Alexis M. Roth

BACKGROUND Women who inject drugs (WWID) are disproportionately impacted by HIV. Pre-exposure prophylaxis (PrEP) could dramatically decrease HIV acquisition, however WWID experience multi-level barriers to engaging in PrEP care, including historical and ongoing trauma. Expressive writing (EW) is a trauma-informed, exposure-based intervention that improves mental health outcomes. Contingency management (CM) is an evidence-based intervention that promotes health behavior change. This randomized controlled trial of “Trauma Intervention for Affect Regulation, Adherence, and Substance Use (TIARAS)” will test the efficacy of EW+CM on HIV risk reduction among WWID. OBJECTIVE The first objective is to compare the efficacy of EW + CM versus an active attention-control condition (neutral writing [NW] + CM) with respect to HIV risk reduction (at 3, 6, and 12-months after randomization). The second objective is to examine secondary outcomes including: mental health (anxiety, depression, and PTSD), engagement in drug treatment and substance use, as well as cost-effectiveness. The third objective is to evaluate the pathways through which the intervention operates using qualitative interviews, mediation analysis (e.g., emotional expression and processing in EW essays) and moderation analysis (e.g., more pronounced among those with higher PTSD severity at baseline). METHODS TIARAS began recruiting in June 2022 and has enrolled 219 adult WWID (≥18 years) receiving a PrEP prescription in the past 4-weeks from a harm reduction agency in Philadelphia (PA, USA). Once enrolled, participants began a 3-month CM protocol that provides cash incentives for objectively verified PrEP adherence and abstinence from opioids and/or stimulants. After a run-in period, participants are randomized 1:1 to the experimental condition (four EW writing sessions plus CM) or the attention-control condition (four neutral writing sessions plus CM). Follow-up data are collected at 3, 6, and 12 months with interviewer-administered surveys, health records, and biological specimen, and with in-depth interviews collected at 3 and 12 months for a subsample of WWID from each intervention group. The primary outcome is HIV risk reduction, operationalized as “reduced” when engaging in syringe sharing or condomless sex during objectively measured periods of PrEP non-adherence and “not reduced” for all other combinations of behaviors during periods of non-adherence. Intent-to-treat analyses will examine the efficacy of EW+CM on HIV risk reduction, mediation of efficacy through mental health (i.e., PTSD symptom severity) and/or polysubstance use, and moderation of efficacy based on social structural determinants of health (e.g., homelessness) and incident traumatic exposures (e.g., arrest, physical assault). RESULTS As of October 2025, TIARAS closed to enrollment and has an anticipated end date in December 2026. Women have been enrolled in equal proportions to both study conditions (n = 95 and 93, for expressing and neutral writing, respectively. Blinding has been maintained, and statistical analyses for the primary and secondary outcomes have not yet been performed. CONCLUSIONS We anticipate that the results of our trial will address a critical gap in the literature by advancing our mechanistic understanding of the potentially bidirectional relationships among mental health, polysubstance use, and HIV risk reduction. CLINICALTRIAL Trial registration: ClinicalTrials.gov number NCT05192434, protocol and statistical analysis plan registered January 14, 2022.

Introduction: Long-acting injectable cabotegravir (CAB-LA) for preexposure prophylaxis (PrEP) is a promising HIV prevention tool for people who inject drugs (PWID), who face elevated HIV risk and barriers to care. While acceptable to PWID, CAB-LA implementation in low-barrier syringe services programs (SSPs) has not been examined. Methods: From August 2023 to July 2025, we conducted semistructured interviews with 12 SSP staff involved in CAB-LA delivery. Interviews were transcribed and analyzed using thematic analysis guided by the Consolidated Framework for Implementation Research. Results: Facilitators included CAB-LA's relative advantage over oral PrEP, external technical support, 340B pharmacy revenue, alignment with SSP mission and workflows, motivated staff, and financial incentives. Barriers included lack of FDA approval for PWID, complex logistics, performance pressures, infrastructure constraints, competing priorities, staff workload, and client outreach and engagement. Conclusion: Integrating CAB-LA into SSPs is promising, but successful implementation requires targeted strategies, including additional resources, workflow adaptations, and enhanced outreach.

The recent rise in HIV incidence among people who inject drugs in the United States highlights an urgent need to improve HIV testing, treatment linkage, and pre-exposure prophylaxis access in this group. Syringe services programs (SSPs) play a critical role by offering or linking clients to these services, yet little is known about how such care is delivered. Informed by the Consolidated Framework for Implementation Research, we conducted qualitative interviews with 41 representatives from 27 SSPs across the United States to characterize the current service delivery landscape, identify barriers to care, and explore modifiable implementation determinants. Rapid qualitative analysis revealed four primary HIV service delivery models: "one-stop shop" offering integrated, on-site HIV testing and follow-up care provided by the SSP; "test and refer" with integrated, on-site testing services followed by referrals to external partners for follow-up care; "co-located services" with SSPs relying on external partner organizations to provide HIV testing (and additional services) on-site; and "hand-off" involving referrals to off-site, external partners for HIV testing and follow-up care. SSPs faced varied implementation challenges, including staffing, funding, and space constraints; competing priorities; availability and accessibility of local partnerships; as well as SSP culture, which values participant autonomy (recipient-centeredness). These contextual factors influenced the feasibility and acceptability of HIV services and why SSPs adopted a particular service delivery model. To strengthen HIV prevention and care in SSPs, tailored implementation strategies are needed that account for programs' unique constraints and capacities.

The current mechanisms in the United States to research and develop novel reversal agents for substances that can lead to overdose are restricted by regulations placed on the pharmaceutical industry. While there are many forms of harm reduction critical to saving lives that require increased investment and research, it is proven that reversal agents, such as naloxone, help prevent overdose morbidity and mortality. In the setting of an evolving crisis of illicit substance use and related overdose with new, increasingly potent substances appearing in communities nationwide, it is essential to implement a structured approach to rapidly develop and deploy efficacious harm reduction tools to save lives. In this article, we review the history of US scheduled drug regulation which aims to mitigate substance use but also paradoxically hinders research into treatments for drug overdose. We also discuss the regulation of drug reversal agents in the context of changing patterns in illicit substance use as well as barriers to the rapid development of medical devices associated with drug reversal agents that address immense public health needs. The overdose epidemic is a national crisis that requires technological solutions in addition to sociopolitical reform. Even if a reversal agent or medication is approved for an emerging substance, the existing regulatory landscape for drug delivery devices discourages the development, access, and widespread adoption of potentially lifesaving treatments. A systematic approach to monitoring the evolution of illicit drugs and a more streamlined regulatory pathway is urgently needed to facilitate the development and deployment of effective harm reduction tools.

Background: Contingency management (CM) is an effective intervention that provides financial incentives as positive reinforcement for reducing opioid or stimulant use. However, it has not been tested in populations of women who inject drugs (WWID) engaging in polysubstance use. Methods: We aimed to compare the feasibility of two CM protocols designed to encourage illicit stimulant and opioid abstinence among WWID participating in an ongoing HIV prevention trial. Participants completed a 3-month CM period during which they submitted thrice weekly urine toxicology screenings (UTOX). In the ‘abstinence from stimulants and opioids’ protocol, participants received a $5 USD incentive when metabolites of stimulants and opioids were not detected in urine. In the ‘partial-abstinence protocol’, they received a $5 USD incentive when metabolites of stimulants or opioids were not detected, thus doubling the potential incentive obtained each visit. Women also received scaling bonuses after three consecutive negative UTOX ($5-$15 USD). We used descriptive statistics to summarize the total number of (1) UTOXs completed and (2) bonuses distributed. Rates of engagement per person per month were calculated (i.e., total number of completed UTOX/3 months*24 participants). Rates of engagement were compared by CM protocol period. Results: Participants were primarily White women (67%) with an average age of 47 years. Self-reported polysubstance use was common (96%) with women reporting injecting an average of 5 times daily (Interquartile Range: 2–7). Participants (N = 24) collectively submitted 177 UTOX during their 3-month CM periods. Rates of non-reactive UTOX results were slightly higher in the partial-abstinence protocol compared to the abstinence from stimulants and opioids protocol (2.9 per month versus 1.0 per month). More bonuses were earned in the partial-abstinence protocol (0.50 bonuses per participant per month) compared to the abstinence from stimulants and opioids protocol (none). There were no study related adverse events in either protocol group during the CM period. Conclusions: Findings demonstrate the feasibility of a CM protocol that provided financial incentives for partial abstinence, periods with documented stimulant or opioid abstinence, as well as abstinence to both, without the occurrence of iatrogenic effects. Future research focusing on CM protocols with more flexible incentive structures remains critical. Trial registration: NCT05192434.

Long-acting injectable PrEP was approved for use in the US in 2021 but roll out has been slow, with few studies exploring uptake among cisgender women who inject drugs (WWID). We purposively recruited 25 WWID within 30-days of receiving a PrEP prescription from a low-barrier clinic co-located with a syringe services program to complete semi-structured interviews about PrEP product choice. We used an intersectional lens to compare decision-making between women choosing injectable PrEP versus oral PrEP and continued enrolling new participants until we reached thematic saturation (12/2022 to 2/2024). Participants represent a diverse sample of WWID (12 women of color) with median age 43 years. Daily injection drug use (72%) and ≥ 1 sex partner (64%) were common. Salient themes from interviews include: (1) PrEP provides women with a valued safety net and initiation is a form of self-preservation. (2) Co-located care, small incentives, and provider respect for WWID's medical autonomy helped participants navigate a multi-visit PrEP intake process. (3) Longer lasting HIV protection with less frequent dosing is preferrable to a shorter acting daily oral medication. When selecting a product, WWID evaluated its attributes against their medical history and personal circumstances like homelessness (64%). Most chose CAB-LA (72%) because it provides longer lasting protection which was a highly valued product attribute. Together, our findings underscore the critical importance of offering multiple PrEP options when implementing HIV prevention strategies that are patient-centered and responsive to the unique needs of WWID.

Women who use illicit drugs (WWUD) experience high rates of co-occurring post-traumatic stress disorder (PTSD) and substance use disorder (SUD) driven by cumulative exposure to trauma and resulting in high HIV risk. This HIV risk environment has been explored among women using the Substance Abuse, Violence, and HIV/AIDS (SAVA) Syndemic Framework. SAVA-focused research describes how women with co-occurring experiences of trauma and illicit drug use report high rates of HIV risk behaviors such as injection drug use, sharing injection equipment, and unprotected sex, which may contribute to the high rates of HIV infections among WWUD. However, the far-reaching effects of cumulative trauma are poorly characterized in WWUD. Current traumatic event indices typically focus on one period of life (i.e., childhood) or assess a single type of trauma (i.e., sexual violence; combat). These tools fail to capture cumulative trauma, which is important in highly traumatized groups such as WWUD who experience high rates of revictimization following traumatic events, resulting in increased severity of PTSD, SUD, and HIV risk exposure. Valid and reliable measurement is needed to generate an accurate assessment of trauma exposure prevalence in this group. Using a concurrent mixed-methods design, this dissertation assessed the validity and reliability of the TLEQ-WWUD, a traumatic events index designed to capture the wide-ranging and unique traumatic experiences of vulnerable cisgender women who use drugs. The index was based on a commonly used and validated trauma index (TLEQ) that was adapted in collaboration with women who have a history of substance use, and experts in trauma treatment and psychology (Chapter 2). Aims 1 and 2 tested the validity of the index using data from a randomized controlled trial designed to reduce HIV acquisition risk among women who injected drugs in the past 6 months (NCT05192434; N=162). Aim 1 assessed the correlation between traumatic experiences (TLEQ-WWUD summary scores) and (1) PTSD (PCL-5 symptom screener), (2) depression, and (3) anxiety symptom scales (predictive validity) (Chapter 3). Aim 2 used logistic regression to assess the association between traumatic experiences (TLEQ-WWUD summary scores) and drug- and sex-related HIV-risk behaviors (predictive validity) (Chapter 4). In Aim 3, the TLEQ-WWUD was administered to a cohort of women who have used illicit substances within 12 months (N=32) (Chapter 5). Participants completed the electronic, self-administered, TLEQ-WWUD on two different occasions, approximately 7 days apart. Test-retest temporal stability was evaluated using intraclass correlation for TLEQ-WWUD summary scores and Gwet's AC1 for each individual event type. At the second assessment, participants completed a semi-structured interview to reflect on their experience completing the TLEQ-WWUD and discuss potential improvements. Across both samples, cumulative trauma and prevalence of each event captured on the TLEQ-WWUD were exceptionally high. In Aims 1 and 2, out of the 21 events on the TLEQ-WWUD, the median number of traumatic events was 14 (IQR: 11,16). Further, women were suffering from mental health concerns such as PTSD (74%; median score: 46 [IQR:32,61]), moderate/severe depression (71%), and anxiety (77%). Results from Aims 1 and 2 provide evidence that the TLEQ-WWUD is a valid tool for measuring cumulative trauma among WWUD. There was a moderate-weak, positive correlation between the TLEQ-WWUD summary score and PTSD ([rho]=0.39 (p<0.01)). Further, women with PTSD reported significantly more traumatic events on average compared to women without PTSD (15 events [IQR:12,17] v. 12 events [IQR:8,14], respectively) (p<0.01). In addition, there was a statistically significant difference in median TLEQ-WWUD scores across anxiety (p<0.01) and depression score groups (p<0.01). In another test of the TLEQ-WWUD's predictive validity, after controlling for age, race/ethnicity, and housing status, cumulative trauma exposure was significantly associated with increased odds of daily injection drug use (OR=1.14, CI:1.04-1.24, p<0.01) and sharing drug use paraphernalia (OR=1.12, 95% CI: 1.02-1.22, p=0.01). Results from Aim 3 provide preliminary evidence of weak-moderate test-retest reliability (ICC=0.38). Agreement coefficients varied across individual traumatic events, with AC1 values ranging from 0.14 (slight agreement) to 0.86 (excellent agreement). Fifteen out of 22 events had moderate to excellent agreement (AC1≥.41), 5 had fair agreement (0.21-0.40) and 2 events had only slight agreement (0.00-0.20). In qualitative interviews, women discussed their experience completing the TLEQ-WWUD and identified key features of the index that supported their mental health safety during the administration process: (1) Women's past experiences managing distress in their daily lives helped them mitigate the emotional impact of the TLEQ-WWUD. (2) Women saw value in the TLEQ-WWUD's potential to build community and raise awareness among healthcare providers. (3) Features of the TLEQ-WWUD administration process, such as self-administration in a private, low-pressure environment supported the acceptability and mental health safety of the index. Findings from each of these aims were compared using triangulation to provide a comprehensive understanding of the psychometric properties of the TLEQ-WWUD as well as key areas for future research and index implementation (Chapters 6-7). Overall, the TIARAS study was the first administration of the TLEQ-WWUD, a traumatic life events questionnaire designed specifically for women who use drugs. Results from Aims 1 and 2 provide evidence that the TLEQ-WWUD is a valid tool for measuring cumulative trauma among WWUD. Our findings are consistent with the SAVA framework, in which syndemic factors such as exposure to trauma (i.e., violence) and drug use dependence have a significant impact on mental health and HIV risk...

Journal of Medical Internet Research - International Scientific Journal for Medical Research, Information and Communication on the Internet #Preprint #PeerReviewMe: Warning: This is a unreviewed preprint. Readers are warned that the document has not been peer-reviewed by expert/patient reviewers or an academic editor, may contain misleading claims, and is likely to undergo changes before final publication, if accepted, or may have been rejected/withdrawn. Readers with interest and expertise are encouraged to sign up as peer-reviewer, if the paper is within an open peer-review period. Please cite this preprint only for review purposes or for grant applications and CVs (if you are the author). Background: For over a decade, drug overdose has been the leading cause of injury and accidental death in the United States. Most fatal overdoses involve opioids and occur during solitary drug use events when no one is available to initiate lifesaving responses (e.g., naloxone).​ While there is a growing interest in devices providing early overdose detection and automated response, little research has engaged end users in a device design process.​ Objective: To describe user experience, perceived harms and benefits, and the acceptability of a shoulder-mounted wearable sensor among people who inject drugs who wore a device prototype for seven days, and to explore real-time responses that could be incorporated into a next generation sensor. Methods: Individuals ≥18 years reporting past week injection drug use were recruited from a walk-in substance use disorder clinic in Camden, NJ, USA. Participants completed a brief survey assessing socio-demographics and recent drug use and were assigned a sensor prototype that they were asked to wear near-continuously for seven days. At endline, they completed semi-structured interviews exploring acceptability, usability, and form and function preferences for next-generation devices with integrated automated response options. Structured field notes and transcripts were analyzed to identify key themes and design considerations. Results: Participants (n=23) had a median age of 41 years. Most were primarily non-Hispanic White (65%) males (61%), experiencing homelessness (57%) who reported daily injection drug use (74%) within 3-months and receipt of opioid use disorder medication within a month (74%). Sixteen completed an exit interview. They found the concept of a shoulder-mounted overdose detection device acceptable and unanimously endorsed the need for long-lasting discreet devices. They emphasized the importance of having multiple response options that wearers could tailor to their individual circumstances and preferences, noting some might prefer an automatic call to emergency services, while others might prefer to alert a peer. Participants expressed a preference for solutions that alert first responders over automated biomedical solutions, such as naloxone injection, because of concerns about device error (e.g., false positives) leading to precipitated withdrawal. Conclusions: After wearing a shoulder-mounted protype, this small group of participants found the idea acceptable and provided feedback to improve usability and design. Data suggest that a variety of devices with differing functions, size, and capacity will be needed to meet user needs and increase the likelihood of adoption once devices come to market.