JAIDS Journal of Acquired Immune Deficiency Syndromes:
Epidemiology and Social Science
Requiring Help Injecting Independently Predicts Incident HIV Infection Among Injection Drug Users
O'Connell, Jacqueline M Msc*; Kerr, Thomas PhD*; Li, Kathy MSc*; Tyndall, Mark W MD, PhD*†; Hogg, Robert S PhD*‡; Montaner, Julio S MD*†; Wood, Evan PhD*†
From the *British Columbia Centre for Excellence in HIV/AIDS, University of British Columbia, St. Paul's Hospital, Vancouver, British Columbia, Canada; †Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada; and ‡Department of Health Care and Epidemiology, University of British Columbia, Vancouver, British Columbia, Canada.
Received for publication July 20, 2004; accepted January 12, 2005.
Supported by the US National Institutes of Health (R01 DA011591-04A1) and Canadian Institutes of Health Research (CIHR) grant (MOP-67262). Evan Wood is supported by the CIHR and the Michael Smith Foundation for Health Research.
Reprints: Evan Wood, Division of Epidemiology and Population Health, British Columbia Centre for Excellence in HIV/AIDS, University of British Columbia, St. Paul's Hospital, 608-1081 Burrard Street, Vancouver, British Columbia V6Z 1Y6, Canada (e-mail: email@example.com).
Background: Requiring help injecting has been associated with syringe sharing among injection drug users (IDUs). No prospective study has fully examined this risk factor and its relation to rates of HIV infection. We investigated whether requiring help injecting illicit drugs was a predictor of HIV infection among a prospective cohort of IDUs.
Methods: The Vancouver Injection Drug User Study is a prospective study of more than 1500 IDUs who have been recruited from the Downtown Eastside of Vancouver since May 1996. At baseline and semiannually, subjects provided blood samples and completed an interviewer-administered questionnaire. The questionnaire elicits demographic data as well as information about drug use, HIV risk behavior, and drug treatment. HIV incidence rates were calculated using Kaplan-Meier methods, and Cox regression determined independent predictors of seroconversion.
Results: A total of 1013 baseline HIV-negative participants were eligible for this study. Within this population, 418 (41.3%) participants had required help injecting during the last 6 months at baseline. Participants requiring help injecting were more likely to be female (odds ratio = 2.3, 95% confidence interval [CI]: 1.8-3.0; P < 0.001), were slightly younger (33.5 vs. 34.9 years of age; P = 0.014), and had fewer years of experience injecting drugs (7 vs. 11 years; P ≤ 0.001). Among participants who required help injecting at baseline, cumulative HIV incidence at 36 months was 16.1% compared with 8.8% among participants who did not require help injecting (log-rank, P < 0.001). In an adjusted model controlling for potential confounding variables, being aboriginal (relative hazard [RH] = 1.68, 95% CI: 1.15-2.48), injecting cocaine daily (RH = 2.71, 95% CI: 1.87-3.95), and requiring help injecting (RH = 1.79, 95% CI: 1.23-2.62) remained independent predictors of HIV seroconversion.
Conclusions: These data demonstrate the need for interventions to reduce the risk of HIV infection among IDUs who require help injecting.
Illicit drug use is associated with a wide array of social and community harms, including diminished social functioning among those addicted, public drug use, and drug-related crime.1-3 In addition, illicit drug use is associated with major health-related harms.4-7 For instance, in our setting, the prevalence of HIV and hepatitis C virus (HCV) infections is estimated to be approximately 30% and 90%, respectively, among injection drug users (IDUs).4,8
Cohort studies of IDUs have helped to identify risks for HIV infection9-12 and have been instrumental in informing HIV prevention strategies.13-15 Many injection-related behaviors among IDUs have been associated with the transmission of infectious diseases. These include syringe sharing and the sharing of other injecting equipment, both of which may be particularly driven by syringe scarcity and amenable to improvement through the expansion of syringe provision strategies.13,14,16-19 More recently, there has been increased interest in risk behaviors for blood-borne disease transmission that are less related to syringe scarcity and may be more related to vulnerabilities related to inexperience, age, lack of education, or other factors that may place IDUs at risk.17,20-22 Identification of such risk characteristics may then serve to inform new interventions aimed at preventing infectious disease transmission among vulnerable IDUs.
The Downtown Eastside of Vancouver has experienced an explosive and ongoing HIV-1 epidemic among IDUs since the mid-1990s.12,23 Despite the fact that Vancouver has a large syringe exchange program, HIV transmission continues to occur at an unacceptably high rate.4,24 The Vancouver HIV epidemic has been attributed, in part, to the high prevalence of cocaine injection12 and the difficulty in accessing syringes.6,23,25,26 At present, however, little is known about requiring help injecting as a risk for blood-borne disease transmission. We and others have recently demonstrated that requiring help injecting is a risk factor for syringe sharing among IDUs in cross-sectional studies,20,22 although the risk of requiring help injecting on HIV seroconversion has not been well examined in prospective studies. The present analyses were thus conducted to evaluate the potential association between requiring help injecting illicit drugs and the incidence of HIV seroconversion among IDUs.
The Vancouver Injection Drug User Study (VIDUS) is a prospective study of IDUs who have been recruited through self-referral and street outreach from Vancouver's Downtown Eastside since May 1996. The cohort has been described previously.23,24,27 Briefly, persons were eligible for the VIDUS if they had injected illicit drugs at least once in the previous month and resided in the greater Vancouver region. At baseline and semiannually, subjects provided blood samples and completed an interviewer-administered questionnaire. The questionnaire elicits demographic data as well as information about drug use, HIV risk behavior, and drug treatment. All participants provided informed consent, and participants were given a stipend ($20 Canadian) at each study visit to compensate them for their time and to facilitate transportation. The study has been approved by the University of British Columbia's Research Ethics Board. The present analyses are restricted to those participants who were recruited between May 1996 and May 2002, were HIV-negative at enrollment, and had at least 1 follow-up visit.
As a preliminary analysis, baseline characteristics stratified by any instances of requiring help injecting in the last 6 months (ever vs. never) were explored. Requiring help injecting was based on the question: “Over the last 6 months, how often did you need someone to help you inject?” This question was added at baseline to examine potential vulnerability to HIV infection among individuals who did not have control over their own injections as a result of requiring the assistance of others. Requiring help injecting was treated as a time-updated variable. Specifically, although this variable was treated as a baseline covariate for the Kaplan-Meier analyses, for all Cox regression analyses, it was treated as a time-updated covariate. Demographic variables included sex, ethnicity (aboriginal vs. other), age, and housing (unstable vs. stable). Unstable housing was defined as living arrangements that include single room-occupancy hotels; transitional living arrangements, including relatives; and homelessness. Drug-using characteristics considered included frequency of cocaine and heroin injection, frequency of crack cocaine use, participation in methadone maintenance therapy, years injecting drugs, and borrowing syringes in the past 6 months. Sexual risk variables included condom use with regular and casual partners. For consistency, variable definitions were identical to those used previously.8,12,23 The Pearson χ2 test was used to compare categoric explanatory variables, and continuous variables were analyzed using the Wilcoxon rank sum test.
The primary end point of interest in this study was the time to HIV seroconversion. The date of seroconversion was estimated using the midpoint between the last negative and the first positive antibody test results. Cumulative incidence rates of HIV infection were calculated for participants who required help injecting and those who did not require help at baseline using Kaplan-Meier methods. Survival curves were compared using the log-rank test. In these analyses, time 0 was defined as the date of enrollment into the study. Participants who consistently remained seronegative were considered to be right-censored at the time of their most recent HIV antibody test result before May 2002. Cox proportional hazards regression was used to assess the independent effect of fixed and time-dependent covariates on time to HIV seroconversion. Variables that were found to be significantly associated with time to seroconversion at the level of P ≤ 0.1 in univariate analyses were considered for inclusion in multivariate Cox regression models. All probability values were 2-sided.
Between May 1996 and May 2003, 1548 individuals had been enrolled into the VIDUS cohort through ongoing recruitment. Of these, 325 (21%) were HIV-positive at baseline. Median age in the VIDUS cohort was 34 years; 557 participants (36%) were women, and 409 (26%) were aboriginal. The median number of follow-up visits was 8. Overall, 1013 participants were eligible for the present study. Among this population, 418 (41.3%) had required help injecting during the last 6 months at baseline, whereas 595 (59.7%) indicated that they had not required help injecting at baseline.
The univariate analysis of baseline characteristics of study participants stratified by requiring help injecting is shown in Table 1. As shown here, participants requiring help injecting were more likely to be female (odds ratio [OR] = 2.3, 95% confidence interval [CI]: 1.8-3.0; P < 0.001), were slightly younger (33.5 vs. 34.9 years; P = 0.014), and had fewer years of experience injecting drugs (7 vs. 11 years; P ≤ 0.001).
As of May 2003, 125 of the 1013 participants had become infected with HIV, yielding a cumulative incidence rate of HIV infection of 14.4% (95% CI: 11.9%-16.8%). Cumulative HIV incidence was almost 2 times higher among participants who required help injecting compared with participants who did not require help injecting at baseline (Fig. 1). Among participants who required help injecting at baseline, cumulative incidence at 36 months was 16.1% compared with 8.8% among participants who did not require help injecting at baseline (log-rank, P < 0.001).
Table 2 presents the results of unadjusted and adjusted Cox proportional hazard analyses of sociodemographic variables, substance use, and sexual risk as well as their association with time to HIV seroconversion. In unadjusted analyses, being aboriginal (P < 0.001), being female (P = 0.022), living in unstable housing (P = 0.012), daily use of cocaine (P < 0.001), borrowing syringes in the last 6 months (P = 0.003), and requiring help injecting (P < 0.001) were identified as significant predictors of seroconversion. A marginal increased risk of seroconversion was observed with respect to daily heroin use (P = 0.072), and a marginal decrease in risk was observed with respect to methadone use (P = 0.086). No significant associations with time to HIV seroconversion were observed for age (P = 0.156), crack cocaine use (P = 0.433), or number of years injecting (P = 0.310). Similarly, there were no significant associations with time to HIV seroconversion and condom use with regular (P = 0.398) or casual (P = 0.340) partners. In the adjusted model controlling for ethnicity, sex, housing, methadone, cocaine, heroin, borrowing syringes in the last 6 months, and help injecting, being aboriginal (relative hazard [RH] = 1.74, 95% CI: 1.18-2.57), using cocaine daily (RH = 2.67, 95% CI: 1.83-3.88), and requiring help injecting (RH = 1.69, 95% CI: 1.15-2.48) remained independent predictors of HIV seroconversion.
In this study, roughly 41% of IDUs reported requiring help injecting at baseline, and participants who required help were almost twice as likely to become infected with HIV after 36 months of follow-up as those who did not require help injecting. In multivariate analyses, requiring help injecting remained an independent predictor of HIV seroconversion after adjustment for other known risk factors. These findings have important implications for public health planning related to HIV prevention and harm reduction, including those measures designed to target this more vulnerable segment of the IDU community.
Predictors of HIV seroconversion in the VIDUS cohort, including aboriginal status and frequent cocaine use, have been discussed elsewhere.4,12 There has been little evaluation of the phenomenon of requiring help to inject and its association with HIV seroconversion among IDUs, however, and our data demonstrate that requiring help to inject independently predicts HIV seroconversion in a setting with widespread access to needle exchange. At present, current harm reduction messages and interventions commonly assume that injections are self-administered; however, our findings suggest that an education campaign is required in IDU communities to inform IDUs of the specific risks of being an injection recipient. Kral et al20 proposed establishing education booths run by current users, past users, or phlebotomists to teach proper injection techniques.20 Indeed, peer-run initiatives have recently been shown to play a major role in reducing harm among Vancouver IDUs by reaching the highest risk drug users with harm reduction services.26 Favorable findings with respect to peer-run initiatives in IDU communities have been reported from elsewhere in Canada17 and abroad.28-31 Thus, peer-run initiatives in conjunction with existing infrastructure, such as community outreach, street nursing, and needle exchange programs, could be investigated as forums to provide education about safer injecting practices.
Assisted injection has been documented in other settings, and several conditions, especially those related to social networks, have been proposed to place IDUs in need of help injecting.20,21 Research into social networks among IDUs has shown that the nature of the relationship between IDUs who use drugs together affects the likelihood of risky injection behaviors.32,33 For instance, in Vancouver and elsewhere, sharing syringes has been found to occur most often in the context of social relationships between IDUs.15,20,25 We think that if harm from assisted injecting is to be reduced, teaching safer injection practices to an entire social network must be pursued. Classically, harm reduction outreach has sought to work with an individual's behavior and access to or use of services. As discussed almost a decade ago by Stimson et al,34 current outreach provision can benefit from implementing “community change” models that seek to engender changes in the social etiquette of drug use within communities of drug injectors. We agree that the social networks through which HIV may be transmitted are the same social networks that may be targeted for HIV prevention as a way of effecting changes among broad populations of drug injectors.
Our study found that younger IDUs and more recent initiates to injecting were most at risk for requiring help injecting and also of HIV seroconversion. In a recent study in Baltimore, young new IDUs who attend shooting galleries early tended to be initiated by older high-risk IDUs and to share and to inject within a high-risk social setting early on.11 Young IDUs were also found to be more likely to require 2 or more “trainers” before being able to self-inject,35 and 1 study in Australia found that more than half of IDUs who had been initiated by another user had subsequently initiated others into injecting.36 Young users have also been found to be at much greater risk for sexually transmitted diseases as a result of their behavioral practices and social networks.37 In our study, help injecting was an independent predictor of HIV infection and did not seem to be confounded by a relation between unsafe sex and HIV risk. Overall, our findings support targeting education to young IDUs early on in their injecting career, with the hope of teaching safe self-injection practices as well as the skills to pass along this information as early after initiation as possible.
Women were overrepresented among injection recipients in this study. These findings support those of Evans et al,21 in which female IDUs in San Francisco were more likely to be injected by another IDU, even after adjusting for other potential confounders. Previously, female IDUs in the VIDUS cohort have been found to be at higher risk for HIV seroconversion than male IDUs,24 and across Canada, women who inject drugs and participate in the survival sex trade are considered to be at increased risk for sexual and drug-related harm, including HIV infection.38 Reasons for these trends may be explained, in part, by the fact that the gender dynamics among IDUs are such that men often control the administration of drugs.24,39,40 Because of these dynamics, women may never learn to inject or may defer to men even if they know how to inject themselves. In a recent cross-sectional study designed to ascertain why injection recipients in the VIDUS cohort require help, we found that some IDUs reported having no viable veins or being anxious or drug sick; among female IDUs, not knowing how to properly inject themselves and injecting into their jugular vein were reasons commonly reported.22 These findings suggest that women who require help injecting need to be targeted specifically for injecting education, including education that informs women of the risks associated with injection via the jugular vein.
A pilot study of supervised injecting facilities has recently been initiated in our setting.18 This supervised injection facility is run under Health Canada guidelines, which, among other restrictions, prohibit assisted injection.41 Kerr et al18 found high levels of reported willingness by Vancouver's IDUs (particularly public injectors) to use a safer injecting facility. This willingness dropped significantly (particularly among women) in the face of prohibition of assisted injection. Extrapolating from the data from this present study, the current restrictions may unfortunately preclude many IDUs who are young, female, and have been recently initiated into injecting drugs (ie, those users most likely to require help injecting) from using the supervised injection site. This policy may also preclude many older injectors with bad veins from using the safe injection site, and thus may put them and others at greater risk of requiring help. Safer injecting education is available at Vancouver's supervised injecting facility; evaluation of this program is underway, and the present study indicates that efforts need to be made to accommodate IDUs who require help injecting at this facility.
Several limitations of this study should be acknowledged. As has been recently described in detail,24,42 recruitment for the VIDUS was nonrandom and the survey is based on self-report. Nevertheless, our study sample population contains more than 20% of the estimated 5000 IDUs who reside in the Downtown Eastside; therefore, we believe that our results are at least representative of the more accessible individuals of the community.43 Socially desirable reporting is always a possibility in such studies; however, previous studies have shown that self-reports of IDUs are valid and that adjustment for measures of socially desirability had only a negligible impact on associations between HIV and risky behaviors.44 In addition, we know of no reason why reporting requiring help injecting would be influenced by socially desirable reporting. A further limitation is that involvement in sexual relationships with individuals of the same sex was not measured for men and women in the VIDUS. Previous studies have shown that these behaviors may be associated with an elevated risk of HIV infection.45,46 It is also noteworthy that studies have shown that some IDUs may be compensated financially or with drugs for providing assistance injecting.20 Interventions to address this risk factor need to consider this concern and the fact that the providers as well as the recipients of assisted injection have to be targeted for intervention. Finally, the complex nature of risk for vulnerable populations such as IDUs may not be adequately measured with our current instruments. We recognize that this quantitative study would benefit from qualitative research strategies designed to help unravel the historical, relational, and cultural processes that often inform HIV-related vulnerability among marginalized populations.
These data demonstrate an elevated risk of incident HIV infection among IDUs who require help injecting. A public health priority toward preventing HIV transmission through assisted injecting should include the development of safer and self-injecting education programs, perhaps with the cooperation of street nursing programs, needle distribution systems, and safer injection facilities. By exploring peer education training and using preexisting programs and infrastructure to serve as a source of additional health and medical services for IDU populations, participants and community health can be expected to benefit, and these programs may also prove to be cost-effective over the long term.
The authors particularly thank the VIDUS participants for their willingness to participate in the study. They also thank Kevin Craib, Richard Harrigan, David Patrick, Patricia Spittal, and Steffanie Strathdee for their research assistance and Bonnie Devlin, John Charette, Caitlin Johnston, Vanessa Volkommer, Steve Kain, Dave Isham, and Peter Vann for their administrative assistance.
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