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PLOS ONE logoLink to PLOS ONE
. 2022 Oct 25;17(10):e0276723. doi: 10.1371/journal.pone.0276723

Interest without uptake: A mixed-methods analysis of methadone utilization in Kyrgyz prisons

Amanda R Liberman 1,*, Daniel J Bromberg 2,3, Taylor Litz 1,¤, Ainura Kurmanalieva 4, Samy Galvez 1,3, Julia Rozanova 1, Lyu Azbel 1, Jaimie P Meyer 1,3, Frederick L Altice 1,3
Editor: Judith I Tsui5
PMCID: PMC9595522  PMID: 36282864

Abstract

HIV incidence continues to increase in Eastern Europe and Central Asia (EECA), in large part due to non-sterile injection drug use, especially within prisons. Therefore, medication-assisted therapy with opioid agonists is an evidence-based HIV-prevention strategy. The Kyrgyz Republic offers methadone within its prison system, but uptake remains low. Screening, Brief Intervention, and Referral to Treatment (SBIRT) is a framework for identifying people who would potentially benefit from methadone, intervening to identify OUD as a problem and methadone as a potential solution, and providing referral to methadone treatment. Using an SBIRT framework, we screened for OUD in Kyrgyz prisons among people who were within six months of returning to the community (n = 1118). We enrolled 125 people with OUD in this study, 102 of whom were not already engaged in methadone treatment. We conducted a pre-release survey followed by a brief intervention (BI) to address barriers to methadone engagement. Follow-up surveys immediately after the intervention and at 1 month, 3 months, and 6 months after prison release assessed methadone attitudes and uptake. In-depth qualitative interviews with 12 participants explored factors influencing methadone utilization during and after incarceration. Nearly all participants indicated favorable attitudes toward methadone both before and after intervention in surveys; however, interest in initiating methadone treatment remained very low both before and after the BI. Qualitative findings identified five factors that negatively influence methadone uptake, despite expressed positive attitudes toward methadone: (1) interpersonal relationships, (2) interactions with the criminal justice system, (3) logistical concerns, (4) criminal subculture, and (5) health-related concerns.

Introduction

Eastern Europe and Central Asia (EECA) is one of the few regions globally where HIV incidence continues to increase [1]. In the Kyrgyz Republic, this increase is largely due to unsafe injection practices, particularly within prisons [1, 2]. Methadone, the most effective treatment for opioid use disorder (OUD) [3, 4], is also highly effective at preventing HIV [5, 6]. While methadone has been available within most Kyrgyz prisons since 2008, uptake among incarcerated people remains low [7, 8]. Previous research has suggested multiple factors for this low uptake. For instance, much has been written about the criminal subculture that governs Kyrgyz men’s prisons, influencing nearly every within-prison behavior including whether an individual has access to heroin [911]. The frequent use of Dimedrol (diphenhydramine), a soporific, in conjunction with methadone in Kyrgyz prisons means that the effects of Dimedrol are often conflated with those of methadone [12, 13]. Finally, current Kyrgyz Ministry of Health guidelines specify low dosages of methadone (30 mg initial dose, increasing by 5-10mg every 7 days), potentially increasing risk of dropout [14].

Release from prison carries a very high risk of death due to overdose [15, 16], particularly among people living with HIV [12, 15, 17]. Given the generally low levels of methadone uptake in Kyrgyz prisons as well as the increased risks surrounding release, we deployed a screening, brief intervention, and referral to treatment (SBIRT) strategy to increase methadone program participation among incarcerated people with OUD who were scheduled to be released from prison within six months.

SBIRT is an evidence-based strategy to identify people with substance use disorders and engage them in care [18]. It has been deployed in multiple community settings in the US with modest effectiveness [1924], although to our knowledge, only one other study (from this lab) has examined its effectiveness in another EECA country [25], and it has not previously been implemented in the Kyrgyz Republic. In this study, we recruited 125 soon-to-be released incarcerated people with OUD in the Kyrgyz Republic who participated in the SBIRT intervention. Additionally, we conducted in-depth interviews with 12 participants before and after their release from prison. The resulting analysis allowed us to investigate both interest and uptake in methadone utilization among soon-to-be-released people with OUD in Kyrgyz prisons. Furthermore, it allowed us to explore some of the reasons behind the lack of methadone uptake, despite professed positive attitudes toward this treatment.

Materials and methods

This study began in October 2016 and remains ongoing in nine prisons in the Kyrgyz Republic. Methods for recruitment have been previously described [13]; ClinicalTrials.gov Identifier for Project MATLINK is NCT04947475. The study used a screening, brief intervention, and referral to treatment (SBIRT) strategy. Briefly, research personnel screened all incarcerated persons between 8 and 180 days from their release date using a single-item screener for opioid use disorder (OUD) followed by the Rapid Opioid Dependence Scale. In total, we recruited 125 people into our sample. Given the utilization of the SBIRT method (i.e., we cannot recruit more people than are eligible participants in the country), a formal sample size/power calculation was not performed.

If OUD was confirmed, potential participants completed informed consent procedures in which research assistants made clear that this study was not affiliated with the prison administration, that surveys and interviews would remain anonymous, that participants could withdraw from the study at any point, and that neither participation nor withdrawal were linked with any rewards or punishments. Ethical approval for the study was provided by the US Department of Health and Human Services, Office for Human Research Protections (OHRP) and by the institutional review boards (IRBs) at Yale University and at the Global Research Institute Foundation in the Kyrgyz Republic. Yale’s IRB included an incarcerated person as a representative.

After enrollment, participants were assessed for initial interest in methadone on a scale from 0 to 10, with 0 indicating no interest in methadone and 10 indicating a plan to begin methadone treatment. Next, participants completed surveys assessing demographic characteristics, OUD severity (using the Addiction Severity Index-Lite [26]), depression (using the CES-D scale [27]), and overall physical and mental health (using the SF-12 [28]). A complete list of survey questions is available (S1 File; results available in S3 File). Participants then underwent testing for HIV, HBV, HCV, and syphilis.

Next, they participated in a brief intervention (BI) guided by motivational interviewing principles in which a trained research assistant explained benefits and dispelled myths relating to methadone treatment both during and after incarceration. The BI informed participants of the risks of substance misuse by illustrating potential adverse health consequences. Additionally, the BI aimed to motivate participants to seek treatment for their substance use disorder. After the BI, participants’ interest in methadone was re-assessed, and if interested, they were referred to a treating physician in the prison to initiate methadone. All study participants, irrespective of methadone enrollment, underwent a second BI one week before release to encourage participants either to initiate methadone treatment or to link to care in the community. Each BI lasted approximately 20 minutes, and afterwards, participants were provided time for questions. The BIs were audio recorded; audio files are available upon request (in the original languages of the BI—Russian & Kyrgyz).

After release, study participants underwent repeat consent procedures and were followed up at 1, 3, and 6 months to assess for methadone interest or uptake or continued opioid use; for 1 individual who did not complete any surveys within 6 months, a 12-month survey was administered. If reincarcerated post-release, study participants were listed as not available for follow-up. Methadone uptake was verified using a state-run methadone registry. To further understand perceptions of methadone in and outside of prison settings, in-depth qualitative interviews were carried out from 12 study participants both pre- and post-release. LA and JR conducted the interviews in Russian. Interviews lasted, on average, 45 minutes and were audio-recorded (See S2 File for interview guide).

The initial coding of these interviews is discussed in a previous paper [13]. For the present paper, the authors used thematic analysis based on risk environment theory to sub-code the data, looking for factors relevant to methadone uptake and utilization before and after release from prison. In this text, information is provided about participants’ levels in the within-prison social hierarchy. An individual can be classified into one of three general categories, in descending order of status: 1) poryadochnyi (“decent one”); 2) neput’ (“one who lost the way”); 3) obizhennyi (“one who has offended”), and one can be promoted or demoted based on various behaviors or interactions with people in other levels of the hierarchy, as described in previous studies [29, 30].

Statistical analysis

Statistical analysis was completed in Microsoft Excel and R. Given that Shapiro-Wilks tests indicated non-normality for all survey questions (p<0.001 for all), paired, one-sided non-parametric (Wilcoxon signed rank) tests were used to compare survey scores at baseline vs. at follow-up (alternative hypothesis: “Survey outcome increased post-intervention”). Participants who had not completed both a baseline and a follow-up survey were excluded from analysis. Primary study outcomes included initiation of methadone, retention in methadone treatment, relapse to heroin, and recidivism.

Results

Findings from the screening, brief intervention and referral to treatment strategy

Between 2016 and 2021, 1,118 soon-to-be-released incarcerated people underwent screening, and 125 (11.2%) screened positive for OUD and enrolled in the study (Fig 1). Study participant characteristics are available in Tables 1 and 2. While information is not available for all of these characteristics for the prison population of the Kyrgyz Republic, the percentage of female prisoners in our study and high rate of infectious diseases like hepatitis C correlate with findings reported by other sources [8, 31]. Of these 125 study participants, 109 completed the pre-release visit questionnaires and attended the brief intervention (BI), a workshop that used motivational interviewing techniques to address barriers to methadone engagement. Of these 109, 63 participated in a one-month follow-up after release, 57 participated in the three-month follow-up, and 55 participated at six-month follow-up (Fig 1). These post-release follow-ups did not have all the same participants; some participants did not participate for the one-month follow-up but attended the three-month follow-up, for example. Participants who did not complete the study did not differ substantially in demographic characteristics from the wider study population.

Fig 1. Modified CONSORT [32] flow diagram.

Fig 1

1,118 incarcerated people scheduled to be released within 6 months were screened for opioid use disorder, and 125 screened positive and consented to participate in the study. Of those, 109 completed the full pre-release visit questionnaire, 63 followed up 1 month post release, 57 followed up at 3 months, and 55 followed up at 6 months. Note that some participants did not complete one follow-up visit but returned later in the study; for example, not all of the 55 participants who completed 6-month follow-up had also completed the 3-month follow-up.

Table 1. Survey participant characteristics.

Variable N % Mean sd Range
Sex
Male 104 92.9
Female 8 7.1
Age 39.8 8.4 (24, 66)
Ethnicity
Kyrgyz 28 24.8
Russian 57 50.4
Uzbek 5 4.4
Other 23 20.4
Marital Status
Partnered 46 40.7
Not partnered 67 59.3
Education
Secondary or less 108 95.6
Beyond secondary 5 4.4
Housing
Self-provided residence (rent/own) 19 16.8
Friend or Relative’s home 71 62.8
Other 23 20.4
Employment
Full/Part-time employment 37 58.7
Unemployed 26 41.3
HIV
Preliminary Positive 25 22.1
Preliminary Negative 88 77.9
Hepatitis B
Preliminary Positive 6 5.3
Preliminary Negative 108 94.7
Hepatitis C
Preliminary Positive 109 95.6
Preliminary Negative 5 4.4
Syphilis
Preliminary Positive 5 4.4
Preliminary Negative 109 95.6
Depression (CESD-10)
Yes 68 60.7
No 44 39.3

This table describes survey participant characteristics (n = 125). However, only 117 participants completed at least part of the questionnaire or infectious disease testing, and many participants left some survey answers blank. For ethnicity, “other” includes ethnicities that fewer than 5 people indicated (Azerbaijani, Belarusian, Dungan, German, Kazakh, Kurdish, Moldovan, Tatar, Turkish, Uighur, or Ukrainian ethnicity).

Table 2. Qualitative interview participant characteristics.

Gender Age Range Ever in methadone program? (bold if taking methadone at follow-up) Status in hierarchy (applies to men only)
Male 41 to 45 yes poryadochnyi
Female 36 to 40 yes
Female 41 to 45 no
Male 31 to 35 yes obizhennyi
Male 46 to 50 yes neput’
Male 46 to 50 no poryadochnyi
Female 26 to 30 yes
Male 36 to 40 no poryadochnyi
Male 31 to 35 no poryadochnyi
Male 41 to 45 yes poryadochnyi
Male 31 to 35 no poryadochnyi
Male 41 to 45 yes poryadochnyi
Male 56 to 60 yes poryadochnyi

This table describes participant characteristics of interviewees. Hierarchy status refers to the within-prison social hierarchy. These include, in descending order of status: 1) poryadochnyi (“decent one”); 2) neput’ (“one who lost the way”); 3) obizhennyi (“one who has offended”). A person could be promoted or demoted based on various behaviors and interactions with people of different hierarchy statuses [29, 30].

Initially, 23 participants were already accessing methadone treatment, and 44 participants expressed interest in initiating methadone treatment. After the BI, 50 (including the 44 named above) expressed interest in initiating treatment; however, only four participants actually initiated treatment (Fig 2). Interest in methadone was assessed on a 10-point Likert scale, and it did not change significantly after the intervention (Table 3, p = 0.135). Additionally, scores on survey questions assessing attitudes toward methadone did not change significantly after the intervention (Table 4). At study initiation, most scores on survey questions were 4 or higher on a 5-point Likert scale—nearly all study participants agreed, for example, that methadone should be available in the community and in prisons. However, these reported positive attitudes toward methadone did not translate into interest, which remained at a median score of 0 out of 10 (Table 3). Of the 50 participants who did express newfound interest in the methadone program following the intervention, only 4 initiated treatment.

Fig 2. Methadone interest cascade for incarcerated Kyrgyz study population.

Fig 2

125 people were initially enrolled in the study, of whom 102 were not already participating in the methadone program. 44 expressed interest before a brief intervention, and 50 expressed interest after (p = 1.00). However, only 4 people joined the methadone program following the intervention.

Table 3. Interest in methadone before and after brief intervention (n = 109).

Before Intervention After Intervention p-value
Interest Score, median (IQR) 0.0 (0–0) 0.0 (0–2) 1.00

Table 4. Mean methadone attitude and knowledge scores at baseline vs. 1-month follow up.

Statement Baseline Mean (SD) Follow Up Mean (SD) p-value
1. Methadone should be available in the community so that all people who suffer from opioid addiction and want methadone can receive it. 4.37 (0.89) 4.50 (0.82) 0.82
2. Methadone should be introduced into prisons so that all incarcerated people who suffer from opioid addiction and want methadone can receive it. 4.38 (0.89) 4.42 (0.92) 0.57
3. Methadone reduces opioid dependent individuals’ consumption of illicit opiates. 4.18 (0.95) 4.27 (0.63) 0.74
4. Methadone reduces opioid dependent individuals’ risk of acquiring or transmitting HIV. 4.35 (0.96) 4.42 (0.86) 0.63
5. Methadone improves adherence to HIV medications in HIV-infected opioid dependent individuals. 3.85 (1.11) 3.87 (1.09) 0.64
6. Methadone increases opioid dependent patients’ adherence to tuberculosis medication. 3.58 (1.19) 3.35 (1.13) 0.19
7. Methadone decreases opioid dependent individuals’ risk of dying from overdose. 4.29 (0.91) 4.40 (0.64) 0.74
8. Methadone reduces addicts’ criminal activities. 4.37 (0.89) 4.29 (0.88) 0.29

Mean methadone attitude and knowledge scores at baseline vs. 1-month follow up (n = 63). Range of responses is 1–5 (1 = strongly disagree, 5 = strongly agree).

Qualitative interview findings

We turned to qualitative interview data to determine some of the reasons behind the discrepancy between professed positive attitudes toward methadone and lack of methadone uptake. Generally, perception of methadone from in-depth interviews revolved around one of five themes: (1) interpersonal relationships, (2) interactions with the criminal justice system, (3) logistical concerns, (4) criminal subculture, and (5) health-related concerns.

Interpersonal relationships

When asked what could be done to increase methadone uptake in the prison, one study participant explained that incarcerated people with OUD faced frequent stigma from medical providers. “Well, with regard to medical care…They sometimes look at us as if we weren’t human beings, you understand, and this really affects a person’s morale, right?” (female, 41–45, never on methadone). Another methadone program participant described how his peers in the prison viewed him, explaining that “…it is obvious people havesome animosity, some loathing, right, to put it simple.” (male, 41–45, on methadone). Another participant not on methadone agreed. “In the prison, normal people won’t communicate with those who use methadone.” (male, 41–45, on methadone).

Fellow incarcerated people tended to describe methadone users as weak or suggestible. One participant explained “there are people who cannot put up with their pain, they go for [methadone] out of despair, even though it doesn’t help them” (female, 41–45, never on methadone). Another said that if a person starts taking methadone within the prison “this is called aping… ‘are you an ape, you saw him doing these moves and now you want [methadone] too,’” (male, 56–60, on methadone). According to a third, methadone participants are “just afraid of getting off it. They’re afraid of withdrawal. (male, 46–50, formerly on methadone).

People on methadone were not considered “sober”, which could be a source of stigma. “You’re in a circle of sober people, no one is shooting up, they’re against it, right, to shoot up, and you are alone among them. Well, they look at you as if you’re an animal” (male, 31–35, on methadone). As another participant explained, “my family…laid down a condition for me, you get over withdrawal, that’s it, come over, we’ll help you… for them it’s all the same thing, whether methadone, heroin, or cocaine, it’s all drugs” (male, 56–60, on methadone). Often study participants had the same beliefs and quest for “sobriety”. When one participant expressed her desire to leave the methadone program, she viewed medical professionals’ discouragement as trying to hold her back from her full potential. “Because if I’m sober, I’m a respected person everywhere… everybody will respect me, and this is what alarms them” (female, 36–40, on methadone). As another participant stated, “I think only a person who doesn’t want to get sober will go on methadone” (male, 46–50, on methadone).

While young people faced numerous social consequences for methadone program participation, among older incarcerated people, methadone was seen as unavoidable. “I told the deputy right away, I’ve been drinking it for so many years, my bones are all soaked with it, with methadone, that’s why I’m not even thinking about quitting and I won’t ever quit. Well, that was it, the conversation was over” (male, 56–60, on methadone). However, these older individuals would strongly discourage younger, newly incarcerated people from entering into the methadone program and would urge them to take up sports or athletic pursuits instead.

Interactions with the criminal justice system

Participants described police as being generally suspicious of people taking methadone in the community, often assuming they were swindling the system to get “free drugs.” This was especially difficult for younger people; police usually left older people alone. Police officers would congregate near methadone programs and arrest people, often framing them for other crimes in the process.

In nearly all interviews, participants described the police as enabling heroin use in the community and framing those who used heroin for other crimes. As one participant explained, “The cops themselves got me hooked on heroin, so that I would work and split [my profits] with them” (female, 36–40, on methadone). As another participant explained, “if my health really deteriorates…it’s better to [take] methadone, only based on the fact that with heroin I’ll go back to prison, they’ll make me admit to someone else’s crimes, they’ll write me down as a contraband dealer again, although I’ve never been a contraband dealer in my life” (male, 46–50, never on methadone). Generally, all interviewees were distrustful of the police and prison systems, and this distrust often extended to the methadone program.

Logistics of taking methadone

Logistical concerns about taking methadone differed within prison and after release. Within prison, concerns included dilution of methadone and loss of access to heroin. As one interviewee explained, “Sometimes they add some water. When the water is added… Of course, we [notice]. And those who don’t feel the difference–they are not real drug users” (female, 26–30, formerly on methadone). Once someone entered the methadone program, they were no longer provided access to the informal within-prison heroin distribution network or to the administration-run needle/syringe program (NSP). Ordinarily, to access the NSP, individuals registered confidentially and were then able to receive injection equipment from nurses located either in the medical area or the barracks, depending on the specific prison. However, those that joined the methadone program were no longer permitted to participate in the NSP. Loss of access to the NSP could be a major life change and was a dealbreaker for some would-be methadone program participants. Those unwilling to give up heroin completely would shy away from the methadone program; some people would leave the methadone program after realizing that they had lost access to heroin and the NSP.

Upon release, incarcerated people were often not provided referrals or tools to find a methadone program in their region, since methadone is only available in certain regions of the Kyrgyz Republic. Additionally, community methadone programs required being tied to a daily clinic, and some participants reported that their program would not allow them to return if they missed a day of their methadone dose. These logistical concerns made accessing methadone in the community difficult, especially for people whose jobs conflicted with the set methadone distribution times.

Criminal subculture

Within Kyrgyz men’s prisons, a strict hierarchy system governs daily life among incarcerated people. This hierarchy, run by an incarcerated-person-led government called the obshchak, has been described previously [29, 30]. Briefly, when a person arrives into prison, he encounters a tribunal of his peers, which assesses whether he is guilty of the crime for which he has been incarcerated, the severity of his crime, and any mitigating factors (for example, positive character references from community members). He is then assigned a hierarchy status based on this assessment (Table 2).

For someone of high hierarchy status, there was little motivation to join the methadone program, and methadone carried social risks. Meanwhile, for someone low in the hierarchy, who was largely denied access to within-prison heroin and had nothing to lose in terms of social status, the methadone program was much more appealing. One high-status person explained his fears about having to choose between hierarchy status and methadone program participation. When one of his friends joined the program, the friend was quickly approached by obshchak enforcers. “‘If you proceed with methadone, we will relocate you and everything you have now, you will lose it. Well, your quality of life would change, get it?’” (male, 41–45, on methadone). Prison medical staff administered methadone daily at a specific, designated location for all methadone program participants irrespective of hierarchy level. Therefore, for someone of higher hierarchy status, joining the methadone program meant potential physical interaction with people of lower hierarchy status or using the same items, like pens or cups. These interactions could lead to demotion within the hierarchy [29].

The obshchak was highly motivated to dissuade people from using methadone, because the obshchak was the major distributer of in-prison heroin. This process was facilitated by the obshchak’s extensive connections outside of the prison. It acted both as a mutual aid fund, collecting and redistributing goods to incarcerated people, and also as a marketplace for various goods and services. This marketplace was facilitated by corruption of official prison staff, who allowed these goods, including heroin, to enter the prison [11]. Heroin served both as a commodity and as a form of currency which could be used to purchase other items within the prison. Incarcerated people could work for the obshchak in exchange for heroin, so methadone uptake resulted in net economic losses for the obshchak. However, some methadone program participants would continue to work for the obshchak as a way of maintaining access to heroin for bartering, although they were absolutely forbidden from keeping any of that heroin for themselves.

Despite its role as heroin provider, many incarcerated people described the obshchak as an ally in the quest for “sobriety”. “[The obshchak] will even help him to quit this methadone. You have strong withdrawal from methadone, and so that he doesn’t get strong withdrawal, they give him, they give him a little heroin, his withdrawal passes, it passes and then they don’t give him heroin or methadone” (male, 36–40, never on methadone). Additionally, the obshchak banned introducing young people to heroin, and such an introduction would result in immediate social consequences and often physical violence.

Health-related concerns

Despite the BI designed to dispel health-related myths about methadone, health-related beliefs featured prominently in qualitative interviews. Most common was the idea that methadone “eats up one’s insides,” leading to a protracted and painful death. It was seen as “just another drug,” no better (and potentially more dangerous) than heroin. One new methadone user described the side effects when he began treatment, “I began to lose weight. I felt weak. What else… my teeth started falling outAnd plus, you’re walking around like a zombie, damn it, not in your full mind” (male, 46–50, on methadone).

Some would-be methadone program participants were also dissuaded from engaging with the program by the lack of euphoria from methadone. Substance use and associated intoxication were seen as an escape from boredom or psychological trauma. Therefore, to potentiate soporific effects of methadone and produce euphoria, some incarcerated people would combine methadone with Dimedrol (diphenhydramine) [13]. These soporific effects contributed to the misperception of methadone as harmful. “Those who take Dimedrol, they… Well, it’s unpleasant, you know- you’re trying to have a conversation with them and they’re talking nonsense, or even fall asleep” (male, 41–45, formerly on methadone). Because of potential occupational risks (i.e., falling asleep while using a saw [33]), the obshchak banned Dimedrol completely. However, many people assumed that anyone who used methadone was bound to use Dimedrol eventually, especially because methadone program participants were seen as exceptionally weak-willed. As one methadone program participant explained, “They believe that those taking methadone would not say no to Dimedrol if they are offered” (male, 41–45, on methadone).

Discussion

We conducted a Screening, Brief Intervention, and Referral to Treatment (SBIRT) to screen all incarcerated people within six months of release from prison in the Kyrgyz Republic and refer those with OUD to methadone treatment after a brief intervention (BI) using motivational interviewing. While nearly all participants endorsed positive attitudes toward methadone in an 8-question survey both before and after the intervention, only 3.9% of those who participated in the BI and were not already in the methadone program decided to join the program.

Some of the observed lack of uptake may be due to a ceiling effect. Twenty-three percent of study participants were already participating in the methadone program at the time of the study. It is possible that individuals who were planning on initiating methadone therapy may have already done so. Therefore, those remaining are the least likely to join the methadone program, as suggested by the low baseline methadone interest scores (Table 3). Social desirability bias, the idea that study participants may try to answer the survey in a way that they believe the researchers want to hear, may also help to explain the positive attitudes toward methadone expressed in the survey (Table 4). The research assistants conducting the qualitative interviews were not actively promoting methadone, whereas those administering the survey questions were part of the team providing the BI to promote methadone use. Therefore, study participants may have been more likely to divulge negative feelings about methadone to the qualitative researchers rather than on the quantitative survey.

Our qualitative analysis indicated that five factors played a major role in determining the lack of methadone uptake: interpersonal relationships, interactions with the criminal justice system, logistics of taking methadone, criminal subculture, and health-related concerns. Between individuals, age played an important role in determining whether one was encouraged to take methadone. Introducing young people to drugs was an egregious crime in the within-prison subculture, as reported in previous literature [33]. Because methadone was seen as just another drug, young people were strongly discouraged from joining the methadone program, and were instead encouraged to participate in athletic activities as a way to achieve sobriety. Meanwhile, older people were seen as more set in their ways, and cultural respect for elders meant that older people were allowed or even encouraged to continue taking methadone as they had been doing. Respect for elders is part of the behavioral code that governs the prison hierarchy system [33, 34]; the phenomenon of older people with OUD being left to their own devices regarding substance use has also been reported among Israeli immigrants from the former Soviet Union [35]. Respect for elders has also been reported in other prison contexts, such as in the United States [36].

Public health has recently come to understand the concept of “risk environments:” how physical, social, economic, and policy environments precipitate and reinforce risk [37]. In this context, in terms of the social environment, people who participated in the methadone treatment program faced negative attitudes and stigma from healthcare workers, peers within the prison, and family members outside of the prison. Common themes were the social perception that those who used methadone were weak or lacked the necessary willpower to obtain sobriety, which was seen as abstaining from all substances including methadone. These ideas of sobriety and personal/community beliefs about methadone and methadone users interacted to discourage methadone uptake. Many of these beliefs regarding methadone and methadone program participants exist in North America as well, including that methadone program participation indications a lack of will power, untrustworthiness, or ongoing addiction (i.e., to methadone instead of heroin) [38, 39].

The challenging political interplay between state and citizen, also known as the “policy environment” [37], was reflected in participants’ deep mistrust of the criminal justice system and the ways this mistrust figured prominently in many interactions. According to study participants, police promoted heroin use to line their own pockets and then framed people who used heroin for any crimes for which they were unable to find a culprit. Police would also often congregate near methadone clinics to arrest people on false charges. Police harassment of people who inject drugs (PWID) in the Kyrgyz Republic has been described in detail in a previous paper [40]. Similar findings have also been reported in other countries in the region, such as Azerbaijan and Ukraine [4042], as well as in the United States, where interviewees for a newspaper article described being followed from their methadone clinics by police and arrested for minor traffic infractions [43].

In terms of the physical risk environment [37], study participants expressed concern about being tied to a daily methadone clinic, potentially limiting one’s work schedule or travel abilities. Within prison, participants discussed dilution of methadone and loss of access to former services, such as heroin through the obshchak. Many of these logistical considerations have been previously described in other contexts; an Italian study found that methadone program participants who were allowed to take their medication at home (with certain stipulations) had significantly higher 12-month retention rates, while similar research in Vietnam found that those with longer commutes to methadone clinics were less likely to remain in the methadone program [44, 45]. More specific to the Kyrgyz prison context, a strict within-prison hierarchy influenced many decisions regarding methadone uptake. Criminal subculture dictated who could interact with whom and whether there would be social consequences for methadone program participation. Meanwhile, heroin was used as a tool of social control within the prison [11].

Given these findings, future methadone program implementation would likely be more successful within-prison if paired with continued access to NSP, if different hierarchy statuses received methadone from different locations, and if methadone were explicitly dissociated from connections to the formal prison administration. In the community, education for family and community members about the uses and benefits of methadone might be useful to reduce stigma surrounding methadone and those who participate in the methadone program.

Limitations of this study include that upon entry into the study and during the BI, participants were made aware that this was a study designed to encourage the use of methadone. Therefore, there was strong potential for social desirability bias, given that participants likely suspected that researchers were expecting positive attitudes toward methadone. Additionally, there was significant loss to follow-up after release; only 55 of the initial 125 study participants completed six-month follow-up. Finally, previous studies of SBIRT have suggested that BI may be insufficient for engaging people in treatment or for long-term substance-use-behavior modification [46].

After performing a screening, brief intervention, and referral to treatment (SBIRT) program among people within six months of release from Kyrgyz prisons, we found that positive attitudes toward methadone did not translate into methadone uptake due to factors relating to personal relationships and stigma, distrust of the criminal justice system, logistical considerations, the specific criminal subculture within Kyrgyz prisons, and health-related concerns about methadone. Future interventions to promote methadone uptake should focus on addressing these factors, especially given the continued high incidence of hepatitis C and HIV in this vulnerable population.

Supporting information

S1 File. Complete list of survey questions.

Full list of survey questions asked of all participants and codebook for reading data.

(PDF)

S2 File. Pre- and post-release interview guides.

English translation and original Russian-language interview guides used to interview study participants pre- and post-release.

(DOCX)

S3 File. Quantitative data.

All deidentified quantitative data; S1 File may be used as a codebook for questions asked.

(XLSX)

S1 Checklist. TREND statement checklist.

(PDF)

S1 Protocol

(PDF)

Data Availability

All relevant quantitative data are within the paper and its Supporting Information files. Data have been deidentified. Individual demographic information has not been shared to prevent potential participant identification; it will be available upon request to the Yale Center for Interdisciplinary Research on AIDS (contact via data manager Delaney Rhoades, delaney.rhoades@yale.edu) for researchers who meet the criteria for access to confidential data. Full interview transcript data cannot be shared publicly because of potential identifiability of our participants. Qualitative data are available from the Yale Center for Interdisciplinary Research on AIDS (contact via data manager Delaney Rhoades, delaney.rhoades@yale.edu) for researchers who meet the criteria for access to confidential data.

Funding Statement

Funding for this study was provided by the National Institute for Drug Abuse (NIDA, drugabuse.gov; K01 DA047194 received by JR, R01 DA029910 received by FLA, & R21 DA042702 received by JPM). DJB’s time devoted to this paper was provided by the National Institute for Mental Health (NIMH, nimh.nih.gov; T32 MH020031) and the Fogarty International Center (fic.nih.gov; D43 TW010540). ARL's time devoted to this paper was provided by a G.E.R.M. award from the Infectious Diseases Society of America (IDSA) Foundation (idsafoundation.org/g-e-r-m). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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Decision Letter 0

Sebastian Shepherd

29 Apr 2022

PONE-D-21-24508Interest without Uptake: A Mixed-Methods Analysis of Methadone Utilization in Kyrgyz PrisonsPLOS ONE

Dear Dr. Liberman,

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Reviewer #1: Partly

Reviewer #2: Partly

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Reviewer #1: No

Reviewer #2: I Don't Know

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Reviewer #1: No

Reviewer #2: Yes

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Reviewer #1: Yes

Reviewer #2: Yes

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5. Review Comments to the Author

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Reviewer #1: My comments are as follows:

1. The manuscript has been submitted as a Clinical Trial, but a thorough reading appears that it is an observational study. However, it turns out that the study is registered in clinicaltrials.gov, with a valid NCT number. More details are needed on why the authors think that this is indeed a clinical trial. It appears there is no randomization, if I am not mistaken. If the study is claimed to be a Clinical Trial, CONSORT guidelines should be followed in reporting the results, or arguments needed on why it maybe ignored.

2. The statistical analysis plan appears mixed up with other information in the Methods section. A separate subsection is desired, which should clearly mention the tests to be used, and what would be the alternatives when standard Gaussian assumptions fail (and where paired t-tests are invalid). Relevant nonparametric method should be stated here.

3. It was really strange to see that the authors didn't provide a sample size/power statement, based on a target effect size they wanted to achieve. This would allow efficient planning to similar future studies. The sample size/power should be computed based on the primary outcome, say at 5% level, and likely one that achieves 80-90% power.

4. The study is longitudinal; it is not clear why a formal longitudinal analysis was not consucted, using mixed-effects models.

5. The analysis is a bit compromised, given that the collected data is "clustered" in nature since there are 9 prisons in total, and subjects recruited in a specific prison appear to be clustered. If one doesn't want to utilize clustered paired tests, or the alternatives, sufficient justification is necessary.

Reviewer #2: This paper addresses the important issue regarding the availability of agonist maintenance therapy to opioid addicted prisoners. Its focus on the Kyrgyz Republic is unique in view of the absence of similar information in other former Soviet Republics. It could be improved by attention to the following points:

a) describe methadone as an evidence-based treatment that reduced opioid use, risk for HIV and opioid overdose, improves overall functioning, and increases the chances for engagement in addiction and other relevant medical treatments. Describing it as the “gold standard” introduces a value judgment that is not necessary.

b) the paper focuses on prisoners who do not want methadone treatment, but it looks like about 20% of the prisoners were on it at the time of incarceration and continued it in prison. This finding needs more emphasis.

c) Can more detail be provided about the “prison hierarchy”? How do prisoners get slotted into the three categories?

d) Were the 11.2% who screened positive addicted to opioids?

e) Findings in Tables 1b and 1c can be likely be summarized in the text.

f) Any thoughts about how to increase acceptability of methadone among prisoners who are not receiving it?

**********

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Reviewer #1: No

Reviewer #2: Yes: George E. Woody, MD

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PLoS One. 2022 Oct 25;17(10):e0276723. doi: 10.1371/journal.pone.0276723.r003

Author response to Decision Letter 0


11 Aug 2022

1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at

https://journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and

https://journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf

Response: Thank you for these clarifying documents. We have updated our manuscript to reflect these formatting changes.

2. Please provide additional details regarding participant consent. In the ethics statement in the Methods and online submission information, please ensure that you have specified what type you obtained (for instance, written or verbal, and if verbal, how it was documented and witnessed). If your study included minors, state whether you obtained consent from parents or guardians. If the need for consent was waived by the ethics committee, please include this information.

Response: Previously, our manuscript had included the following: “If OUD was confirmed, potential participants completed informed consent procedures in which research assistants made clear that this study was not affiliated with the prison administration, that surveys and interviews would remain anonymous, and that participants could withdraw from the study at any point.” We have updated our text to add: “Each participant was given a copy of the informed consent document to read and provided with ample time to read the form and to ask questions. To minimize potential coercion, every participant was read a statement that included the following: “Participation in the study is voluntary. Refusal or consent to participate will not affect the change of conditions of registration in prison and the information will be kept confidential. Personal information about your medical condition or any other information will be available only to you and for research purposes.” Participants were able to opt out of the study at any time and were assured that participation, refusal to participate, or discontinuation of participation were not linked with any rewards or punishments.”

3. In the Methods section of the manuscript, please provide additional information regarding how participants were recruited for the qualitative study, please specify whether an interview guide was used to interview the participants in your study. If yes, please describe and/or include a copy as a Supporting Information file, and finally, please consider including more information on the number of interviewers, their training and characteristics.

Response: Thank you for this feedback. We have modified our information about recruitment: “Briefly, the Department of Penitentiary Institutions in the Kyrgyz Republic provided the study coordinator with a list of all incarcerated persons within 180 days of scheduled release or possible early release. (Those with less than eight days until their release date were excluded.) Research personnel screened all incarcerated persons who met these criteria using a single-item screener for opioid use disorder (OUD) followed by a pre-incarceration assessment of opioid use in the 30 days before incarceration. Those who screened positive then underwent additional screening for opioid dependence using the validated Rapid Opioid Dependence Scale.”

For interview guides, English translations of pre- and post-interview guides have been included as File S2.

Additional information about interviewers was provided as follows: “LA and JR conducted the interviews in Russian, although participants were given the option to have their interviews in Kyrgyz with a trained research associate if they preferred. All participants chose to have their interviews conducted in Russian.”

4. Please provide additional information regarding the considerations made for the prisoners included in this study. For instance, please discuss whether participants were able to opt out of the study and whether individuals who did not participate receive the same treatment offered to participants.

Response: Please see response to Point 2 above.

5. Registration done retrospectively (after enrollment of participants) (TC2/PRTC Note)

Thank you for submitting your clinical trial to PLOS ONE and for providing the name of the registry and the registration number. The information in the registry entry suggests that your trial was registered after patient recruitment began. PLOS ONE strongly encourages authors to register all trials before recruiting the first participant in a study.

As per the journal’s editorial policy, please include in the Methods section of your paper:

1) your reasons for your delay in registering this study (after enrolment of participants started);

2) confirmation that all related trials are registered by stating: “The authors confirm that all ongoing and related trials for this drug/intervention are registered.

Response: The authors confirm that all ongoing and related trials for this drug/intervention are registered. This trial was registered in clinicaltrials.gov on July 1, 2021 which was after enrollment began. While the original intention was to register the study prior to enrollment, this delay was due to a change in staff at the beginning of the study. The timeline of enrollment and data collection for this paper’s self-reported preliminary data (2017-2021) is outlined in the results section (first sentence).

6. During the internal evaluation of the manuscript, we have noted some discrepancies between the study protocol and the manuscript text. In particular please could you provide some clarification on the following:

1) The protocol indicated that the study will be conducted within 7 prisons, however the manuscript text implies that 9 prisons were included. Please could you clarify whether the IRB approved this deviation.

2) A sample size of 120 participants was calculated in the study protocol, however 125 participants were included in the study as reported in the text. As such please could you clarify whether the IRB approved for the inclusion of additional participants in the study.

Furthermore, please could you provide a description of the intervention of the clinical trial and please also report the expected primary and secondary outcomes of the study within the Methods section.

Response: We have updated our information about the intervention to include the following: “Next, [study subjects] participated in a brief intervention (BI) guided by motivational interviewing principles in which a trained research assistant explained benefits and dispelled myths relating to methadone treatment both during and after incarceration. This BI had two aims. First, the BI was designed to inform potential participants on the risks of substance misuse, abuse, and dependency by illustrating the potential hazards and adverse health consequences. Second, the BI aimed to motivate potential participants to reduce risky behavior (e.g., continued drug use) and seek treatment for their substance dependence disorder. After the BI, participants’ interest in methadone was re-assessed as above, and if they were interested, they were referred to a treating physician in the prison to initiate methadone. All participants, irrespective of methadone enrollment, underwent a second BI one week before release to encourage study participants on methadone to link to care or those not on methadone to begin methadone after release.

During each BI, research team members provided evidence-based information on methadone. This information was available to study participants in the community upon release. Study participants were informed of the risks and benefits of methadone, and during the second BI, they learned how to access methadone in their communities. Each BI lasted approximately 20 minutes, and afterwards, participants were provided time for questions. The BIs were audio recorded; audio files are available upon request (files only available in the original languages of the BI—Russian & Kyrgyz).”

We have also added study outcomes: “Primary study outcomes included initiation of methadone, retention in methadone treatment, relapse to heroin, and recidivism.”

As for sample size, the IRB states that we will aim to recruit 120 people into the intervention, as a minimum target. Because the first step of the SBIRT procedure is S-Screening of all eligible participants, there is no way to know how many will screen positive for OUD, with 120 being a general benchmark. This sample size is allowed by the IRB.

Finally, please provide additional information regarding the considerations made for the prisoners included in this study. For instance, please discuss whether participants were able to opt out of the study and whether individuals who did not participate receive the same treatment offered to participants.

Response: Please see response to Point 2 above.

7. In your Data Availability statement, you have not specified where the minimal data set underlying the results described in your manuscript can be found. PLOS defines a study's minimal data set as the underlying data used to reach the conclusions drawn in the manuscript and any additional data required to replicate the reported study findings in their entirety. All PLOS journals require that the minimal data set be made fully available. For more information about our data policy, please see http://journals.plos.org/plosone/s/data-availability.

Upon re-submitting your revised manuscript, please upload your study’s minimal underlying data set as either Supporting Information files or to a stable, public repository and include the relevant URLs, DOIs, or accession numbers within your revised cover letter. For a list of acceptable repositories, please see http://journals.plos.org/plosone/s/data-availability#loc-recommended-repositories. Any potentially identifying patient information must be fully anonymized.

Important: If there are ethical or legal restrictions to sharing your data publicly, please explain these restrictions in detail. Please see our guidelines for more information on what we consider unacceptable restrictions to publicly sharing data: http://journals.plos.org/plosone/s/data-availability#loc-unacceptable-data-access-restrictions. Note that it is not acceptable for the authors to be the sole named individuals responsible for ensuring data access.

We will update your Data Availability statement to reflect the information you provide in your cover letter.

Response: We have uploaded the underlying quantitative data as a Supporting Information file.

8. Please note that in order to use the direct billing option the corresponding author must be affiliated with the chosen institute. Please either amend your manuscript to change the affiliation or corresponding author or email us at plosone@plos.org with a request to remove this option.

Response: The corresponding author is affiliated with Yale University, the chosen institute. These authors were unclear of the need for clarification on this point.

9. Your abstract cannot contain citations. Please only include citations in the body text of the manuscript and ensure that they remain in ascending numerical order on first mention.

Response: Thank you for this feedback. The abstract no longer contains citations.

10. We note you have included a table to which you do not refer in the text of your manuscript. Please ensure that you refer to Table 1a and 1b in your text; if accepted, production will need this reference to link the reader to the Table.

Response: Thank you for this feedback. The original manuscript referenced Table 1, without specifying Tables 1a and 1b in particular. We have updated the reference to Table 1 to specify the individual sub-tables.

11. Please include captions for your Supporting Information files at the end of your manuscript, and update any in-text citations to match accordingly. Please see our Supporting Information guidelines for more information: http://journals.plos.org/plosone/s/supporting-information.

Response: The authors appreciate this helpful list of guidelines. Our initial manuscript did not contain Supporting Information files, but we have added these in response to reviewer/editor comments. We have added the captions at the end of the manuscript as requested.

Reviewer #1: My comments are as follows:

1. The manuscript has been submitted as a Clinical Trial, but a thorough reading appears that it is an observational study. However, it turns out that the study is registered in clinicaltrials.gov, with a valid NCT number. More details are needed on why the authors think that this is indeed a clinical trial. It appears there is no randomization, if I am not mistaken. If the study is claimed to be a Clinical Trial, CONSORT guidelines should be followed in reporting the results, or arguments needed on why it may be ignored.

Response: The authors were requested to disregard this point, per editorial staff.

2. The statistical analysis plan appears mixed up with other information in the Methods section. A separate subsection is desired, which should clearly mention the tests to be used, and what would be the alternatives when standard Gaussian assumptions fail (and where paired t-tests are invalid). Relevant nonparametric method should be stated here.

Response: The authors appreciate this correction and have created a separate sub-section for statistical analysis. Relevant nonparametric methods have been used, as suggested.

3. It was really strange to see that the authors didn't provide a sample size/power statement, based on a target effect size they wanted to achieve. This would allow efficient planning to similar future studies. The sample size/power should be computed based on the primary outcome, say at 5% level, and likely one that achieves 80-90% power.

Response: This study tests the SBIRT method of recruiting people into OAT. During the S-Screening step, we screen all potentially eligible participants (people to be released from Kyrgyz prisons that have MMT) for opioid use disorder. Only those that screen positive are then included in the sample. In our study protocol, we present the target sample as 120 people as approximately 1000 people are released from the Kyrgyz prisons that have MMT every year, as we expected approximately 120 of them to be eligible for inclusion. Indeed, this number was fairly close as we recruited 125 people into the sample.

For the analysis of whether the B-brief intervention component was effective, we cannot recruit more people than there are eligible participants in the country; therefore, a formal sample size calculation was not included.

4. The study is longitudinal; it is not clear why a formal longitudinal analysis was not constructed, using mixed-effects models.

Response: In the analysis we compare OAT interest, knowledge, and attitude scores before and after the brief intervention component of SBIRT, as the goal of this analysis is to determine whether the brief intervention is successful. If we had indication that the intervention might have been successful, we would have been interested in doing a more thorough analysis to make sure that we conservative in our claims. However, the simple analysis presented in the paper did not show a significant difference in scores before/after the intervention. Therefore, we can be confident in the claims we make to the reader.

5. The analysis is a bit compromised, given that the collected data is "clustered" in nature since there are 9 prisons in total, and subjects recruited in a specific prison appear to be clustered. If one doesn't want to utilize clustered paired tests, or the alternatives, sufficient justification is necessary.

Response: Clustered analyses e.g. clustered t-tests, mixed/multilevel models are more conservative as they account for potential additional effects from clustering. As the simple paired t-test was not found to be significant in our analysis, we can be confident that it will be even less significant if we account for additional factors like clustering.

Reviewer #2: This paper addresses the important issue regarding the availability of agonist maintenance therapy to opioid addicted prisoners. Its focus on the Kyrgyz Republic is unique in view of the absence of similar information in other former Soviet Republics. It could be improved by attention to the following points:

a) describe methadone as an evidence-based treatment that reduced opioid use, risk for HIV and opioid overdose, improves overall functioning, and increases the chances for engagement in addiction and other relevant medical treatments. Describing it as the “gold standard” introduces a value judgment that is not necessary.

Response: The authors appreciate this feedback and have revised their original statement about methadone as follows: “Medication-assisted therapy with opioid agonists is an evidence-based HIV-prevention strategy that decreases the risk of opioid overdose, improves overall functioning, and increases engagement with other medical treatments [1–3].”

b) the paper focuses on prisoners who do not want methadone treatment, but it looks like about 20% of the prisoners were on it at the time of incarceration and continued it in prison. This finding needs more emphasis.

Response: The authors appreciate this astute observation. We have added the following: “Twenty-three percent of study participants were already participating in the methadone program at the time of the study. It is possible that individuals who were planning on initiating methadone therapy may have already done so.”

c) Can more detail be provided about the “prison hierarchy”? How do prisoners get slotted into the three categories?

Response: Thank you for this feedback. The authors have aimed to provide clarification by adding the following: “Briefly, when a person arrives into prison, he encounters a tribunal of his peers, which assesses whether he is guilty of the crime for which he has been incarcerated, the severity of his crime, and any mitigating factors (for example, positive character references from community members).”

d) Were the 11.2% who screened positive addicted to opioids?

Response: Yes; these individuals screened positive for opioid use disorder (OUD). The manuscript has been updated to clarify this point.

e) Findings in Tables 1b and 1c can likely be summarized in the text.

Response: While the authors understand the reviewer’s suggestion, we believe that these tables allow for a more in-depth portrayal of participant characteristics and provide visual comparison between those who completed and those who chose not to complete the study.

f) Any thoughts about how to increase acceptability of methadone among prisoners who are not receiving it?

Response: Thank you for this point of clarification. As we specify in the original manuscript, “Given these findings, future methadone program implementation would likely be more successful within-prison if paired with continued access to NSP, if different hierarchy statuses received methadone from different locations, and if methadone were explicitly dissociated from connections to the formal prison administration.”

Attachment

Submitted filename: Reviewer Response Letter PLOS.docx

Decision Letter 1

Hugh Cowley

6 Sep 2022

PONE-D-21-24508R1Interest without Uptake: A Mixed-Methods Analysis of Methadone Utilization in Kyrgyz PrisonsPLOS ONE

Dear Dr. Liberman,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

Please see further comments from the reviewers below. One reviewer has has requested changes, particularly regarding clarity of the text, details regarding the prison system, and regarding how MM fits within broader negative social pressure and stigma regarding addiction. The reviewer has also suggested some opportunities to add context to this study. Please ensure you address each of the comments raised.

Please submit your revised manuscript by Oct 20 2022 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

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If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols.

We look forward to receiving your revised manuscript.

Kind regards,

Hugh Cowley

Staff Editor

PLOS ONE

[Note: HTML markup is below. Please do not edit.]

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: All comments have been addressed

Reviewer #2: (No Response)

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2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: (No Response)

Reviewer #2: Yes

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3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: (No Response)

Reviewer #2: I Don't Know

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4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: (No Response)

Reviewer #2: (No Response)

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5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: (No Response)

Reviewer #2: No

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6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: (No Response)

Reviewer #2: Overall: This is a unique paper about addiction treatment in a part of the world where little is known about it. The use of two Russian-speaking staff to collect data likely allowed the research team to get unique information about inmate infrastructures within prisons. Outcome results are clear but the text is hard to read and could be shortened by 40-50%. Suggestions are: a) the authors mix stigma with negative attitudes about methadone maintenance (MM). Stigma applies to addiction in general; MM has its own stigma within the overall stigma of addiction. b) The negative attitudes about MM may represent what can happen when MM is started in a country where there have been laws against it for many years. I presume this is true in the Kyrgyz Republic since it likely had laws prohibiting use of opioids for treating opioid addiction when it was part of the Soviet Union. The authors might consider adding information about similar attitudes in the U.S. Examples are that MM “eats up your insides”; it “gets into your bones”; it is “just another drug”, not a rx; that people on mm are “weak”. c) The BNDD tried to arrest Dr. Dole, and it might be interesting to document it if one or more references can be found. It’s an excellent example of the very negative police response in the early day of methadone. Wyoming still may not allow MM and if so, could be an example of this lingering negativity about MM. d) Consider mentioning DSM-5 and ICD-11 where a patient can be in remission if on MM, buprenorphine, or naltrexone. e) Consider mentioning that MM is available in prisons in most EU countries. Modify the statement that the Kyrgyz Republic is one of “few countries”. e) Add a comment on how SBIRT has shown weak to modest effectiveness in the U.S. and not studies on former Soviet States. f) can more details be added about how new arrivals are classified within the prison system. The system the authors describe is unique. g) translations of Russian names relevant here. h) Is the prison infrastructure re methadone use common to all prisons? If so, could its description be shortened? i) what is the relationship between prison management and the way prisoners are classified? It appears as if prisoners are put into the groupings by other prisoners. j) does the MOH put out info on MM? k) consider limiting the number of English translations of Russian words; repeating the same words makes the paper more difficult to read l) It’s nor surprising that few started MM in view of the negative social pressure about it. Comments along those lined could be added since this negativity may explain why so few who were not on methadone started it.

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7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

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Reviewer #1: No

Reviewer #2: No

**********

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

PLoS One. 2022 Oct 25;17(10):e0276723. doi: 10.1371/journal.pone.0276723.r005

Author response to Decision Letter 1


8 Sep 2022

1. Outcome results are clear but the text is hard to read and could be shortened by 40-50%.

The authors thank the reviewer for this suggestion. This version of the text has been revised and shortened from 8742 words to 7098 words.

2. The authors mix stigma with negative attitudes about methadone maintenance (MM). Stigma applies to addiction in general; MM has its own stigma within the overall stigma of addiction.

The authors have applied the reviewer’s suggestion and have edited the section about stigma to clarify.

3. The negative attitudes about MM may represent what can happen when MM is started in a country where there have been laws against it for many years. I presume this is true in the Kyrgyz Republic since it likely had laws prohibiting use of opioids for treating opioid addiction when it was part of the Soviet Union. The authors might consider adding information about similar attitudes in the U.S. Examples are that MM “eats up your insides”; it “gets into your bones”; it is “just another drug”, not a rx; that people on mm are “weak”.

The authors thank the author for this suggestion and have added the following sentence (lines 366-369): “Many of these beliefs regarding methadone and methadone program participants exist in North America as well, including that methadone program participation indications a lack of will power, untrustworthiness, or ongoing addiction (i.e., to methadone instead of heroin) [42,43].”

4. The BNDD tried to arrest Dr. Dole, and it might be interesting to document it if one or more references can be found. It’s an excellent example of the very negative police response in the early day of methadone. Wyoming still may not allow MM and if so, could be an example of this lingering negativity about MM.

While the authors were not able to find a reference regarding the attempted arrest of Dr. Dole, they have added a source regarding police harassment of MM patients in the United States (lines 378-380): “Similar findings have also been reported… in the United States, where interviewees for a newspaper article described being followed from their methadone clinics by police and arrested for minor traffic infractions [47].”

5. Consider mentioning DSM-5 and ICD-11 where a patient can be in remission if on MM, buprenorphine, or naltrexone.

The authors thank the reviewer for this suggestion. However, they have chosen not to include these given the differing definitions of remission in the DSM-5-TR vs the ICD-11. The ICD-11 defines “sustained full remission” as “After a diagnosis of Opioid dependence, and often following a treatment episode or other intervention (including self-intervention), the person has been abstinent from opioids for 12 months or longer (Source: ICD-11 for Mortality and Morbidity Statistics (who.int)). Meanwhile, the DSM-5-TR allows methadone patients to receive a diagnosis of early or sustained remission, as long as the specifier “on maintenance therapy” is added (Source: Psychiatry Online | DSM Library). Given these differing definitions, we have chosen not to mention either definition of remission in this text.

6. Consider mentioning that MM is available in prisons in most EU countries. Modify the statement that the Kyrgyz Republic is one of “few countries”.

We thank the reviewer for this suggestion, and we have modified the statement in question (line 29).

7. Add a comment on how SBIRT has shown weak to modest effectiveness in the U.S. and not studies on former Soviet States.

We thank the reviewer for this suggestion, and we have modified lines 67-70 to reflect this point.

8. can more details be added about how new arrivals are classified within the prison system. The system the authors describe is unique.

As described in lines 276-280, “Briefly, when a person arrives into prison, he encounters a tribunal of his peers, which assesses whether he is guilty of the crime for which he has been incarcerated, the severity of his crime, and any mitigating factors (for example, positive character references from community members). He is then assigned a hierarchy status based on this assessment (Table 1b).”

9. translations of Russian names relevant here.

The authors have attempted to remove as many of the Russian transliterations as possible to encourage ease of reading.

10. Is the prison infrastructure re methadone use common to all prisons? If so, could its description be shortened?

As described in the text (line 274), this infrastructure is common to men’s prisons in the Kyrgyz Republic. Its description has been shortened as requested.

11. what is the relationship between prison management and the way prisoners are classified? It appears as if prisoners are put into the groupings by other prisoners.

To answer the reviewer’s question, incarcerated people are put into the groupings by their peers, as described in lines 276-280. This is an informal prison governmental system, not affiliated with the official prison administration (more details about this relationship have been described in a previous paper, Liberman et al. 2021).

12. does the MOH put out info on MM?

The authors thank the reviewer for this question, and have added a note about MOH guidelines for MM (lines 57-59).

13. consider limiting the number of English translations of Russian words; repeating the same words makes the paper more difficult to read

The authors thank the reviewer for this suggestion, and have attempted to eliminate as many English transliterations of Russian words as possible to promote ease of reading throughout the text.

14. It’s not surprising that few started MM in view of the negative social pressure about it. Comments along those lined could be added since this negativity may explain why so few who were not on methadone started it.

The authors thank the reviewer for this suggestion, highlighted in lines 365-367: “These ideas of sobriety and personal/community beliefs about methadone and methadone users interacted to discourage methadone uptake.”

Attachment

Submitted filename: Reviewer Response Letter 9.8.docx

Decision Letter 2

Judith I Tsui

26 Sep 2022

PONE-D-21-24508R2Interest without Uptake: A Mixed-Methods Analysis of Methadone Utilization in Kyrgyz PrisonsPLOS ONE

Dear Dr. Liberman,

Thank you for submitting your manuscript to PLOS ONE and for your patience during this review process as there have been a number of transitions in the handling of this manuscript. We invite you to submit a revised version of the manuscript that addresses the points raised during the review process.  As you can see there are just a few additional requests/clarifications that have been raised by the reviewers. It is my belief that these final responses/clarifications will result in a manuscript that is acceptable for publication and that the research will be an important contribution to the community of Plos One readers. 

Please submit your revised manuscript by Nov 10 2022 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

  • A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.

  • A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.

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Reviewer #1: The manuscript has been submitted as a Clinical Trial! I was surprized to see that there is no mention of a formal sample size/power calculation, and the study data has been analyzed, without any perspective on that. That needs to be added, or justification provided on why that is missing!

Reviewer #2: This is a much-improved manuscript. A few suggestions for additional improvements are: 1) Can the authors provide details about heroin availability in the prisons? In the U.S. heroin distribution would not be tolerate. How is this situation managed in the prisons? It appears to be an informal distribution network that is tolerate by prison administrators. Do all the guards participate or only a few? More details would be interesting if possible. 2) How is methadone treatment administered in the prisons? Do prisoners come to medical units for daily observed dosing? Is methadone brought to them by medical staff every day? 3) Where is the NSP located and how to prisoners access it?

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Reviewer #2: Yes: George E. Woody, MD. Emeritus Professor, Department of Psychiatry. Perelman School of Medicine at the University of Pennsylvania

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PLoS One. 2022 Oct 25;17(10):e0276723. doi: 10.1371/journal.pone.0276723.r007

Author response to Decision Letter 2


6 Oct 2022

1. The manuscript has been submitted as a Clinical Trial! I was surprized to see that there is no mention of a formal sample size/power calculation, and the study data has been analyzed, without any perspective on that. That needs to be added, or justification provided on why that is missing!

The authors thank the reviewer for this suggestion. This was addressed in a previous round of reviews (7.27.22), and the original comment and response are provided below. Additionally, the text has been updated to incorporate the answer provided below:

“Comment: It was really strange to see that the authors didn't provide a sample size/power statement, based on a target effect size they wanted to achieve. This would allow efficient planning to similar future studies. The sample size/power should be computed based on the primary outcome, say at 5% level, and likely one that achieves 80-90% power.

Response: This study tests the SBIRT method of recruiting people into OAT. During the S-Screening step, we screen all potentially eligible participants (people to be released from Kyrgyz prisons that have MMT) for opioid use disorder. Only those that screen positive are then included in the sample. In our study protocol, we present the target sample as 120 people as approximately 1000 people are released from the Kyrgyz prisons that have MMT every year, as we expected approximately 120 of them to be eligible for inclusion. Indeed, this number was fairly close as we recruited 125 people into the sample.

For the analysis of whether the B-brief intervention component was effective, we cannot recruit more people than there are eligible participants in the country; therefore, a formal sample size calculation was not included.”

2. Can the authors provide details about heroin availability in the prisons? In the U.S. heroin distribution would not be tolerate. How is this situation managed in the prisons? It appears to be an informal distribution network that is tolerate by prison administrators. Do all the guards participate or only a few? More details would be interesting if possible.

The authors thank the reviewer for this suggestion. They have added the following text: “The obshchak was highly motivated to dissuade people from using methadone, because the obshchak was the major distributer of in-prison heroin. This process was facilitated by the obshchak's extensive connections outside of the prison. It acted both as a mutual aid fund, collecting and redistributing goods to incarcerated people, and also as a marketplace for various goods and services. This marketplace was facilitated by corruption of official prison staff, who allowed these goods, including heroin, to enter the prison [11]. Heroin served both as a commodity and as a form of currency which could be used to purchase other items within the prison.”

It is difficult to estimate a percentage of official prison staff who participate in the informal heroin distribution system, so this specific detail was not included.

3. How is methadone treatment administered in the prisons? Do prisoners come to medical units for daily observed dosing? Is methadone brought to them by medical staff every day?

The authors thank the reviewer for this suggestion and have added the following: “Prison medical staff administered methadone daily at a specific, designated location for all methadone program participants irrespective of hierarchy level. Therefore, joining the methadone program meant potential physical interaction with people of lower hierarchy status or using the same items, like pens or cups. These interactions could lead to demotion within the hierarchy [29].”

4. Where is the NSP located and how to prisoners access it?

The authors thank the reviewers for this clarification point. The specific location of the NSP depends on the prison; some are located in the medical area, whereas other are in the barracks. Participants register confidentially in the program, and there is a low threshold for entry. Nurses distribute the clean equipment. Although the NSP is not a central focus of this paper, we have clarified this in the text with the following: “Ordinarily, to access the NSP, individuals registered confidentially and were then able to receive injection equipment from nurses located either in the medical area or the barracks, depending on the specific prison. However, those that joined the methadone program were no longer permitted to participate in the NSP.”

Attachment

Submitted filename: Reviewer Response Letter 9.30.docx

Decision Letter 3

Judith I Tsui

13 Oct 2022

Interest without Uptake: A Mixed-Methods Analysis of Methadone Utilization in Kyrgyz Prisons

PONE-D-21-24508R3

Dear Dr. Liberman,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

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Kind regards,

Judith I Tsui

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

Acceptance letter

Judith I Tsui

17 Oct 2022

PONE-D-21-24508R3

Interest without Uptake: A Mixed-Methods Analysis of Methadone Utilization in Kyrgyz Prisons

Dear Dr. Liberman:

I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department.

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on behalf of

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PLOS ONE

Associated Data

    This section collects any data citations, data availability statements, or supplementary materials included in this article.

    Supplementary Materials

    S1 File. Complete list of survey questions.

    Full list of survey questions asked of all participants and codebook for reading data.

    (PDF)

    S2 File. Pre- and post-release interview guides.

    English translation and original Russian-language interview guides used to interview study participants pre- and post-release.

    (DOCX)

    S3 File. Quantitative data.

    All deidentified quantitative data; S1 File may be used as a codebook for questions asked.

    (XLSX)

    S1 Checklist. TREND statement checklist.

    (PDF)

    S1 Protocol

    (PDF)

    Attachment

    Submitted filename: Response to PLOS.docx

    Attachment

    Submitted filename: Reviewer Response Letter PLOS.docx

    Attachment

    Submitted filename: Reviewer Response Letter 9.8.docx

    Attachment

    Submitted filename: Reviewer Response Letter 9.30.docx

    Data Availability Statement

    All relevant quantitative data are within the paper and its Supporting Information files. Data have been deidentified. Individual demographic information has not been shared to prevent potential participant identification; it will be available upon request to the Yale Center for Interdisciplinary Research on AIDS (contact via data manager Delaney Rhoades, delaney.rhoades@yale.edu) for researchers who meet the criteria for access to confidential data. Full interview transcript data cannot be shared publicly because of potential identifiability of our participants. Qualitative data are available from the Yale Center for Interdisciplinary Research on AIDS (contact via data manager Delaney Rhoades, delaney.rhoades@yale.edu) for researchers who meet the criteria for access to confidential data.


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