Prevalence and correlates of HCV infection among methadone maintenance attendees: implications for HCV treatment

International Journal of Drug Policy 15 (2004) 93–101

Prevalence and correlates of HCV infection among methadone maintenance attendees: implications for HCV treatment Anita M. Loughlin a,∗ , Robert Schwartz b,1 , Steffanie A. Strathdee a,2 a

Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, 615 N. Wolfe Street, Baltimore, MD 21205, USA b Open Society Institute-Baltimore, 201 N. Charles Street, Baltimore, MD 21201 USA Received 15 April 2002; received in revised form 23 September 2003; accepted 9 October 2003

Abstract The HCV epidemic is thriving among often disadvantaged drug users. Current drug or alcohol use and underlying mental illness are contraindications for HCV treatment according to HCV treatment guidelines put forth by the U.S. National Institutes of Health. The authors determined the prevalence and the correlates of HCV infection among methadone maintenance treatment (MMT) participants in Baltimore, MD, USA and assessed the feasibility and public health importance of providing HCV treatment to drug users in this setting. Self-reported HCV infection and barriers to medical care were identified by an interviewer-administered survey. Individuals unaware of their HCV serostatus received an anti-HCV antibody EIA test. Correlates of HCV infection and barriers to HCV treatment were explored using logistic regression. To date, among 558 MMT participants, HCV prevalence was 64.7% and exceeded 90% among individuals reporting ever injecting drugs or sharing equipment. Factors independently associated with prevalent HCV infection included: increasing age (30–39 years: AOR: 0.82, 95% CI: 0.28, 2.42; 40–49 years: AOR: 3.42, 95% CI: 1.17, 9.99; 50+ years: AOR: 5.83, 95% CI: 1.70, 20.0); annual income of less than or equal to $5000 (AOR: 2.04, 95% CI: 1.23, 3.39); HIV infection (AOR: 2.11, 95% CI: 1.03, 4.36); prior HBV-infection, (AOR: 13.3, 95% CI: 6.53, 27.2); HBV immunisation (AOR: 3.60, 95% CI: 2.07, 6.27); years in MMT (AOR: 1.13, 95% CI: 1.03, 1.24); using drugs but not injecting in past month (AOR: 0.49 95% CI: 0.28, 0.87) and injecting drugs in past month (AOR: 6.5, 95% CI: 2.74, 15.4); and reporting a mental health problem (AOR: 2.86, 95% CI: 1.14, 7.20). Four barriers—lack of medical insurance, current alcohol or drug use and mental illness—would prevent 77% of the MMT participants from accessing HCV medical care and treatment according to criteria specified by NIH HCV treatment guidelines. MMT programmes represent an opportunity to counsel, screen, evaluate and provide ongoing HCV medical care and treatment. © 2003 Elsevier B.V. All rights reserved. Keywords: Hepatitis C; Drug users; Methadone; Treatment; Prevalence; Co-morbidity

Introduction Hepatitis C virus (HCV) infection is an urgent public health problem. The U.S. Centers for Disease Control (CDC) estimates that at least 60% of current infections in the U.S. are attributed to injection drug use (IDU) (Alter, Kruszon-Moran, & Nainan, 1999). 80 to 85 percent (Lauer & Walker, 2001; Thomas, Vlahov, & Solomon, 1995; Williams, 1999) of HCV-infected IDUs remain infected, asymptomatic, unaware of their HCV status, and capable of transmitting the virus and thus constitute the primary reservoir for sustaining the epidemic. HCV is four times more ∗

Corresponding author. Tel.: +1-410-955-8175; fax: +1-410-955-1383. E-mail addresses: [email protected] (A.M. Loughlin), [email protected] (R. Schwartz), [email protected] (S.A. Strathdee). 1 Tel: +1-410-234-1091; fax: +1-410-234-2816. 2 Tel: +1-410-614-4255; fax: +1-410-955-1383. 0955-3959/$ – see front matter © 2003 Elsevier B.V. All rights reserved. doi:10.1016/j.drugpo.2003.10.005

prevalent than HIV infection, with an estimated 2.7 million chronic infections in the United States (Alter et al., 1999) and approximately 170 million infections globally (WHO, 1999). Worldwide, HCV prevalence among IDU ranges from 50 to 90% (Apichartpiyakul et al., 1999; Bobkov, Samokhvalov, & Lvov, 2001; Johnson, Fisher, & Fenaughtly, 1998; Lamden, Kennedy, & Beeching, 1998; Mansson, Moestrup, & Nordenfelt, 2000; Smyth, Keenan, & O’Connor, 1999; Taylor et al., 2000). Among drug using populations, HCV incidence ranges between 13 and 22 per 100 person-years, (Brunton, Kemp, & Raynel, 2000; Crofts, Nigro, & Oman, 1997; Garfein, Doherty, Monterroso, 1998; van Beek, Dwyer, & Dore, 1998) and is highest among the susceptible pool of young IDUs. One Australian study has demonstrated incidence as high as 75.6 per 100 person-years for injectors aged 20 years and younger (van Beek et al., 1998). Among the chronically HCV-infected, approximately 70%

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(Poynard, Bedossa, & Opolon, 1997) will develop chronic hepatitis and 10% will develop cirrhosis within 20 years (Rodger et al., 2000). The incidence of hepatocellular carcinoma is one to 4% per year (Lauer & Walker, 2001). HCV induced end-stage liver disease accounts for most of the liver transplants and results in 8000–10,000 annual deaths in the United States (CDC, 1998a). The morbidity and mortality secondary to HCV infection is expected to triple over the next two decades (CDC, 1998a; Williams, 1999). Parenteral exposure transmits HCV efficiently; HCV is 10 times more infectious than HIV (Gerberging, 1995). The high prevalence of HCV infection and continued sharing of needles and injection equipment among IDUs leads to continued opportunities for exposure. In some U.S. settings, an estimated 80% of IDUs acquire their infection within 2 years from initiating injection drug use (Alter et al., 1999; Garfein, Vlahov & Galai, 1996; Thomas et al., 1995). Thus, a majority of IDUs may become infected prior to seeking drug treatment or despite use of existing needle exchange programmes (Brunton et al., 2000; Crofts et al., 1997; Hagan, McGough, & Thiede, 1999; Lamden, Kennedy, & Beeching, 1998; Mansson et al., 2000; Smyth, Keenan, & O’Connor, 1999; Taylor et al., 2000; van Beek et al., 1998). Prevention strategies include preventing HCV transmission, which has proven to be difficult, and reducing risk of advanced liver disease. The fact that only half of HCV-infected individuals are aware of their infection (Gordon, 1999), necessitates improved counseling and testing strategies as well as accessible HCV medical care (CDC, 1998a). HCV screening of high-risk populations has shown to be cost effective (Gordon, 1999), yet in the U.S. there is no widely accessible and affordable screening and confirmatory HCV testing and counseling procedure. Neither are there governmental financial provisions for the initial medical evaluation, ongoing care, counseling, hepatitis B or hepatitis A immunisations, or HCV treatment. Drug or alcohol addiction alone no longer qualifies individuals for Medicaid, a jointly funded U.S. federal-state health insurance programme. For a large number of HCV-infected drug users, medical insurance coverage therefore may be a principal barrier to appropriate HCV medical care. Considerable controversy has risen about the management of chronic HCV infection, due to potential rare but grave side-effects of combination interferon alpha (INF␣) based and ribavirin antiviral treatment. The most common side-effect are “flu-like” symptoms (Lauer & Walker, 2001); 1–30% of patients develop a more serious event, such as, emotional lability and depression, induction of autoimmune disorder, or a hematological abnormality (Lauer & Walker, 2001). Exacerbation of underlying psychiatric disease, an expected INF␣ complication, and the rarer risk of suicide or drug use relapse are concerns raised when considering treating active or recovering drug users (Lauer & Walker, 2001). A 1997 U.S. National Institutes of Health (NIH) consensus statement on the management of Hepatitis C infec-

tion (NIH, 1997) did not recommend HCV treatment for individuals with ongoing use of alcohol or drugs, history of psychiatric illness, or those with other contraindications (e.g. advanced age, decompensated liver disease, or severe co-morbidity) (Davis & Rodrigue, 2001; NIH, 1997). These guidelines were adopted as national and international recommendations (CDC, 1998a; EASL, 1999). Unfortunately, some health care providers may have interpreted the NIH guidelines to exclude HCV-infected drug users enrolled in methadone maintenance treatment (MMT) from these possibly live-saving HCV therapies (Stephenson, 2001). Poor adherence to treatment, treatment side-effects and risk of re-infection are reasons that may or may not warrant the withholding of HCV antiviral treatment from drug users (Edlin, Seal, & Lorvick, 2001). Edlin et. al. questioned the evidence of each potential reason for withholding HCV treatment. They argued that drug users—especially those in recovery—can achieve good adherence to medication. They state that contraindications such as depression can be treated and side effects carefully monitored in a supportive medical care environment. Risk of re-infection is low among IDUs who are in treatment or no longer injecting, and increased access to clean needles via needle exchange or prescription can further reduce this risk. Edlin et al. also argue that antiviral treatment options should be available to all patients and decisions to treat be based upon individual characteristics. They conclude that to withhold treatment solely on the basis of drug use is unethical. Baltimore City, the largest city in Maryland, is home to an estimated 38,000 IDUs (Beilenson, 1997). The Baltimore Substance Abuse Systems, the city’s substance abuse authority, has embarked on an aggressive expansion and enhancement of its treatment system. There are 12,000 publicly funded MMT slots that serve about 27,000 drug users per year. As part of the enhancement of the treatment system, the city has targeted integrated ancillary services (such as medical care) within the drug treatment centres. This ongoing study, is part of the city’s enhancement strategy, aims to assess barriers to medical care and estimate the prevalence of blood borne infections, including HCV, among MMT participants. Medical care and treatment of HCV infection is an important unmet health care need among drug users in Baltimore and elsewhere. In anticipation that revisions to the NIH consensus guidelines for HCV therapy will be considered, it is important to begin to evaluate of the effectiveness and safety of HCV antiviral treatment among drug users enrolled in MMT as the next step. Such studies will provide important insights for HCV treatment of active drug users. In this study, we describe the burden of HCV infection in an urban, U.S., MMT population, its associated co-morbidities, correlates of infection and barriers to HCV diagnosis and treatment. Lastly, we estimate the proportion of the MMT population that could access HCV medical care and receive HCV treatment under the existing guidelines.

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Methods

Statistical analysis

Study population

Statistical analyses were performed using SAS 6.12 software (SAS institute, Cary, NC). Prevalent HCV infections included all participants who self-reported having been diagnosed as HCV-infected, as well as those who were diagnosed as anti-HCV antibody positive through the study’s serologic screening. We determined the most conservative estimate of chronic HCV infection prevalence, assuming that 80% of all HCV infections (self-reported or newly detected anti-HCV antibody) were chronic (Lauer & Walker, 2001; Thomas et al., 1995; Williams, 1999). Individuals who were unaware of their HCV serostatus and who refused HCV testing were excluded from the analysis. To describe the general characteristics of this MMT population, frequencies were calculated for categorical variables and means were calculated for continuous variables. To determine univariate associations, t-tests, chi-square tests, prevalence odd ratios (OR) and 95% confidence intervals (CI) were performed. Stratified analyses and multivariate logistic regression models were used to identify factors independently associated with prevalent HCV infection, assessing both confounding and interaction. Adjusted prevalence odds ratios (AOR) and 95% CI from the final logistic regression model were reported. A substantial number of HCV cases were aware of their HCV infection. To compare known HCV cases to newly tested anti-HCV antibody positive cases both single variable differences and multivariate associations were assessed. Only the AOR and 95% CI from the multivariate logistic regression model from this comparison are presented. The main analyses identified co-factors for HCV infection and barriers to HCV treatment. For these analyses, the HCV-infected group included both the self-reported HCV-infected and anti-HCV antibody positive participants, and HCV-infected individuals were compared to HCV-uninfected individuals (Tables 1 and 2). Finally, we determined the proportion of MMT participants who could theoretically access HCV medical care and who qualify to receive HCV antiviral treatment based upon medical insurance needs and specific contraindications outlined by the 1997 NIH guidelines for HCV therapy (NIH, 1997).

Between July and November 2001, the study had enrolled 594 individuals attending three publicly funded MMT programmes. All participants were required to be at least 18 years old and receiving methadone treatment. Participation was voluntary and individuals could enroll if they had been diagnosed with HCV infection, previously. Prior to enrollment participants were given information about the study and signed a consent form. The Johns Hopkins School of Public Health’s Committee on Human Research approved the study. Study methods An initial interviewer-administered interview collected data pertaining to demographic, socioeconomic, medical insurance status, self-reported health history for the previous 12 months, perceived barriers to medical care, current alcohol and drug use, history of HCV, HIV, and HBV infection and the HBV and HAV immunisation acceptability. Health education on HCV transmission risk-reduction and prevention, as well as medical care and treatment options were provided. Due to financial constraints, HCV antibody screening was limited to participants with unknown HCV status, and confirmation of chronic infection by HCV RNA PCR could not be conducted. All participants who consented to be tested received preand post-test counseling and were tested for HIV, HBV and HCV infection. Individuals who received positive HCV tests results or who self reported having an HCV diagnosis were given a referral for medical care, and were offered a HBV immunisation series if required and an HAV immunisation series if they had been HCV-infected. Participants received 10 dollars for completing the baseline visit and an additional 10 dollars when they returned to receive their test results. Laboratory methods The Maryland State Health Department Laboratory completed all serology. An anti-HCV enzyme immunoassay (EIA) identified the presence of anti-HCV antibodies. The assay has high sensitivity (95%) and when used in high-risk populations such as IDUs, has high specificity (>95%) (Fried, 1999; Gretch, 1997). The positive predictive value in IDU populations is above 90% (Fried, 1999) and is expected to be equally high among an MMT population. HIV infection was confirmed by repeat anti-HIV EIA and Western Blot analysis. HBV status was categorised as (1) active infection, based on presence of HBV surface antigen; (2) past infection, based on presence of antibodies to core protein and the absence of HBV surface antigen, and (3) vaccinated, based on presence of antibody to HBV surface antigen only.

Results Of 594 participants, only 36 (6.1%) were neither tested nor self-reported having had HCV infection and were excluded from this analysis. These 36 individuals did not differ by age, sex, gender, income or insurance status from the 558 (94%) with known HCV status. The study population was 42.5% male, 84.8% African American and the mean age of the study population was 41.2 years (range 19–67 years) (Table 1). Over half (56.6%) had an annual income of 5000 dollars or less; 45.7% had

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Table 1 Correlates of HCV infection among current MMT participants Characteristics

Total MMT population

HCV status Infected N

Population Male genderb African Americanc Age (years) mean [S.D.] Age groups (years) <30 30–39 40–49 50+ Annual income <$5000 $5001–$10,000 $10001+ Income Source Paid salary Public assistance Other Employed in last 30 days Full time Part time/occasional Not working Type of medical insurance Private insurance/HMO Medicare/veterans administration Medicaid/medical assistance No insurance Self reported barriers to medical care Problem with addiction/drug use Own mental/emotional state Medical condition/disability HIV statusd Self-reported positive Tested positive Negative HBV statuse Active infection Previous infection Vaccinated Negative Health conditions had in past 12 months Heart problem/hypertension Diabetes Mental health problem HCV risk factors Ever injected drugs Ever shared/syringes Ever sex with an injector Ever trade sex Entered MMT >1 time Years in MMT Mean [S.D.] Drank alcohol in past month Average days per week have alcohol Less than once a week 1–2 days per week 3–4 days per week 5–6 days per week Everyday Used drugs in the past month Average days per week using drugs Less than once a week 1–2 days per week

558 236 (42.3) 473 (84.8) 42.1 [7.9]

376 178 (47.3) 304 (80.9) 44.1 [7.5]

29 169 273 87

14 72 215 75

(5.2) (30.3) (48.9) (15.6)

(3.7) (19.2) (57.8) (20.0)

(%)a

OR (95% CI) Negative N 182 58 (31.9) 169 (92.9) 37.8 [6.9] 15 97 58 12

(%)a 1.92 (1.33, 2.79) 0.34 (0.18, 0.64) 1.13 (1.09, 1.16)

(8.2) (53.3) (31.9) (6.6)

Reference 0.80 (0.36, 1.75) 3.97 (1.81, 8.70) 6.69 (2.59, 17.3)

316 (56.6) 125 (22.4) 117 (21.0)

227 (60.4) 78 (20.7) 71 (18.9)

89 (48.9) 47 (25.8) 46 (25.3)

1.65 (1.06, 2.58) 1.08 (0.64, 1.81) Reference

181 (32.5) 319 (57.3) 57 (10.2)

104 (27.7) 231 (61.6) 40 (10.7)

77 (42.3) 88 (48.4) 17 (9.3)

Reference 1.94 (1.32, 2.85) 1.74 (0.92, 3.30)

105 (18.8) 90 (16.1) 363 (65.1)

61 (16.2) 52 (13.8) 263 (69.9)

44 (24.2) 38 (20.9) 100 (54.9)

Reference 0.99 (0.56, 1.75) 1.90 (1.21, 2.98)

141 29 150 227

87 22 109 149

(44.1) (9.1) (46.9) (41.4)

(39.9) (10.1) (50) (40.5)

54 7 41 78

(52.9) (6.9) (40.2) (43.3)

Reference 1.95 (0.78, 4.87) 1.65 (1.01, 2.71) 1.18 (0.76, 1.82)

74 (13.3) 29 (5.2) 21 (3.8)

58 (15.4) 25 (6.6) 19 (5.1)

16 (8.8) 4 (2.2) 2 (1.1)

1.91 (1.06, 3.42) 3.19 (1.09, 9.30) 4.82 (1.11, 20.9)

91 (16.3) 16 (2.9) 409 (73.3)

79 (21.0) 13 (3.5) 252 (67.0)

12 (6.6) 3 (1.6) 157 (86.3)

4.1 (2.17, 7.77) 2.7 (0.76, 9.62) Reference

14 161 148 199

10 151 105 76

4 10 43 123

(2.2) (5.5) (23.6) (67.6)

4.05 (1.23, 13.4) 24.4 (12.1, 49.3) 3.95 (2.51, 6.23) Reference

90 (23.9) 27 (7.2) 51 (13.6)

21 (11.5) 5 (2.7) 11 (6.0)

2.43 (1.46, 4.06) 2.75 (1.04, 7.25) 2.45 (1.24, 4.82)

383 (68.6) 288 (51.6) 354 (63.4) 136 (24.4) 187 (33.9) 2.79 [3.6] 198 (35.5)

349 (92.8) 272 (72.3) 287 (76.3) 104 (27.7) 268 (72.4) 3.2 [4.1] 133 (35.5)

34 (18.7) 16 (8.8) 67 (36.8) 32 (17.6) 84 (46.4) 1.9 [2.1] 65 (35.7)

56.3 18.1 5.58 1.78 2.25 1.16 0.99

(32.7, (10.2, (3.79, (1.14, (1.56, (1.07, (0.68,

96.6) 32.4) 8.21) 2.77) 3.26) 1.26) 1.43)

49 86 27 6 29 240

30 55 21 5 21 159

19 31 6 1 8 81

Reference 1.12 (0.55, 2.22 (0.76, 3.17 (0.34, 1.66 (0.61, 0.90 (0.63,

2.32) 6.49) 29.2) 4.50) 1.29)

(2.5) (28.9) (26.5) (35.7)

111 (19.9) 32 (5.7) 62 (11.1)

(24.9) (43.7) (13.7) (3.0) (14.7) (43.2)

70 (29.0) 103 (42.7)

(2.7) (40.2) (27.9) (20.2)

(22.7) (41.7) (15.9) (3.8) (15.9) (42.4)

42 (26.6) 65 (41.1)

(29.2) (47.7) (9.2) (1.5) (12.3) (45.0)

28 (33.7) 38 (45.8)

Reference 1.14 (0.61, 2.13)

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Table 1 (Continued ) Characteristics

Total MMT population

HCV status Infected N

3–4 days per week 5–6 days per week Everyday Injected drugs in past month

23 9 36 101

(9.5) (3.7) (14.9) (18.2)

14 9 28 91

(8.9) (5.7) (17.7) (24.3)

(%)a

OR (95% CI) Negative N 9 0 8 10

(10.8) (0.0) (9.6) (5.6)

(%)a 1.04 (0.40, 2.72) – 2.33 (0.93, 5.85) 5.45 (2.76, 10.8)

a

Number (percent) unless designated as mean (S.D.). Compared to female. c Compared to White (non-Hispanic) race. d Unknown HIV status: total population 42 (7.5%), HCV-infected 32 (8.5%), HCV-uninfected 10 (5.5%). e Unknown HBV status: total population 36(6.5%), HCV-infected 34 (9.0%), HCV-uninfected 2 (1.1%). b

less than a high school education; 65.1% were not currently employed, 57.3% were receiving public assistance or social security income and 95.0% reported living in a house or apartment. Three hundred and twenty-one (58.6%) reported having medical insurance. Of the 558 study participants, 156 (28.0%) self-reported their HCV infection and 402 (72.0%) were unaware of their infection and agreed to be tested. Of these 402 individuals, 220 (54.7%) were anti-HCV antibody positive and 182 (45.3%) were anti-HCV antibody negative. Combining the individuals who self-reported HCV infection and newly diagnosed HCV infections, a total of 367 (67.4%) individuals had been infected with HCV. Therefore, the prevalence of chronic HCV infection among the MMT participants was at least 53.9%, given that 80% of all HCV-infected individuals remain chronically infected. Among the 383 (68.6%) individuals who reported ever having injected drugs, 349 (91.1%) had been infected with HCV. Not surprisingly, of the 288 (51.6%) individuals who reported ever sharing nee-

dles or injecting paraphernalia, 94.4% had been infected with HCV. Differences between individuals with known HCV infection and newly diagnosed HCV infection Individuals with known HCV infection did not differ from individuals with newly diagnosed HCV infection by gender, age, education, income, employment or medical insurance status, or current drug and alcohol use status. In a multivariate model, compared to individuals who were newly diagnosed anti-HCV antibody positive in this study, participants with known HCV infection were less likely to be African American (AOR: 0.33, 95% CI: 0.18, 0.61), were more likely to be receiving public assistance (AOR: 2.07, 95% CI: 1.16, 3.69), to be knowingly HIV-infected (AOR: 1.87, 95% CI: 1.87, 2.07), and to report having a mental health problem in the past year (AOR: 1.99, 95% CI: 1.00, 3.96). Demographic and socioeconomic correlates of HCV infection

Table 2 Correlates of HCV infection among MMT participants: Multivariate logistic regression model Characteristic Age group (years by decade)

AOR (95% CI) –

Age groups (years) <30 30–39 40–49 50+

Reference 0.82 (0.28, 2.42) 3.42 (1.17, 9.99) 5.83 (1.70, 20.0)

Annual income <$5000 $5001+

2.04 (1.23, 3.39) Reference

HIV infection

2.11 (1.03, 4.36)

Comparing demographic differences between HCVinfected and non-infected participants, HCV-infected individuals were more likely to be older (mean age: 44.1 years versus 37.8 years, P < 0.001) and male (47.3% versus 31.9%, P = 0.001). White participants were three times more likely to be HCV-infected compared to African Americans or those of other races (OR: 2.92; 95% CI: 1.57, 5.44). There were no differences between HCV-infected and non-infected participants with respect to level of education or housing status. Compared to HCV-uninfected individuals, HCV-infected individuals were approximately 1.5–2 times more likely to be earning <5000 dollars per year, to be unemployed, to be receiving public assistance or social security income, and to have Medicaid health insurance (Table 1).

HBV status Previous infection Vaccinated Negative

13.3 (6.53, 27.2) 3.60 (2.07, 6.27) Reference

Health history and HCV infection risk factors

Time in methadone (years) Abstaining from drug use Injected drugs in past month Mental health problem in past year

1.13 (1.03, 1.24) 2.04 (1.16, 3.56) 13.1 (5.17, 33.2) 2.62 (1.04, 6.58)

Of the 376 HCV-infected individuals, 92 (24.5%) were HIV infected, compared to 15 (8.2%) of individuals without HCV infection (P = 0.001). Compared to HCV-uninfected individuals, HCV-infected individuals were four times more

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likely to self-report their HIV infection (Table 1). Nearly half (42.9%) of the HCV-infected individuals had been HBV infected compared to 14 (8.2%) of HCV-uninfected individuals (P < 0.001). HCV-infected participants were 4 times more likely to have received a HBV vaccine then HCV-uninfected individuals (Table 1). Of the 156 individuals who self-reported their HCV infection, only 72 participants (46.2%) reported having a liver or kidney problem in the past year. Individuals reporting heart disease/hypertension, diabetes or a mental health problem were more than twice as likely to be HCV infected. As expected, compared to HCV-uninfected individuals, HCV-infected individuals were 56 times more likely to report ever injecting drugs, 18 times more likely to have ever shared needles or injecting equipment, 6 times more likely to have ever had sex with an IDU, and approximately twice as likely to have ever traded sex for drugs or money (Table 1). Methadone treatment, continued alcohol and drug use and mental health problems HCV-infected individuals were two times more likely to have previously been enrolled in a MMT programme (Table 1). On average, HCV-infected individuals had attended MMT for a longer period then HCV-uninfected individuals (mean number years in MMT: 3.20 versus 1.96 years, respectively, P < 0.001). The odds of being HCV-infected increased with the number of years a participant had attended MMT (Table 1). Similar proportions of HCV-infected and HCV-uninfected participants reported drinking alcohol (35.5% versus 35.7%, respectively, P = 0.78), and the number of days per week alcohol was consumed did not differ by HCV-serostatus. Similarly, the reporting of any drug use by HCV-infected and HCV-uninfected individuals did not differ (42.4% versus 45.0% respectively, P = 0.56), nor did these groups differ in terms of the number of days per week drugs were used. Conversely, HCV-infected individuals were 5.5 times more likely to have reported having had injected drugs in the past month compared to non-infected participants (24.3% versus 5.6%, P = 0.001).

Barriers to HCV treatment HCV-infected *

N 376

Percentage of Total HCV cases 100.0%

Have Medical Insurance †

219

58.2%

Abstaining from Drug Use

131

34.8%

Abstaining from Alcohol

99

26.3%

When asked about barriers to medical care, compared to HCV-uninfected individuals, HCV-infected individuals were more likely to identify problems with their drug use or addiction (OR: 1.91; 95% CI: 1.06, 3.42); their own mental or emotional state (OR: 3.19; 95% CI: 1.09, 9.30) and having another medical condition or disability (OR: 4.82, 95% CI: 1.11, 20.9). Correlates for HCV infection In a multivariate model, co-factors consistently associated with prevalent HCV infection among this MMT population were increasing decade of age, annual income of $5000 or less, HIV infection, prior HBV-infection, HBV immunisation, years in MMT, injecting drugs in the past month, and reporting a mental health problem (Table 2). HBV immune status and HBV and HAV immunisation acceptability Among the study participants, 26.5% of adults were vaccinated, 31.4% had been HBV infected, and 35.7% were not vaccinated and remain susceptible to infection. When asked, 536 (96.1%) participants stated that they would take both a HBV vaccine and HAV vaccine, if they had not already been infected. Accessibility of HCV medical care and treatment for HCV-infected MMT participants As depicted in Fig. 1, taking into account factors that would affect accessibility to HCV care, of the 376 HCV-infected individuals, only 219 (58.2%) had medical insurance that would enable them to seek care for their HCV infection. Applying criteria specified as contraindications for HCV therapy according to the NIH consensus guidelines for HCV therapy, 131 of the remaining 219 participants (59.8%) reported currently abstaining from drug use; of these 99 were also abstaining from alcohol use. Of the 99 remaining individuals, 13 (13%) reported having

Proportion of the HCV MMT population with insurance and no contraindication for treatment according to 1997 NIH Consensus Guidelines. Self-reported HCV infection Private Insurance/HMO Not using drugs Not using alcohol

MC

Anti-HCV antibody positive Medicaid/Medical Assistance Excluded from HCV treatment (77.1%)

No self-reported No Self Reported 86 22.9% mental health problem Mental Health Problem * 41.5% Self reported their HCV infection and 58.5% Recently tested positive for anti-HCV antibody † 40.0% Insured have Private Insurance; 10.0% have Medicare (MC) or Veterans Administration Insurance and 50.0% reporting having Medicaid or medical assistance Fig. 1. Proportion of HCV-infected MMTP participants “eligible” for HCV treatment.

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a mental health problem in the past year, which may disqualify them from HCV treatment. Therefore, of the 376 HCV-infected individuals, only 86 (22.9%) could access health care and be considered eligible for HCV treatment in accordance with 1997 NIH guidelines (NIH, 1997).

Discussion The HCV epidemic is thriving among drug users, a population that is traditionally disadvantaged and marginalised from the medical care system. The unmet health care needs reflected in our HCV-infected MMT population are similar to needs of the greater drug using communities in the United States and developed countries. At diagnosis, the population is older and has probably been infected for many years, and some—but not all—continue to use drugs and drink alcohol. Some suffer from both chronic physical and mental health illness. They are mostly underemployed, underinsured, and are often an ethnic or racial minority. Injection drug use or sharing injecting equipment has placed them at risk of HCV, HBV and HIV infection. In this study, 67.6% of MMT clients had been infected with HCV. However, HCV prevalence was 91.1% among clients who reported a history of injection drug use, which is consistent with earlier reports (Apichartpiyakul et al., 1999; Bobkov et al., 2001; Mansson et al., 2000). All HCV-infected individuals require some medical care—to determine if their infection remains chronic, to evaluate the extent of their liver disease, to monitor progression of their infection, and to be treated, if necessary. Continued risk reduction messages, health education specific to their infection, receipt of necessary vaccines, and alcohol abuse counseling are also important benefits of medical care among HCV-infected drug users. Knowledge of their HCV infection may facilitate enduring substance abuse treatment attendance, reduction of unsafe injecting or any drug use, and may motivate individuals to seek alcohol dependence treatment. Unfortunately, in the U.S., obtaining a HCV test and confirmation of their HCV infection remains a barrier to on going HCV medical care. Seventy-four percent of our study population did not know their HCV status. While HCV testing is recommended and shown to be cost effective among high-risk populations (Gordon, 1999), and while the infrastructure for screening, counseling and referral is available at HIV testing sites, STD clinics (Gunn et al., 2001), needle exchange sites, and substance abuse treatment sites, the implementation of routine HCV testing remains an unmet health care need among injection drug users. Providing hepatitis A and hepatitis B vaccine to HCV-infected adults protects patients from potential liver damaging infections that could hasten the progression of their liver disease (CDC, 1998a). An effective and preventative hepatitis B vaccine has been available since 1986. It is encouraging that HCV-infected individuals were three times

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more likely to have received HBV vaccine compared to uninfected individuals, but in general HBV vaccine coverage was unacceptably low. In addition to being vulnerable to HBV infection through injection drug use or sexual activity, HCV-infected drug users are at increased risk of fulminate HAV infection (CDC, 1998b). Our data suggests that MMT clients would receive both HBV and HAV vaccines, this in turn would help reduce the public health burden of these infections and prevent the hastening of HCV disease. HCV treatment may avert future cases of cirrhosis, hepatocellular carcinoma, and end-stage liver disease, as well as potentially reducing HCV transmission risks by reducing HCV viral load or eradicating HCV infection through successful treatment. The treatment of recovering and active drug users, the greatest reservoir of HCV disease, must be considered to diminish the overall HCV disease burden. However, considerable financial and social barriers set drug users apart from traditional consumers of medical care. Although HCV treatment concludes within one year, the necessary medications and intensive monitoring of liver function and viral load are expensive (Wong, 1999). In our MMT population, greater than 40% of HCV-infected individuals had no health insurance or had annual incomes below the poverty level. It is likely that treating HCV-infected individuals in MMT populations or who are actively using drugs would incur additional costs, such as, ongoing adherence counseling, evaluation and treatment of psychiatric disorders, case-management and outreach efforts. A second barrier to HCV treatment among active and former drug users is mental illness, specifically depression. Clinical depression exists in 25–50% of the drug using population (Davis & Rodrigue, 2001; Grassi, Mondardini, & Pavanati, 2001; Knowlton, Hoover, & Chung, 2001a; Knowlton, Latkin, & Schroeder, 2001b; O’Connor, Selwyn, & Schottenfeld, 1994). Providers are concerned with both the influence of depression on adherence, and the rare risks of worsening depression and suicide resulting from interferon treatment (Davis & Rodrigue, 2001; NIH, 1997). In our study, only 11% of the population reported having a mental illness in the past year. Although we concede that self-reported measures of mental illness may underestimate pre-existing psychiatric disease in this population, it will be worthwhile to study the extent to which sub-clinical levels of depression or depression that is successfully managed through treatment is a real rather than a perceived contraindication to HCV therapy. Substance use is an obstacle to both medical care and antiviral treatment (Celentano, Galai, & Seth, 2001; Celentano, Vlahov, & Cohn, 1998; Knowlton et al., 2001a; Strathdee, Palepu, & Cornelisse, 1998). On average, our population has been in a MMT programme for three years and over half of our study population reported abstaining from drugs and alcohol use. Furthermore, the majority of current users enrolled in the MMT programmes we studied were not daily users. As is the case with HIV antiretroviral therapy (Antela et al., 1997; Celentano et al., 2001; Strathdee et al., 1998),

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MMT can be an important gateway to HCV treatment. The infrastructure of MMT sites also provide an important opportunity for the provision of HCV treatment, monitoring adherence and monitoring and treating side-effects. We acknowledge limitations in our study. First, we studied a self-selected volunteer population of MMT participants. Individuals with known HCV infection or symptoms may have selected to enroll or to remain out of the study, thus we cannot ensure that our estimate of HCV prevalence is an under- or over-estimate. Our measures of HCV infection include self-report and anti-HCV antibody screening, neither of which is a direct measure of chronic HCV infection or severity of liver disease indicative of treatment; nevertheless, we conservatively assumed that 80% of HCV infections represented chronic infections (Lauer & Walker, 2001; Thomas et al., 1995; Williams, 1999) that would require treatment. Misclassification of HCV infection may have resulted by the inclusion of self-reported HCV cases. In our study, 28 participants who self-reported there HCV diagnosis received an HCV antibody test; all had positive tests for HCV antibody. All information, including alcohol and drug use, medical history and mental illness was self-reported. Drug and alcohol use is often underreported due to inclination of interviewees to give socially desirable responses (Latkin, Vlahov, & Anthony, 1993). Likewise, self-reported medical histories and mental illness may have been underestimated. Despite these limitations, we have aimed to estimate the burden of HCV infection among MMT clients in Baltimore and assessed barriers to appropriate medical care. We illustrate that just four barriers to medical care—health insurance, continued drug or alcohol use, and underlying mental illness would prohibit 77% of our HCV-infected, MMT population from receiving HCV medical care, preventive care and effective HCV treatment. Programmes such as substance abuse treatment, needle exchange and outreach are important components to a HCV prevention plan, and such venues may facilitate entry into medical care. HCV medical care and treatment remains an unmet health care need among active and recovered drug users. Without subsidy, this population will continue to have limited access to HCV testing, preventive HBV and HAV vaccines, as well as HCV treatment and care. Through government aid, provisions in Medicaid for HIV health care, drug assistance programmes, and Ryan White funding in the United States-HIV medical care, treatment and services are more accessible to HIV infected individuals. This accessibility extends to active and recovering drug users. As with HIV, it is unlikely that HCV treatment will be widely available to individuals in the developing world without governmental supplementation of costs. Our data highlight the need to evaluate strategies for treating drug-using populations with chronic medical problems. MMT programmes offer a variety of services—medical care and case-management, along with substance abuse counseling and treatment. Landmark studies have demonstrated that implementation of HCV treatment within the

substance abuse treatment is feasible, that depression and other side-effects can be treated, and that the treatment of HCV-infected drug users can be both can be both safe and effective (Backmund, Meyer, & VonZielonka, 2001; Jowett, Agarwal, & Smith, 2001; Sylvestry, 2001, 2002). Additional studies are needed to assess the safety and effectiveness of HCV treatment among MMT clients and active drug or alcohol users, especially as new therapeutic regimens continue to evolve. Further research is needed to find ways to increase accessibility and acceptability of HCV treatment among drug using populations. The evaluation of programmes to increase adherence and/or reduce relapse, such as offering directly observed HCV treatment within the context of MMT need to be evaluated. As cohorts of drug users begin to be treated, we need continue to assess the HCV infection and re-infection rates and continue to evaluate HCV prevention strategies.

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