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Transitions to Injecting Drug Use Among Noninjecting Heroin Users: Social Network Influence and Individual Susceptibility

Neaigus, Alan PhD*†; Gyarmathy, V. Anna PhD, MS, MPH*‡; Miller, Maureen PhD; Frajzyngier, Veronica M. MPH*; Friedman, Samuel R. PhD§∥; Des Jarlais, Don C. PhD§¶

JAIDS Journal of Acquired Immune Deficiency Syndromes: April 1st, 2006 - Volume 41 - Issue 4 - p 493-503
doi: 10.1097/01.qai.0000186391.49205.3b
Epidemiology and Social Science

Objectives: To determine the incidence/predictors of transitions to injecting among noninjecting heroin users (NIUs).

Methods: Street-recruited NIUs in New York City, March/1996-March/2003, were interviewed for a prospective cohort study about social network influence (communication promoting injecting; exposure to injectors) and individual susceptibility. A transition to injecting was the first drug injection following baseline. Hazards ratios (HRs) (P < 0.05) were estimated by Cox proportional hazards regression, stratified by baseline injecting history.

Results: Of 369 (64% of 579) followed, former-injectors were more likely to transition to injecting (33% or 53/160 vs. 12% or 25/209; 16.0/100 person-years-at-risk [pyar] vs. 4.6/100 pyar; HR = 3.25). Independent predictors among never-injectors included using ≥2 bags of heroin daily (HR = 7.0); social network influence (communication) and homelessness (HR = 6.3); shorter-term heroin use (HR = 5.3); social network influence (exposure) and physically abused (HR = 4.7); friends approve/condone drug injecting (HR = 3.5); lower perceived social distance from injectors (HR = 2.9); and younger age at first heroin use (HR = 1.2). Independent predictors among former-injectors were social network influence (communication) and lower perceived social distance from injectors (HR = 3.4); white race/ethnicity (HR = 2.0); not very afraid of needles (HR = 1.8); and younger age (HR = 1.1).

Conclusions: The risk of initiating injecting was lower than the risk of resuming injecting. Social network influence facilitates transitioning to injecting among those susceptible. Interventions to prevent injecting should address both social network influence and individual susceptibility.

From the *Institute for International Research on Youth at Risk, National Development and Research Institutes, Inc., New York, NY; †Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY; ‡Department of Mental Health, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD; §Institute for AIDS Research, National Development and Research Institutes, Inc., New York, NY; ∥Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD; and ¶Baron Edmond de Rothschild Chemical Dependency Institute, Beth Israel Medical Center, New York, NY.

Received for publication December 21, 2004; accepted September 2, 2005.

Funded by the United States National Institute on Drug Abuse, grant DA09920: "Non-injecting heroin users, new injectors and HIV risk."

Reprints: Alan Neaigus, National Development and Research Institutes, Inc., 71 West 23rd Street, 8th Floor, New York, NY 10010 (e-mail:

Heroin users in many countries have increasingly adopted noninjecting routes of heroin administration, eg, intranasal use.1-7 In New York City, the percentage of heroin users entering publicly funded drug treatment who reported intranasal use as their primary route of administration increased steadily from 25% in 1988 to 60% in 1999 and has remained consistently high since.8

Many noninjecting heroin users (NIUs) may be at risk of making a transition to injecting drug use (IDU), thereby becoming at parenteral risk of acquiring or transmitting HIV, the hepatitis B virus (HBV), and the hepatitis C virus (HCV). Moreover, transitions to injecting among infected NIUs may increase the number of infected IDUs and further the spread of these pathogens among IDUs and, particularly for HIV and HBV, their sex partners. Given these serious health consequences, it is essential to assess transitions to injecting among NIUs and the risk factors for transition.

A strong and consistent finding is that NIUs who are former drug injectors are at higher risk of making a transition to injecting than NIUs who have never injected.9-11 In addition, the risk of making a transition to injecting among NIUs may be a function both of individual attributes that increase NIUs' susceptibility to transitioning to injecting and of social network influence that favors drug injecting. Among the factors that may increase individual susceptibility are drug use practices9,10,12-17; an inability to adapt to declines in the purity, quantity, and availability of heroin and increases in the price of heroin18,19; heroin dependence and drug treatment status9,10,14,20; personal traumatic events, such as sex abuse21,22; attitudes about the social status of drug injectors16,23,24; fear of HIV/AIDS16,24-26; and not being afraid of using needles to inject.19,26

Several studies have found that NIUs with IDU social network members are at greater risk of injecting,9,10,14,27,28 which may be a consequence of social network influence from IDUs.16,19,27,29 Social network influence may affect individual behavior through direct communication or, indirectly, through exposure to and comparison with network members who engage in the behavior.30-32 Moreover, social network influence may be a facilitator that increases the probability of a transition to injecting among those who are already susceptible because of individual attributes, such as being heroin dependent.

In this paper we examine the relationship of social network influence and current individual susceptibility, as well as the independent effects of sociodemographic and other individual background factors, to making a transition to injecting drug use among NIUs in New York City during a period in which noninjecting heroin use increased dramatically. We hypothesize that the risk of making a transition to injecting will not only differ by injecting history but, given greater individual susceptibility, will be more likely to occur if social network influence facilitates a transition to injecting. The analysis is stratified by injecting history, because the risk factors for making a transition to injecting among never-injectors (initiating injecting) may differ from those among former-injectors (resuming injecting).9-11

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Recruitment and Procedures

Between March 1996 and September 2002, 579 NIUs were recruited in the Lower East Side/East Village area of Manhattan in New York City for a prospective cohort study to determine the incidence and risk factors for making a transition to injecting and the prevalence, incidence, and risk factors for infection with HIV, HBV, and HCV. Participants were non-treatment recruited using a combination of targeted sampling, street outreach, and chain referral sampling methods.33-35 An open cohort design, with continuous sampling throughout the study, was adopted.10,36 Follow-up interviews were scheduled at 6-month intervals following baseline and were administered in the period from September 1996 through March 2003. Standard procedures (eg, sending out appointment letters and conducting outreach at "hang-out" spots) were used to retain participants in the study.

Those eligible to enter the study were 18 years of age or older, had used noninjected heroin in the 30 days prior to the baseline interview, and either had never injected drugs or, for former-injectors, had not done so in the prior 6 months. Eligibility was verified using urine or hair toxicology tests to detect opiate metabolites, inspection of arms and other visible body sites to ensure that there were no fresh injecting marks, a structured screening questionnaire, and ethnographic methods.33 After giving their informed consent, participants were interviewed in private by trained interviewers using a structured questionnaire at the research office located in the area of recruitment. At the completion of each interview, participants were pretest counseled about HIV, HBV, and HCV infection risk by a trained phlebotomist/counselor. Blood specimens were drawn by venipuncture from consenting participants and tested for HIV-1 antibody (enzyme immunoassay with Western blot confirmation, Abbott, Abbott Park, IL), antibody to the HBV core antigen (Abbott, CORZYME immunoassay), and HCV antibody (Abbott, EIA 2.0). Participants returning for their results received post-test counseling. Referrals to health and social services and to drug treatment were available. After completing each interview, participants were given a small monetary payment for their time and travel expenses. All procedures involving human subjects were approved by the Institutional Review Board at National Development and Research Institutes, Inc. Additional descriptions of study protocols are available elsewhere.11,33,37-39 Further information can be obtained from the first author.

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Measures and Variables

To determine whether a transition to injecting had occurred, participants were asked at each follow-up interview if they had injected illicit drugs since their last interview, and the date when this first occurred. Injecting was defined for participants as intravenous (into the veins), intramuscular (into the muscles), or subcutaneous (under the skin only, or "skin popping") and included self-injection or injection by others. A transition to injecting is defined as the first injection of illicit drugs since the baseline interview. Potential explanatory variables were grouped into sociodemographic and other individual background characteristics (as measured at the baseline interview); current individual susceptibility; and social network influence.

Social network influence variables were based on participants' responses to questions about specific people with whom they had had contact in the prior 30 days and with whom they had used drugs or had sex, or to whom they would go for advice or for emotional or material support. Summary measures of social network influence were obtained using principal-components analysis with varimax rotation on 6 social network influence variables. Variables with factor loadings >0.6 were used to derive 2 orthogonal factors: "communication promoting drug injecting" and "exposure to current injecting drug users" (Table 1).



Principal-components analysis with varimax rotation was also conducted on 7 variables measuring personal attitudes about drug injectors. Variables with factor loadings >0.6 were used to derive 2 orthogonal factors: "perceived social distance from IDUs" and "perceiving injecting as stigmatized" (the direction was lower perceived social distance and lower stigmatization of injecting) (Table 1). Because the distributions of the factor scores on all 4 factors were skewed, the factor scores were dichotomized at the median.

The Severity of Dependence Scale was used to measure the perceived severity of heroin dependence for the prior 30 days, with a cut-off of ≥6 (range 0-15) indicating heroin dependence.20 Depression in the prior 30 days was measured using a shortened 8-item version of the 20-item Center for Epidemiological Studies Depression Scale (CES-D).40,41 A score of ≥7 is an indicator of having clinically significant levels of depressive symptoms.

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Statistical Analysis

Separate analyses were conducted for never-injectors and former-injectors. Participants who reported never injecting but who tested HCV seropositive at baseline (n = 27) were excluded from the analysis, because HCV infection may indicate prior injecting experience. The days at risk were derived from the number of days in the interval between the baseline interview date and either the date of the first injection or, for those who did not make a transition to injecting, the final interview date. Rates for transitioning to injecting are reported per 100 person-years at risk (pyar). Kaplan-Meier analyses estimated the cumulative incidence of transitioning to injecting. Differences in the transition incidence by injecting history are assessed by the log-rank test. Cox proportional hazards regression was used to analyze the predictors of making a transition to injecting. Each interview visit was analyzed as an independent unit of analysis, with variables that could vary over time between follow-up visits treated as time-independent using the counting method of Cox proportional hazards regression.42,43

The variables for current individual susceptibility analyzed as predictors of making a transition to injecting were for the most recent period prior to the period in which the transition to injecting occurred or, for right-censored observations, for the most recent period prior to the period reported in the final interview. Because social network influence may diffuse among network members over time,32,44 the social network influence variables analyzed measured any social network influence occurring from 30 days prior to the baseline interview up to and including the most recent period prior to the transition to injecting period or, for right-censored observations, up to and including the most recent period prior to the final interview period.

Interaction terms between current individual susceptibility variables and social network influence variables were created and coded as: 1 = social network influence favoring drug injecting and current individual susceptibility for injecting drugs vs. 0 = no social network influence favoring drug injecting or no current individual susceptibility for injecting drugs.45

Univariate analyses and multivariate Cox proportional hazards regression analyses using stepwise methods with backwards elimination were conducted in 2 stages. In the first stage, univariate analyses followed by preliminary multivariate analyses were conducted separately for the interaction terms and then for the sociodemographic and individual background and current individual susceptibility variables. In the second stage, variables that remained significant at P < 0.20 in the separate preliminary multivariate analyses from the first stage were pooled and entered into a final multivariate Cox proportional hazards regression analysis. Variables statistically significant at P < 0.05 in the pooled final multivariate analysis were retained in the final models.

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Follow-Up Characteristics

Of 579 eligible participants due for follow-up, 369 (64%) were followed up, including 160 former-injectors (43%) and 209 never-injectors (57%). Former-injectors were more likely to be followed than never-injectors (70% or 160/228 vs. 60% or 209/351, P < 0.01). The mean number of months followed up was significantly shorter for former-injectors (24.9 vs. 31.2). Never-injectors generated 543.3 person-years of follow-up time and former-injectors 332.0 person-years (Table 2).



For both groups, those followed were older, less likely to be white, and more likely to have ever been or currently be in drug treatment. Among never-injectors only, those followed were less likely to be homeless. There were no significant differences in baseline drug use characteristics by follow-up status in either group (data not shown).

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Baseline Characteristics of the Follow-Up Sample

At study entry, those followed up were predominantly (66%) male and had a mean age of 34.6 years (Table 2). Hispanics were the most numerous (44%) race/ethnic group. Many were low income and had not graduated from high school, and just over a quarter (28%) were homeless.

Two-thirds had ever been in drug treatment and a quarter were currently in drug treatment. The mean age at first heroin use was 22.5 years, and the mean number of years since first using heroin was 12.0. Among former-injectors, the mean number of years since last injecting any drugs was 8.1. Daily heroin use was reported by 40%, and current crack and noncrack cocaine use was common (40% and 43%, respectively). Most (91%) reported always using noninjected heroin intranasally ("sniffing").

Of those serotested, 10% were HIV seropositive in both groups. Evidence of prior infection with HBV was significantly higher among former-injectors (49% vs. 21%), and over half (57%) of former-injectors were HCV seropositive. Only half (53%) of those testing HIV seropositive reported being HIV infected, and very few testing HBV and HCV seropositive reported being infected (16% and 12%, respectively).

Other significant baseline differences between never-injectors and former-injectors are shown in Table 2.

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Transition Rates

Seventy-eight participants (21%) made a transition to injecting, with former-injectors significantly more likely to report a transition than never-injectors (33% or 53/160 vs. 12% or 25/209; P < 0.001) (Table 3). The overall transition rate was 8.9/100 pyar (95% CI: 7.0 to 11.0). Former-injectors made a transition at a significantly faster rate (16.0/100 pyar, 95% CI: 12.0 to 20.5 vs. 4.6/100 pyar, 95% CI: 3.0 to 6.6; HR = 3.25, 95% CI: 2.0 to 5.2) (Fig. 1). The cumulative incidence was 55.4% for former-injectors vs. 18.0% for never-injectors (P < 0.0001).





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Predictors of Initiating Injecting Among Never-Injectors

In univariate analysis, the strongest significant individual attribute predictors (hazards ratio [HR] ≥3.0 or ≤0.33, P < 0.05) of initiating injecting included white race/ethnicity; identifying as a woman who has sex with women; using ≥2 bags of heroin a day; attempting suicide since the prior interview; and having any friends who think it is "OK" to inject drugs (Table 3). Several interaction variables between social network influence and current individual susceptibility were significant (P < 0.05), with most having crude HRs of ≥3.0 (Table 4). In the final multivariate analysis, the independent predictors of initiating injecting included the interaction of greater communication promoting drug injecting and being homeless; the interaction of greater exposure to current IDUs and being physically abused; using ≥2 bags of heroin a day; duration of heroin use of <9 years; having any friends who think it is "OK" to inject drugs; lower perceived social distance from IDUs; younger age at first heroin use; and any crack use in the past 30 days (protective) (Table 5).





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Predictors of Resuming Injecting Among Former-Injectors

In the univariate analysis of individual attributes among former-injectors, only white race/ethnicity was both significant and had a HR ≥ 3.0 (Table 3). Significant (P < 0.05) interaction terms are indicated in Table 4, with the majority having HRs ≥3.0. In the final multivariate analysis, the independent predictors of resuming injecting among former-injectors included the interaction of greater communication promoting drug injecting and lower perceived social distance from IDUs; white race/ethnicity; not being very afraid of injecting self with needles; younger age; and daily alcohol use (protective) (Table 5).

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In this 7-year longitudinal study of NIUs, the rate of transition into injecting was almost 9 per 100 pyar, with a 5th of those followed up making a transition to injecting. Moreover, the risk of making a transition to injecting was considerably higher among former-injectors than among never-injectors. Although it appears that noninjecting heroin use does not always lead to injecting drug use for either never-injectors or former-injectors, for some NIUs it may not be a consistent route of heroin administration, especially among former-injectors, as earlier studies in New York City9 and Amsterdam10 also demonstrated. Among never-injectors, the rate of transition, at 4.6 per 100 pyar, was relatively low compared with that found among never-injectors in Amsterdam10 and Montreal.28 The lower rate in New York City may reflect sampling variation, intercity differences in the average purity of heroin (in New York City purity has remained high-averaging >60% pure during the past decade),3,8,16 or the long-term effects of HIV prevention and control efforts in New York City.46

Among never-injectors, the hypothesis that social network influence facilitates a transition to injecting among those with greater individual susceptibility is supported by the findings. Two network facilitation variables predicted initiation into injecting. Those who were homeless and who had social network members who engaged in greater direct communication with them that promoted drug injecting were more likely to initiate injecting. These homeless NIUs may be receptive to direct social influence promoting injecting because they may have fewer social contacts with non-IDUs (who may provide a protective social influence)47 and greater social contact with homeless drug users who may be more likely to inject drugs.28,29,48 Those who were recently physically abused and had greater exposure to current IDUs were also more likely to initiate injecting. NIUs who have experienced physical (or sexual) abuse22 may seek to self-medicate the physical and emotional pain often associated with such abuse17,22,49 and may be receptive to social influence promoting drug injecting. Other variables associated with making a transition to injecting that may also reflect current or past social network influence include the perception that friends approve of or condone drug injecting, and lower perceived social distance from IDUs.

The individual attribute variables associated with initiating injecting are consistent with other studies. Using ≥2 bags of heroin a day prior to initiation confirms that those using more heroin are at greater risk of initiating injecting.10 High-volume heroin users are more likely to be heroin dependent14 and may have a more expensive heroin habit, which would increase their motivation for making a transition to injecting.26,50 Never-injectors who are younger or shorter-term heroin users may also be less experienced in how to self-regulate their heroin use, or may be more willing to experiment with different routes of drug administration, and may initiate injecting more rapidly than older or longer-term NIUs who have never injected.18,23,51,52 Crack use, which was protective, may provide an alternative to using heroin and, in New York City, may indicate less social contact with IDUs, most of whom inject heroin.

The findings among former-injectors also lend support to the social network facilitation hypothesis. The strongest predictor of resuming injecting was having social network members who engaged in greater direct communication with them that promoted drug injecting and having lower perceived social distance from IDUs. Many former-injectors had, or may still have, social contact with IDUs, and are likely to have relatively low perceived social distance from IDUs. However, among former-injectors, lower perceived social distance from IDUs was not sufficient by itself to significantly increase the risk of resuming injecting, but instead was facilitated by direct communication from social network members promoting drug injecting.

Other risk factors among former-injectors included sociodemographic and other individual attributes. Those who identified as "white" race/ethnicity were at greater risk of resuming injecting. Other studies have also found that race/ethnicity, which is likely to be a marker for other factors, is associated with making a transition to injecting.10,17,20,50,53 The greater risk of resuming injecting among white NIUs may also indicate that, in New York City, many nonwhite NIUs, particularly those who are African American/black, are avoiding injecting drug use.46,54 Younger former-injectors may be more likely to resume injecting for reasons that may be similar to those among never-injectors who are shorter-term heroin users or who adopted heroin use at a younger age. Not being very afraid of injecting oneself with needles may indicate a greater level of experience with injecting drugs, which may reduce any practical or emotional barriers against injecting.5,12,16,18,23 Alcohol use was protective among former-injectors, possibly because it is a legal alternative to heroin and may be used for self-regulating heroin use, as was found in the ethnographic component of this study,18 although alcohol use is a serious health risk among those infected with HCV.55

A comparison of the final multivariate models among never-injectors and former-injectors suggests that never-injectors may be less resistant to indirect social influence promoting drug injecting. For never-injectors with increased individual susceptibility, but not for former-injectors, a transition to injecting was predicted by indirect social influence, eg, through greater exposure to current IDUs. Importantly, compared with former-injectors, never-injectors are also at increased risk of injecting if they are high-volume heroin users, which may indicate less capacity to self-regulate the volume of heroin use and reflect their lower participation in drug treatment programs.

The relatively low (for New York City) baseline seroprevalence (10%) of HIV among both never- and former-injectors, which is lower than the average of about 20% among IDUs in New York City found in recent studies,54,56 is evidence that noninjecting heroin use may help reduce, although not eliminate, HIV infection risk. However, because 21% of never-injectors tested positive for prior infection with HBV at baseline, NIUs may be at considerable risk of sexually transmitted infections, including HIV, HBV, and other infections. Moreover, the high (57%) baseline seroprevalence of HCV among former-injectors strongly suggests that HCV spreads rapidly among IDUs and increases the urgency to prevent transitions to injecting drug use by NIUs.

The transition to injecting by NIUs appears to be neither universal nor rapid, especially among never-injectors. Therefore, there is a substantial window of opportunity for prevention. A basic intervention among NIUs is to reduce heroin dependence and to encourage the cessation of heroin use by increasing the availability, access to, and continuity of appropriate and effective treatment for opiate addiction. NIUs' social networks should also be used for interventions.29,57-59 For example, interventions among never-injectors should prevent the diffusion of injecting drug use.32,44 by using their social networks to foster preventive communication, norms, and practices among network members and by reducing the level of indirect social influence from exposure to current IDUs, such as by providing stable housing and assistance in reestablishing contact with sympathetic relatives and friends who do not inject drugs. Among former-injectors, social network interventions can be used to develop a peer culture opposed to the resumption of injecting drug use. Because trauma stemming from physical and sexual abuse may increase individual susceptibility, interventions are also needed to address long-term psychological and other health effects of such trauma. Given the multiple and related risk factors for making a transition to injecting, there appears to be a need for comprehensive and concurrent intervention strategies targeted to specific NIU subpopulations.

The data have several limitations. The moderate follow-up rate may have decreased statistical power, although the follow-up rate approaches that of other studies conducted among non-treatment recruited drug users in New York City, with follow-up rates of 68%,60 70%,61 and 80%,9 and the HRs for most final significant predictors were close to ≥2.0. Some significant interaction terms in univariate analysis may have occurred by chance because of multiple comparisons62; however, all the interaction terms remaining in the final multivariate models were also statistically significant in univariate analysis. Although continuing participation in a cohort study may generate social desirability bias, when variables from the Marlowe-Crowne social desirability scale63 were entered into the final models, they were not significant and the HRs of the other variables remained stable and significant. Finally, chain referral sampling methods can introduce sampling biases; however, there was no significant difference in the percentage of participants recruited by study participants already in the study between former-injectors and never-injectors (35% vs. 33%, P < 0.69) and between those who made a transition to injecting and those who did not (27% vs. 36%, P < 0.27).

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Preventing the transition to injecting drug use among NIUs is fundamental to preventing and controlling HIV, HBV, and HCV epidemics among heroin users and from them to their sex partners. The prevention of transitions to injecting among infected NIUs can help prevent an increase in the number of infected IDUs, and reducing transitions to injecting among uninfected NIUs can help shrink the pool of drug users susceptible to parenterally transmitted infections and reduce the spread of infections to their sex partners. Preventing transitions to injecting among noninjecting heroin users (as well as noninjecting users of other hard drugs), by focusing on social network influence as well as individual susceptibility, is essential in helping to break the chain of drug injecting-related epidemics of HIV and similarly transmitted pathogens and in preventing other adverse health outcomes related to drug injecting.

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The authors thank the members of the research staff who have worked on the study, including Gilbert Ildefonso, Stephen Sifaneck, Xavier Andrade, Kristine Ziek, Peter Blasko, Jesse de Jesus, and other research staff. This research would not have been possible without the consent and assistance of the drug users who agreed to participate in the study.

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noninjecting heroin users; IDU; transitions to injecting; risk factors for IDU; social networks; individual susceptibility

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