Predictors of engagement in screening for a hepatitis C virus (HCV) treatment trial in a rural Appalachian community.

An HCV treatment trial was initiated in September 2019 to address the opioid/hepatitis C virus (HCV) syndemic in rural Kentucky. The focus of the current analysis is on participation in diagnostic screening for the trial. Initial eligibility (≥18 years of age, county resident) was established by phone followed by in-person HCV viremia testing. 900 rural residents met the inclusion criteria and comprised the analytic sample. Generalized linear models were specified to estimate the relative risk of non-attendance at the in-person visit determining HCV eligibility. Approximately one-quarter (22.1%) of scheduled participants were no-shows. People who inject drugs were no more likely than people not injecting drugs to be a no-show; however, participants ≤35 years of age were significantly less likely to attend. While the median time between phone screening and scheduled in-person screening was only 2 days, each additional day increased the odds of no-show by 3% (95% confidence interval: 2%-3%). Finally, unknown HCV status predicted no-show even after adjustment for age, gender, days between screenings and injection status. We found that drug injection did not predict no-show, further justifying expanded access to HCV treatment among people who inject drugs. Those 35 years and younger were more likely to no-show, suggesting that younger individuals may require targeted strategies for increasing testing and treatment uptake. Finally, streamlining the treatment cascade may also improve outcomes, as participants in the current study were more likely to attend if there were fewer days between phone screening and scheduled in-person screening.

Longitudinal trends in nonmedical prescription opioid use in a cohort of rural Appalachian people who use drugs.

Rural Appalachia remains an epicenter of the prescription opioid epidemic. In 2008, a cohort study was undertaken to examine longitudinal trends in nonmedical prescription opioid use (NMPOU). Eight waves of data (2008-2020) from the Social Networks among Appalachian People (SNAP) cohort were utilized for the current analysis. Only those who reported recent (past 6-month) NMPOU at baseline are included (n = 498, 99%). Mixed-effects logistic regression was used to model factors associated with NMPOU over time. Recent NMPOU declined significantly over the past decade (p < .001). However, 54.1% of participants still engaged in NMPOU at their most recent follow-up. Receipt of benefits for a physical or mental disability (adjusted odds ratio [aOR]: 3.11, 95% Confidence Interval [CI]: 1.98, 4.90) and self-described poor health status (aOR: 3.67, 95% CI: 1.61, 8.37) were both associated with NMPOU. All treatment modalities (methadone maintenance, residential, outpatient counseling) tested in the model, with the notable exception of detoxification, were associated with significantly lower odds of NMPOU. Although significant declines in prescription opioid misuse were observed in the cohort, more than half of all participants were engaged in NMPOU more than a decade after entering the study. Substance use disorder (SUD) treatment (excluding detoxification) was shown associated with reduced odds of continued NMPOU; therefore, increasing access to evidence-based treatments should be a priority in rural areas affected by the ongoing opioid epidemic.

Privacy, Confidentiality, and Safety Considerations for Conducting Geographic Momentary Assessment Studies Among Persons Who Use Drugs and Men Who Have Sex with Men.

Geographic momentary assessments (GMA) collect real-time behavioral data in one's natural environment using a smartphone and could potentially increase the ecological validity of behavioral data. Several studies have evaluated the feasibility and acceptability of GMA among persons who use drugs (PWUD) and men who have sex with men (MSM), but fewer have discussed privacy, confidentiality, and safety concerns, particularly when illegal or stigmatized behavioral data were collected. This study explores perceptions regarding privacy, confidentiality, and safety of GMA research among PWUD and MSM recruited in three different settings (rural Appalachia, a mid-sized city in the South, and a mid-Atlantic city). Between November 2014 and April 2017, we recruited 35 PWUD from rural Appalachian Kentucky (N = 20) and Baltimore, Maryland (N = 15) and 20 MSM from Lexington, Kentucky to complete semi-structured qualitative interviews. Through thematic analyses, we identified and compared privacy, confidentiality, and safety concerns by demographic characteristics, risk behaviors, and setting. Privacy, confidentiality, and safety concerns varied by setting, age, smartphone ownership, use of illegal drugs, and history of drug-related arrests. Among those who used drugs, participants reported concerns with being tracked and burden associated with carrying and safeguarding study phones and responding to survey prompts. Privacy and confidentiality concerns were noted in each setting, but tracking concerns were greatest among Baltimore participants and led many to feel that they (or others) would be unwilling to participate or comply with study procedures. While locations considered to be sensitive varied by setting, participants in all settings said they would take measures to prevent sensitive information from being collected (i.e., intentionally disable devices, leave phones at home, alter response times). Privacy, confidentiality, and safety concerns may limit the accuracy of risk location information, study compliance, and participation. As concerns were often greatest among those engaging in illegal behaviors and with the highest risk behaviors, selection bias and non-response bias could negatively influence the representativeness and validity of study findings.

Using Network and Spatial Data to Better Target Overdose Prevention Strategies in Rural Appalachia.

This analysis uses network and spatial data to identify optimal individuals to target with overdose prevention interventions in rural Appalachia. Five hundred and three rural persons who use drugs were recruited to participate in the Social Networks among Appalachian People Study (2008-2010). Interviewer-administered surveys collected information on demographic characteristics, risk behaviors (including overdose history), network members, and residential addresses. We restricted the sample to individuals with at least one confirmed relationship to another study participant (N = 463). Using dyadic analyses (N = 1428 relationships), we identified relationship-level correlates of relationships with network members who have previously overdosed. We then examined individual- and network-level factors associated with (1) having at least one first-degree alter (i.e., network member) with a prior overdose and (2) each additional network member with a prior overdose (N = 463 study participants). Overall, 28% of the sample had previously overdosed and 57% were one-degree away from someone who previously overdosed. Relationships with those who had overdosed were characterized by closer residential proximity. Those with at least one network member who previously overdosed were more geographically central and occupied more central network positions. Further, the number of network members with an overdose history increased with decreasing distance to the town center, increasing network centrality, and prior enrollment in an alcohol detox program. Because fatal overdoses can be prevented through bystander intervention, these findings suggest that strategies that target more central individuals (both geographically and based on their network positions) and those who have previously enrolled in alcohol detox programs with overdose prevention training and naloxone may optimize intervention reach and have the potential to curb overdose fatalities in this region.

Network-Based Research on Rural Opioid Use: an Overview of Methods and Lessons Learned.

PURPOSE OF REVIEW: The purpose of this paper is to provide a thorough overview of methods used for recruitment, network data collection, and network data management in a network-based study of rural people who use drugs (PWUD) and to offer methodological recommendations for future research on rural drug use. RECENT FINDINGS: The Social Networks among Appalachian People (SNAP) study recruited a cohort of 503 rural PWUD via respondent-driven sampling (RDS) and has retained more than 80% of eligible participants over 7-9 years. SNAP has yielded important methodological insights, including that (1) RDS referral was non-random and disproportionately involved kin and (2) interviewer-administered questionnaires were successful in eliciting accurate name and age information about network members. The SNAP experience suggests that RDS was a successful recruitment strategy for rural PWUD and questionnaires administered by community-based interviewers in the context of a Certificate of Confidentiality could elicit detailed data on PWUD risk networks.

Implementing Treatment of Opioid-Use Disorder in Rural Settings: a Focus on HIV and Hepatitis C Prevention and Treatment.

PURPOSE OF REVIEW: To describe the epidemiology of opioid-use disorder in the rural United States (U.S.) as it pertains to HIV and hepatitis C transmission and treatment resources. RECENT FINDINGS: Heroin and fentanyl analogs have surpassed prescription opioids in their availability in rural opioid markets adding to HIV and hepatitis C (HCV) and overdose risks. Only 18% of rural individuals live in towns with inpatient services which are of limited quality and utility. Opioid treatment programs that provide methadone are not located in rural areas and only 3% of the primary care providers have the ability to prescribe buprenorphine. National models and resources have been established but lack implementation in rural areas leading to ongoing HIV and HCV transmission and overdose. Addressing the adverse impact of opioids in the rural U.S. will require a concerted effort to implement effective treatments according to national standards.

Drug Use and Incarceration among Rural Appalachian Women: Findings From a Jail Sample.

BACKGROUND/OBJECTIVE: The purpose of this paper is to examine drug use and incarceration history among rural Appalachian women. METHODS: This study involved random selection, screening, and interviews with rural women from local jails in Appalachia. RESULTS: Of the women randomly selected and screened, 97% met criteria for substance use intervention. Significant factors associated with incarceration history included age, education, custody status, and mental health. A significant interaction was observed between male sex partners and drug use on incarceration history. CONCLUSIONS: Study findings suggest that the drug/crime relationship among rural Appalachian women is associated with their high-risk home environment, partner relationships, and mental health. Specifically, in addition to drug use, factors such as family and child relationships, anxiety, victimization, and relationships with partners should also be considered in the trajectory of criminal careers among rural Appalachian women.

Examining the Social Context of Injection Drug Use: Social Proximity to Persons Who Inject Drugs Versus Geographic Proximity to Persons Who Inject Drugs.

In this analysis, we used social network and spatial data to examine associations between people's drug injection status and their social and/or spatial proximity to others who injected drugs. We recruited 503 rural Kentucky residents who used drugs to participate in the Social Networks among Appalachian People (SNAP) Study (2008-2010). Interviewer-administered surveys collected information on recent (past 6 months) sex, drug-use, and social-support network members (n = 897 ties). Using network simulations, we determined a threshold for the association between social proximity to others who injected drugs and recent injection status ("socially proximal" was defined by a shortest path ≤2). We defined "geographically proximal" as the median road-network distance between pairs of individuals who both injected drugs (≤7 miles (≤11.2 km)). Logistic regression was used to determine the independent and joint associations between the number of socially and/or geographically proximal injecting peers and a person's injection status. After adjustment, the odds of recent injection increased by 0.4% for each injecting peer who was geographically proximal but not socially proximal, 12% for each geographically and socially proximal injecting peer, and 22% for each injecting peer who was socially proximal but not geographically proximal. When implementing network-based interventions which promote cessation of injection drug use, investigators should consider collecting sociometric network data to examine whether the intervention diffuses through the network and whether there are additive or threshold effects.

African American women and sexually transmitted infections: The contextual influence of unbalanced sex ratios and individual risk behaviors.

This study uses data from 564 African American women to examine the correlates of lifetime prevalence of a sexually transmitted infection (STI). Specifically, we test the effects of perceptions about the availability of African American males, five partner characteristics, and drug history. At the bivariate-level, women with an STI diagnosis were significantly more likely to have dated a man who was married, older, had sex with another man, involved in concurrent partnerships, and had been incarcerated. About half of the participants stated it was difficult to find an eligible African American male and attributed the limited pool of same-race partners to drug trafficking, a lack of monogamy, and high rates of incarceration. Multivariate analyses revealed having dated a man who had concurrent sexual partnerships or had been incarcerated, as well as drug use during sex were positively associated with ever having an STI. Individual and contextual implications are addressed.

Silence Surrounding Hepatitis C Status in Risk Relationships Among Rural People Who Use Drugs.

Hepatitis C virus (HCV) has reached epidemic proportions in rural Central Appalachia in recent years. We sought to identify demographic, behavioral, and interpersonal characteristics associated with HCV serostatus disclosure among high risk people who use drugs (PWUD) in Appalachian Kentucky. HCV antibody-positive participants (n = 243), drawn from the fifth follow-up assessment of a longitudinal study of rural PWUD, completed interviewer-administered questionnaires eliciting demographic and interpersonal characteristics, risk behaviors, and information about HCV disclosure. We assessed correlates of HCV disclosure using gender-stratified multivariate logistic regression. Participants reported having disclosed their HCV-positive status to a current sex partner (44.0%), family member (35.8%), close friend (9.5%), or past sex partner (6.6%). Of those reporting current (n = 72) or past (n = 215) injection drug use (IDU), only 2.8% disclosed to current and 0.9% disclosed to past IDU partners, respectively. Female participants were more likely than male participants to disclose to current sex partners and family member(s). In multivariate analyses, adjusting for time since testing HCV positive, older age and lifetime history of drug treatment were associated with decreased odds of HCV disclosure among females, while only lifetime history of drug treatment was associated with decreased odds of HCV disclosure among males. In summary, the almost complete absence of disclosure to current or former injection drug use partners was concerning. However, most participants (69.1%) reported disclosing their HCV status to at least one of their social referents, suggesting that family members, partners, and friends of people living with HCV could play a critical role in encouraging uptake of treatment. Although further research is warranted, it is clear that interventions are needed to encourage HCV disclosure among those most at risk of transmitting HCV.

Correlates to seroprevalent herpes simplex virus type 2 among rural Appalachian drug users.

Herpes simplex virus type 2 (HSV-2) is the most common cause of genital ulcer disease and, along with substance abuse, an important HIV risk factor. Therefore, the purpose of this study was to examine HSV-2 seroprevalence in a sample of drug users in rural Appalachia. Rural Appalachian individuals age 18 or older reporting non-medical use of prescription opioids, heroin, crack/cocaine, or methamphetamine in the past 6 months (n = 499) were included. Behavioral, demographic, and sexual network data were collected using interviewer-administered questionnaires. Participants' serum was tested for HSV-2 antibodies using the Biokit rapid test (Lexington, MA). The estimated population seroprevalence of HSV-2 was 14.4% (95%CI: 9.6-19.4%). Only 8.8% were aware of being HSV-2+, and unprotected sex was reported in 80% of serodiscordant sexual relationships. In a multivariate model, female gender, age, older age at first oral sex, and frequency of unprotected sex in the sexual network were independently associated with HSV-2 seropositivity. Despite lower seroprevalence than that reported in similar studies of substance abusers, targeted interventions to reduce sexual risk behavior are warranted in this underserved population. Network-informed approaches with particular focus on women, older individuals, and those engaging in frequent unprotected sex are recommended.

Relationship-level analysis of drug users' anticipated changes in risk behavior following HIV vaccination.

Formative research into the behavioral factors surrounding HIV vaccine uptake is becoming increasingly important as progress is made in HIV vaccine development. Given that the first vaccines on the market are likely to be partially effective, risk compensation (i.e., increased risk behavior following vaccination) may present a concern. This study characterized the relationships in which HIV vaccine-related risk compensation is most likely to occur using dyadic data collected from people who use drugs, a high-risk group markedly underrepresented in extant literature. Data were collected from 433 drug users enrolled in a longitudinal study in the USA. Respondents were asked to provide the first name and last initial of individuals with whom they had injected drugs and/or had sex during the past six months. For each partner, respondents reported their likelihood of increasing risk behavior if they and/or their partner received an HIV vaccine. Using generalized linear mixed models, relationship-level correlates to risk compensation were examined. In bivariate analysis, risk compensation was more likely to occur between partners who have known each other for a shorter time (odds ratio [OR]=0.95, 95% confidence interval [CI]: 0.90-0.99, p=0.028) and between those who inject drugs and have sex together (OR=2.52, CI: 1.05-6.04, p=0.039). In relationships involving risk compensation, 37% involved partners who had known each other for a year or less compared to only 13% of relationships not involving risk compensation. Adjusting for other variables, duration (OR: 0.95, CI: 0.90-1.00, p=0.033) was associated with risk compensation intent. These analyses suggest that risk compensation may be more likely to occur in less established relationships and between partners engaging in more than one type of risk behavior. These data provide further support for the need to expand measures of risk compensation in HIV vaccine preparedness studies to assess not only if people will change their behavior, but also with whom.

Understanding the rural-urban differences in nonmedical prescription opioid use and abuse in the United States.

Nonmedical prescription opioid misuse remains a growing public problem in need of action and is concentrated in areas of US states with large rural populations such as Kentucky, West Virginia, Alaska, and Oklahoma. We developed hypotheses regarding the influence of 4 factors: (1) greater opioid prescription in rural areas, creating availability from which illegal markets can arise; (2) an out-migration of young adults; (3) greater rural social and kinship network connections, which may facilitate drug diversion and distribution; and (4) economic stressors that may create vulnerability to drug use more generally. A systematic consideration of the contexts that create differences in availability, access, and preferences is critical to understanding how drug use context varies across geography.

Reducing risky relationships: a multisite randomized trial of a prison-based intervention for reducing HIV sexual risk behaviors among women with a history of drug use.

Women involved in the criminal justice system, particularly those with a history of drug use, are at elevated risk of HIV infection, yet few HIV prevention interventions have been tailored for delivery to incarcerated women. Drawing on the Relational Model, the Reducing Risky Relationships for HIV (RRR-HIV) intervention was developed and evaluated in a multisite randomized clinical trial. Women with weekly drug use prior to incarceration (n = 444) who were incarcerated within correctional institutions in four states were randomized to (1) the RRR-HIV intervention consisting of an HIV educational video, five group sessions, and one postrelease booster session or (2) a control condition consisting of the HIV educational video. The RRR-HIV intervention combined didactic and interactive content regarding seven "thinking myths" about intimate relationships that may result in decisions to engage in risky sexual behaviors. Data were collected while women were still incarcerated and approximately 90 days following release from prison by trained interviewers. A negative binomial regression (NBR) model of unprotected sexual behaviors at the 90-day follow-up indicated that RRR-HIV participants reported fewer unprotected sexual behaviors than women in the control condition once the analysis was adjusted for study site. Future studies should examine the sustainability of the RRR-HIV intervention's effect on risk reduction. Implementation research is needed to determine whether delivery of this intervention by correctional staff or peers, rather than research staff, yields similar reductions in unprotected sexual behaviors.

HIV vaccine acceptability among high-risk drug users in Appalachia: a cross-sectional study.

BACKGROUND: A vaccine could substantially impact the HIV epidemic, but inadequate uptake is a serious concern. Unfortunately, people who use drugs, particularly those residing in rural communities, have been underrepresented in previous research on HIV vaccine acceptability. This study examined HIV vaccine acceptability among high-risk drug users in a rural community in the United States. METHODS: Interviewer-administered questionnaires included questions about risk behavior and attitudes toward HIV vaccination from 433 HIV-negative drug users (76% with history of injection) enrolled in a cohort study in Central Appalachia. HIV vaccine acceptability was measured on a 4-point Likert scale. Generalized linear mixed models were used to determine correlates to self-report of being "very likely" to receive a 90% effective HIV vaccine (i.e. "maximum vaccine acceptability", or MVA). Adjusted odds ratios (AORs) and corresponding 95% confidence intervals (CIs) are reported. RESULTS: Most (91%) reported that they would accept a preventive HIV vaccine, but concerns about cost, dosing, transportation constraints, vaccine-induced seropositivity, and confidentiality were expressed. Cash incentives, oral-administration, and peer/partner encouragement were anticipated facilitators of uptake. In multivariate analysis, men were significantly less likely to report MVA (AOR: 0.33, CI: 0.21 - 0.52). MVA was more common among participants who believed that they were susceptible to HIV (AOR: 2.31, CI: 1.28 - 4.07), that an HIV vaccine would benefit them (AOR: 2.80, CI: 1.70 - 4.64), and who had positive experiential attitudes toward HIV vaccination (AOR: 1.85, CI: 1.08 - 3.17). MVA was also more common among participants who believed that others would encourage them to get vaccinated and anticipated that their behavior would be influenced by others' encouragement (AOR: 1.81, 95% 1.09 - 3.01). CONCLUSIONS: To our knowledge, this study was among the first to explore and provide evidence for feasibility of HIV vaccination in a rural, high-risk population in the United States. This study provides preliminary evidence that gender-specific targeting in vaccine promotion may be necessary to promoting vaccine uptake in this setting, particularly among men. The data also underscore the importance of addressing perceived risks and benefits, social norms, and logistical constraints in efforts to achieve widespread vaccine coverage in this high-risk population.

Does the new formulation of OxyContin® deter misuse? A qualitative analysis.

The purpose of this qualitative study is to understand changing illicit drug use patterns in rural Appalachia since a new formulation of OxyContin® was released with the goal of deterring diversion and misuse. Participants (n = 25) from a longitudinal study of rural drug users (N = 192) were approached to participate in semistructured qualitative interviews between April and June 2011. The primary finding is that the majority of participants switched from using the original formulation OxyContin to immediate-release oxycodone. We discuss the implications and limitations of these findings.

Examining the social and behavioral dynamics of substance use in a longitudinal network study in rural Appalachia.

BACKGROUND: Prior studies have shown that individuals and their peers often have similar substance use behaviors, but the mechanisms driving these similarities - particularly in rural settings, are not well understood. The primary objectives of this analysis are to (1) identify factors that contribute to relationship turnover and maintenance within a rural network of persons who use drugs (PWUD), (2) determine whether assimilation and/or homophily shape participants use of injection drugs, heroin, and stimulants (methamphetamine and cocaine), and (3) assess the extent that these mechanisms influence networks ties and/or behaviors and whether these effects vary across time. METHODS: Sociometric network data were collected from a cohort of PWUD in rural Eastern Kentucky at baseline (2008-2010) and at four follow-up visits conducted approximately semiannually. Stochastic actor-oriented models (SAOMS) were used to model network structure and participant behaviors as jointly dependent variables and to identify characteristics associated with the maintenance, dissolution, and formation of network ties and changes in drug use behaviors. RESULTS: Findings suggest (1) greater network stability over time for reciprocal and transitive relationships, (2) both homophily and assimilation played a greater role in shaping injection drug use (IDU) initiation and cessation than they did in shaping heroin and stimulant use, and (3) the importance of these mechanisms appeared consistent over time. CONCLUSION: Given the stability of particular network structures and evidence of both homophily and assimilation with respect to drug-use behaviors, interventions that leverage social networks could be used to motivate health-promoting behaviors.

Kentucky Outreach Service Kiosk (KyOSK) Study protocol: a community-level, controlled quasi-experimental, type 1 hybrid effectiveness study to assess implementation, effectiveness and cost-effectiveness of a community-tailored harm reduction kiosk on HIV, HCV and overdose risk in rural Appalachia.

INTRODUCTION: Many rural communities bear a disproportionate share of drug-related harms. Innovative harm reduction service models, such as vending machines or kiosks, can expand access to services that reduce drug-related harms. However, few kiosks operate in the USA, and their implementation, impact and cost-effectiveness have not been adequately evaluated in rural settings. This paper describes the Kentucky Outreach Service Kiosk (KyOSK) Study protocol to test the effectiveness, implementation outcomes and cost-effectiveness of a community-tailored, harm reduction kiosk in reducing HIV, hepatitis C and overdose risk in rural Appalachia. METHODS AND ANALYSIS: KyOSK is a community-level, controlled quasi-experimental, non-randomised trial. KyOSK involves two cohorts of people who use drugs, one in an intervention county (n=425) and one in a control county (n=325). People who are 18 years or older, are community-dwelling residents in the target counties and have used drugs to get high in the past 6 months are eligible. The trial compares the effectiveness of a fixed-site, staffed syringe service programme (standard of care) with the standard of care supplemented with a kiosk. The kiosk will contain various harm reduction supplies accessible to participants upon valid code entry, allowing dispensing data to be linked to participant survey data. The kiosk will include a call-back feature that allows participants to select needed services and receive linkage-to-care services from a peer recovery coach. The cohorts complete follow-up surveys every 6 months for 36 months (three preceding kiosk implementation and four post-implementation). The study will test the effectiveness of the kiosk on reducing risk behaviours associated with overdose, HIV and hepatitis C, as well as implementation outcomes and cost-effectiveness. ETHICS AND DISSEMINATION: The University of Kentucky Institutional Review Board approved the protocol. Results will be disseminated in academic conferences and peer-reviewed journals, online and print media, and community meetings. TRIAL REGISTRATION NUMBER: NCT05657106.

Individual and network factors associated with prevalent hepatitis C infection among rural Appalachian injection drug users.

OBJECTIVES: We determined the factors associated with hepatitis C (HCV) infection among rural Appalachian drug users. METHODS: This study included 394 injection drug users (IDUs) participating in a study of social networks and infectious disease risk in Appalachian Kentucky. Trained staff conducted HCV, HIV, and herpes simplex-2 virus (HSV-2) testing, and an interviewer-administered questionnaire measured self-reported risk behaviors and sociometric network characteristics. RESULTS: The prevalence of HCV infection was 54.6% among rural IDUs. Lifetime factors independently associated with HCV infection included HSV-2, injecting for 5 or more years, posttraumatic stress disorder, injection of cocaine, and injection of prescription opioids. Recent (past-6-month) correlates of HCV infection included sharing of syringes (adjusted odds ratio = 2.24; 95% confidence interval = 1.32, 3.82) and greater levels of eigenvector centrality in the drug network. CONCLUSIONS: One factor emerged that was potentially unique to rural IDUs: the association between injection of prescription opioids and HCV infection. Therefore, preventing transition to injection, especially among prescription opioid users, may curb transmission, as will increased access to opioid maintenance treatment, novel treatments for cocaine dependence, and syringe exchange.

Factors associated with high-frequency illicit methadone use among rural Appalachian drug users.

BACKGROUND: In recent years there has been a sharp increase in the use of illicit methadone as well as methadone-related overdose deaths. OBJECTIVE: The purpose of this study was to describe factors associated with low- and high-frequency methadone use in a cohort of rural Appalachian drug users. METHODS: Interviews assessing sociodemographics, illicit drug use and drug treatment, psychiatric disorders, health and sociometric drug network characteristics were conducted with 503 rural drug users between 2008 and 2010. A two-level mixed effects regression model was utilized to differentiate low- (one use per month or less in the past six months) versus high-frequency (daily or weekly use in the past six months) illicit methadone users. RESULTS: The lifetime prevalence of illicit methadone use in this population was 94.7% (n = 476) and slightly less than half (46.3%) were high-frequency users. In the mixed effects regression model, initiating illicit methadone use at a younger age was associated with high-frequency illicit methadone use. Taking a prescribed medication for a physical problem, undergoing additional weeks of outpatient drug free treatment, daily OxyContin® use in the past month, and having fewer ties and second-order connections in the drug network reduced the odds of high-frequency illicit methadone use. CONCLUSIONS: Rates of illicit methadone use and high-frequency illicit methadone use among this sample of rural drug users were considerably higher than those previously reported in the literature. Health practitioners in rural areas should routinely screen for illicit opioid use, including methadone.