HCV Synthesis Project: Preliminary analyses of HCV prevalence in relation to age and duration of injection

International Journal of Drug Policy 18 (2007) 341–351

Review

HCV Synthesis Project: Preliminary analyses of HCV prevalence in relation to age and duration of injection Holly Hagan a,∗ , Don C. Des Jarlais a,b , Rebecca Stern a , Corina Lelutiu-Weinberger a , Roberta Scheinmann a , Shiela Strauss a , Peter L. Flom a a

Center for Drug Use and HIV Research, National Development and Research Institutes (NDRI), 71 West 23rd Street, 8th Floor, New York, NY 10010, United States b Baron Edmond de Rothschild Chemical Dependency Institute, Beth Israel Medical Center, 160 Water Street, 24th Floor, New York, NY 10038, United States

Received 9 November 2006; received in revised form 11 January 2007; accepted 18 January 2007

Abstract Early acquisition of hepatitis C virus (HCV) infection appears to affect a substantial proportion of injection drug users (IDUs)—between 20 percent and 90 percent. Analysing the range of HCV prevalence estimates in new injectors may help identify factors that can be modified to reduce HCV transmission. The HCV Synthesis Project is a meta-analysis of studies of HCV epidemiology and prevention in drug users worldwide. In this preliminary analysis, we examined data from 127 studies of IDUs that reported HCV prevalence in relation to age or year since onset of drug injection, analysing heterogeneity and calculating summary statistics where appropriate. Six studies reported gender-specific HCV prevalence rates among young or new injectors; the group mean prevalence was 47 percent for men and 44 percent for women (NS). Group mean age for HCV-negatives was 24.7 years (range 24–28) and 26.1 years (range 21–31) for HCVpositives (n = 8 studies). Data were examined from 13 studies that compared HCV prevalence among young injectors to older injectors using 5-year age categories; substantial variation was present within these categories such that measures of central tendency were not calculated. Similarly, among studies reporting HCV prevalence among IDUs in relation to 1-year intervals of duration of injection (<1 year, <2 years, and <3 years), considerable variability was observed. Notably, there were studies in each category that reported prevalence of 70 percent or higher among recent-onset drug injectors. Our findings confirm previous studies reporting high risk of acquiring HCV shortly after onset of injection; thus, HCV prevention programmes must emphasize methods to reach new injectors. Future research should (1) report data on time to infection in depth, (2) provide detailed information on study methodology, and (3) characterize the research setting with respect to underlying factors that affect injection practices and networks. This will permit synthesis of a greater number of studies and may lead to the identification of factors that impede HCV transmission. © 2007 Elsevier B.V. All rights reserved. Keywords: Hepatitis C; Prevention; Injection drug use; Youth; Epidemiology; Meta-analysis

Contents Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

∗

Corresponding author. Tel.: +1 212 845 4465; fax: +1 917 438 0894. E-mail address: [email protected] (H. Hagan).

0955-3959/$ – see front matter © 2007 Elsevier B.V. All rights reserved. doi:10.1016/j.drugpo.2007.01.016

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Acknowledgments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Introduction Hepatitis C virus is hyperendemic in injection drug users throughout the world (Hagan & Des Jarlais, 2000; Hocking, Crofts, Aitken, & MacDonald, 2001; McMahon & Tortu, 2003; Roy et al., 2002; Wasley & Alter, 2000; Williams, Ansell, & Milne, 1997). Shortly after HCV was discovered in 1989, a number of HCV serosurveys of IDUs in the US, western Europe and Australia were carried out, and these showed relatively uniform high prevalence (65–90 percent) (Bell et al., 1990; Crofts et al., 1993; Goldberg et al., 2001; MacDonald et al., 2000; Smyth, Keenan, & O’Connor, 1998; Thomas et al., 1995; van Ameijden, van den Hoek, Mientjes, & Coutinho, 1993; van den Hoek, van Haastrecht, Goudsmit, de Wolf, & Coutinho, 1990). Recently, examples of rising HCV prevalence – in excess of 80 percent – over a relatively short time period have been reported in IDUs in regions where drug injection is an emerging phenomenon, most notably in Asia and eastern Europe (Cao et al., 1999; Garten et al., 2003; Lai et al., 2001; Nanping, Li, Zhu, & Zou, 2003). Some early cross-sectional studies in the US and Europe suggested rapid acquisition of HCV following onset of drug injection (Garfein, Vlahov, Galai, Doherty, & Nelson, 1996; Kelen et al., 1992; van Ameijden et al., 1993; van den Hoek et al., 1990), but in more recent years there have been reports of low or declining prevalence in young injectors, for example in the UK (Goldberg et al., 2001; Hope et al., 2001), and in the US (Des Jarlais et al., 2005; Hahn, PageShafer, Lum, Ochoa, & Moss, 2001; Thorpe, Ouellet, Levy, Williams, & Monterroso, 2000). In The Netherlands, HCV prevalence rates have remained essentially unchanged among young injectors from 1985 to 2004 (44 percent) (van de Laar et al., 2005). Public health efforts to control infectious diseases seek to identify host, agent and environmental factors that may be manipulated to prevent exposure and transmission of the agent (Heymann, 2004). Unfortunately, among drug injectors, multiple factors favour acquisition of HCV. Relevant host factors, that is, characteristics of susceptible IDUs that place them at elevated risk of HCV, include injection practices that lead to direct percutaneous blood exposure via receptive syringe sharing, and other practices associated with lowerdose or indirect blood exposure such as drug preparation equipment sharing and re-use of tourniquets (Crofts, Jolley, Kaldor, van Beek, & Wodak, 1997; Gyarmathy, Neaigus, Miller, Friedman, & Des Jarlais, 2002; Hagan et al., 2001; Hahn et al., 2001, 2002; Miller et al., 2002; Smyth, Barry, & Keenan, 2005; Thorpe et al., 2002; van Beek, Dwyer, Dore, Luo, & Kaldor, 1998). Viral factors that favour transmission in this population include the fact that a high proportion of patients infected with HCV become infectious carriers, and

348 348

that HCV is highly efficiently transmitted by blood exposure (Gerberding, 1995). Significant environmental factors include the large reservoir of HCV infection that exists in most IDU-populations, which increases the likelihood of injection with an HCV-infectious individual. Awareness of HCV serostatus among HCV-positive IDUs has been shown to be relatively low (approximately 30–40 percent) so that many infectious IDU may not realize they can transmit HCV (Kwiatkowski, Corsi, & Booth, 2002). Injection settings may be chaotic and the process of injection may be rushed, so that even an IDU who is well-informed regarding safe practices and knows his or her serostatus may transmit or be exposed to HCV by unintentional use of contaminated equipment (Rhodes et al., 2006a). Policing activities that discourage possession of injection equipment can also contribute to HCV risk (Rhodes et al., 2006b). Clearly, prevention of HCV among drug injectors continues to be a significant public health challenge. In the 17 years since HCV was identified, there have been approximately 400 reports of HCV prevalence and incidence in IDUs, and their association with risk factors. Progress toward HCV prevention will be informed by identifying circumstances and individual characteristics that are associated with variability in infection rates. Understanding variation in time to infection is highly useful to guide the targeting of education, screening and, potentially, HCV vaccination efforts. In this paper, we present preliminary data from our synthesis of research on time at risk in relation to HCV infection, to highlight consistencies (and inconsistencies) that may guide prevention programmes, and to point out gaps in knowledge.

Methods This research team is currently conducting a meta-analysis of research studies of the epidemiology and prevention of HCV in drug users worldwide. The scope of the meta-analysis (the HCV Synthesis Project) includes published and unpublished reports describing the epidemiology of HCV infection (incidence and prevalence), the molecular epidemiology of HCV genotypes, and the co-occurrence of HIV, HCV and other hepatitis virus infections in drug users. Data collection began in August 2004 and ended in December 2006; this paper is based on data collected through September 2006. Preliminary quantitative analyses are underway, and final analyses await the completion of data collection and quality assurance procedures. Thus, the data included in this paper represent initial quantitative analyses of variables related to time at risk (age and duration of drug injection). In the HCV Synthesis Project, the population of interest includes injection and non-injection drug users of heroin,

H. Hagan et al. / International Journal of Drug Policy 18 (2007) 341–351

cocaine and amphetamine, because both groups of individuals have been identified as having a biologically plausible risk of exposure to HCV via drug use, including percutaneous exposure (via injection drug use) and mucous membrane exposure to HCV-positive blood via sharing of straws or pipes used to administer drugs (non-injection drug use). Data from IDU and NIDU studies are analysed separately, as they differ substantially in the likelihood of HCV infection, and because their drug-related risk factors are quite dissimilar. A separate report synthesizes HCV epidemiology and prevention among NIDUs (Scheinmann et al., 2006); the analysis presented in this paper focuses on studies of IDUs. Automated searches of published literature were carried out on electronic databases (MEDLINE, PsychInfo, ERIC, Dissertation Abstracts, Sociological Abstracts, and Current Contents) using the following search terms: (hepatitis C or HCV) and (intravenous drug abuse or intravenous drug use or drug misuse or drug addict or injecting drug use or drug abuse or IDU) and (prevention or risk factor or epidemiology or prevalence or incidence or seroprevalence or seroincidence or genotype or co-infect* or coinfect*). Manual search methods included footnote chasing and hand searching of journals and proceedings from scientific conferences related to hepatitis, HIV, infectious diseases and harm reduction; Internet searches of Web sites for government public health organizations and international health or drug control organizations are also conducted. Reports published after 1988 were included in the search. To be included in the HCV Synthesis Project, data reports must have included either estimates of prevalence, incidence, measures of association, HIV/HCV co-infection or HCV genotype distributions in samples of eligible drug users. HCV status must have been determined by serologic testing of either sera or saliva. Note that some reports included multiple studies, that is, individual studies were coded if separate HCV prevalence or incidence estimates were given for samples recruited using different study methods or with different demographic characteristics. In this paper, we indicate separate studies appearing in a report by appending “study 1”, “study 2”, and so forth to the report ID. Data coding was carried out by senior research assistants who had graduate training in research methods, and received additional training in HCV epidemiology, drug use and metaanalytic methods. The coding was reviewed by the Project Director and Principal Investigator, and any unresolved issues were discussed to reach consensus. The coding form included items related to study methods (design, inclusion criteria, recruitment method, recruitment locations, method of determining IDU/NIDU status, specimen type, and HCV test method) and characteristics of the sample (e.g., duration of drug use, type of drugs used, and frequency of use). AntiHCV prevalence and incidence estimates, relative risks and odds ratios (both crude and adjusted, with their 95 percent confidence intervals) were collected for the total sample and (where provided) in relation to epidemiologic factors of interest (i.e., person, place, and time characteristics). Coding

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generally involved recording data as given in the report; however, in many cases, some calculation was needed to obtain the data. In other cases, data values were approximated from data shown in graphs. Approximations are indicated in data tables using footnotes. For this report, we carried out preliminary quantitative analyses of HCV prevalence in relation to gender, age and duration of injection. Separate HCV prevalence estimates were given for males and females in 58 studies; we analysed these data to determine whether there were gender differences in HCV prevalence among young/new versus older/longerterm injectors. Among the studies in our database that reported prevalence in relation to age, duration of injection, or both, we focused on a subset that compared HCV prevalence between young/new and older/longer-term injectors. Age and duration of injection data were not uniformly reported across the studies, and some studies did not report prevalence separately for young or new injectors. However, there were several studies that reported HCV prevalence using similar age intervals (<20, 20–25, and >25); some overlap between the intervals was present, for example, two reported HCV prevalence among those aged ≤20, and the remaining studies used <20 as the cut point. In our database there were a number of studies that reported HCV prevalence in relation to duration of injection for those injecting <1 year, <2 years, and <3 years. These categories were chosen to examine whether there were consistent incremental differences in prevalence within the first 3 years of drug injection. There was also a group of studies that reported mean age or mean duration of injection for HCV-positive versus HCV-negative IDUs with their standard deviations. We did not exclude studies that had an upper or lower limit for age or duration of injection as part of their exclusion criteria. There were additional studies that reported mean values for these variables that were not included because the standard deviations were not given and their inclusion in the computed group means substantially reduced the estimated group variance. Tests of heterogeneity were carried out within categories, while summary estimates (group means, overall prevalence and their 95 percent confidence limits) were calculated only where tests of heterogeneity were not statistically significant. In each of the analyses presented here, it can be assumed that the studies shown are not necessarily inclusive of all studies published to date, as retrieval and coding for the HCV Synthesis Project is not yet complete. The paper is restricted to studies that reported specific analyses that could be combined and were informative in terms of understanding the initial period of susceptibility to HCV infection among IDUs.

Results As of May 1, 2006, the HCV Synthesis Project had identified 2021 reports that met screening criteria; of these, 934 (46 percent) were eligible for coding. The 934 reports included studies of HCV prevalence, incidence, HIV/HCV

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co-infection and HCV genotype distributions among drug users. For this analysis we identified a subset of 127 studies, including 58 studies that reported HCV prevalence in relation to gender, 78 studies that reported HCV prevalence in relation to age, and 75 studies that reported prevalence in relation to duration of injection. Among the 58 studies that reported HCV prevalence in relation to gender, we found little overall variation (Aarons et al., 2004; Abdala et al., 2003; Allwright et al., 2000; Anand, Fonseca, Walle, Powell, & Williams, 1992; Bell et al., 1990; Bolumar et al., 1996; Butler et al., 1999; Crofts et al., 1995; de Carvalho et al., 1996; Denis et al., 2000; Fingerhood, Jasinski, & Sullivan, 1993; Garfein et al., 1998; Gil, Navarro, Casanovas, Rubio, & Dols, 1999; Goldberg, Cameron, & McMenamin, 1998; Gombas et al., 2000; Hahn et al., 2001; Haydon et al., 1998; Hernandez-Aguado et al., 2001; Hope et al., 2001; Judd et al., 2005; Kemp, Miller, Lungley, & Baker, 1998; Kennedy et al., 1998; Kwiatkowski et al., 2002; Laskus et al., 1992; Long et al., 2001; Love & Stanzeit, 1994; MacDonald et al., 2000; Maher, Chant, Jalaludin, & Sargent, 2004; McCoy et al., 2004; McIntyre et al., 2001; Miller et al., 2002; Montella et al., 2005; Murrill et al., 2002; Ompad, Fuller, Vlahov, Thomas, & Strathdee, 2002; Patrick et al., 2001; Patti et al., 1993; Ruan et al., 2004; Siragusa, Passarino, Mollo, & Tappero, 2001; Smyth et al., 2005; Smyth, Keenan, & O’Connor, 1999; Stark, Muller, Bienzle, & Guggenmoos-Holzmann, 1996; Stark et al., 1995; Steffen, Blattler, Gutzwiller, & Zwahlen, 2001; Tor et al., 1990; Tortu, Neaigus, McMahon, & Hagen, 2001; van Beek, Buckley, Stewart, MacDonald, & Kaldor, 1994; van de Laar et al., 2005; van den Hoek et al., 1990; Weissenbacher et al., 2003). Summing across all studies, the total number of male injectors included was 20,669; and the number of female injectors was 7,424. Fifteen studies reported significant differences between men and women, including nine studies with significantly higher prevalence among men (Abdala et al., 2003; Fingerhood et al., 1993; Hope et al., 2001 [study 3]; Maher et al., 2004; McCoy et al., 2004; McIntyre et al., 2001 [study 3]; Montella et al., 2005; Murrill et al., 2002 [study 2]; Weissenbacher et al., 2003), and six studies with significantly higher prevalence among women (Butler et al., 1999; Crofts et al., 1995; MacDonald et al., 2000 [studies 2 and 3]; Siragusa et al., 2001; Stark et al., 1996). The magnitude of these differences was substantial in some cases, with odds ratios varying between 0.2 and 3.8 (data not shown). These 58 studies included 6 that limited recruitment to young or new injectors; we examined whether gender differences were present in these studies expecting that if gender differences in HCV risk exist they would tend to be evident among young injectors and would wane as time at risk accrues. Among 52 studies that did not restrict the sample with respect to age or duration of injection, the weighted mean HCV prevalence for men was 64.0 percent (95 percent confidence limit (CL) 63.4–64.7 percent) and 65.5 percent for women (95 percent CL 64.4–66.7 percent). Summarizing across these 52 studies, the Mantel-Haenzsel weighted odds ratio for the

difference in HCV prevalence between males and females was 1.0 (95 percent CL 0.94–1.07 percent), and the crude odds ratio was 0.95, indicating that there were no significant differences between males and females. Among six studies of young or new injectors (age limit of 30 or younger, or duration of injection 2 years or fewer), mean prevalence for males was 47.0 percent (95 percent CL 43.5–50.6 percent), and mean prevalence for females was 43.8 percent (95 percent CL 39.7–48.0 percent) (Garfein et al., 1998; Hahn et al., 2001; Miller et al., 2002; Ompad et al., 2002; Smyth et al., 1999; van de Laar et al., 2005). Summarizing across these six studies, the Mantel-Haenzsel weighted odds ratio for the difference in HCV prevalence between young males and young females was 1.07 (95 percent CL 0.84–1.36 percent) and the crude odds ratio was 1.14, indicating no significant differences between males and females among recent-onset injectors. There were eight studies that reported mean age for HCVpositive versus HCV-negative injectors, as shown in Table 1 (Bell et al., 1990; Coppola et al., 1996; Esteban et al., 1989; Latt et al., 2000; Mathei, Robaeys, van Damme, Buntinx, & Verrando, 2005; Robinson, Reynolds, & Robinson, 1995; Trisler, Seme, Poljak, Celan-Lucu, & Sakoman, 1999). These studies were carried out in Europe, Australia and New Zealand, and five of the eight were in drug treatment settings (Coppola et al., 1996; Mathei et al., 2005; Robinson et al., 1995; Trisler et al., 1999). Years of enrolment spanned 1986–2005. The total sample size was 1057 IDUs (in individual studies, the sample size ranged between 83 and 225), and overall HCV prevalence across the studies was 77.7 percent. There was little variability in estimates of mean age for HCV-positive versus HCV-negative subjects across studies. For the HCV-positives, mean age ranged between 21 and 31, and the group mean age was 26.1 (SD 4.9 years). Mean age for HCV-negatives ranged from 24 to 28, and the group mean age for HCV-negatives was 24.7 (SD 5.2 years). Age did not differ significantly between the two groups (p = .15). Twelve studies compared HCV prevalence among young injectors (aged ≤20, and 20–25) to older injectors (older than 25) using similar age categories, as shown in Table 2 (Bair et al., 2005; Balogun et al., 2003; Eicher, Crofts, Benjamin, Deutschmann, & Rodger, 2000; Goldberg et al., 1998; Hahn et al., 2001; Kemp et al., 1998; MacDonald et al., 2000; Patti et al., 1993; Siragusa et al., 2001; van Beek et al., 1994). These studies were carried out in Europe, Australia/New Zealand, Asia and the US. There was substantial variability in recruitment setting in these studies (including street outreach, drug treatment, needle exchange, and medical settings). HCV prevalence in the total samples for the studies was highly variable, ranging between 36 percent and 98 percent. Tests for heterogeneity within each age group were all statistically significant, so measures of central tendency were not calculated. In the youngest age category (N = 800 injectors aged ≤ 20), HCV prevalence ranged between 11 percent and 98 percent. In five studies of IDUs aged ≤ 20, prevalence was less than 20 percent, and in four studies, it was between 20 percent and 40

Table 1 Studies of injection drug users comparing mean age of HCV-positive to HCV-negative subjects Location

Year(s) of enrolment

Recruitment setting

Sample

HCV-positive (N)

Anti-HCV prevalence (percent)

Mean age of HCV-positive subjects (years) (±SD)

Mean age of HCV-negative subjects (years) (±SD)

Bell et al. (1990) Coppola et al. (1996) Esteban et al. (1989) Latt et al. (2000) Mathei et al. (2005) Robinson et al. (1995) Trisler et al. (1999)—Study 1 Trisler et al. (1999)—Study 2

Australia Italy Spain Australia Belgium New Zealand Slovenia Croatia

1986–1989 1992–1993 Unspecified 1992–1995 1999–2000 1992–1994 2005 1996

Medical setting Drug treatment center Medical setting Pregnancy/postpartum Drug treatment center Drug treatment center Drug treatment center Drug treatment center/ medical setting

172 137 83 131 225 92 115 102

148 111 59 125 178 71 59 70

86 81 71 95 79 77 51 69

25.6 (±4.0) 26.7 (±4.8) 26.6 (±4.5) 28.7 (±0.5) 21.2 (±6.2) 30.8 (±5.8) 27.8 (±6.2) 26.9 (±5.6)

24.9 (±5.1) 23.7 (±4.1) 25.8 (±4.1) 25.6 (±0.8) 24.0 (±7.3) 28.1 (±5.4) 25.1 (±5.2) 23.7 (±4.7)

Table 2 Studies comparing HCV prevalence among young injectors (age < 25) to older injectors Report ID

Location

Enrolment years

Recruitment setting

Sample

HCV-positive (N)

<20 years old (or as specified)

20–25 years old (or as specified)

>25 years old (or as specified)

489

Anti-HCV prevalence (percent) 37

Balogun et al. (2003)

UK

1995–1996

1329

Eicher et al. (2000) Goldberg et al. (1998)—Study 1 Goldberg et al. (1998)—Study 2 Hahn et al. (2001)

India UK

1996 1990

Surveillance in genitourinary medicine clinics Street outreach HIV clinic

8/76 = 11 percent

48/276 = 17 percent (20–24 years old)

434/977 = 44 percent (≥25 years old)

191 295

187 264

98 90

56/57 = 98 percent (14–19 years old) 22/24 = 92 percent (15–19 years old)

68/70 = 97 percent (20–24 years old) 118/130 = 91 percent (20–24 years old)

63/64 = 98 percent (≥25 years old) 124/141 = 88 percent (≥25 years old)

UK

1995

HIV clinic

370

285

77

5/17 = 29 percent (15–19 years old)

59/91 = 65 percent (20–24 years old)

221/262 = 84 percent (≥25 years old)

US

1997–1999

308

140

46

13/72 = 18 percent (15–19 years old)

56/138 = 41 percent (20–24 years old)

71/98 = 73 percent (25–29 years old)

241

156

65

5/14 = 36 percent (≤20 years old)

27/67 = 40 percent (21–25 years old)

122/160 = 76 percent

1995

Street outreach and community based organizations Drug treatment center and community Needle exchange

Kemp et al. (1998)

New Zealand

1994

MacDonald et al. (2000)—Study 1 MacDonald et al. (2000)—Study 2 MacDonald et al. (2000)—Study 3 Patti et al. (1993) Siragusa et al. (2001) van Beek et al. (1994)

Australia

979

617

63

18/65 = 28 percent

88/226 = 39 percent (20–24 years old)

510/681 = 75 percent (≥25 years old)

Australia

1996

Needle exchange

1463

746

51

25/138 = 18 percent

80/363 = 22 percent (20–24 years old)

640/953 = 67 percent (≥25 years old)

Australia

1997

Needle exchange

1699

850

50

35/184 = 19 percent

101/440 = 23 percent (20–24 years old)

707/1072 = 66 percent (≥25 years old)

Italy Italy Australia

1990–1991 1977–1996 1991–1992

645 793 201

409 601 118

63 76 59

8/21 = 38 percent (≤20 years old) 28/49 = 57 percent (15–20 years old) 5/30 = 17 percent (15–19 years old)

83/143 = 58 percent (21–25 years old) 102/141 = 72 percent (21–25 years old) 33/65 = 51 percent (20–24 years old)

304/447 = 68 percent 243/300 = 81 percent 80/106 = 76 percent (≥25 years old)

US

2000–2001

Drug treatment center Medical examiner Primary health center targeting IDUs Correctional

Bair et al. (2005)

53

19

36

19/53 = 36 percent (10–18 years old)

NA

NA

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Report ID

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percent. Two studies reported prevalence above 90 percent, in India (Eicher et al., 2000) and in the UK (Goldberg et al., 1998); these same studies reported high prevalence across all age groups. Across all studies, there were 2150 IDUs aged 20–25 years old; the range of HCV prevalence was quite broad, between 17 percent and 97 percent. The category of IDUs older than 25 included 5,261 subjects and the lower bound of the range was 44 percent. Within studies, differences in HCV prevalence rates across age categories did not follow a consistent pattern, and there was no evident pattern of variation in prevalence across studies in relation to time (year of enrolment), place (study location) or study method (recruitment setting). We focused our analysis of HCV prevalence and number of years since first injection on the initial years following onset. In Table 3, we show data from a number of studies that reported HCV prevalence among IDUs who had injected less than 1 year (Alizadeh, Alavian, Jafari, & Yazdi, 2005; Chang et al., 1999; Christensen, Krarup, Niesters, Norder, & Georgsen, 2000; Garfein et al., 1996; Shirin, Ahmed, Iqbal, Islam, & Islam, 2000; Smyth et al., 1999), less than 2 years (Bell et al., 1990; Coppola et al., 1996; Eicher et al., 2000; Garfein et al., 1998; Hope et al., 2001; Judd et al., 2005; Rhodes et al., 2006b) or less than 3 years (Allwright et al., 2000; Craine, Walker, Williamson, Brown, & Hope, 2004; Denis et al., 2000; Diaz et al., 2001; Hernandez-Aguado et al., 2001; Maher et al., 2004). Substantial variation apparent within categories was confirmed by statistically significant tests of heterogeneity. In the first panel of Table 3, prevalence among those injecting less than 1 year ranged between 12 percent (a 1996–1997 study in Bangladesh by Shirin et al., 2000) and 66 percent (a 1988–1992 study in Baltimore by Garfein et al., 1996). A recent study from Iran reported prevalence of 28 percent among those injecting just 1 year (Alizadeh et al., 2005). In the second panel of Table 3, data are shown from seven studies reporting HCV prevalence among IDUs injecting 2 years or fewer; the range was 21 percent (a 1994 study from Baltimore by Garfein et al., 1998) to 97 percent (a 1996 study in India by Eicher et al., 2000). In the lower panel of Table 3, data from studies reporting HCV prevalence among those injecting 3 years or fewer are shown (Allwright et al., 2000; Craine et al., 2004; Denis et al., 2000; Diaz et al., 2001; Hernandez-Aguado et al., 2001; Maher et al., 2004). One study from the UK reported low prevalence of 16 percent (Craine et al., 2004), but, again, within this category the range was quite broad (with a maximum of 73 percent). In fact, in each category of duration of drug injection (<1 year, <2 years, and <3 years) there were studies reporting 70 percent prevalence.

Discussion This study examined HCV prevalence in relation to time at risk using several different approaches. Importantly, a substantial degree of variation in prevalence was present among

studies included in this analysis, which precluded the calculation of summary estimates for young and new injectors. We found that there were no differences in mean age comparing HCV-positives to HCV-negatives, but most of the studies that reported these statistics were conducted in drug treatment programmes where the age range may be less variable than in other recruitment locations. We also did not find gender differences in HCV prevalence among young or new injectors. There are several limitations of this analysis. As mentioned, this is a preliminary examination of HCV acquisition using prevalence data from studies that used similar categories for reporting age or duration of use. Our approach may have isolated findings that each study found to be meaningful: that is, reporting of HCV prevalence statistics in relation to categories of age or duration of injection may depend on sample size and the underlying distribution, but there may also be a tendency to group the data to highlight high HCV prevalence categories. This is a fundamental weakness of any meta-analysis, namely that data can only be analysed as they are presented. Future analyses of data from the HCV Synthesis Project will examine whether variation in HCV infection among young or new injectors is random or can be attributed to host characteristics (risk behaviour) or environmental factors (HCV prevalence in the community, availability of sterile injection equipment) that can be modified, and the degree to which sampling methods are related to HCV prevalence estimates. Studies have reported highly variable rates of HCV seroconversion in new injectors (Hagan et al., 2001; Hahn et al., 2002; Lucidarme et al., 2004; Smyth, O’Connor, Barry, & Keenan, 2003; Thorpe et al., 2002; van Beek et al., 1998). In two studies, HCV seroincidence rates among those injecting less than 2 years was between 18 and 27 infections per 100 person-years (PY) at risk (Hagan et al., 2001; Lucidarme et al., 2004). In a study in Sydney, the rate of infection among those injecting 1 year or less was 133/100 PY (Maher et al., 2006) versus 74/100 PY in Ireland (Smyth et al., 2003) and only 8/100 PY in a study of Chicago IDUs (Thorpe et al., 2002). A study in San Francisco reported that HCV seroincidence among those injecting less than 3 years was 27/100 PY, and 37/100 PY among those injecting 4–7 years (Hahn et al., 2002). Another study calculated that the weighted average time to HCV seroconversion among Seattle IDUs was 3.4 years, using prevalence and incidence data among young injectors (Hagan, Thiede, & Des Jarlais, 2004). We believe that the most important findings from this analysis concern the lack of homogeneity in the studies of HCV prevalence and incidence among IDUs. We found homogeneity only among studies that examined gender differences and for age differences between HCV seropositive and HCV seronegative injecting drug users. There was statistically significant heterogeneity among studies examining HCV prevalence in relation to age, duration of injection, or both.

Table 3 Studies comparing HCV prevalence among duration of use categories Location

Enrolment years

Recruitment setting

Inclusion criteria

Sample

Percentage of anti-HCV prevalence

Prevalence by duration of injection category <1 year (as specified)

>1 year (as specified)

Alizadeh et al. (2005) Chang et al. (1999)

Iran Taiwan

2002 1994–1996

IDU ever IDU ever; male

149 247

31.5 67.2

28 percent (<1 year) 57 percent (≤1 year)

40 percent (>1 year) 74 percenta (>1 year)

Christensen et al. (2000) Garfein et al. (1996) Shirin et al. (2000) Smyth et al. (1999)

Denmark US Bangladesh Ireland

1996–1997 1988–1992 1996–1997 1993–1996

Correctional Drug treatment center and Correctional Correctional Multiple settings Drug treatment center Drug treatment center

IDU ever IDU last 1 year; 18–29 years old IDU ever IDU injected for <25 months

140 312 129 353

87.1 76.9 24.8 52.1

79 percent (≤1 year) 66 percenta (≤1 year) 12 percent (<1 year) 44 percent (≤1 year)

97 percent (>1 year) 81 percenta (>1 year) 36 percent (≥1 year) 64 percent (>1 year)

Report ID

Location

Enrolment years

Recruitment setting

Inclusion criteria

Sample

Percentage of anti-HCV prevalence

Prevalence by duration of injection category <2 years (as specified)

>2 years (as specified)

Bell et al. (1990) Coppola et al. (1996) Eicher et al. (2000) Garfein et al. (1998) Hope et al. (2001)

Australia Italy India US UK

1986–1989 1992–1993 1996 1994–1996 1997–1998

IDU ever IDU ever IDU last month IDU last 1 year; 18–29 years old IDU last 4 weeks

172 137 191 229 2943

86.0 81.0 97.9 37.6 30.4

71 percenta (≤2 years) 62 percenta (<2 years) 97 percent (<2 years) 21 percent (<2 years) 7 percent (<2 years)

91 percenta (>2 years) 84 percenta (≥2 years) 98 percent (≥2 years) 49 percent (>2 years) 39 percent (>2 years)

Judd et al. (2005)—Study 1

Scotland

2001–2002

34.5

29 percent (<2 years)

37 percent (>2 years)

Scotland

2001–2002

IDU last 1 month; started injecting 1996 or later IDU last 1 month; starting IDU 1996 or later

354

Judd et al. (2005)—Study 2

366

57.0

36 percent (<2 years)

64 percent (>2 years)

Rhodes et al. (2006b)

Russia

2003

Medical setting Drug treatment center Street outreach Various Agencies and community Needle exchange and street outreach Drug treatment, needle exchange, and street outreach Non-treatment settings

IDU past 28 days

1473

63.8

40 percent (<2 years)

68 percenta (>2 years)

Report ID

Location

Enrolment years

Recruitment setting

Inclusion criteria

Sample

Percentage of anti-HCV prevalence

Prevalence by duration of injection category <3 years (as specified)

>3 years (as specified)

Allwright et al. (2000) Craine et al. (2004)

Ireland Wales

1998 2001–2002

IDU ever IDU ever

509 153

81.3 23.0

65 percent (<3 years) 16 percent (<3 years)

85 percent (≥3 years) 26 percent (>3 years)

Hernandez-Aguado et al. (2001) Maher et al. (2004)

Spain Australia

1990–1996 1999–2002

Correctional Drug treatment center/needle exchange Public health clinic Multiple settings

3238 377

85.0 36.6

73 percent (≤3 years) 28 percent (<3 years)

91 percent (>3 years) 43 percent (≥3 years)

Denis et al. (2000)

Belgium

1995–1998

244

78.3

70 percent (≤3 years)

86 percent (>3 years)

Diaz et al. (2001)—Study 1

US

1997–1998

Drug treatment center/medical setting Street outreach

IDU ever IDU last 6 months; anti-HCV serostatus not known to be positive IDU ever

357

42.0

22 percent (≤3 years)

56 percent (>3 years)

Diaz et al. (2001)—Study 2

US

1997–1998

Street outreach

18–29 years old; IDU last 6 months OR IDU less than 3 years 18–29 years old; IDU last 6 months OR IDU less than 3 years

200

52.0

33 percent (≤3 years)

66 percent (>3 years)

a

H. Hagan et al. / International Journal of Drug Policy 18 (2007) 341–351

Report ID

Approximated value.

347

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There are many possible sources of the significant heterogeneity among the prevalence and incidence studies. These would include differences in research methods including recruitment and sampling, characteristics of the subjects, geographic location, time period in which the data were collected, and the existence and scale of HIV and HCV prevention programmes. Underlying differences in study settings related to injection network characteristics, features of injection locations, and level of police activity may also contribute to heterogeneity in HCV infection rates. This suggests that mixed-methods research (integrating quantitative and qualitative methods) would add to our understanding of HCV variability. Understanding the heterogeneity should help identify persons at highest risk for HCV infection and provide insight into potentially effective programmes and circumstances that reduce HCV transmission among injecting drug users. We are, however, far from having certain knowledge in these areas. Our understanding of how to reduce HCV infection among drug injectors may advance if studies report in detail (1) study methodology such as recruitment setting and sampling approach, (2) data on HCV prevalence and incidence in relation to age and years since first injection, and (3) descriptions of the social setting that gives rise to the study population, such as information on availability of harm reduction services and the presence of heavy policing and other factors that may deter safe injection. This would permit synthesis of data across studies, and lead to insights that cannot be drawn from any single study.

Acknowledgments This research was funded by NIDA Grant Number R01 DA018609. The authors would like to acknowledge the Center for Drug Use and HIV Research (P30 DA121041) for its support and assistance.

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