Cost-effectiveness of Direct Antiviral Agents for Hepatitis C Virus Infection and a Combined Intervention of Syringe Access and Medication-assisted Therapy for Opioid Use Disorders in an Injection Drug Use Population.

BACKGROUND: There are too many plausible permutations and scale-up scenarios of combination hepatitis C virus (HCV) interventions for exhaustive testing in experimental trials. Therefore, we used a computer simulation to project the health and economic impacts of alternative combination intervention scenarios for people who inject drugs (PWID), focusing on direct antiviral agents (DAA) and medication-assisted treatment combined with syringe access programs (MAT+). METHODS: We performed an allocative efficiency study, using a mathematical model to simulate the progression of HCV in PWID and its related consequences. We combined 2 previously validated simulations to estimate the cost-effectiveness of intervention strategies that included a range of coverage levels. Analyses were performed from a health-sector and societal perspective, with a 15-year time horizon and a discount rate of 3%. RESULTS: From a health-sector perspective (excluding criminal justice system-related costs), 4 potential strategies fell on the cost-efficiency frontier. At 20% coverage, DAAs had an incremental cost-effectiveness ratio (ICER) of $27 251/quality-adjusted life-year (QALY). Combinations of DAA at 20% with MAT+ at 20%, 40%, and 80% coverage had ICERs of $165 985/QALY, $325 860/QALY, and $399 189/QALY, respectively. When analyzed from a societal perspective (including criminal justice system-related costs), DAA at 20% with MAT+ at 80% was the most effective intervention and was cost saving. While DAA at 20% with MAT+ at 80% was more expensive (eg, less cost saving) than MAT+ at 80% alone without DAA, it offered a favorable value compared to MAT+ at 80% alone ($23 932/QALY). CONCLUSIONS: When considering health-sector costs alone, DAA alone was the most cost-effective intervention. However, with criminal justice system-related costs, DAA and MAT+ implemented together became the most cost-effective intervention.

Injection-related hepatitis C serosorting behaviors among people who inject drugs: An urban/rural comparison.

Although previous research has focused on injection drug use behaviors in both urban and rural settings, few have drawn direct comparisons between adjacent rural and urban areas. Using data from the National HIV Behavioral Surveillance study as well as original data collected in a similar fashion, we compare the risk behaviors of people who inject drugs (PWID) in San Juan, Puerto Rico, with those of PWID in nearby rural areas. Specifically, we examine whether one's own hepatitis C (HCV) infection status can be used to predict whether one asked their most recent co-injection partner about their HCV status. Acquiring such information allows injectors to seek out co-injection partners of concordant status as a way to minimize the risk of viral transmission. Results indicate that urban PWID with a known HCV+ status were more likely to know their last co-injector partner's HCV status than were their peers with a negative or unknown HCV status. However, this relationship was not present in the rural data. These findings suggest that there are different risk norms in rural and urban PWID communities and that interventions successful in one type of community may not be so in others.

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.

Agency and social constraint among victims of domestic minor sex trafficking: A method for measuring free will.

Human agency has been a focus of philosophical and sociological concern from early debates about "free will" to recent themes in poststructuralism. Debates over the proper understanding of structure, agency, and constraint are hindered by the fact that few if any empirical measures of these concepts have been proposed. As sociologists have long recognized, the total results of the decisions of a group's members can be viewed as a distribution, and parameters can be fit to obtain a description of observed distributions. Here we propose the use of negative binomial curve to model population survival outcomes, and suggest that the parameters of such a curve represent reasonable surrogates for measures of agency, opportunity, and constraint when the decision process can be thought of as akin to a Bernoulli process. To provide an illustration of this approach, we discuss participation of legal minors in commercial sex (commonly referred to as victims of domestic minor sex trafficking (VDMST) or commercially sexually exploited children (CSEC)). In popular and advocacy-based accounts, considerable focus has been placed on the relative powerlessness of female VDMST. Using the proposed modeling technique, we test the extent to which male versus female VDMST appear to possess greater agency (or function under more limiting constraint) when deciding whether to remain in sex work or "leave the life". Contrary to existing literature, our results indicate that male and female underage sex workers are experiencing similar levels of agency, and differ mainly in opportunity, and constraint. Other individual circumstances are shown to contribute to varying levels of agency and constraint among sex workers, including street work status, community trouble, drug use, and the availability of an alternative income.

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.

The Interaction of Risk Network Structures and Virus Natural History in the Non-spreading of HIV Among People Who Inject Drugs in the Early Stages of the Epidemic.

This article explores how social network dynamics may have reduced the spread of HIV-1 infection among people who inject drugs during the early years of the epidemic. Stochastic, discrete event, agent-based simulations are used to test whether a "firewall effect" can arise out of self-organizing processes at the actor level, and whether such an effect can account for stable HIV prevalence rates below population saturation. Repeated simulation experiments show that, in the presence of recurring, acute, and highly infectious outbreaks, micro-network structures combine with the HIV virus's natural history to reduce the spread of the disease. These results indicate that network factors likely played a significant role in the prevention of HIV infection within injection risk networks during periods of peak prevalence. They also suggest that social forces that disturb network connections may diminish the natural firewall effect and result in higher rates of HIV.

Needle acquisition patterns, network risk and social capital among rural PWID in Puerto Rico.

BACKGROUND: People who inject drugs (PWID) take on significant risks of contracting blood-borne infection, including injecting with a large number of partners and acquiring needles from unsafe sources. When combined, risk of infection can be magnified. METHODS: Using a sample of PWID in rural Puerto Rico, we model the relationship between a subject's number of injection partners and the likelihood of having used an unsafe source of injection syringes. Data collection with 315 current injectors identified six sources of needles. RESULTS: Of the six possible sources, only acquisition from a seller (paid or free), or using syringes found on the street, was significantly related to number of partners. CONCLUSIONS: These results suggest that sources of syringes do serve to multiply risk of infection caused by multi-partner injection concurrency. They also suggest that prior research on distinct forms of social capital among PWID may need to be rethought.

Using Network Sampling and Recruitment Data to Understand Social Structures Related to Community Health in a Population of People Who Inject Drugs in Rural Puerto Rico.

OBJECTIVE: This research examined the social network and recruitment patterns of a sample of people who inject drugs (PWIDs) in rural Puerto Rico, in an attempt to uncover systematic clustering and between-group social boundaries that potentially influence disease spread. METHODS: Respondent driven sampling was utilized to obtain a sample of PWID in rural Puerto Rico. Through eight initial "seeds", 317 injection drug users were recruited. Using recruitment patterns of this sample, estimates of homophily and affiliation were calculated using RDSAT. RESULTS: Analyses showed clustering within the social network of PWID in rural Puerto Rico. In particular, females showed a very high tendency to recruit male PWID, which suggests low social cohesion among female PWID. Results for (believed) HCV status at the time of interview indicate that HCV+ individuals were less likely to interact with HCV- individuals or those who were unaware of their status, and may be acting as "gatekeepers" to prevent disease spread. Individuals who participated in a substance use program were more likely to affiliate with one another. The use of speedballs was related to clustering within the network, in which individuals who injected this mixture were more likely to affiliate with other speedball users. CONCLUSION: Social clustering based on several characteristics and behaviors were found within the IDU population in rural Puerto Rico. RDS was effective in not only garnering a sample of PWID in rural Puerto Rico, but also in uncovering social clustering that can potentially influence disease spread among this population.

Understanding differences in HIV/HCV prevalence according to differentiated risk behaviors in a sample of PWID in rural Puerto Rico.

BACKGROUND: Blood contained in needles and injection equipment has been identified as a vector for HIV and HCV transmission among people who inject drugs (PWID). Yet, there is often a wide discrepancy in prevalence for both viruses. While microbiological differences between viruses influence prevalence, other variables associated with the way drugs are acquired and used, also play a role. METHODS: Respondent-driven sampling (RDS) methods recruited a sample of 315 current intravenous drug users in rural Puerto Rico. Information about type and frequency of use, HIV and HVC risk behaviors (sharing needles, cookers, cotton, and water), sexual behaviors, and alcohol use was collected. HIV and HCV statuses were assessed via rapid antibody tests. T tests compare means of participants who tested positive (reactive) to those who tested negative. Logistic regression analyses were used to validate the association of the risk factors involved. RESULTS: Tests showed a significant difference in HIV (6%) and HCV (78.4%) prevalence among a population of current PWID. The main risk behaviors in HCV transmission are the sharing of injection "works", (e.g., cookers, cotton, and water). Sharing works occurred more than twice as often as the sharing of needles, and HCV+ and HCV- individuals reported the same needle sharing habits. CONCLUSIONS: Washing and rinsing injection works with water seems to prevent HIV transmission, but it is unable to prevent HCV infection. While education about the need to clean injection equipment with bleach might be beneficial, equipment sharing--and the subsequent risk of HVC--might be unavoidable in a context where participants are forced to pool resources to acquire and use intravenous drugs.

Respondent-driven sampling to assess outcomes of sexual violence: a methodological assessment.

Sexual violence is pervasive in eastern Democratic Republic of Congo (DRC). Survivors of sexual violence encounter numerous challenges, and women with a sexual violence-related pregnancy (SVRP) face even more complex sequelae. Because of the stigma associated with SVRP, there is no conventional sampling frame and, therefore, a paucity of research on SVRP outcomes. Respondent-driven sampling (RDS), used to study this "hidden" population, uses a peer recruitment sampling system that maintains strict participant privacy and controls and tracks recruitment. If RDS assumptions are met and the sample attains equilibrium, sample weights to correct for biases associated with traditional chain referral sampling can be calculated. Questionnaires were administered to female participants who were raising a child from a SVRP and/or who terminated a SVRP. A total of 852 participants were recruited from October 9, 2012, to November 7, 2012. There was rapid recruitment, and there were long referral chains. The majority of the variables reached equilibrium; thus, trends established in the sample population reflected the target population's trends. To our knowledge, this is the first study to use RDS to study outcomes of sexual violence. RDS was successfully applied to this population and context and should be considered as a sampling methodology in future sexual violence research.

A stochastic agent-based model of pathogen propagation in dynamic multi-relational social networks.

We describe a general framework for modeling and stochastic simulation of epidemics in realistic dynamic social networks, which incorporates heterogeneity in the types of individuals, types of interconnecting risk-bearing relationships, and types of pathogens transmitted across them. Dynamism is supported through arrival and departure processes, continuous restructuring of risk relationships, and changes to pathogen infectiousness, as mandated by natural history; dynamism is regulated through constraints on the local agency of individual nodes and their risk behaviors, while simulation trajectories are validated using system-wide metrics. To illustrate its utility, we present a case study that applies the proposed framework towards a simulation of HIV in artificial networks of intravenous drug users (IDUs) modeled using data collected in the Social Factors for HIV Risk survey.

Theory, measurement and hard times: some issues for HIV/AIDS research.

Economic and political instability and related "big events" are widespread throughout the globe. Although they sometimes lead to epidemic HIV outbreaks, sometimes they do not-and we do not understand why. Current behavioural theories do not adequately address these processes, and thus cannot provide optimal guidance for effective intervention. Based in part on a critique of our prior "pathways" model of big events, we suggest that cultural-historical activity theory (CHAT) may provide a useful framework for HIV research in this area. Using CHAT concepts, we also suggest a number of areas in which new measures should be developed to make such research possible.

A reexamination of connectivity trends via exponential random graph modeling in two IDU risk networks.

Patterns of risk in injecting drug user (IDU) networks have been a key focus of network approaches to HIV transmission histories. New network modeling techniques allow for a reexamination of these patterns with greater statistical accuracy and the comparative weighting of model elements. This paper describes the results of a reexamination of network data from the SFHR and P90 data sets using Exponential Random Graph Modeling. The results show that "transitive closure" is an important feature of IDU network topologies, and provides relative importance measures for race/ethnicity, age, gender, and number of risk partners in predicting risk relationships.

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.

Social Network Analysis of an Agricultural Center: Stakeholders and the Transfer of Information.

We conducted a social network analysis (SNA) of Central States Center for Agricultural Safety and Health (CS-CASH) to describe stakeholder networks for agricultural Research and Education/Outreach. This was a two-phase study. First, the Leader Survey went to N = 9 CS-CASH leaders to identify their key stakeholders. Next, the Stakeholder Survey was sent to these stakeholders to learn about their stakeholder collaborations, interactions, and communications. The Pajek Network Analysis measured SNA metrics for density, centrality, betweenness, k-core, and created the sociograms. The Leader Survey had a 100% response rate and generated N = 337 unique stakeholders. Most were researchers (44%) and educators (20%), with a primary sphere of influence in Nebraska-only (40%). The Stakeholder Survey had 46% response rate, and generated N = 199 names in the extended Education/Outreach network and N = 140 in the extended Research network. Stakeholders in both networks were employed mostly in universities/schools (61%) or non-profits (15%). Both networks had a single main component and 7/9 CS-CASH leaders had central roles in these components. CS-CASH is well positioned in the extended stakeholder networks based on SNA metrics. Stakeholders utilize CS-CASH resources, and they seek and exchange information with its leaders. To strengthen knowledge transfer, it will be useful to build on connections with stakeholders outside academia.

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.

"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.

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.

Social Integration and Domestic Violence Support in an Indigenous Community: Women's Recommendations of Formal Versus Informal Sources of Support.

Throughout North America, indigenous women experience higher rates of intimate partner violence and sexual violence than any other ethnic group, and so it is of particular importance to understand sources of support for Native American women. In this article, we use social network analysis to study the relationship between social integration and women's access to domestic violence support by examining the recommendations they would give to another woman in need. We ask two main questions: First, are less integrated women more likely to make no recommendation at all when compared with more socially integrated women? Second, are less integrated women more likely than more integrated women to nominate a formal source of support rather than an informal one? We use network data collected from interviews with 158 Canadian women residing in an indigenous community to measure their access to support. We find that, in general, less integrated women are less likely to make a recommendation than more integrated women. However, when they do make a recommendation, less integrated women are more likely to recommend a formal source of support than women who are more integrated. These results add to our understanding of how access to two types of domestic violence support is embedded in the larger set of social relations of an indigenous community.