.

127 Although the side effects can be daunting,

strategies exist for managing them. Side effects can be alleviated by interventions such as

the following:

• Prophylactic treatment for depression (i.e., before initiation of HCV therapy)

• Treatment of insomnia and anxiety as needed

• Dose reductions or use of growth factors to manage anemia and neutropenia

• Administration of the weekly shot of pegylated interferon on Friday night to

mitigate side effects during the work week

• Tylenol for aches and fever

• Small, light meals; antiemetics or dronabinol (Marinol) for nausea and loss of

appetite

• Adequate hydration. 
26

The Week 12 Early-Stopping Rule

Although treatment discontinuations occur for other reasons—usually side effects 

and adverse events—many clinicians and their coinfected patients may decide to stop

treatment at Week 12 if the patient does not have an early virological response (EVR),

defined as achieving a 2-log drop in HCV RNA or undetectable HCV RNA after 12

weeks of treatment. As with HCV monoinfection, the likelihood of SVR in the absence

of EVR is extremely low. Clinical trials of HCV treatment in HIV/HCV-coinfected

patients have reported that 94 to 100 percent of participants who did not have EVR also

did not achieve SVR.96,128,129 Some clinicians and patients may prefer to continue HCV

treatment in the absence of an EVR because some patients may have a delayed response

to treatment. The Week 12 “early-stopping rule,” however, spares nonresponders from

the side effects and expense of HCV treatment.

Treating HCV: Long-Term Benefits

In HCV monoinfection, follow-up studies of people who experience SVR have found that

more than 85 percent maintain undetectable HCV RNA levels for up to 10 years after

completion of HCV treatment130-132; retrospective studies have reported a reduction in

liver-related deaths, especially among people who have SVR.133,134 Data on long-term

outcomes of coinfected patients are limited; one study reported that no HCV-related

clinical complications occurred among sustained virological responders after a mean

posttreatment follow-up period of 58 months.135 

Treatment of HCV offers significant benefits to people with coinfection, even in the

absence of SVR. HCV treatment may improve the condition of the liver, even in virologic

nonresponders.88,136 Moreover—and crucially—HCV treatment may increase tolerability

of antiretroviral therapy for HIV/AIDS.137
27

Treatment of Acute HCV

Treating HCV during acute infection has a major impact on treatment outcome. The

biggest barrier to treatment of acute HCV is that it is rarely diagnosed; therefore,

screening for acute HCV, when suspected, is crucial. In HCV monoinfection, HCV

treatment during acute or early infection has been associated with high rates of SVR—

80 to 98 percent—in nonrandomized, uncontrolled trials.15,138 Treating acute HCV may

be a promising approach in HIV/HCV-coinfected patients as well; an open-label,

uncontrolled study reported that 16 of 27 HIV-positive men (59 percent) treated during

acute or early HCV infection achieved SVR after 24 weeks of treatment with pegylated

interferon and weight-based ribavirin.139 The optimal regimen, duration, and time to

initiate treatment are not clear, and problems with toxicity and limited efficacy have

been reported.140-143 
HCV therapy has been successful even

when the patients have not abstained

from continued drug or alcohol use or

are on daily methadone. . . . [I]t is

recommended that treatment of active

injection drug use be considered on a

case-by-case basis, and that active

injection drug use in and of itself not be

used to exclude such patients from

antiviral therapy.

30

—National Institutes of Health

Consensus Statement on Management of

Hepatitis C (2002) 
29

Clinical and systemic barriers to treating HCV coinfection are substantial. For example,

patients often have psychiatric or medical comorbidities, struggle with addiction to

drugs and alcohol and have chaotic lives. These issues must be overcome, because all

PLWHA should receive HCV education and screening, HAV and HBV vaccination, and

counseling on alcohol use and HCV transmission. All providers should offer these

services, regardless of whether HCV treatment is offered onsite.

Some clinics will decide to offer onsite HCV treatment and care on the basis of the

following factors:

• Local priorities

• Demographics and needs of patient population

• Access to consultation or collaboration with a gastroenterologist or hepatologist

• Lack of an acceptable referral option that offers culturally competent care and

treatment. 

Models have been developed for addressing HCV in PLWHA, including referral and comanagement, co-locating services, and integrated care. Some clinics may not have the

capacity to treat coinfected patients for HCV and thus refer patients to a gastroenterologist

or hepatologist. 

Although referral may be the most economically feasible and realistic option for some sites

and providers, this approach has drawbacks and has been shown to be minimally effective

in securing continuity of care over time. Disappointing follow-up rates among coinfected

patients referred to liver specialists have been reported; for example, Clanon and

colleagues reported that less than 10 percent of their coinfected patients kept their

appointments.68 Low follow-up rates can be improved by identifying liver specialists

who are experienced with or are willing to treat coinfected patients, by establishing and

maintaining a relationship between HIV and liver specialists, and by developing a

4 . EXPANDING ACCESS TO TREATMENT
30

communication mechanism among providers. Support groups can help bolster referral

follow-up rates, both by word of mouth and by group members’ accompanying each

other to appointments.57,144

Co-location of liver specialty care in an HIV clinic may be a viable option, because many

patients with HIV prefer “one-stop shopping” at a familiar and comfortable place. Colocation also enhances communication and collaboration among providers. Care can be

co-located by providing a liver specialist at an HIV clinic one or two afternoons per

month.When referral and co-location are not feasible, clinicians may need to provide

their coinfected patients with educational resources (see Chapter 7).

Integrating Care: Starting a Coinfection Clinic

Care and treatment for HCV coinfection have been successfully integrated into several

different venues, including CARE Act–funded clinics, VA programs, and methadone

clinics. Many use a multiple-visit model to counsel, educate, screen, vaccinate,

diagnose, and assess patients for HCV treatment (Figure 5). People who have opened

coinfection clinics agree that the key element is a dedicated, full-time nurse or physician

assistant who is able to schedule appointments, educate patients, facilitate support

groups, provide one-on-one counseling, work on reimbursement for medications,

manage side effects of treatment, and secure case management and transportation

services for patients.1,67,68,70,144-147 Most coinfection clinics have a dedicated nurse or doctor

who is available by pager on a 24-hour basis; they report that patients do not abuse this

service.

The Coinfection Clinic at Alameda County Medical Center, Oakland, CA

In Oakland, CA, Kathleen Clanon and her colleagues established a coinfection clinic in

2001 because so few of their coinfected patients were being treated for HCV by

gastroenterologists; less than 10 percent were keeping appointments. The clinic has a

monthly coinfection session and weekly support group meetings. Liver biopsies are

performed at the HIV clinic by a gastroenterologist who uses a borrowed portable
31

Figure 5. Multiple-Visit Model for Providing HCV Care and Assessing Treatment Options

Provide HAV, HBV, and HCV education, including a discussion of risk behaviors. Screen for or vaccinate

against HAV/HBV. Test for HCV antibodies.

Test for HCV RNA, if positive for HCV antibodies. Refer patient to education or support group, to

individualized counseling and education sessions, or both; include information on alcohol consumption.

Discuss ongoing risk and offer risk-reduction counseling and provide referral to drug and alcohol

treatment, if appropriate.

Visit 2

Visit 1

Give patient the results of HCV RNA testing. If HCV infection is diagnosed, discuss 

HCV natural history in coinfected persons along with risks and benefits of HCV treatment (side effects and

strategies for management, efficacy, and prognostic factors). Assess for medical contraindications to HCV

treatment. Offer additional testing (genotype, liver function test). Discuss biopsy and schedule, if appropriate.

Assess need for mental health services; refer to mental health provider, if appropriate. Refer patient to

education or support group; to individualized counseling and education sessions; or both, as appropriate.

Visit 3

Assess all parameters for treatment eligibility (HIV/HCV, other clinical, mental health, and psychosocial).

Share results from tests (genotype/liver panel and biopsy, if one has been performed). Discuss treatment

and assess treatment readiness. If appropriate, initiate HCV treatment.

Visit 4
32

ultrasound machine. Patients recover from the biopsy in the HIV clinic, where they are

already accustomed to receiving care. The key elements of the program are as follows:

• Sufficient funding to hire a dedicated nurse to provide monitoring and support

for patients receiving treatment

• A cooperative relationship with a gastroenterologist, who has become part of the

treatment team

• A patient support group.

So far, 35 patients at Alameda County Medical Center have been treated or are currently

being treated. “It’s a slow movement and needs to be built up,” says Michael Harank,

Preparing for the Future: New Treatments for Hepatitis C

Clinicians and coinfected patients who are reluctant to treat HCV, given the limitations and toxicities of the

current treatment, can anticipate therapeutic advances in HCV treatment in the coming years. Despite a

promising pipeline of new HCV therapies, pegylated interferon is likely to remain the backbone of HCV

therapy for some time, because most new drugs will need to be used in combination with interferon to avoid

the development of resistance—an approach paralleling combination therapy for HIV. Coinfected people

may need to wait even longer for new drugs, because HCV treatment trials in coinfected people often lag

behind trials in people with HCV monoinfection, despite growing pressure from advocates. 

Many different types of drugs are in development. Although a trial of an HCV protease inhibitor, BILN-2061,

was discontinued, proof-of-concept for this class of drugs was established and two HCV protease inhibitors

are in clinical trials.148 Agents in development include helicase and polymerase inhibitors, drugs targeting the

internal ribosomal entry site, and small interfering RNA.148
who coordinates care and facilitates the education and support group.57 The SVR rate

among Clanon’s patients is astoundingly high: 53 percent. That rate can be attributed to

a combination of factors: favorable HCV genotype, adherence to treatment, prompt

management of side effects, consistent support from peers and staff, and eligibility

criteria that include abstinence from drugs and alcohol prior to initiating HCV

treatment and a CD4 cell count of more than 350/mL. 

Clinic staff recommend the following approach to treatment:

• Maintain the full dose of pegylated interferon and ribavirin. Use growth factors

instead of dose reduction, and consider pretreatment with erythropoietin.

• Assess for depression before initiating treatment, and reassess on a monthly basis.

Pretreat for depression with selective serotonin reuptake inhibitors if the patient

has a history of depression or a moderately high depression score prior to

treatment. Switch medication if necessary.

• Advise patients to drink at least 3 liters of water per day; doing so seems to

reduce pain, fatigue, and headaches. Almost all patients who drink sufficient

quantities of water report no need for additional pain medication.68

• Encourage patients to utilize other services that can help them stay in care and

manage quality of life.57,68,147 

Miriam Hospital’s Immunology Center, Providence, RI 

In contrast to many other coinfection treatment providers, Lynn Taylor and her

colleagues at the Miriam Hospital do not exclude coinfected drug and alcohol users

from HCV treatment. Patients at Taylor’s coinfection clinic often have advanced liver

disease and unfavorable HCV genotypes, so the main goals of treatment often are to

delay HCV progression and improve liver histology, not necessarily to achieve SVR.

The coinfection clinic opened in 2001 as part of Miriam Hospital’s Immunology Center,

which provides CARE Act–funded clinical care to more than 1,000 PLWHA, 43 percent

33
of whom are coinfected. Care and treatment for HIV and HCV are multidisciplinary.

Treatment plans are made on an individualized basis. Coordinated psychiatric care,

addiction treatment, and home-based case management are provided through

collaboration with a community-based mental health agency, and the clinic has a

collaborating hepatologist.56

The coinfection clinic takes place on 2 half-day sessions each month. At their first visit,

patients receive comprehensive, individualized education. A support group meets once

per week for breakfast, and the clinic offers monthly group educational sessions, the

opportunity for individual sessions, and educational materials in English and Spanish.

Patients often speak with one another on the telephone when they are unable to come to

sessions. An interventional radiologist performs liver biopsies, which are not required for

treatment. Weekly injections of pegylated interferon are given at the clinic, and patients

are given a week’s supply of ribavirin at that time. Directly observed administration of

pegylated interferon allows for assessment and management of side effects. The

adherence rate for weekly clinic visits has been 99 percent. So far, none of Taylor’s 17

patients has discontinued treatment because of ongoing drug use or relapse. Five patients

are currently receiving therapy, and seven have completed 48 weeks of HCV treatment.

So far, one patient completing 48 weeks of treatment has achieved SVR.1,56

“This can be done with just two people,” Taylor says.1

us Statement on Management of Hepatitis C: 200

34
“I was reluctant at first but realized that

we can do a better job because of what

we already know about adherence and

supporting people. HIV providers are

already accustomed to working in

advance of peer reviewed data and using

treatment with low efficacy and lots of

toxicities. This doesn’t have to be cuttingedge; you, too, can have a coinfection

clinic.”147

—Kathleen Clanon, MD

Alameda County Medical Center

Oakland, CA
HCV Treatment: Estimating the Cost

Providers planning to offer care and treatment to coinfected patients must adequately plan

to meet client needs. Part of this planning means estimating the cost of care and

establishing mechanisms for paying for it. HIV service providers are operating in a world

with growing health care costs and growing HIV prevalence among the poor and

uninsured. Many HIV/HCV-coinfected patients are also poor and underserved, and most

rely on public support to meet care and treatment needs. Thus, providers must ask, Will

we be overwhelmed by the high costs of providing HCV care and treatment to coinfected

patients?

By any standard, HIV diagnostics and treatment are expensive, as are the interventions

for management of side effects, and providers must plan accordingly. Most Medicaid

programs include medications for HCV treatment in their formularies, and 17 State

AIDS Drug Assistance Programs (ADAPs) cover pegylated interferon and ribavirin (see

Access to HCV Treatment and ADAPs, p. 42). 

• The cost of a 30-day supply of ribavirin (based on a dose of 800 mg/day) ranges

from $500 to $1,100, depending on the manufacturer.*

• The cost of four once-weekly injections of pegylated interferon also varies by

product and ranges from $1,300 to $1,500 per month.

But as discussed in the preceding pages, most people living with HCV do not receive

treatment. It is hoped that improvements in access to high-quality, culturally competent

care services will increase the number of people who do receive HCV treatment. But

given the low utilization today of treatment—which is, by far, the most expensive

element of care for coinfected patients—the cost of providing comprehensive HCV

services will be less than prevalence data might suggest.

37

* All costs described in this section are based on prices listed at drugstore.com (accessed May 22, 2005).

BARRIERS AND KEY ISSUES

sens

5 .
38

Working With Patients Who Have Multiple Needs

Underserved coinfected patients may face many barriers to care, but many of those

barriers can be successfully addressed. For example, case management can link

coinfected patients with services that help mitigate the effects of poverty and lack of

health insurance. Users of illicit substances can be offered buprenorphine, methadone,

or referral to other drug treatment services. Patients with uncontrolled psychiatric

disorders can be offered the opportunity to work with a psychiatrist or a psychologist

as part of preparing for HCV treatment.

Concerns About Relapse to Active Drug Use and Reinfection

Clinicians and their patients have valid concerns about HCV treatment in active or

recovering illicit substance users. The side effects of interferon are similar to those of opiate

withdrawal, and patients have relapsed or reported cravings during HCV treatment.55,67,111,149

Clinicians have an opportunity to intervene and support such patients by providing

referrals to counseling, support groups, 12-step programs, and drug treatment or by

initiating therapy with methadone or buprenorphine rather than discontinuing treatment.

Some clinicians increase methadone dosage during HCV treatment to ameliorate cravings

and side effects of HCV treatment.67,150 One study reported that occasional drug use during

HCV treatment did not have a significant effect on response to HCV treatment111; another

continued HCV treatment for people who had relapsed to active drug use. No significant

difference in response rates to HCV treatment was found among drug-free patients, those

who relapsed before reinitiating methadone maintenance, and those who relapsed and did

not reinitiate methadone maintenance during HCV treatment.149 

The use of pain medication to manage the side effects of HCV treatment may be a

problem for patients who want to remain drug free. One clinician has developed an

innovative strategy: Patients sign a contract stipulating that they will get help in

discontinuing pain medication if needed.70 

Although reinfection with HCV after treatment has been a concern among clinicians

who are considering treating injection drug users, few cases of HCV reinfection have

been reported.151 Concern about reinfection with HCV and other blood-borne

pathogens can be addressed by providing counseling to reduce exposure to blood borne

pathogens, making referrals to drug treatment and other harm-reduction modalities

appropriate to the patient. 
Depression and HCV Treatment

Depression is a common comorbidity of HIV and HCV, and it is common among drug

users.152-157 Treating depression among PLWHA has improved adherence to antiretroviral

therapy158 and is a key management strategy for interferon-induced depression. 

Schaefer and colleagues reported that patients with a psychiatric history were

successfully treated for HCV when a pretreatment psychiatric evaluation and ongoing

multidisciplinary care were offered with HCV treatment.110 Some clinicians and patients

prefer to start antidepressants prior to HCV treatment, whereas others favor

antidepressant use only if it becomes necessary. Because treatment discontinuations

often occur due to psychiatric adverse events, it is sensible to avert such events when

possible by incorporating mental health care into HCV treatment planning.

Treatment Eligibility and Uptake

According to Practice Guidelines: Diagnosis, Management and Treatment of Hepatitis C,

from the American Association for the Study of Liver Diseases (AASLD), the

“characteristics of persons for whom therapy is currently contraindicated” are as

follows:

• Major, uncontrolled depressive illness

• Renal, heart, or lung transplantation recipient

• Autoimmune hepatitis or other condition known to be exacerbated by interferon

and ribavirin

• Untreated hyperthyroidism

• Pregnancy or inability or unwillingness to comply with adequate contraception

• Severe concurrent disease, such as severe hypertension, heart failure, significant

coronary artery disease, poorly controlled diabetes, or obstructive pulmonary

disease

• Age younger than 3 years old

• Known hypersensitivity to drugs used to treat HCV.

44p1155 

Providers should note that alcohol and drug use are not on this list. Many providers

establish their own eligibility criteria, which may or may not reflect treatment

guidelines. Some do not treat active drug or alcohol users, whereas others have used

adherence to medical appointments as an alternative criterion for active users.56,74,111 

39
Fleming and colleagues assessed HCV treatment eligibility in a cohort of 274 HIV/HCVcoinfected patients at an inner-city coinfection clinic. Only 33 (12 percent) were eligible

for treatment. Reasons for treatment ineligibility included the following issues:

• Nonadherence to clinic visits* 

• Active psychiatric disease*

• Ongoing injection drug or alcohol use*

• Advanced HIV disease*

• Decompensated liver disease

• Comorbid conditions (refractory anemia, renal or cardiac disease).

Only 21 of the 33 eligible patients initiated HCV treatment; 9 of the 21 patients

prematurely discontinued their treatment due to acute psychiatric illness (n=4), medical

complication (n=4), or loss to follow-up (n=1). Four patients were on HCV treatment

when the paper was written. Ultimately, of the eight patients who have completed

treatment, only two achieved SVR.55

In a study of treatment uptake among HCV mono- and coinfected veterans, Bini and

colleagues found that only 69 percent of coinfected patients who were eligible for HCV

treatment agreed to initiate treatment. The main reasons for treatment refusal were

worries about potential side effects of current therapy and desire to postpone treatment

until better options are available.159

Rauch and colleagues assessed eligibility for HCV treatment among 107 coinfected

patients in the Swiss HIV Cohort Study, using the following exclusion criteria:

• CD4 cell count of less than 250/mm3

• Anemia (hemoglobin level less than 11 g/dL)

• Cytopenia (neutrophil levels of less than 1.5.109 cells/L or a platelet count of less

than 70.109 cells/L)

• Liver diseases other than hepatitis C

• Decompensated liver disease

40

* Does not reflect AASLD treatment guidelines.
• Significant comorbidities (e.g., psychiatric disorders, seizures, cardiopulmonary

disease, immunologically mediated diseases)

• Uncontrolled addiction (illicit drug abuse or alcohol consumption of more than 40 g/day)

• Pregnancy

• Poor adherence to prescribed drugs (according to the physician).

Of the 107 patients, a total of 82 (77 percent) were ineligible for HCV treatment; most

(73 percent) had more than one ineligibility criterion, and 33 percent had more than

three. Of the 25 eligible candidates, 16 refused treatment because of fear of side effects

and concern about the duration of HCV therapy, and 4 with HCV genotype 1 declined

treatment because they had mild fibrosis. Only nine patients started HCV treatment.160

Treating Anemia and Neutropenia With Growth Factors

Two commonly reported hematologic toxicities of HCV treatment—anemia and

neutropenia—can be managed with growth factors or by dose reductions in ribavirin (for

anemia) or pegylated interferon (for neutropenia). Dose reduction may compromise

efficacy of therapy, however, and anemia may become treatment limiting, particularly for

HIV-positive patients. Growth factors are extremely expensive; a month’s supply of

treatment for anemia or neutropenia costs about $8,000. Some State ADAPs cover

growth factors, and they may be accessible through patient assistance programs (see

Chapter 7).

Despite the price of HCV treatment and growth factors, treating HCV with pegylated

interferon and ribavirin may be cost-effective in HIV/HCV coinfection. Two recent

models from Wong and colleagues assessed the economic value of HCV treatment in

HIV/HCV coinfection; the researchers based their calculations on the costs of treatment

in Spain and the United States.161,162 HCV treatment was determined to be cost-effective

in people with a Metavir biopsy score of F2, indicating moderate liver disease, and a

CD4 cell count of more than 200/mL. The cost-effectiveness of treatment increased for

coinfected patients with a CD4 cell count of more than 350/mL because their risk for

developing serious liver disease increased with longer life expectancy. The authors of the

studies assumed that HCV treatment would be discontinued at Week 12 in the event of

virological nonresponse. In the U.S. study, the cost of growth factors was included in

the analysis; nonetheless, treatment was still considered cost-effective. 

41
Access to HCV Treatment and ADAPs

Currently, 20 State ADAPs provide access to interferon; 17 States also cover pegylated

interferon and ribavirin. Many ADAPs provide access to at least some of the drugs needed

to manage side effects of HCV treatment along with vaccinations for HAV and HBV. Table

7 provides a list of which drugs are available in each State as of March 2006.

According to a survey from the National Association of State and Territorial AIDS

Directors (NASTAD), only 216 ADAP participants were being treated for HCV during

July 2004. The following reasons were cited for low treatment uptake: 

• Side effects of the medication (n=6)

• Patients and providers not aware that HCV treatment had recently been added to

the formulary (n=4)

• Providers not treating HCV or not trained in treating HCV (n=2)

• Provider requiring liver biopsy created a barrier to treatment (n=1)

• Client eligible for patient assistance programs (n=1) 

• Preferred drugs not included on the formulary (n=1; California’s ADAP does not

cover pegylated interferon).163

To offer HCV treatment in the context of limited resources, some ADAPs have developed

cost-containment measures for their HCV programs. For example, Maryland’s ADAP has

medical eligibility criteria stating that the patient’s HCV infection must, “in the

judgment of the clinician . . . be expected to be eradicated. . . . Treatment for histological

benefit alone is not eligible.” The physician must “treat to cure,” not to maintain the

patient’s current condition. Maryland’s ADAP also requires a liver biopsy for genotype

1. So far, HCV treatment uptake has been limited: Only $35,000 of the $2,000,000

dedicated to HCV treatment was used in 2005.164 The Washington State ADAP has

implemented a monthly copayment of $10.00 to $25.00, based on income, for all

formulary drugs; the copayment is collected at the pharmacy. 

State ADAP programs report that financial impact of adding HCV treatment to their

formularies has been minimal. As of September 2001, ADAP programs in New York,

California, Massachusetts, and New Jersey reported that they were spending less than 1

percent on HCV treatment.165

42
43

Other Contact

Information & Wait Lists

for ADAP (as of 3/06)

HAV & HBV

PEG-IFN RBV SSRIs EPO G-CSF Vaccine

Alabama (334) 206-5364 X Waiting list 

Alaska (907) 561-0453 X Waiting list 

Arizona (602) 364-3610 X X X X X X

Arkansas (501) 661-2118 Waiting list 

California (916) 449-5900 X X X

Covers standard IFN 

X X and consensus IFN* 

Colorado (303) 372-1713

Connecticut (800) 233-2503 X X X X X X

Delaware (302) 739-3032 X X X X X X Covers standard IFN

District of Columbia 

(202) 724-4900 X X X X Covers standard IFN

Florida (850) 245-4335 X X X

Georgia (404) 657-3129 X

Hawaii (808) 732-0026 X X X Waiting list

Idaho (208) 334-6657 Waiting list 

Illinois (800) 825-3518 Covers standard IFN

Indiana (317) 233-7450 X Waiting list 

Iowa (515) 242-5838 Waiting list

Kansas (785) 296-8701

Kentucky (800) 420-7431 X Waiting list

Louisiana (504) 568-7474

Maine (207) 287-5551

Table 7. State ADAP Coverage of HCV Treatment,Therapies for Side Effect Management, and HAB/HBV

Vaccines (as of March 2006)166,167

State and Information
44

Table 7 (cont’d). State ADAP Coverage of HCV Treatment,Therapies for Side Effect Management, and

HAB/HBV Vaccines (as of March 2006)166,167

State and Information

Maryland (800) 205-6308 X X X X X Covers standard IFN

Massachusetts 

XXX XX X

Covers all 

(800) 228-2714 FDA-approved drugs

Michigan (888) 826-6565 X X X X X X Covers standard IFN

Minnesota:Twin Cities 

metro area: (651) 582-1980 X

Other areas: (800) 657-3761

Mississippi (601) 960-7723 X X X

Missouri (573) 751-6439 X X

Montana (406) 444-4744 X X X Waiting list

Nebraska (402) 559-4673 X Waiting list

Nevada (775) 684-5952 X

New Hampshire

(603) 271-4502 or X X X

(800) 852-9945 x4502

New Jersey 

XXX XX X

Covers all 

(609) 984-6125 FDA-approved drugs

New Mexico (609) 984-6125 X X

New York (800) 542-2437 XXX XX XCovers HCV

diagnostic tests 

North Carolina (919) 715-3111 Waiting list

North Dakota (800) 472-2180 X X X X

Ohio (800) 777-4775 X X

Oklahoma (405) 271-4636

Other Contact

Information & Wait Lists

for ADAP (as of 3/06)

HAV & HBV

PEG-IFN RBV SSRIs EPO G-CSF Vaccine
State and Information

Other Contact

Information & Wait Lists

for ADAP (as of 3/06)

HAV & HBV

PEG-IFN RBV SSRIs EPO G-CSF Vaccine

45

Table 7 (cont’d). State ADAP Coverage of HCV Treatment,Therapies for Side Effect Management, and

HAB/HBV Vaccines (as of March 2006)166,167

Oregon (800) 805-2313 X X

Pennsylvania (800) 922-9384 X X

Puerto Rico (787) 763-4575 X X X X X Covers standard IFN

Rhode Island 

(401) 277-2320 x107 XXX Covers standard IFN

South Carolina (800) 856-9954 X

South Dakota (800) 592-1861 X

Tennessee (615) 741-7500 X X X X X Covers HCV genotype

Texas (800) 255-1090 Covers standard IFN

Utah (801) 538-6397

Vermont (802) 863-7253 X X X

Virginia (804) 864-8019 XX X X

Washington (800) 272-2437 X X X

Covers standard IFN,

HCV genotype, and

RNA tests

West Virginia (304) 558-2950 Waiting list

Wisconsin (800) 991-5532 X X X Covers standard IFN

Wyoming (307) 777-5800 X X

ADAP, AIDS Drug Assistance Program; EPO, epoetin-alfa (erythropoietin alfa); G-CSF, granulocyte-colony stimulating factor

(filagrastim); HAV, hepatitis A virus; HBV, hepatitis B virus; HCV, hepatitis C virus; PEG-IFN, pegylated interferon; RBV, ribavirin;

SSRIs, selective serotonin reuptake inhibitors.

Note: Formularies are subject to change.

* Consensus interferon (interferon alfacon-1) is a synthetic interferon that combines elements of several naturally produced

interferons. It is used to treat people who have not responded to previous HCV treatment.
[I]nitiating HCV treatment is almost

never an emergency; there’s no reason for

clinics to exceed what they feel they can

safely handle at any given time. A clinic

thinking about beginning an HCV

treatment program should assess its

resources, start slowly, and build capacity

as [staff] gain experience.145

—Michael Rigsby, MD 

Director, VA HIV and Hepatitis C

Program Office
47

CONCLUSION

sens

6 .

In the United States, HCV coinfection is a major contributor to morbidity and mortality

among PLWHA. Many coinfected people are from traditionally underserved, uninsured,

and hard-to-reach communities. HIV/HCV coinfection is linked with psychiatric

disorders, drug and alcohol dependence, poverty, homelessness, incarceration, and

race.168,169,170 Those barriers are amplified by limited access to HCV diagnostic testing and

treatment and restrictive eligibility criteria for treatment. The side effects and limited

efficacy of drug therapy in people with HIV/HCV coinfection create additional obstacles

for coinfected patients and their clinicians. Despite these challenges, HCV can be

successfully treated in PLWHA. 

CARE Act providers have already developed innovative models for delivering HCV care

and treatment.56,68,171 The CARE Act community has a wealth of experience in providing

culturally competent care and treatment to underserved individuals and diverse

communities. Providers have demonstrated the capacity to respond to changes in care

and treatment paradigms, patient demographics and, most significantly, decreasing

resources in the face of increasing need. Thus, the CARE Act community is ideally

suited to tackle HCV/HIV coinfection. 

Addressing coinfection seems daunting, but that is not the reality. Not all coinfected

patients require HCV treatment, and not every clinic will—or should—provide

comprehensive treatment services for coinfected patients. All HIV treatment providers,

however, should develop a supportive structure for coinfected patients, whether or not

they plan to deliver HCV drug treatment onsite. Specifically, providers should provide

screening, education, and support—services that can be coordinated and delivered by

clinic staff, case managers, and peers.56,57,67,68 Those services create the foundation for

referrals when onsite care is not feasible. 

Referring patients to off-site providers may seem like the best option for many

HIV/AIDS services providers. Many liver specialists, however, are not comfortable

treating HIV-positive people and do not have experience treating patients with multiple

psychosocial needs. Fortunately, experienced HIV care providers have many tools at
their disposal with which to increase their capacity to deliver HCV care and treatment,

including collaboration with culturally competent liver specialists, miniresidency

programs, journal clubs, consultation, and co-locating care.

In the coming years, we are likely to see significant progress in HCV treatment, echoing

the advent of HAART in HIV disease. Several therapies have entered clinical trials, and

early data are promising. Novel, potent oral agents may significantly shorten the course

of treatment and increase SVR rates. Yet, coinfected patients will not benefit from

upcoming improvements in HCV treatment unless care and treatment are delivered in

a supportive, multidisciplinary context. Coinfected patients require education and

integrated medical, mental health, and addiction treatment services.

As CARE Act providers have learned during more than 15 years of experience with HIV

disease, a strong infrastructure is crucial for successful delivery of care and treatment,

particularly for people with multiple diagnoses. Models for delivering HCV care must

be developed now—to meet current needs, anticipate therapeutic improvements, and

accommodate corresponding increases in HCV treatment uptake among people with

HIV/HCV coinfection. The CARE Act community has successfully reached underserved

PLWHA and increased the length and quality of their lives, and it has the skill and

expertise to do the same for coinfected persons. 

48
51

RESOURCES

sens

7 .

PATIENT ASSISTANCE PROGRAM INFORMATION

GENERAL

Helping Patients.org (Pharmaceutical Research and Manufacturers of America

[PhRMA]-sponsored Web site)

www.helpingpatients.org/intro.php 

Partnership for Prescription Assistance (PhRMA-sponsored Web site)

(888) 4PPA-NOW (888-477-2669). 

www.pparx.org/intro.php

Needy Meds.com (State and local programs; downloadable patient assistance

program applications) 

www.needymeds.com/programs/applications.shtml

HEPATITIS C TREATMENT

Roche (pegylated interferon alfa-2a [Pegasys] and Copegus [ribavirin])

For reimbursement information: 877-PEGASYS

www.pegasys.com/resources/pegassist.asp

Schering (pegylated interferon alfa-2b [PEG-Intron] and Rebetol [ribavirin])

The National Association of State and Territorial AIDS Directors and ScheringPlough have initiated the Commitment to Community Program. When HCV

treatment is not included in a State ADAP formulary, the Commitment to

Community Program will provide 1,500 slots for ADAP participants. This

program is administrated via Schering’s Commitment to Care Program: (800) 521-

7157.

http://pegintron.com/pegintron/commitment.html 

Valeant (interferon alfacon-1[Procrit])

www.infergen.com/wt/page/reimbursement

www.infergenaspine.com

1-888 move fwd (1-888 668-3393) 

GROWTH FACTORS

Ortho-Biotech (epoetin alfa [Procrit])

(800) 553-3851; fax (800) 987-5572

www.procrit.com/immunology/help/program.html
Amgen (filagrastim [Neupogen] and pegfilagrastim [Neulasta])

Reimbursement Connection (800) 272-9376

www.reimbursementconnection.com/neulasta/other_programs/

other_programs_services.jsp#safetynet_program

www.neulasta.com/professional/reimbursement/rc.jsp

RESOURCES FOR PROVIDERS

AIDS Education and Training Center Mountain Plains

HIV/Hepatitis C Center of Excellence

www.aids-ed.org/aidsetc?page=ab-01-11

American Association for the Study of Liver Diseases

Strader DB, Wright T, Thomas DL, Seeff LB; American Association for the Study of

Liver Diseases. Practice guideline: diagnosis, management, and treatment of

hepatitis C. Hepatology. 2004;39:1147-71. 

Australasian Society for HIV Medicine (ASHM)

Dore G, Sasadeusz J, eds. Coinfection—HIV and Viral Hepatitis: A Guide for Clinical

Management. Rev. ed. Darlinghurst, NSW, Australia: ASHM; 2005.

www.ashm.org.au/index.php?PageCode=1305&SD=10&DExpand=1 

Benson CA, Kaplan JE, Masur H, Pau A, Holmes KK. 

Treating opportunistic infections among HIV-infected adults and adolescents.

MMWR. 2004;53(RR15);1-112. 

www.cdc.gov/mmwr/preview/mmwrhtml/rr5315a1.htm 

Centers for Disease Control and Prevention 

Viral Hepatitis C (Web site)

www.cdc.gov/ncidod/diseases/hepatitis/c/index.htm 

Federal Bureau of Prisons 

Clinical Practice Guidelines for the Prevention and Treatment of Viral Hepatitis 

http://nicic.org/Library/016972 

Hepatitis Resource Network

Information on Management Algorithms, Educational Resources, and Clinical

Trials 

(Web site) 

www.h-r-n.org/ 

National Institutes of Health

Consensus Statement on Management of Hepatitis C: 2002 

http://consensus.nih.gov/cons/116/091202116cdc_statement.htm

52
U.S. Department of Health and Human Services

Guidelines for the Use of Antiretroviral Agents in HIV-Infected Adults and Adolescents.

2005. http://aidsinfo.nih.gov/guidelines/default_db2.asp?id=50 

U.S. Department of Veterans Affairs

VA National Hepatitis C Program 

http://hepatitis.va.gov/vahep?page=home-00-00 

• Management of Psychiatric and Substance Use Disorders in Patients With Hepatitis C: 

A Reference for Hepatitis C Care Providers

http://hepatitis.va.gov/vahep?page=tp03-gd-01 

• Treatment of Patients With Cirrhosis and Portal Hypertension, October 2003, v.1

http://hepatitis.va.gov/vahep?page=tp08-01-rr 

• Treatment Recommendations for Patients With Chronic Hepatitis C

http://hepatitis.va.gov/vahep?page=tp03-01-04-01 

• Clinician Tools: http://hepatitis.va.gov/vahep?page=tm-ct-00 

RESOURCES FOR PATIENTS

AIDS Community Research Initiative of America

Viral Hepatitis and HIV (Web site)

www.acria.org/treatment/treatment_edu_viral_hep.html 

Hepatitis C Support Project

HCV Advocate (Web site) 

www.hcvadvocate.org 

HIV and Hepatitis.com

www.hivandhepatitis.com

National AIDS Treatment Advocacy Project

www.natap.org 

Treatment Action Group

Swan T, Raymond D. Hepatitis C Virus and HIV/HCV Coinfection: A Critical Review of

Research and Treatment. New York: Treatment Action Group; 2004.

www.aidsinfonyc.org/tag/coinf/hcv2004

U.S. Department of Veterans Affairs

VA National Hepatitis C Program

Patient and Community Education (Web site)

http://hepatitis.va.gov/vahep?page=tm-ce-00 

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ACKNOWLEDGMENTS

The publisher wishes to express thanks to the following individuals:

Linda Anders, MPH

Kathleen Clanon, MD

Michael Harank, RN

Margaret Hoffman-Terry, MD

Carol Katz, NP

Marian Kerbleski, RN 

Alain Litwin, MD

Michael Rigsby, MD

Lynn Taylor, MD