People Who Inject Drugs (PWID)

"We estimated nearly 3.7 million people, or 1.5% of the US adult population, injected drugs in 2018. This estimate is more than 5 times the most recent US estimate of ∼774,000 from 2011 [25]. Much of this increase is likely attributable to increases in IDU, but it is important to consider methodological differences in the creation of this 2018 estimate vs the 2011 estimate. The 2011 estimate was based on self-reported IDU among respondents to household surveys [26], but the present estimate combines available data on substance-specific overdose deaths and treatment admissions with cohort and cross-sectional data collected from known PWID. Applying the same data sources and analytic methods used for the 2018 estimate to 2011 yields an estimated 1.3 million PWID in 2011, which suggest the 2018 estimate is closer to 3 times higher than in 2011. By any measure, these estimates suggest the number of PWID has increased substantially in the U.S. during the past decade.

"One of the primary contributions of this estimate is the transparent, replicable nature of the methods described. Overdose data specifically among PWID in the United States continue to be relatively sparse, both in research and surveillance data. We used the best data currently available for each input, which are subject to limitations in some cases given data sparsity. For example, we used the meta-analyzed ratio of fatal to nonfatal overdose among PWID in OECD countries rather than a ratio specific to the United States, which was unattainable given currently available data. The uncertainty associated with this meta-analyzed ratio is reflected in confidence intervals around estimates presented here. Our intention is that, as surveillance systems implemented in the United States in recent years mature [39], resulting data can be used to refine and update this PWID population size estimate.

"Notwithstanding data input limitations, this updated estimate provides a data point for monitoring the US PWID population size over time and can inform strategies to reduce transmission of infectious diseases. In recent years, political will has been building to eliminate HCV and HIV infections in the United States [27, 28]. Both bloodborne infections disproportionately affect PWID but are highly preventable using evidence-based interventions, such as provision of sterile syringes through syringe services programs and substance use treatment [40–43], as well as treatment of prevalent infections with antiretroviral therapy [44] and direct-acting antivirals [45]. Increases in IDU prevalence will threaten the success of elimination strategies for HCV and HIV infections in the absence of concomitant increases in availability of harm reduction services and treatment for both infectious diseases and substance use. These services will need to be substantially scaled up nationally to meet the needs of nearly 4 million people [46].

"In addition to the high burden of infectious diseases, PWID experience preventable mortality and morbidity due to drug overdose. Overall, the rate of overdose deaths increased from approximately 6 per 100,000 persons to 22 per 100,000 persons during 1999–2019 [21], and provisional data indicate the number of overdose deaths increased by another 31% during just 1 year of the pandemic era from March 2020 to March 2021 [24]. During the pandemic era in particular, many questions remain about the extent to which increased overdose mortality rates are attributable to injection initiation vs changes in injection behaviors or the drug supply as well as to disruptions in access to treatment and recovery support services and harm reduction services. These estimates provide a prepandemic baseline and can improve our understanding of potential increases vs changes in pandemic-era injection behavior."

"This report describes data from 11,437 PWID who participated in NHBS in 2018, of whom 69% identified as male, 30% female, and 1% transgender; 39% were white, 33% were black, and 21% were Hispanic or Latino; 36% were aged ≥50 years (Table 1). Among all participants, 26% had no health insurance, 21% had not visited a health care provider, and the household income of 75% of participants was at or below the federal poverty level.

"In 2018, 6% of participants with a valid NHBS HIV test result tested positive for HIV (Table 2). By gender, HIV prevalence was as follows: 6% among males, 6% among females, and 28% among transgender. By race and ethnicity, HIV prevalence was as follows: 9% among blacks, 8% among Hispanics or Latinos, and 4% among whites.

"CDC recommends that persons at increased risk of HIV infection, including PWID, undergo HIV testing at least annually [10]. Among participants who did not report a previous HIV-positive test result or who had received their first HIV-positive test result less than 12 months before the interview, 55% reported that they had been tested for HIV in the 12 months before the interview, and 90% reported that they had ever been tested (Table 3).

"Among participants who reported being tested for HIV in the 12 months before the interview, 66% reported their most recent test was performed in a clinical setting while 29% reported being tested in a nonclinical setting, such as an HIV counseling and testing site, an HIV street outreach program or mobile unit, a SSP, or at home (Table 4)."

"From January–June 2020 to July–December 2022, the number of overdose deaths with evidence of smoking doubled, and the percentage of deaths with evidence of smoking increased across all geographic regions. By late 2022, smoking was the predominant route of use among drug overdose deaths overall and in the Midwest and West regions. Increases were most pronounced when IMFs were detected, with or without stimulants. Increases in the number and percentage of deaths with evidence of smoking, and the corresponding decrease in those with evidence of injection, might be partially driven by 1) the transition from injecting heroin to smoking IMFs [Illicitly Manufactured Fentanyl] (3,4), 2) increases in deaths co-involving IMFs and stimulants that might be smoked†††† (1), and 3) increases in the use of counterfeit pills, which frequently contain IMFs and are often smoked (7). Motivations for transitioning from injection to smoking include fewer adverse health effects (e.g., fewer abscesses), reduced cost and stigma, sense of more control over drug quantity consumed per use (e.g., smoking small amounts during a period versus a single injection bolus), and a perception of reduced overdose risk among persons who use drugs (3,5,8). These motivations might also signify lower barriers for initiating drug use by smoking, or for transitioning from ingestion to smoking; compared with ingestion, smoking can intensify drug effects and increase overdose risk (9). Despite some risk reduction associated with smoking compared with injection (e.g., fewer bloodborne infections), smoking carries substantial overdose risk because of rapid drug absorption (5,9).

"Nearly 80% of overdose deaths with evidence of smoking had no evidence of injection; persons who use drugs by smoking but do not inject drugs might not use traditional syringe services programs where harm reduction messaging and supplies are often provided. In response, some jurisdictions have adapted harm reduction services to provide safer smoking supplies or established health hubs to expand reach to persons using drugs through noninjection routes.§§§§ In addition, harm reduction services (e.g., peer outreach and provision of fentanyl test strips for testing drug products and naloxone to reverse opioid overdoses), messaging specific to smoking drugs, and linkage to treatment for substance use disorders can be integrated into other health care delivery (e.g., emergency departments) and public safety (e.g., drug diversion) settings.

"The percentage and number of deaths with evidence of injection decreased across regions and drug categories. Observed decreases might reflect transitions to noninjection routes and response to public health efforts to reduce injection drug use because of its risk for overdose and infectious disease transmission (3,4,10). Despite these declines, more than 4,000 drug overdose deaths had evidence of injection during July–December 2022. Syringe services programs help to engage persons who use drugs in services (10); sustained efforts to provide sterile injection supplies, additional harm reduction tools, and linkage to treatment for substance use disorders, including medications for opioid use disorder, are important for further reduction in the number of overdose deaths from injection drug use. Lessons learned from implementing syringe services programs could be applied to other harm reduction and outreach models to reach more persons who use drugs by any route."

"Common SSTIs include cellulitis (Figure 1) and skin abscesses (Figure 2),⁵ and SSTI is common in PWIDs. In one needle exchange program (N = 152), 17.8% (n = 27) had an active abscess and 19.7% (n = 30) had a chronic wound.⁶ The upper extremities were the most common place for an abscess, and the lower extremities were most common for chronic wounds. In a study of active (injected in the past 30 days) PWIDs (N = 201) recruited in San Francisco between 2011 and 2013, Dahlman and colleagues⁷ noted the self-reported prevalence of lifetime SSTIs was about 70%. These infections can lead to serious morbidity and costly emergency room visits and hospitalizations. By assessing billing records through chart abstraction for 349 PWIDs in Florida, SSTIs were reported in 64% (n = 223); the total cost to the hospital for services rendered to treat injection drug use-related infections for a year was approximately $11.4 million.⁸ According to the Hospital Episode Statistics for England 1997–2016, about 6% (n = 63,671) of SSTIs and vascular infections are injection related.9 The most common causes were cutaneous abscess, phlebitis, and cellulitis. The number of injection-related admissions increased 33% per year from 1997 and 1998 through 2003 and 2004.⁹

"Two terms are important to aid in the understanding of SSTIs in PWIDs: skin popping and speedballing. Skin popping is extravasal (intramuscular or subcutaneous) injection into confined tissue compartments. When injected into a vascular space, drugs are quickly diluted. This dilution effect does not occur when drugs are injected into skin or muscle.¹⁰ Subcutaneous and intramuscular injections also bypass exposure to the bloodborne immunologic response, which may increase the risk of infection.¹¹

"Speedballing is injecting heroin in combination with a vasoconstrictor such as cocaine or methamphetamine. This decreases local blood flow to the injection site and exacerbates ischemia.11 The addition of crack cocaine to heroin is rationalized as providing a 'better high.'¹² The use of crack cocaine in speedballing has been associated with the deterioration of injection sites.¹² In general, speedballing is associated with an increased risk of infection.¹³"

"Globally, there are nearly 15.6 million people (aged 15–64) who inject drugs (PWID), with an estimated 2.6 million PWID in North America (Degenhardt et al., 2017). Canada and the United States (US) have both seen significant increases in the rate of injection drug use, as well as a rise in the rate of infections and fatal overdose related to injection drug use (Jacka et al., 2020; Levitt et al., 2020). The risk of fatal overdose significantly increases when people inject drugs alone, and may be prevented with timely intervention (i.e. administration of naloxone, an overdose prevention medication) (Colledge et al., 2019). There is also an increased risk of disease transmission (e.g. HIV, hepatitis) and serious infections associated with injecting drugs, which are often related to using unsterile equipment, injecting in unhygienic settings, or rushed injections (Colledge et al., 2019). The increase in injection drug use and the risks associated with using alone, in unhygienic or unsupervised settings necessitate the need for services that support safe injection practices among PWID."

"Importantly, our results show that evidence of injection was more prevalent among decedents with xylazine and heroin and/or fentanyl detections. Despite limited literature on the health effects of chronic xylazine use, regular injection of xylazine has been associated with skin ulcers, abscesses and lesions in Puerto Rico.^{2 3} Semistructured interviews with people who use xylazine in Puerto Rico revealed that regular use of xylazine leads to skin ulcers.⁴ As skin ulcers are painful, people may continually inject at the site of the ulcer to alleviate the pain as xylazine is a potent α2-adrenergic agonist that mediates via central α2-receptors, which decreases perception of painful stimuli.¹ People may self-treat the wound by draining or lancing it, which can exacerbate negative outcomes.⁸ While Philadelphia has seen a rise in skin and soft tissue infections relating to injection drug use, it is not yet clear whether or not this is due to increased presence of xylazine in the drug supply.⁹"

"People who use heroin (PWUH) have increased morbidity and mortality compared to the general population [1]. A syndemic of opioid overdose, human immunodeficiency virus (HIV), hepatitis C virus (HCV), skin and soft tissue infections (SSTI), and infective endocarditis accounts for many of the poor health outcomes among PWUH [2,3,4,5]. Heroin can be consumed in several ways, including injection and smoking [6]. High-risk injection behaviors, including syringe sharing and reuse of non-sterile injection equipment, are established routes of HIV and HCV transmission and increase risk of SSTI and infective endocarditis [7,8,9]. Opioid overdose is a common cause of mortality among PWUH, with higher overdose risk among those who inject [10,11,12].

"Because smoking heroin does not injure the skin or introduce non-sterile equipment into blood or tissue, this method of consumption does not entail the same risk of blood-borne infections or SSTI compared to injection. While similar pharmacological effects can be achieved by smoking or injecting heroin, peak plasma concentrations are 2–4 times lower when heroin is smoked, which may reduce risk of lethal opioid overdose [13, 14]. Programs that encourage PWUH to transition from injecting to smoking heroin may decrease injection frequency and thereby reduce harms associated with heroin use, including risks of infection and overdose [15]. Distribution of smoking equipment may also help PWUH avoid using pipes fashioned from cans or other poor-quality materials that easily crack or overheat, thereby reducing risk of developing burns or cuts on the lips that can serve as sites of infection [16,17,18]. Pipe distribution programs may also reduce pipe sharing, a risk behavior potentially associated with respiratory virus or HCV transmission [17,18,19,20]."

"In this pilot pretest–posttest quasi-experimental study, we saw a lower proportion of SSP clients exclusively inject heroin and a higher proportion of SSP clients consume heroin through both injection and smoking after the implementation of a heroin pipe distribution program. The proportion of SSP clients who reported syringe reuse was also lower following the heroin pipe distribution intervention. We did not observe any difference in self-reported health outcomes associated with drug use between the pre- and post-intervention periods; however, the short follow-up period and small sample size of this pilot study may have contributed to this null finding. Our results suggest heroin pipe distribution may be a novel RTI that can be added to existing SSPs to further reduce harms associated with heroin use. This study also highlights the potential for public health service innovations to be developed by marginalized communities and the importance of placing PWUD in leadership positions in efforts to optimize harm reduction programming.

"Despite the non-randomized design of this pilot study, several findings suggest heroin pipe distribution may have prompted changes in heroin consumption behaviors among PWUH. The proportion of SSP clients who exclusively injected heroin was lower by a quarter, while the proportion who both injected and smoked heroin was higher by over a quarter after heroin pipe distribution began. Twenty-four percent of respondents who used heroin reported heroin pipe distribution had reduced their heroin injection. Higher proportions of SSP clients who received heroin pipes exclusively smoked heroin or both smoked and injected heroin compared to SSP clients who did not receive a heroin pipe. We are unaware of any prior published research investigating heroin pipes as an RTI; however, pre–post-analyses examining foil distribution at SSPs in Europe found similar changes in drug consumption behaviors, with up to 85% of SSP clients having used foil to inhale rather than inject heroin on at least one occasion [23, 28]. Our non-randomized study design cannot control for confounding and prevents firm conclusions as to whether this observed shift from injection to smoking can be attributed to the intervention. Additionally, only 14% of respondents who used heroin completed surveys during both the pre- and post-intervention periods, and thus, outcomes may have been impacted by changes in the SSP client population across time periods. Further experimental research is needed to clarify the causal relationship between heroin pipe distribution and reductions in heroin injection. Study designs that are randomized by individual may be complicated by heroin pipe sharing across intervention and control groups. Cluster randomization may better control for contamination given extensive social networks and resource exchange among PWUD [29]."

"There are an estimated 15.6 million people who inject drugs (PWID) globally (3.2 million women and 12.5 million men). Among these persons, an estimated 17.8% are living with HIV, 52.3% are Hepatitis C (HCV)-antibody positive, and 9.1% are Hepatitis B (HBV) surface antigen positive [1]. PWID are also at high risk for skin and soft tissue infections and infective endocarditis [2–5]. In addition, injection drug use increases risks for fatal and nonfatal overdose [6–9]. Global estimates suggest that 82.9% of PWID primarily inject opioids, underscoring the urgency of implementing evidence-based response strategies to mitigate the range of adverse consequences associated with the opioid crisis [1]."

"The emergence of xylazine has led to several unintended consequences for PWUD [People Who Use Drugs] across North America, such as tissue necrosis and heightened sedation, the latter of which has potential implications for elevated risk of overdose and social consequences (such as being robbed or assaulted) [5, 21]. Here, we identified how the emergence of xylazine has also precipitated a range of behavioral responses among PWUD, with implications for their individual health and the broader healthcare system [22].

"We identified dynamic communication processes through which information about xylazine emerged and spread among SSP staff and clients, ultimately leading to a formal response by the SSP via the use of XTS [17]. Notably, the initial identification of xylazine was driven by clients’ firsthand experiences with the unregulated opioid supply. Clients then shared their observations and experiences with SSP staff, underscoring the importance of building trust and listening to client expertise, which can serve as an early warning system for emerging adulterants prior to adverse consequences. In contrast, many of the official accounts of xy-lazine adulteration are based on overdose surveillance data or medical examiner reports [9, 13–15, 23], which can take time to process. In addition, most official early warning systems focus on mass spectrometry or drug seizure data, which may involve a time lag and is resource intensive [24, 25], especially in the Southern U.S. where comprehensive drug-checking services are sparse [26, 27]. Integrating qualitative insights from PWUD into current early warning systems may provide another avenue for proactive intervention that can indicate the presence of a novel adulterant using relatively few resources and can be scaled locally via SSPs or other settings that serve PWUD (e.g., drug treatment facilities). Indeed, improved collaboration between harm reduction programs and surveillance professionals, including medical examiners and crime laboratory personnel, could circumvent and augment delays in reporting systems. Of course, caution is needed in the development and deployment of warning systems to avoid sensationalizing harms or generating “alert fatigue,” where PWUD and their communities are inundated with information [28, 29]. These findings also emphasize the benefit of embedding research within harm reduction settings to further empower these organizations in responding to emerging challenges."

"Within a large cohort of people with opioid use disorder in New South Wales, Australia, we performed a self-controlled study to test the effect of incarceration and OAT transitions on the risk of hospitalization with injection drug use-associated bacterial infections. Compared to time between five and 52 weeks continuously living in the community, incidence of injecting-related infections increased before incarceration; was similar during the first two weeks of incarceration; and then substantially decreased among people in prison for more than three weeks. Risk was again elevated in the weeks immediately following release from prison. Compared to time between five and 52 weeks continuously receiving OAT, incidence of injecting-related infections was highest during the weeks both before and after OAT initiation and OAT discontinuation. Overall, we found that risk for injecting-related bacterial infections varies greatly within-individuals over time. Social contextual factors likely contribute to the substantially raised risks around transitions in incarceration and OAT exposure. People entering and leaving prison, and people starting and stopping OAT, may benefit from improved access to harm reduction programs and health and social services to prevent injecting-related bacterial infections. Changes in the risk of hospital admissions with injecting-related infections in and out of prison and OAT may also reflect changes in the ability to access primary and secondary health services.

"The increase in risk immediately following prison release may reflect return to injection use, poor access to health and social supports, and material deprivation (poverty and homelessness) (Binswanger et al., 2012; Joudrey et al., 2019; Treloar et al., 2021). This underscores that people leaving prison would benefit from better health, social, and economic supports, and linkages to harm reduction services and primary care. The excess risk for injecting-related infections during this time period (when compared to people injecting drugs in the community at other times, we estimate 1.45 times the risk, 95% CI 1.22-1.72) may be more modest than that seen for overdose (e.g., 2.44 times higher fatal overdose rate in a cohort study from New South Wales, Australia (Degenhardt et al., 2014); 2.76 times higher nonfatal overdose risk in a self-controlled cases series from British Columbia, Canada (Keen et al., 2021)). Incarceration often leads to loss of opioid tolerance, especially among people not receiving OAT in prison (Degenhardt et al., 2014; Joudrey et al., 2019), which likely increases overdose risk more so than infection risk. Given that the median duration of prison stay was only 16 days, excess risk of infection-related hospitalization after release may also reflect people seeking treatment outside prison for infections that initially developed before or during incarceration (Lloyd et al., 2015)."

"Canada is in the midst of a devastating overdose crisis that has been further exacerbated by the COVID-19 pandemic and, in particular, the subsequent increased toxicity of the drug supply [1]. Between January 2016 and June 2022, close to 33,000 people died from an overdose in Canada, with the provinces of British Columbia, Ontario, and Alberta accounting for 88% of those deaths [2]. Fentanyl, and to a lesser extent fentanyl analogues, have contributed to a sharp rise in the toxicity of the unregulated drug supply and fatal overdoses [2]. Between January and June 2022, fentanyl was detected in 76% of overdose deaths in Canada [2]. In Ontario, fentanyl is involved in 88% of fatal overdoses [3]. In Toronto, this number rises to 93% [3]."

"UNODC, UNAIDS, WHO and the World Bank jointly estimate that some 11.2 million persons worldwide injected drugs in 2020. There has been no measurable change in the estimated global prevalence of injecting drug use from the previous estimate for 2019, which was also 0.22 per cent of the population aged 15–64. However, any trend data must be viewed with caution as the methodologies used to produce national or subnational PWID population size estimations may have changed.

"Approximately 59 per cent of PWID worldwide reside in East and South-East Asia, Eastern Europe and North America. Injecting drug use remains particularly prevalent in Eastern Europe and, to a lesser extent, Central Asia and Transcaucasia, and North America, with rates that are 5.8, 2.6 and 2.5 times the global average, respectively."

"Safer supply programs are not designed or implemented with the explicit goal of changing injection practices. However, the experiences of clients and providers help us understand how a structural intervention, such as safer supply, can impact other aspects of IDU (e.g., frequency of injection) and its associated health risks (e.g., HIV, HCV, etc.). As Perlman and Jordan [37] point out, structural interventions are important because “structural factors contribute potently to creating the context that renders individuals and areas vulnerable to the syndemic of [overdose, HCV, and HIV]” (p.109). These interventions work upstream, to change the “risk environment” [38, 39], rather than solely focusing on mitigating the downstream consequences at the level of the individual. Our study findings suggest that changing the “risk environment,” by providing an alternative to the toxic drug supply, creates more opportunities for risk reduction. Changes in injection practices identified in this analysis offer a compelling example.

"Our findings suggest that clients enrolled in safer supply programs changed their injection practices in three intersecting ways: (1) they changed how often they injected, (2) they changed what they injected, and (3) they changed their mode of consumption (from injecting to swallowing or snorting). These findings add to existing research [16,17,18] by providing a more dynamic understanding of injection practices in the context of safer supply programs and further supporting the idea that safer supply can contribute to reducing injection-related health risks in addition to overdose risks [40]. We posit that safer supply programs have the potential to address disease prevention and health promotion gaps that other stand-alone downstream harm reduction interventions (e.g., needle and syringe programs) cannot address, by working upstream and providing a safer alternative to fentanyl. As Rhodes [38] reminds us, harm reduction interventions such as needle and syringe exchange programs are crucial, but their effectiveness at preventing injection-related health risks can be undermined by a particular “risk environment.” For example, if a particular shift in the drug supply results in people injecting more frequently, such is the case with fentanyl, an HIV outbreakFootnote1 could occur even in jurisdictions where needle and syringe exchange programs are available [38].

"It is important to note, however, that not all changes in injection practices could be attributed directly to safer supply programs. We identified several indirect factors, such as poor venous access and having to inject hydromorphone tablets not intended for intravenous administration (for more on this, see study by Ivsins and colleages [17] and guidance by the British Columbia Centre on Substance Use [42]), which shaped the decision to stop injecting. Having the option of taking safer supply medications orally made this decision possible, but it is unclear if all clients who stopped injecting would have done so if they had access to a range of injectable safer supply medications and/or had better venous access. Moreover, it is unclear to what extent clients continued to inject because the safer supply medications dosage/potency was not meeting their needs, as suggested by clients who spoke of the need to supplement with fentanyl, and/or because they wanted to continue injecting. Future research should aim at exploring these nuances because safer supply programs are not intended as interventions to stop clients from injecting. If clients want to inject, they should be able to do so and access injectable safer supply medications (including injectable hydromorphone) as well as sterile supplies and supervised safer consumption services—a priority echoed in a recent report on substance use patterns and safer supply preferences of PWUD in British Colombia [43]."

"Overall, the number of PWID per 10,000 persons aged 15–64 years varied from 31 to 345 across MSAs [Metropolitan Statistical Areas], median 104.4 (mean 127.4; standard deviation 66.7; percentile range 76–162) in 1992 and from 34 to 324 across MSAs, median 91.5 (mean 103.6; standard deviation 56.4; percentile range 61–125 ) in 2007 indicating an overall decline in PWID prevalence across MSAs.

"Figure 5 shows the overall trajectory of the PWID prevalence rates based on the multilevel model. Trend analysis of the overall results is consistent with a decline in the early study period, followed by an increase in 2000–02, and then remaining stable thereafter over time. On average there has been very little change since 2002 (mean 105.0) to 2007 (mean 103.6). Overall, across the 96 MSAs the mean PWID prevalence mostly decreased during our study period, as did the dispersion of estimates over time."