Participants of a mail delivery syringe services program are underserved... by nextdistro

International Journal of Drug Policy 99 (2022) 103474

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Research paper

Participants of a mail delivery syringe services program are underserved by other safe sources for sterile injection supplies Benjamin T Hayes a,∗, Jamie Favaro b, Dan Coello b, Czarina N. Behrends c, Andrea Jakubowski a, Aaron D. Fox a a

Division of General Internal Medicine, Monteﬁore Medical Center, Bronx, NY, USA NEXT Harm Reduction, New York, NY, USA c Population Health Sciences, Weill Cornell Medicine, New York, NY, USA b

a r t i c l e

i n f o

Keywords: Harm reduction Syringe services program Mail delivery Women

a b s t r a c t Background: In the United States, accessing sterile injection supplies remains challenging for many people who inject drugs (PWID). Although women are less likely to inject drugs than men, women who do inject are disproportionately affected by IDU-related complications. Needle Exchange Technology (NEXT), the first formal online accessed mail delivery syringe services program (SSP) in the US, may overcome access barriers. We evaluated whether NEXT was reaching women participants and people without access to other safe sources of sterile injection supplies. Methods: This cross-sectional study examined NEXT participants who enrolled in the mail-delivery SSP from February 2018 through March 2021. All NEXT participants completed an online questionnaire during enrollment, which included sociodemographic and clinical characteristics and injection-related risk factors (including prior sources of sterile injection supplies). Multivariable logistic regression (MVR) was used to examine associations between gender and prior use of safe sources of injection supplies (i.e., SSPs or pharmacies). Results: 1,032 participants received injection supplies. Median age was 34 and participants were mostly cisgendered women (55%) and white (93%). 34% reported infection with HCV; women were more likely to report HCV infection than men (38% vs 28%; p < 0.01). 68% of participants acquired injection supplies from less safe sources. Few participants exclusively used safe sources for injection supplies (26%). In adjusted MVR analysis, women participants had significantly lower odds than men of having exclusively used safe sources for injection supplies (adjusted OR 0.71, 95% CI 0.52, 0.98). Conclusion: Our findings suggest that NEXT services are utilized by women and people without prior access to sterile injection supplies. Women participants were less likely than men to have exclusively used safe sources for sterile injection supplies. Future research should explore women’s preference for mail-delivery over in-person SSPs and determine whether online accessed mail delivery services can reach other underserved populations of PWID.

Background An estimated 1 million people in the United States (US) injected drugs from 2019 to 2020, and increases in injection drug use (IDU) have resulted in increases in new hepatitis C virus (HCV) infections, skin and soft-tissue infections, and HIV outbreaks among people who inject drugs (PWID) (Alpren et al., 2020; Capizzi et al., 2020; Centers for Disease Control and Prevention, 2020; Ciccarone et al., 2016; Peters et al., 2016; Wurcel et al., 2016). The infectious complications of IDU are preventable with adequate access to sterile injection supplies. Yet, despite

∗

Corresponding author. E-mail address: bhayes@monteﬁore.org (B.T. Hayes).

worsening IDU-related complication rates, the US has not made commensurate eﬀort to assure that PWID have access to these supplies. Accessing sterile injection supplies in the US remains challenging for most PWID. One review estimated that PWID in the US have access to only 20% of the quantity of new sterile syringes that the World Health Organization recommends to eﬀectively reduce blood-born pathogen transmission (Larney et al., 2017). There are few places where PWID can formally access sterile injection supplies, but syringe services programs (SSPs) and pharmacies are authorized to distribute syringes to PWID in most states. Attending SSPs reduces PWID’s risk of blood-born infections, such as HIV and HCV, and may reduce hospitalizations from

B.T. Hayes, J. Favaro, D. Coello et al.

International Journal of Drug Policy 99 (2022) 103474

skin and soft-tissue infections (National Research Council (US) and Institute of Medicine (US) Panel on Needle Exchange and Bleach Distribution Programs, 1995; Tomolillo et al., 2007; Wodak & McLeod, 2008). However, SSPs are primarily located in urban areas, with very little availability in non-urban areas. For example, SSPs are located in only 7% of 220 US counties that are most vulnerable to IDU-related HCV and HIV outbreaks (amfAR, 2017; Van Handel et al., 2016). Pharmacy distribution is equally limited. Even in regions with laws explicitly allowing the non-prescription sale of syringes to PWID, PWID still frequently face resistance from pharmacists (Chiarello, 2016; Meyerson et al., 2018; Meyerson et al., 2019). One “secret shopper” study showed that as few as 21% of pharmacies will sell syringes for this purpose (Pollini et al., 2015). As a result, most PWID are left without a reliable source of sterile syringes. Limiting sterile syringe access particularly impacts women who inject drugs. Although women are less likely to inject drugs than men, women who do inject are disproportionately affected by IDU-related complications, such as HIV, HCV infection, and overdose (Boyd et al., 2018; Esmaeili et al., 2017; Iversen et al., 2015; Leung et al., 2019; Lum et al., 2005; Nerlander et al., 2017; Page et al., 2019; Zibbell et al., 2018). A large international multicohort study found women who inject drugs to have 38% higher risk of incident HCV than men (Esmaeili et al., 2017). Intersecting social and structural forces, such as gendered interpersonal violence, gendered social norms, poverty and criminalization increase the overall vulnerability of women to the health risks of using drugs (Boyd et al., 2018; Iversen et al., 2015). Women who are racial or ethnic minorities, people who are transgender, and people who are in sexual minority groups also face overlapping social and structural forces that further marginalize women who use drugs (Boyd et al., 2018; Lyons et al., 2015; Netherland & Hansen, 2017; Vaezazizi et al., 2019). Although harm reduction programs, such as SSPs, attend to some needs of women who inject drugs, they may also inadvertently replicate the social and structural forces that undermine women’s autonomy and safety (Boyd et al., 2018). For example, in settings that are largely staffed and attended by males, women may feel unwelcome or unsafe, or face greater stigma (Boyd et al., 2018; El-Bassel & Strathdee, 2015). Additionally, women who are primary parental caregivers may lack child care support to attend in-person services or may be concerned about losing child custody if identified as a PWID (El-Bassel & Strathdee, 2015; Iversen et al., 2015). More research is needed to understand the factors that may limit or facilitate women’s participation in SSPs in the US, however there has been a compelling argument by many advocates to design more harm reduction that address the specific needs of women. Without reliable access to SSPs or pharmacies that will sell sterile syringes, PWID are left to find alternative sources for injection supplies, such as friends, acquaintances, or people selling drugs. Early investigations of injection practices in urban settings suggest that women rely more heavily upon these secondary sources of syringes – often without knowledge of whether acquired supplies have been used previously (Barnard, 1993; Bourgois et al., 2004; Epele, 2002; Sherman et al., 2001; Wagner, Jackson Bloom, Hathazi, Sanders, & Lankenau, 2013). These dynamics have not been well studied in non-urban settings. Additionally, secondary sources of syringes are subject to the same geographic and social limitations as primary in-person sources. Without access to sterile syringes, PWID inject more frequently with used syringes and engage in other high-risk injection practices (Allen et al., 2019). Thus, finding an SSP model that is easily accessible, readily available and acceptable to all PWID is imperative. Taking advantage of the ubiquity of internet access and the broad geographic reach of the US Postal Service, online access and mail delivery of sterile injection supplies may better reach underserved populations. Needle Exchange Technology (NEXT) Harm Reduction is the first formal mail delivery harm reduction program in the US, founded with the explicit goal of overcoming geographic barriers that limit access to SSPs and pharmacies (Hayes et al., 2021; Yang et al., 2021). Confirming that

this innovative model reaches people without access to other sterile syringe sources would provide support for service expansion. Our objective in this study was to examine the risk profile of NEXT participants focusing on whether NEXT was reaching cis-gendered women and people without access to reliable sources of sterile syringes. Preliminary data gathering from NEXT program staff had already suggested there were low numbers of participants from other groups that may be marginalized from SSPs, such as racial and ethnic minorities. We hypothesized that NEXT would be reaching a high proportion of people without access to reliable sources of sterile syringes and that women participants would be less likely than men to have been exclusively using SSPs and pharmacies for sterile syringes prior to using NEXT. We hypothesized that NEXT would be reaching a high proportion of people without access to reliable sources of sterile syringes and that women participants would be less likely than men to have been exclusively using SSPs and pharmacies for sterile syringes prior to using NEXT. These data will be used to optimize NEXT’s services and develop other harm reduction interventions that target underserved PWID. Methods This cross-sectional study used data collected at the time of enrollment for first-time NEXT SSP participants. The Institutional Review Board of the Albert Einstein College of Medicine approved the study protocol with a waiver for informed consent. Program overview NEXT was founded in 2018 with the goal of overcoming barriers to in-person SSPs. NEXT offers supplies that are generally available at inperson SSPs, including sterile injection supplies, naloxone for overdose prevention, and equipment to safely dispose of syringes, such as sharps containers and devices to clip off needle points. Using a web-based platform, NEXT allows participants to confidentially order supplies for mail delivery and provides harm reduction education and links to harm reduction services available by state. There are no costs to participants. When people do not have an address at which they can receive mail, NEXT will mail to post office general delivery. To support local SSP programs, program staff screen all applicants for their proximity to an inperson SSP and refer them to local programs when feasible. Participants may request supplies for themselves and for other people. The website is available in English and Spanish. The program has established partnerships with many local SSPs throughout the US. Participants This study included data from all NEXT participants who enrolled for the first time from February 2018, the first date of service delivery, through March 2021. For our analysis, we excluded fourteen participants who reported not injecting drugs. All participants were over 18 years old. Data collection NEXT’s website prompts participants to complete a confidential questionnaire when they request harm reduction supplies. The questionnaire asked about sociodemographics, health status, and drug use behaviors. All measures are self-reported. Data were provided to the research team without personal identifiers. Measures Prior sources of injection supplies Participants reported how they accessed syringes and other injection supplies at the time they enrolled in NEXT services. All responses were in a free-text format. The lead author (BH) reviewed all responses 2

B.T. Hayes, J. Favaro, D. Coello et al.

International Journal of Drug Policy 99 (2022) 103474

and made preliminary categories based on the most common replies: pharmacies; syringe services programs (SSPs); other online sources (for example Amazon.com); friends, acquaintances, or people selling drugs; reusing old supplies; sharing with others; or no current source. The categories were then discussed with three authors (JF, CB, and AF). Consensus was reached to group sources that assured access to sterile syringes (pharmacies, SSPs, and other online sources) as “safe sources of injection supplies,” and other categories (friends, acquaintances, people selling drugs, sharing, reusing, and/or no sources) as “less safe sources.” Participants were able to report more than one category of syringe source. We considered participants to be “exclusively” using safe sources if they only reported sources that fell within the “safe sources” grouping. We also created individual variables for each speciﬁc source of syringes (“pharmacies,” “SSPs,” “online sources,” or “friends, acquaintances, people selling drugs, sharing, reusing, and/or no sources”).

than themselves. Participants reported past 12-month history of experiencing an overdose (yes/no/unsure) and having witnessed an overdose (yes/no/unsure). If participants reported being unsure about experiencing or witnessing an overdose, their responses were categorized as “no”.

Analysis We used descriptive statistics (e.g., median and proportions) to tabulate baseline demographic and risk-factor data, such as prevalence of chronic infectious diseases (HIV and HCV), self-reported past year overdoses, having witnessed an overdose, and prior sources of injections supplies. We examined bivariate associations between gender and all other covariates, as well as bivariate associations between all covariates and exclusively using safe sources for injection supplies. Chi-square or Fisher’s exact tests were used to compare dichotomous outcomes; ttests or Wilcoxon rank sum were used to compare continuous variables. Next, we examined whether gender was associated with exclusively using safe sources of supplies using unadjusted odds ratio (OR) and 95% conﬁdence interval (CI). Multivariable logistic regression (MVR) was used to examine the association between gender and exclusively using safe sources for injection supplies (yes/no). We included in the model all variables of demographic interest (age, race, and ethnicity) and variables that we considered most likely to coufound the association between gender and the primary outcome (housing status, insurance status, HCV status, and use of heroin, opioid analgesics, and methamphetamine). Interactions were assessed between the primary exposure of interest, gender, and all covariates. Collinearity between gender (women/men) and parenting (yes/no) was tested using variation inﬂation factor (VIF). If the VIF was greater than 10, then parenting would be removed from the model. Reported P-values are two-tailed. All analysis were run using STATA (Version 16.1, College Station, TX) software.

Gender Participants reported gender as either man, woman, genderqueer/non-binary gender, transgender man, or transgender woman. For descriptive analyses, genderqueer/non-binary gender and transgender were grouped together because of the small sample sizes (n = 4 and n = 28, respectively). For bivariate and multivariable analyses, we used a binary gender variable (women/men) to compare cis-gendered women’s access to safe syringe sources to cis-gendered men’s. We decided not to group transgender men and transgender women into the binary gender categories because of evidence that transgender men and transgender women who inject drugs face diﬀerent risks and barriers to SSPs (Herbst et al., 2008). Also, because of the small sample sizes of transgender or genderqueer/non-binary gender individuals, these individuals were not included in the analysis. Health status Participants responded yes or no to having the following chronic health conditions: HIV, HCV, diabetes, cardiovascular disease, respiratory disease, or mental health condition. We analyzed only self-reported infection with HIV (yes/no) and HCV (yes/no) as the most relevant health risks related to sterile syringe access.

Results Baseline characteristics of program participants

Current drug use Participants reported current drug use by substance used in the 30 days prior to enrolling in NEXT. Participants responded yes or no to having used the following substances: heroin, other opioids (such as OxyContin, Vicodin, Percocet, etc.), prescribed or nonprescribed methadone, prescribed or non-prescribed buprenorphine, methamphetamine, cocaine, crack-cocaine, marijuana, alcohol, benzodiazepines, synthetic marijuana, and other. We limited our analysis to heroin, other opioids, methamphetamine, and benzodiazepines.

1032 participants received injection supplies. Sociodemographic and injection risk characteristics of NEXT participants are shown in Table 1. Median age was 34 (IQ range: 30–40) and participants were mostly cisgendered women (55%) and white (93%). Less than half of participants were parenting (46%). Most participants were stably housed (57%) and uninsured (51%). Women were more likely to identify as LGBQ (24% vs 11%; p < 0.01) and less likely to identify as Latinx (3% vs 6%; p = 0.01). Women were more likely than men to be parenting (58% vs 31%; p < 0.01) and to have health insurance (53% vs 44%; p < 0.01).

Other covariates Sexual orientation was self-reported as straight, lesbian, gay, or queer. Race and ethnicity were self-identified (Caucasian/white, African American/Black, Asian or Pacific Islander, Native American/American Indian, Alaskan Native, or no identification; Hispanic, Latina, Latino, or Latinx). There were very few respondents who identified as Asian or Pacific Islander, or no identification, thus we categorized these identities together as “other.” Participants reported whether they were parenting (yes/no). Housing was reported as “homeless,” “housed and living with family or friends,” or “housed and renting or owning a home or apartment.” Respondents also categorized their housing as either stable or unstable. We made a new variable that was “stably housed” or “homeless/unstably housed”, as a measure of people with secure versus unsecure living conditions. Participants self-reported insurance status (yes/no/unsure); “yes” could include public or private insurance. We created a binary insurance variable (yes/no) and counted “unsure” as not having insurance. Participants reported (yes/no) whether they planned to distribute supplies they received from NEXT to people other

Health status 34% reported infection with HCV, while 1% reported HIV infection. Women were signiﬁcantly more likely to report HCV infection than men (38% vs 28%; p < 0.01) and less likely to report HIV infection (0.4% vs 2%; p = 0.01).

Drug use Methamphetamine was the drug most commonly used in the past 30 days (82%), followed by heroin (72%), benzodiazepines (39%), and opioid analgesics (34%). Men were more likely to report heroin use (76% vs 67%; p < 0.01).

Overdoses A substantial percentage of participants had overdosed in the prior year (28%), and most had witnessed an overdose (72%). 3

B.T. Hayes, J. Favaro, D. Coello et al.

International Journal of Drug Policy 99 (2022) 103474

Table 1 Baseline sociodemographic characteristics and bivariate analysis among participants enrolling in syringe services program at NEXT, an online mail-delivery SSP (N = 1032).∗ Bivariate analysis with exclusively using safe sources for injection supplies ◊

Bivariate analyses with gender 𝜙 Characteristic ∗

Age (n = 1,023) , median (IQR), mean (95% CI) Gender (women/men) Women Men Genderqueer or transgender LGBQ (yes) Latinx (yes) ∗∗ Race white AA, Black NA, AN Other (API, no ID) Parenting (yes) Housing Stably housed Homeless or unstably housed Health Insurance (yes) Chronic disease HCV HIV Current Drug Use (yes) Heroin Opioid analgesics Benzodiazepines Methamphetamines Overdose (OD), past year (yes) OD (n = 1028)∗ Witnessed OD (n = 1028)∗ Prior sources of injection supplies (yes) Safe sources Pharmacies SSPs Online Less safe sources Friends, acquaintances, people selling drugs, sharing, reusing, and/or no sources Plans to give supplies to other people (yes)

n (%)

Women

Men

P-value

Yesn = 268 (26.0%)

Non = 764 (74.0%)

P-value

34 (30,40)

35 (34, 36)

36 (35, 37)

0.33

35 (34, 36)

0.63

129 (50.4) 127 (49.6) 12 (4.5) 47 (17.5) 14 (5.2)

416 (57.2) 311 (42.8) 37 (4.9) 151 (19.8) 33 (4.3)

0.07

252 (94.0) 5 (1.9) 5 (1.9) 6 (2.2) 107 (39.9)

711 (93.1) 13 (1.7) 14 (1.8) 26 (3.4) 366 (47.9) 417 (53.8) 358 (46.2) 317 (41.5)

<0.01

545 (55.4) 438 (44.6) 49 (4.8) 198 (19.2) 47 (4.6)

132 (24.2) 17 (3.1)

46 (10.5) 27 (6.2)

963 (93.3) 18 (1.7) 19 (1.8) 32 (3.1) 473 (45.8)

513 (94.1) 4 (0.7) 11 (2.0) 17 (3.1) 317 (58.2)

405 (92.5) 14 (3.2) 7 (1.6) 12 (2.7) 135 (30.8)

584 (56.6) 448 (43.4) 502 (48.6)

330 (59.4) 226 (40.7) 297 (53.4)

239 (54.3) 201 (45.7) 194 (44.1)

<0.01

177 (65.3) 94 (34.7) 185 (69.0)

349 (33.8) 12 (1.2)

209 (37.6) 2 (0.36)

125 (28.4) 9 (2.1)

<0.01 0.011

72 (26.9) 3 (1.1)

277 (36.3) 9 (1.2)

<0.01 0.94

740 (71.7) 355 (34.4) 401 (38.9) 847 (82.1)

374 (67.3) 197 (35.4) 214 (38.5) 458 (82.4)

332 (75.5) 144 (32.7) 167 (38.0) 352 (80.0)

<0.01 0.37 0.86 0.34

184 (68.7) 66 (24.6) 96 (35.9) 207 (77.2)

556 (72.8) 289 (37.8) 305 (39.9) 640 (83.7)

0.28 <0.01 0.21 0.02

291 (28.3) 737 (71.7)

159 (28.6) 405 (72.8)

116 (26.6) 306 (70.2)

0.49 0.36

72 (26.9) 181 (67.5)

219 (28.8) 556 (73.2)

0.56 0.08

299 (29.0) 116 (11.2) 56 (5.4)

153 (27.5) 67 (12.1) 32 (5.8)

135 (30.7) 45 (10.2) 21 (4.8)

0.27 0.36 0.49

— — —

701 (67.9)

390 (70.1)

286 (65.0)

0.084

—

792 (76.7)

432 (77.7)

329 (74.8)

0.28

210 (78.4)

582 (76.2)

0.51

<0.01 0.022 0.037

<0.01 0.1

0.75 0.39 0.54 0.78

0.03 <0.01

IQR= interquartile range; CI=confidence intervals; LGBQ= Lesbian, gay, bisexual, or questioning; AA= African American; NA= Native American; AN=Alaskan Native; API=Asian or Pacific Islander; ID=identification. ∗ Total number of respondents indicated for each measure only if missing responses. ∗∗ Includes Hispanic, Latina, and Latino. ◊ Exclusively using safe sources defined as reporting only pharmacies, SSP, online ordering. 𝜙 Genderqueer and transgender were excluded from the bivariate analysis.

Prior sources of injection supplies Most participants acquired injection supplies from less safe sources (friends, acquaintances, people selling drugs, sharing, reusing, and/or no sources) (68%). Few participants exclusively acquired injection supplies from safe sources (26%). Of all the study participants, pharmacies were the most common safe source (29%). SSPs and other online were uncommon sources (11% and 6% respectively).

Association between exclusively using safe sources for injection supplies and gender In unadjusted analysis, women and men participants did not have significantly different odds of exclusively using safe sources for injection supplies (unadjusted OR 0.75, 95% CI 0.56, 1.0). In the MVR analysis, including age, ethnicity, race, parenting, housing status, insurance status, and past 30-day use of opioid analgesics, women participants had significantly lower odds than men of exclusively using safe sources for injection supplies (adjusted OR 0.71, 95% CI 0.52, 0.98) (Table 2). Participants who were parenting or had unstable housing also had significantly lower odds of exclusively using safe sources for injection supplies than those who were not parenting (adjusted OR 0.69, 95% CI 0.50, 0.95) or had stable housing (adjusted OR 0.62, 95% CI 0.45, 0.84), respectively. Participants who were insured had significantly higher odds of exclusively using safe sources for injection supplies than those who were uninsured (adjusted OR 3.0, 95% CI 2.2, 4.2). Participants who used opioid analgesics had significantly lower odds of exclusively using safe sources for injection supplies than those who did not use opioid analgesics (OR 0.58, 95% CI 0.41, 0.82). Age, ethnicity, and race were

Distribution of supplies to other people Most people planned to provide supplies they received from NEXT to other people (77%). Association between exclusively using safe sources for injection supplies and risk proﬁle Exclusively using safe sources for injection supplies was signiﬁcantly associated with several factors: not being a parent or parenting (vs. parenting), stable (vs. unstable) housing, and having health insurance, and not reporting HCV infection. All associations between exclusively using safe sources for supplies and participant characteristics are shown in Table 1. 4

B.T. Hayes, J. Favaro, D. Coello et al.

International Journal of Drug Policy 99 (2022) 103474

Table 2 Results of the multivariable model showing unadjusted and adjusted odds ratio of cis-gendered women and exclusively using safe sources for injection supplies, February 2018 – October 2020; (n = 970). Unadjusted

∗,†

Women (men) Age (continuous) Latinx (non-Latinx) Non-white race (white) Parenting (not parenting) Unstable housing (stable) Insured (Uninsured) HCV infection (no infection) Use of heroin (no use) Use of opioid analgesics (no use) Use of methamphetamine (no use) ∗ †

Adjusted

OR (95% CI)

Standard Error

p-value

OR (95% CI)

0.75 (0.56, 1.0) 0.99 (0.98, 1.0) 1.1 (0.56, 2.2) 0.93 (0.52, 1.7) 0.70 (0.53, 0.94) 0.61 (0.45, 0.82) 3.1 (2.3, 4.2) 0.70 (0.51, 0.96) 0.81 (0.59, 1.1) 0.50 (0.36, 0.70) 0.67 (0.47, 0.96)

0.11 0.0081 0.39 0.28 0.10 0.092 0.48 0.11 0.13 0.084 0.12

-2.0 -0.77 0.29 -0.26 -2.4 -3.3 7.2 -2.2 -1.3 -4.1 -2.2

0.50 0.44 0.77 0.80 0.02 <0.01 <0.01 0.03 0.19 <0.01 0.031

0.72 (0.52, 0.99) 1.0 (0.98, 1.0) 0.86 (0.41, 1.8) 0.72 (0.39, 1.3) 0.70 (0.50, 0.97) 0.63 (0.46, 0.87) 3.0 (2.2, 4.1) 0.81 (0.58, 1.1) 0.60 (0.63, 1.2) 0.58 (0.41, 0.82) 0.81 (0.56, 1.2)

Standard Error 0.12 0.0088 0.32 0.23 0.12 0.10 0.49 0.14 0.15 0.11 0.16

z -2.0 -0.45 -0.41 -1.0 -2.2 -2.8 6.8 -1.2 -0.74 -2.9 -1.1

p-value 0.046 0.66 0.68 0.30 0.03 <0.01 <0.01 0.21 0.46 <0.01 0.29

Genderqueer and transgender were excluded from this analysis. Label in parenthesis indicates reference group.

not signiﬁcantly associated with exclusively using safe sources for injection supplies.

Our analysis based on gender emphasizes the importance of targeted interventions for women who inject drugs. In our sample, more women reported HCV infection than men. The extant literature reflects that injection drug use, HCV and HIV infection are all more common among men than women in the general US population (Centers for Disease Control and Prevention (CDC), 2019; National Institute on Drug Use (NIDA), 2020; Zibbell et al., 2018); however, women who inject drugs often have elevated risks of acquiring HCV and HIV in comparison to men (Esmaeili et al., 2017; Lansky et al., 2014; Leung et al., 2019). This elevated risk is driven by a confluence of social, structural and environmental factors. Women who inject drugs frequently rely upon someone else to inject their drugs or to prepare their drugs for injection, which is a critical point for transmitting bloodborne infections (Wagner, Jackson Bloom, Hathazi, Sanders, & Lankenau, 2013). When women have men injection partners, they are more likely to use injection supplies after their partner and report a lack of agency to negotiate safe injecting practices (Des Jarlais et al., 2012; Roberts et al., 2010). Women who inject drugs are also more likely to engage in sex-work and face other social circumstances, such as homelessness, which have been associated with engaging in behaviors that increase HCV and HIV infection risk (Lum et al., 2005; Nerlander et al., 2017). In our study, parenting was also independently associated with not exclusively using safe sources for injection supplies. This is a novel finding that may indicate an important barrier to sterile injection supplies. One explanation is that parents may avoid being seen at in-person SSPs due to fear of stigma, discrimination, and police harassment. Research has identified these as common reasons for PWID to avoid SSPs (Paquette et al., 2018; Tempalski et al., 2007). Even in areas where sterile syringe distribution is sanctioned by the authorities, PWID maintain concerns about police interference and potential legal consequences. (Beletsky et al., 2011; Beletsky et al., 2014; Davis et al., 2005) Although these concerns apply to all PWID, people with children may fear losing custody or being separated from their children by incarceration. Research in other countries has suggested that parents who use drugs lack the social support to seek services regarding drug use, and may lack the ability to step-away from their caregiving duties to attend in-person programs (El-Bassel & Strathdee, 2015). Future research will be important to fully understand the advantages and limitations of the NEXT program. Qualitative methods could provide more in-depth information about why women enrolled in NEXT, and interviewing other underserved groups of PWID, such as people of color, could determine how they view the acceptability of similar harm reduction services. For example, people who lack reliable internet access may prefer in person services, while others may be concerned about the privacy of receiving mail-delivered packages. In our sample, there was a large proportion of people with unstable housing, and understanding how they received packages would inform the feasibility of scaling

Discussion In our cross-sectional analysis of enrollment data from an onlineaccessed mail delivery harm reduction program cis-gendered women were less likely than cis-gendered men to have exclusively been using safe sources, which highlights women’s needs for services like NEXT’s. Participants who were parenting were also less likely to have exclusively been using safe sources, independent of gender, which may represent a unique barrier to access harm reduction services for PWID. Our finding that NEXT participants generally were using unreliable sources for injection supplies when they enrolled in the program emphasizes the value of NEXT as an alternative harm reduction model. Acquiring syringes through acquaintances increases the likelihood of sharing or reusing another person’s injection supplies, which increases HCV or HIV transmission risk (National Research Council (US) and Institute of Medicine (US) Panel on Needle Exchange and Bleach Distribution Programs, 1995; Wodak & McLeod, 2008). Using syringes multiple times also imparts risk of microbial contamination and skin or soft-tissue infection (Chambers, 2021). Infection with HCV was common among participants in this study. In cross-sectional analyses, we cannot be certain about a causal relationship between prior syringe source and infectious complications, but preventing syringe sharing between participants with HCV or HIV infection and others should be a priority. NEXT can provide a safe source of sterile syringes. The high proportion of cis-gendered women participants may indicate that the online-order and mail-delivered model is particularly acceptable to women who inject drugs. Traditionally, women compromise 30–39% of SSP participants in the US (Behrends et al., 2018; Des Jarlais et al., 2015), yet women represented greater than half of NEXT participants. This sample of women also had disproportionately low access to safe sources of syringes previously, therefore, the online accessed maildelivery approach may help women overcome barriers to harm reduction supplies. For example, the remote and private nature of this model may address the gender-specific challenges faced by women who inject drugs, such as stigma, and fear of losing child custody (Des Jarlais et al., 2012; El-Bassel & Strathdee, 2015; Lum et al., 2005; Nerlander et al., 2017; Roberts et al., 2010). Harm reduction interventions in the US have been critiqued for maintaining gender neutral approaches, without explicit consideration of the unequal impact of drug use harms between genders, and there has been a call to develop alternative strategies that address the specific needs of marginalized women (Collins et al., 2019). Future research should explore how the online accessed mail-delivery meets the needs of women who inject drugs. 5

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this model for individuals with a range of housing statuses. Measuring behavior change, injection-related risks, and incident HIV or HCV infection in prospective studies would also bolster our understanding of the impact of NEXT. Additionally, analyses that account for the geographic distribution of NEXT requests would allow us to examine regional demand for services vs relative availability of SSPs. The strengths of our study were examining the participants of a highly innovative program of mail-delivered syringes, use of multivariable analysis to account for confounders, and a confidential platform for collection of self-reported data. The main limitation to our study was that the cross-sectional design limits our ability to make causal inferences from observed associations. There were other limitations. The enrollment form was not designed as a study instrument, which required us to use operationalized outcome measures. For example, sources of injection supplies were based on a free text responses where participants could include one or many answers. It is possible that participants may have not reported all of their prior sources for syringes leading to overestimation of those exclusively using safe sources. Nevertheless, this bias should not differentiate by gender, thus, should not affect our primary analysis. Similarly, although a few participants volunteered that they shared or reused their supplies, these questions were not explicitly asked and could be underreported. This information would be important to better characterize the risk behaviors of this sample and should be explore in future investigation. Another limitation is that the findings from this predominantly white sample of PWID with access to the internet may not be generalizable to other groups of PWID. Ensuring access to safe sources of injection supplies for other underserved groups is important and deserves further investigation. Finally, the study did not include data on participants’ reasons for using NEXT services, which would provide important contextual information about the risk environment of participants. Injection drug use poses very serious individual and public health risks. These risks are preventable if PWID have sterile syringes for every injection. Women who inject drugs are at particularly high risk of poor health outcomes compared to men, yet they face unique obstacles to accessing sterile syringes. Our findings suggest that NEXT does indeed reach high risk, underserved PWID, including cis-gendered women who are not regularly using safe sources for injection supplies. NEXT provides proof of concept for online accessed mail-delivery of harm reduction supplies, and future studies should examine the effectiveness of this intervention in reducing health risks associated with drug use.

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Funding This research was supported by the National Institute Allergy and Infectious Diseases CFAR [grant number P30AI124414]. Dr. Fox is supported by the National Institutes of Health under grant R01DA044878. Declarations of Interest Jamie Favaro is the founder of NEXT Harm Reduction, a non-proﬁt organization whose work is highlighted in the article. Daniel Coello is the Program Coordinator for NEXT Harm Reduction. The other authors have no potential conﬂicts of interest to disclose. References Allen, S. T., Grieb, S. M., O’Rourke, A., Yoder, R., Planchet, E., White, R. H., & Sherman, S. G. (2019). Understanding the public health consequences of suspending a rural syringe services program: A qualitative study of the experiences of people who inject drugs. Harm Reduction Journal, 16(1), 33. 10.1186/s12954-019-0305-7. Alpren, C., Dawson, E. L., John, B., Cranston, K., Panneer, N., Fukuda, H. D., . . . Buchacz, K (2020). Opioid use fueling HIV transmission in an urban setting: An outbreak of HIV infection among people who inject drugs-Massachusetts, 2015-2018. American Journal of Public Health, 110(1), 37–44. 10.2105/ajph.2019.305366. amfAR. (2017). Syringe services programs and the opioid epidemic. Retrieved December 10 from https://www.amfar.org/ssp-opioid-epidemic/. Barnard, M. A. (1993). Needle sharing in context: Patterns of sharing among men and women injectors and HIV risks. Addiction, 88(6), 805–812. 10.1111/j.1360-0443.1993.tb02094.x. 6

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