Background: The research proposed herein investigates factors associated with substance use trajectories leading to injection drug use (injection) and the circumstances surrounding injection within two different populations of injection drug users (IDUs). This study aims to identify factors associated with: (1) initiation of substance use through injection, (2) lifetime and current agua celeste use (an inhalant unique to Northern Mexico), and (3) time to initiation of sex work, and initiation of injection.

Methods: Three manuscripts form the basis of this dissertation using existing data from two datasets. Manuscript 1 uses data from IDU from the Proyecto El Cuete phase III dataset, and Manuscript 2 and 3 use data from female sex workers who inject drugs (FSW-IDU) in the Mujer Mas Segura dataset.

Results: Manuscript 1 identified a sub-group of IDUs who initiated illicit drug use by injecting the drug (`injection first'). `Injection first' IDUs were more likely to first inject heroin and inject alone, but were not significantly riskier in their current drug use or sexual behaviors compared to IDUs who used illicit drugs prior to injection. Manuscript 2 found that only FSW-IDUs in Ciudad Juarez reported agua celeste use and prevalence overall (53%) and within the past 6 months (47%) was high. Manuscript 3 identified that early abuse and illicit drug use was associated an accelerated time to initiation of both sex work and injection. Low education and a perceived need to enter sex work to support family were associated with a shorter time to sex work initiation, and geographical migration was found to decelerate time to injection initiation. Having an intimate partner suggest sex work and injecting to deal with feelings of depression accelerated time to both sex work and injection initiation when they occurred at the same age.

Conclusions: The unique populations of IDUs studied and novel research questions make the findings within this dissertation valuable to the larger field of research on substance use careers. These findings build on previous literature showing that inhalant use is an important risk factor for subsequent injection and may help identify possible avenues for intervention that can delay or prevent onset of initiation of injection drug use and/or sex work.

Background: Overdose and infectious disease are major causes of morbidity and mortality among people who use drugs (PWUD). Harm reduction is a public health approach to reducing the negative consequences of criminalized substance use. This dissertation explored access to and utilization of harm reduction practices and services among PWUD in Tijuana, Baja California, Mexico and San Diego, California, United States (U.S.).Methods: This dissertation utilized survey data from the La Frontera binational cohort study. Chapter 1 compared overdose prevention strategies utilized by PWUD in Tijuana (n=343) and San Diego (n=143) between May 2022–March 2023. Latent class analysis (LCA) identified underlying groups of PWUD based on their probabilities of utilizing these strategies. Chapter 2 compared Tijuana (n=345) and San Diego (n=129) participant scores on a safe injection self-efficacy (SISE) scale between October 2020–September 2021 and assessed correlates of SISE score levels using ordinal logistic regression. Chapter 3 assessed naloxone accessibility among PWUD in San Diego between December 2021–December 2022 using qualitative interviews (N=20) and survey data (N=194). Results: Chapter 1 revealed that participants’ primary overdose prevention strategies were trying to avoid fentanyl among Tijuana residents (84%) and trying to stop/reduce injecting among San Diego residents (52%). LCA revealed four latent classes among Tijuana participants characterized by unique overdose prevention strategies. Chapter 2 demonstrated that Tijuana residents had lower mean SISE scores than San Diego residents (1.93 vs. 3.46 out of 4). Among Tijuana participants, White race and previous San Diego residence were positively associated with greater SISE scores, whereas HCV and HIV seropositivity, homelessness, fentanyl use, polysubstance co-injection, and greater injection frequency were negatively associated. Chapter 3 showed that among PWUD in San Diego, 24% reported never having accessible naloxone, 52% sometimes did, and 24% always did. Qualitative findings revealed PWUD generally felt naloxone was easy to obtain in San Diego due to community distribution from harm reduction providers and satellite distribution among peers, but experienced some barriers. In quantitative analyses, greater naloxone accessibility was positively associated with female sex, witnessing an overdose, and knowing where to get free naloxone, while monthly income ≤USD$500 was negatively associated. Conclusions: These findings highlight multi-level opportunities to improve access to harm reduction services in Tijuana and San Diego, including drug checking, naloxone distribution and overdose response education, and medications for opioid use disorder (MOUD). Additionally, PWID in Tijuana could benefit from syringe service program (SSPs) expansion and safe injection self-efficacy education.

Background: Sex trafficking is a human rights abuse that carries particularly negative health and social consequences, including HIV and sexually transmitted infections (STIs). While HIV/STI infection and sex trafficking have been linked in Asia, the context of these associations and their applicability in Mexico is poorly understood.

Aims: Aims of this dissertation were to (1) Critically review evidence linking mobility, trafficking, and HIV vulnerability in Mexico and Central America; (2) Explore associations between features of the risk environment, sex work and drug use history, and underage sex work among female sex workers (FSWs) in Tijuana and Cd. Juarez, Mexico; and (3) Describe and "unpack" sex trafficking and its relationship to HIV/STI vulnerability among formerly trafficked FSWs in Tijuana.

Methods: This study employed qualitative and quantitative methods to investigate sex trafficking, mobility and HIV vulnerability. In Chapter 2, a critical review of the epidemiology and context of HIV vulnerability among mobile populations in Central America and Mexico was conducted. Chapter 3 draws upon questionnaires and HIV/STI testing among FSWs (n=624) in Tijuana and Cd. Juarez. In Chapter 4, in-depth interviews were conducted with formerly trafficked FSWs in Tijuana (n=31).

Results: Chapter 2 found that among mobile groups in Central America and Mexico, social isolation, socio-economic impacts of displacement, gender inequalities, and stigma/discrimination strongly shape HIV/STI risk. In Chapter 3, underage sex work entry was positively associated with inhalants as the first drug used, forced first injection, number of drug treatment attempts, and recent receptive syringe-sharing. Number of recent condom negotiation attempts with steady partners and depression as a reason for first injecting were negatively associated with underage entry into sex work. In Chapter 4, sex trafficking was linked to elevated HIV/STI vulnerability through gender-based violence, economic vulnerability, migration, and stigma.

Conclusions: These findings contribute to a foundation of knowledge to advocate for strategies to reduce sex trafficking and HIV. Multi-level, intersectoral interventions to prevent sex trafficking and HIV infection are needed for vulnerable youths, migrants, and FSWs in Mexico-U.S. border cities; recommended components include strengthening the response to gender-based violence, peer-delivered prevention, and the provision of shelter, food, job placements, and psychological support.

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The opioid epidemic in the United States has contributed to a rise in drug injection-related disease transmission and infection. People who inject drugs (PWID) are at an increased risk of developing bacterial infections such as Methicillin-resistant Staphylococcus aureus (MRSA). This study examines the prevalence and correlates of MRSA infections and related abscesses amongst PWID in San Diego, California, and Tijuana, Mexico, to better inform harm reduction practices. This is a cross-sectional study conducted from June 2022 until November 2022 in which PWID (N = 187) participating in an ongoing cohort study completed interviewer-administered questionnaires and MRSA swabs nasally and at abscess sites (if present). Chi-Square Tests of Independence, Fisher’s Exact Tests, and Wilcoxon Rank Sum Tests were used to identify potential risk factors. Analysis revealed significant associations between injection practices, structural factors (e.g. homelessness), and prevalent MRSA infections. These positive associations between arm injections, homelessness, and MRSA infections emphasize the need for structural interventions that reduce the barriers PWID face when accessing resources that would improve their health outcomes.