"It didn't hurt me": patients' and providers' perspectives on unsupervised take-home doses, drug diversion, and overdose risks in the provision of medication for opioid use disorder during COVID-19 in San Juan, Puerto Rico.

BACKGROUND: During the COVID-19 pandemic, clinics offering medication for opioid use disorder (MOUD) needed to rapidly introduce unsupervised take-home dosing, while relapsing patients and patients unable to enter treatment faced increased risks of fentanyl-related overdose deaths and other drug-related harms. Based on a qualitative study of people who inject drugs (PWID) receiving MOUD treatment and MOUD staff in Puerto Rico, this paper documents the lived experiences of patients and providers during this period and the risk perceptions and management strategies to address substance misuse and drug diversion attributable to unsupervised take-home-dose delivery. METHODS: In-depth qualitative interviews were conducted with patients (N = 25) and staff (N = 25) in two clinics providing MOUD in San Juan, Puerto Rico, during 2022. Patients and staff were receiving or providing treatment during the pandemic, and patients reported injection drug use during the past thirty days. RESULTS: Patients were overwhelmingly male (84%), unmarried (72%), and unemployed (52%), with almost half (44%) injecting one to three times a day. Mean time in treatment was 7 years. Staff had a mean age of 46 years with more than half of the sample (63%) female. The majority of patients believed that unsupervised take-home dosing had no significant effect on their treatment adherence or engagement. In contrast, providers expressed concerns over the potential for drug diversion and possible increased risks of patient attrition, overdose episodes, and poor treatment outcomes. CONCLUSION: This study underscores the importance of insider perspectives on harm-reduction changes in policy implemented during a health crisis. Of note is the finding that staff disagreed among themselves regarding the potential harms of diversion and changes in drug testing protocols. These different perspectives are important to address so that future pandemic policies are successfully designed and implemented. Our study also illuminates disagreement in risk assessments between patients and providers. This suggests that preparation for emergency treatment plans requires enhanced communication with patients to match treatments to the context of lived experience.

Immune profiling in Puerto Rican injection drug users with and without HIV-1 infection.

Antiretroviral therapy has been effective in suppressing HIV viral load and enabling people living with HIV to experience longer, more conventional lives. However, as people living with HIV are living longer, they are developing aging-related diseases prematurely and are more susceptible to comorbidities that have been linked to chronic inflammation. Coincident with HIV infection and aging, drug abuse has also been independently associated with gut dysbiosis, microbial translocation, and inflammation. Here, we hypothesized that injection drug use would exacerbate HIV-induced immune activation and inflammation, thereby intensifying immune dysfunction. We recruited 50 individuals not using injection drugs (36/50 HIV+) and 47 people who inject drugs (PWID, 12/47 HIV+). All but 3 of the HIV+ subjects were on antiretroviral therapy. Plasma immune profiles were characterized by immunoproteomics, and cellular immunophenotypes were assessed using mass cytometry. The immune profiles of HIV+/PWID-, HIV-/PWID+, and HIV+/PWID+ were each significantly different from controls; however, few differences between these groups were detected, and only 3 inflammatory mediators and 2 immune cell populations demonstrated a combinatorial effect of injection drug use and HIV infection. In conclusion, a comprehensive analysis of inflammatory mediators and cell immunophenotypes revealed remarkably similar patterns of immune dysfunction in HIV-infected individuals and in people who inject drugs with and without HIV-1 infection.

"The Drug Sellers Were Better Organized than the Government": A Qualitative Study of Participants' Views of Drug Markets during COVID-19 and Other Big Events.

"Big events", such as wars, economic crises, pandemics, or natural disasters, affect the risk environment in which people use drugs. While the impact of big events on injection risk behaviors and access to drug-treatment services is well documented, less is known about the effects of big events on drug markets. Based on self-reporting data on drug availability among people who use drugs (PWUD) in the aftermath of Hurricane Maria in Puerto Rico and during the COVID-19 lockdown in a Midwestern US state, this study aims to document the effects of big events on drug markets. Qualitative data on the effects of Hurricane Maria on drug markets are based on participants' self-reporting (N = 31). Data collection started after the hurricane and ended in 2020. Data on changes to the drug supply during the COVID-19 lockdown were collected based on semi-structured interviews with PWUD (N = 40) in a Midwestern US state. Findings show that while the drug markets might have initially been affected by big events, most effects were temporary. Drug availability, pricing, and quality might have suffered some initial fluctuations but stabilized as the drug markets absorbed the initial shocks caused by the hurricane and the lockdown measures. In preparation for increasingly more frequent and virulent pandemics and natural disasters, health infrastructures should be strengthened to prevent not only overdose episodes and deaths but also drug-related harms.

Substance use, injection risk behaviors, and fentanyl-related overdose risk among a sample of PWID post-Hurricane Maria.

BACKGROUND: While natural disasters like hurricanes are increasingly common, their long-term effects on people who inject drugs are not well understood. Although brief in duration, natural disasters can radically transform risk environments, increasing substance use and drug-related harms. METHODS: Based on a study of people who inject drugs (PWID) and injection risk behaviors in rural Puerto Rico, the present study uses data from two different phases of the parent study. Data for 110 participants were collected from December 2015 to January 2017, soon before Hurricane Maria landed in September 2017; the 2019 phase, in the aftermath of the hurricane, included a total of 103 participants. The present study's main analyses used data from 66 PWID who participated in both the pre-Maria and post-Maria interviews (66 individuals measured at two time points, for a total of 132 observations), using mixed-effects binomial logistic regression to examine recent overdose experiences pre- and post-Maria. A separate descriptive analysis included all 103 participants from the 2019 interview. RESULTS: After Hurricane Maria, some declines in injection frequency were observed (the percentage of people reporting injecting monthly or less increased from 3.0% before Hurricane Maria to 22.7% after Hurricane Maria). However, fewer PWID reported using a new needle for most or all injections. In the pre-Maria interview, 10.6% of participants indicated they had experienced an overdose during the year of the interview and/or the calendar year prior, and this figure increased to 24.2% in the post-Maria interview. In the regression analysis, the odds of reporting an overdose during the interview year and/or calendar year prior were three times as high post-Maria, relative to pre-Maria (odds ratio 3.25, 95% confidence interval 1.06-9.97). CONCLUSION: Substance use patterns, injection risk behaviors, and overdose episodes and deaths differed after Hurricane Maria, relative to before the hurricane, yet it is unclear to what extent these changes also reflect the simultaneous arrival of fentanyl. In preparation for future natural disasters, it is imperative to strengthen the health infrastructure by enhancing access and curbing barriers to syringe services programs and medications for opioid use disorder, particularly in rural or underserved locations.

Employing Respondent Driven Sampling (RDS) to recruit people who inject drugs (PWID) and other hard-to-reach populations during COVID-19: Lessons learned.

Background: Respondent Driven Sampling (RDS) is an effective sampling strategy to recruit hard-to-reach populations but the impact of the COVID-19 pandemic on the use of this strategy in the collection of data involving human subjects, particularly among marginalized and vulnerable populations, is not known. Based on an ongoing study using RDS to recruit and study the interactions between HIV infection, injection drug use, and the microbiome in Puerto Rico, this paper explores the effectiveness of RDS during the pandemic and provided potential strategies that could improve recruitment and data collection. Results: RDS was employed to evaluate its effectiveness in recruiting a group of people who inject drugs (PWID) and controls (N = 127) into a study in the midst of the COVID-19 pandemic. The participants were distributed among three subsets: 15 were HIV+ and PWID, 58 were HIV- PWID, and 54 were HIV+ and not PWID. Findings: Results show that recruitment through peer networks using RDS was possible across all sub-groups. Yet, while those in the HIV+ PWID sub-group managed to recruit from other-sub groups of HIV- PWID and HIV+, this occurred at a lower frequency. Conclusion: Despite the barriers introduced by COVID-19, it is clear that even in this environment, RDS continues to play a powerful role in recruiting hard-to-reach populations. Yet, more attention should be paid at how future pandemics, natural disasters, and other big events might affect RDS recruitment of vulnerable and hard-to-reach populations.

Treatment trajectories and barriers in opioid agonist therapy for people who inject drugs in rural Puerto Rico.

BACKGROUND: Research has shown medication for opioid use disorder (MOUD) to have positive effects, including reducing HIV and HCV transmission, but important barriers to access remain among people who inject drugs (PWID). Barriers include lack of social and familial support, bureaucracy, distance to treatment, poverty, and homelessness. However, we know little about how these barriers interact with each other to shape PWID's drug treatment access and retention. METHODS: We used qualitative methods with a dataset from a study conducted during 2019 with 31 active PWID residing in rural Puerto Rico. The study gathered ethnographic data and narratives about treatment trajectories to document the lived experiences of PWID as they moved in and out of treatment. RESULTS: Participants were at least 18 years old; 87.7% were male, the mean age was 44.1 years, and the mean age at first injection was 22 years. Participants identified homelessness, lack of proper ID or other identifying documents, and previous negative experiences with MOUD as the main barriers to treatment entry and retention. In addition, PWID's belief that MOUD simply substitutes an illegal drug for a legal one, while furthering drug dependence by chronically subjecting patients to treatment, constitutes an additional barrier to entry. Findings from this study demonstrate that MOUD barriers to access and retention compound and are severely affected by poverty and other forms of vulnerability among PWID in rural Puerto Rico. CONCLUSION: Policies to increase access and retention should consider barriers not in isolation but as an assemblage of many factors.

"He's under oath": Privacy and Confidentiality Views Among People Who Inject Drugs Enrolled in a Study of Social Networks and Human Immunodeficiency Virus/Hepatitis C Virus Risk.

Despite the promise of social network research, this method raises important ethical questions regarding privacy and confidentiality. Although researchers and bioethicists have considered research obligations in relation to marginal or vulnerable populations, the views of people who inject drugs (PWIDs) have not been sufficiently considered. To elicit participants' views of research obligations, we conducted in-depth interviews with a subset (n = 40) of active PWIDs enrolled in a large social network study. Findings suggest participants have an expectation of confidentiality but believe this obligation need not be absolute and can be waived if a participant violates community norms or place others at risk. Ethics boards should recognize that marginalized populations are able to articulate complex moral views about privacy and confidentiality. Engaging participants in dialogue about the responsible conduct of research presents an opportunity to correct under- or overestimations of research vulnerabilities when such decisions are restricted to the perspectives of investigators or Institutional Review Board members.

Competing forces of withdrawal and disease avoidance in the risk networks of people who inject drugs.

We analyze a network of needle-sharing ties among 117 people who inject drugs (PWID) in rural Puerto Rico, using exponential random graph modeling to examine whether network members engage in partner restriction to lower their risk of contracting HIV or hepatitis C (HCV), or in informed altruism to prevent others from contracting these infections. Although sharing of used syringes is a significant risk factor for transmission of these diseases among PWID, we find limited evidence for partner restriction or informed altruism in the network of reported needle-sharing ties. We find however that sharing of needles is strongly reciprocal, and individuals with higher injection frequency are more likely to have injected with a used needle. Drawing on our ethnographic work, we discuss how the network structures we observe may relate to a decision-making rationale focused on avoiding withdrawal sickness, which leads to risk-taking behaviors in this poor, rural context where economic considerations often lead PWID to cooperate in the acquisition and use of drugs.

"Money Helps": People who inject drugs and their perceptions of financial compensation and its ethical implications.

This study documents how people who inject drugs (PWID) in rural Puerto Rico perceive payments for participating in HIV epidemiological studies. In-depth interviews were conducted among a subset (n = 40) of active PWID older than 18 years of age who had been previously enrolled in a much larger study (N = 360). Findings suggest that financial compensation was the main motivation for initially enrolling in the parent study. Then, as trust in the researchers developed, participants came to perceive compensation as part of a reciprocal exchange in which they assisted researchers by providing a trustful account of their experiences and researchers reciprocated with financial support.

Establishing trust in HIV/HCV research among people who inject drugs (PWID): Insights from empirical research.

BACKGROUND: The establishment of trust between researchers and participants is critical to advance HIV and HCV prevention particularly among people who inject drugs (PWID) and other marginalized populations, yet empirical research on how to establish and maintain trust in the course of community health research is lacking. This paper documents ideas about trust between research participants and researchers amongst a sub-sample of PWID who were enrolled in a large, multi-year community health study of social networks and HIV/HCV risk that was recently conducted in rural Puerto Rico. METHODS: Qualitative research was nested within a multi-year Social Network and HIV/HCV Risk study involving N = 360 PWID > 18 years of age living in four small, rural Puerto Rican communities. Semi-structured interviews were conducted between March 2017 and April 2017 with a subset of 40 active PWID who had been enrolled in the parent study. Interview questions invited participants to draw upon their recent experience as research participants to better understand how PWID perceive and understand participant-researcher trust within the context of HIV/HCV-related epidemiological research. RESULTS: Fear of police, stigma and concerns regarding confidentiality and anonymity were identified as structural factors that could compromise participation in HIV/HCV-related research for PWID. While monetary compensation was an important motivation, participants also valued the opportunity to learn about their HIV/HCV status. During their participation in the study, gaining knowledge of safe injection practices was perceived as a valuable benefit. Participant narratives suggested that PWID may adopt an incremental and ongoing approach in their assessment of the trustworthiness of researchers, continuously assessing the extent to which they trust the research staff throughout the course of the research. Trust was initially generated through peer Respondent Driven Sampling recruitment. Research staff who maintained a presence in the community for the entire duration of the prospective study reinforced trust between participants and the research team. CONCLUSION: Although PWID face numerous structural barriers to research-related trust in HIV/HCV research, we found that using a peer-based recruitment method like RDS, and employing a research staff who are knowledgeable about the targeted population, culturally sensitive to their needs, and who maintain a long-term presence in the community may help mitigate many of these barriers. The reputation of the research is built incrementally as participants join the study. This contributes to a "street reputation" that grows as current or former participants vouch for the study. Establishing trust was identified as only the first step towards building a collaborative relationship with participants, and our findings suggest that steps to address criminalization and stigmatization also are necessary to support research trust.

Latent Risk Subtypes Based on Injection and Sexual Behavior Among People Who Inject Drugs in Rural Puerto Rico.

BACKGROUND: People who inject drugs (PWID) in Puerto Rico engage in high levels of injection and sexual risk behavior, and they are at high risk for HIV and hepatitis C (HCV) infection, relative to their US counterparts. Less is known, however, about the clustering of risk behavior conducive to HIV and HCV infection among rural Puerto Rican communities. OBJECTIVES: The purpose of this study was to examine concurrent injection and sexual risk subtypes among a rural sample of PWID in Puerto Rico. METHODS: Data were drawn from a respondent-driven sample collected in 2015 of 315 PWID in 4 rural communities approximately 30-40 miles from San Juan. Latent class analysis (LCA) was used to examine risk subtypes using 3 injection and 3 sexual risk indicators. In addition, demographic and other PWID characteristics were examined as possible predictors of latent class membership. RESULTS: Four LCA subtypes were identified: low risk (36%), high injection/low sexual risk (22%), low injection/high sexual risk (20%), and high risk (22%). Younger age and past year homelessness predicted high risk latent class membership, relative to the other classes. In addition, daily speedball use predicted membership in the high injection/low sexual risk class, relative to the low risk and low injection/high sexual risk classes. CONCLUSION/IMPORTANCE: The findings suggest ways in which PWID risk clusters can be identified for targeted interventions.

Injection Partners, HCV, and HIV Status among Rural Persons Who Inject Drugs in Puerto Rico.

BACKGROUND: The prevalence of hepatitis C (HCV) and HIV among persons who inject drugs (PWID) and the ability of these diseases to spread through injection networks are well documented in urban areas. However, less is known about injection behaviors in rural areas. OBJECTIVES: This study focuses on the association between the number of self-reported injection partners with the PWID's self-reported HCV and HIV status. Injection networks provide paths for infection and information to flow, and are important to consider when developing prevention and intervention strategies. METHODS: Respondent driven sampling was used to conduct 315 interviews with PWID in rural Puerto Rico during 2015. Negative binomial regression was used to test for associations between the number of self-reported injection partners and self-reported HCV and HIV statuses. Multinomial logistic regression was used to test for associations with the participant's self-reported HCV and HIV statuses. RESULTS: Self-reported HCV status is significantly associated with injection risk network size. Injection partner networks of self-reported HCV- respondents are half what is reported by those with a positive or unknown status. Self-reported HIV statuses are not associated with different numbers of injection partners. CONCLUSIONS: Smaller injection networks among those who self-report a HCV- status suggests that those who believe their status to be negative may take protective action by reducing their injection network compared to those have a self-reported HCV+ or an unknown status. Although the cross-sectional design of the study makes it difficult verify, such behavior has implications for prevention programs attempting to prevent HCV transmission.

Rural and urban injection drug use in Puerto Rico: Network implications for human immunodeficiency virus and hepatitis C virus infection.

Understanding the short- and long-term transmission dynamics of blood-borne illnesses in network contexts represents an important public health priority for people who inject drugs and the general population that surrounds them. The purpose of this article is to compare the risk networks of urban and rural people who inject drugs in Puerto Rico. In the current study, network characteristics are drawn from the sampling "trees" used to recruit participants to the study. We found that injection frequency is the only factor significantly related to clustering behavior among both urban and rural people who inject drugs.

Rural and urban comparisons of polysubstance use profiles and associated injection behaviors among people who inject drugs in Puerto Rico.

INTRODUCTION: In contrast to urban populations, little is known about polysubstance use among rural people who inject drugs (PWID), particularly in Puerto Rico where injection drug use and related health consequences are prevalent. The aim of the study is to compare injection and non-injection substance use profiles among separate urban and rural samples of Puerto Rican PWID. MATERIAL AND METHODS: Data for the urban sample come from 455 PWID who participated in the CDC's National HIV Behavioral Surveillance survey of injection drug use in San Juan. The data for the rural sample come from 315 PWID residing in four rural cities approximately 40-miles from San Juan. Latent class analysis was used to derive separate urban and rural profiles of weekly injection and non-injection substance use. Injection behaviors were examined as possible correlates of latent class membership. RESULTS: Five latent classes were identified in the urban sample, and three latent classes were identified in the rural sample. Classes were similar across samples; however, key differences emerged. Both samples had classes of primary heroin injectors, primary speedball injectors, and cocaine-heroin injectors. The urban sample had one high polysubstance class. Polysubstance use profiles that shared similar characteristics between samples also shared similar injection patterns, with some variation. DISCUSSION: Variations in substance use patterns and associated health risks are likely shaped by social and geographic boundaries. CONCLUSIONS: Understanding variations in substance use patterns across rural and urban locales may improve surveillance efforts and tailor desistance and harm reduction efforts at the state and local levels.