"If they get out of drug rehab centers, they're on their own": Opportunities and challenges for people released from compulsory drug rehabilitation centers to communities in Vietnam.

INTRODUCTION: Compulsory drug rehabilitation is a major governmental response to illicit drug use in Vietnam and other countries in Asia. Long-term compulsory rehabilitation is associated with negative health, social and economic outcomes. The transition to community-based services for people released from compulsory drug rehabilitation has been problematic not only in Vietnam. This study utilized the WHO Health System Building Blocks Framework to examine the opportunities and challenges for people with substance use disorders (SUD) who are released from compulsory drug rehabilitation back into the community. METHODS: Between October 2021 and August 2022, we interviewed people with SUD who had recently returned from or were preparing to leave compulsory drug rehabilitation (n = 25), their family members (n = 20) and professionals working in the field of drug rehabilitation (n = 28) across three cities in Vietnam. Additionally, we conducted a review of policy documents to complement the interview data. RESULTS: The study identified opportunities and challenges within Vietnam's drug rehabilitation system concerning leadership and governance, financing, workforce, information systems and service delivery for people with SUD. Key opportunities include a legal framework that emphasizes community-based support for people with SUD, a government-funded national network of lay social workers, and ongoing efforts to connect people to community-based services. We found significant challenges caused by the lack of clear instructions for implementing supportive policies, inadequate funding for community-based services, persisting stigma from providers towards people with SUD and unavailability of community-based drug treatment other than methadone. CONCLUSION: Vietnam continues with compulsory drug rehabilitation yet endorses recovery-oriented policies to address substance use issues. Substantial challenges hinder the effective implementation of these policies. Our study recommends reinforcing existing policies and enhancing recovery-oriented community-based services by improving the quality of data collection, building capacity of lay social workers who facilitate linkages to services and expanding community-based drug treatment options.

Using ADAPT-ITT framework to tailor evidence-based interventions for addressing methamphetamine use among methadone patients in Vietnam.

INTRODUCTION: Methamphetamine use threatens positive treatment outcomes in substance use and HIV, for people with opioid use disorders (POUD) in many countries. This paper describes the adaptation of four evidence-based interventions (EBI) (motivational interviewing, contingency management, Matrix group model and SMS text messaging) for treating methamphetamine use among POUD receiving methadone maintenance therapy in Vietnam. METHODS: Following the ADAPT-ITT (Assessment-Decision-Administration-Production-Topical experts-Training-Testing) framework, we conducted 16 focus group discussions with POUD (n = 25) and providers (n = 22) at four methadone clinics in two largest cities (Hanoi in the North, Ho Chi Minh City in the South) to assess patterns of methamphetamine use and to get feedback on proposed EBIs. The proposed EBIs were properly adapted and used to train providers in two of the four methadone clinics. The revised EBIs were tested over 12 weeks among 42 POUD on methadone who use methamphetamine. Post-intervention feedback served to fine-tune the revised EBIs. RESULTS: Insights about patterns of methamphetamine use suggested that EBIs should focus on different triggers to methamphetamine use among POUD receiving methadone treatment in the two cities. All EBIs should emphasise family-related topics to build a strong motivation for treatment. Participants suggested when, where and how each EBI should be delivered. Most participants were satisfied with the adapted EBIs. Limited human resources at methadone clinics might hinder implementation of the adapted EBIs. DISCUSSION AND CONCLUSIONS: We successfully completed the adaptation of EBIs for POUD who use methamphetamine on methadone in Vietnam. The pilot testing of the adapted EBIs demonstrated feasibility and acceptability. TRIAL REGISTRATION: NCT04706624. Registered 13 January 2021. https://clinicaltrials.gov/ct2/show/NCT04706624.

The mediation effects of sexual self-efficacy in the relationship between psychosocial wellbeing and depressive symptoms among female migrant workers in Vietnam.

BACKGROUND: Depression is a common mental disorder that significantly contributes to the global burden of disease. Studies have consistently reported that migrant workers experience higher levels of depressive symptoms, especially women. AIMS: This study aimed to examine the mediation role of sexual self-efficacy on the relationship between psychological wellbeing, and depressive symptoms among young female migrant workers in Vietnam's industrial zones. METHODS: A cross-sectional study was conducted among 1061 female migrant workers aged 18 to 29 from January to November 2020 in Hanoi, Vietnam. Anonymous interview questionnaires were used to collect data on demographic characteristics, psychosocial wellbeing (PWB), sexual self-efficacy, and depressive symptoms. Mediation analysis was conducted to explore the mediation effect of sexual self-efficacy on the relationship between PWB and depressive symptoms. RESULTS: Nearly 8% of the female migrant workers reported experiencing depressive symptoms. The final mediation model showed that the effect of overall psychological wellbeing on depressive symptoms was partially mediated by sexual self-efficacy. Specifically, 4.1% of the effect of overall PWB on depressive symptoms was mediated through sexual self-efficacy. In the PWB subdimension analyses, sexual self-efficacy mediated 14.3% of the effect of personal growth, 8.8% of the effect of purpose in life, 8.0% of the effect of autonomy, and 7.8% of the effect of environmental mastery on depressive symptoms, respectively. CONCLUSION: The study findings demonstrate that sexual self-efficacy plays an important role in the relationship between psychosocial wellbeing and depressive symptoms among female migrant workers in industrial zones in Vietnam. Improving psychosocial wellbeing and promoting sexual health including sexual self-efficacy should be prioritized when addressing depressive symptoms and mental health concerns among industrial zone female migrant workers in Vietnam, which may also be applicable in other low- and middle-income countries with similar socio-cultural settings.

Patient-provider relationships: Opioid use disorder and HIV treatment in Vietnam.

Background: The provider-patient relationship has been implicated as a positive force in health outcomes. This study examined the provider-patient relationship in the setting of integrated, partially-integrated, and non-integrated opioid use disorder (OUD) and HIV care models in Vietnam. Objective: To examine the provider-patient relationship in the setting of integrated, partially integrated, and non-integrated OUD and HIV treatment in North Vietnam. Methods: Between 2013 and 2018, we conducted face-to-face qualitative interviews with 44 patients living with HIV and OUD and 43 providers in northern Vietnam. These were analyzed using a semantic, inductive approach to qualitative thematic analysis. Results: Several themes were identified. 1) Trust was important to the patient-provider relationship and sensitive to provider attitudes and competence. 2) Patients perceived greater provider competence and understanding of patient health problems in integrated treatment. 3) Patient-provider relationships were initially superficial but deepened over time, facilitated by continuity of care. Conclusions: Patient perceptions of competence and respect were important to feeling cared for. Providers felt empathy and competence came with more experience caring for patients with OUD and HIV.

Findings from a pilot study of buprenorphine population pharmacokinetics: A potential effect of HIV on buprenorphine bioavailability.

BACKGROUND: Buprenorphine is widely used in the treatment of opioid use disorder (OUD). There are few pharmacokinetic models of buprenorphine across diverse populations. Population pharmacokinetics (POPPK) allows for covariates to be included in pharmacokinetic studies, thereby opening the potential to evaluate the effect of comorbidities, medications, and other factors on buprenorphine pharmacokinetics. This pilot study used POPPK to explore buprenorphine pharmacokinetics in patients with and without HIV receiving buprenorphine for OUD. METHODS: Plasma buprenorphine levels were measured in 54 patients receiving buprenorphine for OUD just prior to and 2-5 h following regular buprenorphine dosing. A linear one-compartment POPPK model with first-order estimation was used to evaluate buprenorphine clearance (CL/F) and volume of distribution (V/F). Covariates included weight and HIV status. RESULTS: All HIV+ patients reported complete past-month adherence to taking antiretroviral therapy that included either efavirenz or nevirapine. Buprenorphine CL/F was 76% higher in HIV+ patients (n = 17) than HIV- patients (n = 37). Buprenorphine V/F was 41% higher in the HIV+ patients. CONCLUSIONS: POPPK can be used to model buprenorphine pharmacokinetics in a real-world clinical population. While interactions between ART and buprenorphine alter buprenorphine CL/F, we also found alteration in V/F. Proportionate changes in CL/F and V/F might indicate a primary effect on bioavailability (F) rather than two separate effects. These findings indicate reduced buprenorphine bioavailability in patients with HIV.

An adaptive design to screen, treat, and retain people with opioid use disorders who use methamphetamine in methadone clinics (STAR-OM): study protocol of a clinical trial.

BACKGROUND: Methamphetamine use could jeopardize the current efforts to address opioid use disorder and HIV infection. Evidence-based behavioral interventions (EBI) are effective in reducing methamphetamine use. However, evidence on optimal combinations of EBI is limited. This protocol presents a type-1 effectiveness-implementation hybrid design to evaluate the effectiveness, cost-effectiveness of adaptive methamphetamine use interventions, and their implementation barriers in Vietnam. METHOD: Design: Participants will be first randomized into two frontline interventions for 12 weeks. They will then be placed or randomized to three adaptive strategies for another 12 weeks. An economic evaluation and an ethnographic evaluation will be conducted alongside the interventions. PARTICIPANTS: We will recruit 600 participants in 20 methadone clinics. ELIGIBILITY CRITERIA: (1) age 16+; (2) Alcohol, Smoking and Substance Involvement Screening Test (ASSIST) scores ≥ 10 for methamphetamine use or confirmed methamphetamine use with urine drug screening; (3) willing to provide three pieces of contact information; and (4) having a cell phone. OUTCOMES: Outcomes are measured at 13, 26, and 49 weeks and throughout the interventions. Primary outcomes include the (1) increase in HIV viral suppression, (2) reduction in HIV risk behaviors, and (3) reduction in methamphetamine use. COVID-19 response: We developed a response plan for interruptions caused by COVID-19 lockdowns to ensure data quality and intervention fidelity. DISCUSSION: This study will provide important evidence for scale-up of EBIs for methamphetamine use among methadone patients in limited-resource settings. As the EBIs will be delivered by methadone providers, they can be readily implemented if the trial demonstrates effectiveness and cost-effectiveness. TRIAL REGISTRATION: ClinicalTrials.gov NCT04706624. Registered on 13 January 2021. https://clinicaltrials.gov/ct2/show/NCT04706624.

The Relationship of Dioxin Levels in Serum of 9-Year-Old Vietnamese Children and Their Mothers' Breast Milk.

In this study, we measured the concentrations of polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs) in the blood of 9-year-old children living in a dioxin hotspot area and a nonexposed area in Vietnam. Forty-five blood samples were collected in the hotspot area while twelve pooled blood samples were collected in the nonexposed area. We found that the dioxin level of children in the hotspot was significantly higher than that of children in the nonexposed area. The total TEQ of PCDD/Fs in the hotspot and the nonexposed was 10.7 and 3.3 pg TEQ/g fat, respectively. However, TCDD, the maker of Agent Orange, was not detected in the blood of children in the hotspot area. In the hotspot area, four congeners 1,2,3,4,6,7,8-HpCDD, 1,2,3,4,7,8-HxCDF, 1,2,3,6,7,8-HxCDF, and 1,2,3,4,6,7,8-HpCDF in mothers' breast milk showed a significantly positive correlation with those in children's serum although the correlations of 1,2,3,7,8-PeCDD and 2,3,4,7,8-PeCDF were not significant. In addition, the duration of breastfeeding also correlates with dioxins in children. These results suggested that children in the hotspot area were exposed to dioxin through mothers' milk and other foods or environmental factors. The present study is the first study that shows dioxin levels in Vietnamese children.

"I'm not like others": stigma navigation by people who inject drugs in Vietnam.

Background: People who inject drugs are subjected to great stigmatization in many parts of the world. How they deal with stigma is closely linked to how stigma means to them. Understanding the strategies individuals employ to cope with these negative attitudes and what resources they mobilize in this process gives useful insights for clinical work and policy development. Methods: We conducted 12 months of field observation in 2017 and 2018 and 54 in-depth interviews with people who inject drugs in Haiphong, Vietnam. Grounded theory underpinned our sampling and data analysis. Results: The strategies participants used to manage stigma were both information and tension management. Many participants not only concealed their drug use but actively cultivated a pro-social image based on Vietnamese cultural virtues such as selflessness, hard work or harmonious living with others. Participants withdrew from social relationships to distance themselves from the stereotype of a money-begging drug user. They used techniques of neutralization to emphasize their good character and reframe their drug-related issues in a different light in order to negotiate their social status with their interlocutors. Conclusion: People who inject drugs endorse the same social values and aspirations as nonusers. A good support structure and resources could help them to cope more effectively with stigma.

Prevalence, Anatomic Distribution, and Correlates of Chlamydia trachomatis and Neisseria gonorrhoeae Infections Among a Cohort of Men Who Have Sex With Men in Hanoi, Vietnam.

BACKGROUND: Neisseria gonorrhoeae (NG) and Chlamydia trachomatis (CT) disproportionately affect men who have sex with men (MSM). Data on the prevalence, anatomical distribution, and correlates of NG and CT infections among MSM in Vietnam are limited. METHODS: Between July 2017 and April 2019, MSM 16 years or older without HIV were enrolled into an observational cohort study. Baseline data, including sociodemographics, sexual behavior, and HIV status, were collected. Testing for NG and CT were performed on urine, rectal, and pharyngeal specimens. Multivariate logistic regression models identified factors associated with NG and CT infections at baseline. RESULTS: In total, 1489 participants underwent NG/CT testing. The median age was 22 years (interquartile range, 20-26 years). There were 424 (28.5%) NG or CT infections: 322 (21.6%) with CT and 173 (11.6%) with NG. Rectal infections were most common for CT (73.9%), whereas pharyngeal infections were most common for NG (70.5%). Independent risk factors for CT or NG infection included ≥2 sex partners in the prior month (adjusted odds ratio [aOR], 2.04; 95% confidence interval [CI], 1.44-2.91), condomless anal sex (aOR, 1.44; 95% CI, 1.12-1.86), and meeting sex partners online (aOR, 1.35; 95% CI, 1.03-1.76). Recent genitourinary or rectal symptoms were not associated with infections. CONCLUSIONS: The overall and extragenital prevalences of NG and CT infections were high within this sample of young MSM without HIV in Hanoi. Testing limited to urethral specimens would have missed nearly three-quarters of CT and NG infections, supporting the need for routine testing at multiple anatomic sites.

Elevated trauma exposure and mental health burden among men who have sex with men in Vietnam.

The purpose of this study was to characterize trauma exposure and mental health burden among men who have sex with men (MSM) in Hanoi, Vietnam. Participants comprise 100 HIV-positive and 98 high-risk, HIV-negative MSM, ranging from 18 to 29 years of age. Data were collected using the Childhood Trauma Questionnaire, Traumatic Events Inventory, Patient Health Questionnaire-9, Generalized Anxiety Disorder-7, and PTSD Symptom Scale. A subset of participants (n = 12) were also interviewed to evaluate community perception of the prevalence, causation, and available treatment options for mental health issues within the MSM community in Vietnam. In our sample, 23.2% reported having experienced moderate-to-severe childhood physical abuse; 18.7% physical neglect; 13.6% emotional abuse; 11.1% emotional neglect; and 26.8% sexual abuse. Such trauma exposure continued into adulthood and manifested most commonly in the form of interpersonal violence. Approximately 37.4% of the sample met the criteria for probable PTSD; 26.8% for moderate-to-severe depression; and 20.2% for moderate-to-severe anxiety. Neither exposure nor mental health burden differed by serostatus. Linear regression revealed that childhood emotional abuse was the only sub-type of trauma significantly associated with depression, anxiety, and PTSD symptoms. The majority of interviewees believed that mental health burden was higher among MSM relative to the general population and attributed this to their vulnerability to interpersonal violence and lack of available coping resources. However, few believed that these mental health issues warranted clinical attention, and only one participant was able to identify a mental health service provider. Our findings suggest that trauma exposure and mental health burden are prevalent among MSM, irrespective of serostatus, and much higher than what has been previously reported among the general population in Vietnam.

Feasibility, Acceptability, and Design of a Mobile Ecological Momentary Assessment for High-Risk Men Who Have Sex With Men in Hanoi, Vietnam: Qualitative Study.

BACKGROUND: Men who have sex with men (MSM) are at a disproportionate risk for HIV infection and common mental disorders worldwide. In the context of HIV, common mental disorders are important and are frequent drivers of suboptimal prevention and treatment outcomes. Mobile ecological momentary assessments (EMAs), or the repeated sampling of people's behaviors and psychological states in their daily lives using mobile phones, can clarify the triggers and HIV-related sequelae of depressive-anxious symptoms and contribute toward the design of ecological momentary interventions (EMIs) that cater to the contextually varying needs of individuals to optimize prevention and treatment outcomes. OBJECTIVE: This study aims to characterize the feasibility and acceptability of mobile EMA among high-risk MSM in Hanoi, Vietnam. It aims to evaluate the perceived relevance, usability, and concerns of this group with regard to the content and delivery of mobile EMA and the potential of leveraging such platforms in the future to deliver EMIs. METHODS: Between January and April 2018, a total of 46 participants were recruited. The participants completed 6 to 8 mobile EMA surveys daily for 7 days. Surveys occurred once upon waking, 4 to 6 times throughout the day, and once before sleeping. All surveys queried participants' perceived safety, social interactions, psychological state, and mental health symptoms. The morning survey further queried on sleep and medication use within the past 24 hours, whereas the night survey queried on sexual activity and substance use and allowed participants to share an audio recording of a stressful experience they had that day. At the end of the week, participants were interviewed about their experiences with using the app. RESULTS: Participants completed an average of 21.7 (SD 12.7) prompts over the 7-day period. Excluding nonresponders, the average compliance rate was 61.8% (SD 26.6%). A thematic analysis of qualitative interviews suggested an overall positive reception of the app and 5 recurring themes, which were centered on the relevance of psychological and behavioral items to daily experiences (eg, mental health symptoms and audio recording), benefits of using the app (eg, increased self-understanding), worries and concerns (eg, privacy), usability (eg, confusion about the interface), and recommendations for future design (eg, integrating more open-ended questions). CONCLUSIONS: Mobile EMA is feasible and acceptable among young MSM in Vietnam; however, more research is needed to adapt EMA protocols to this context and enhance compliance. Most participants eagerly provided information about their mental health status and daily activities. As several participants looked toward the app for further mental health and psychosocial support, EMIs have the potential to reduce HIV and mental health comorbidity among MSM.

Correlates of methamphetamine use severity among patients receiving methadone maintenance treatment for opioid use disorder in Vietnam.

OBJECTIVES: To assess the severity of methamphetamine use among methadone maintenance treatment (MMT) patients in Vietnam with opioid use disorder and concurrent methamphetamine use, and to identify risk factors associated with higher severity of methamphetamine use. METHODS: We used survey data and medical record abstractions from 428 people with opioid use disorder who also use methamphetamine while partaking in methadone treatment in five clinics in Hanoi, Vietnam. We used multinomial logistic regression to assess other risk factors and problems associated with high methamphetamine use severity. RESULTS: Those who reported injecting heroin in the past 3 months (AOR = 4.05, 95% CI [1.30, 12.55], p = 0.02), having a longer history of lifetime heroin use (AOR = 1.13, 95% CI [1.03, 1.24], p < 0.01), and having higher cravings (AOR = 1.97, 95% CI [1.31, 2.98], p < 0.01) and fatigue (AOR = 1.25, 95% CI [0.96, 1.61], p = 0.09) related to methamphetamine withdrawal had greater odds of high methamphetamine use severity. One of five clinics had a significantly higher percentage of methamphetamine use severity than others. CONCLUSION: Successful MMT in patients with opioid use disorder in Vietnam may additionally require methamphetamine-focused screening and intervention.

Incarceration and compulsory rehabilitation impede use of medication for opioid use disorder and HIV care engagement in Vietnam.

BACKGROUND: Non-prescribed opioid use is illegal in Vietnam. People who are apprehended for use of non-prescribed opioids may be arrested and incarcerated or sent to compulsory rehabilitation centers. For those on medication to treat opioid use disorder (MOUD), incarceration in either setting may disrupt treatment. This study estimates the effects of incarceration and compulsory rehabilitation on MOUD and HIV treatment outcomes in Vietnam. METHODS: Data are from a clinical trial testing the effects of MOUD on HIV viral suppression in six Vietnamese HIV clinics. Participants were assessed quarterly for 12 months. We assessed the associations between incarceration or compulsory rehabilitation during months 0-9 and study outcomes of receipt of MOUD, HIV clinic engagement, and antiretroviral therapy prescription during months 9-12, among those who were released by month 9 of the study, using logistic regression and zero-inflated negative binomial models. RESULTS: At nine months, 25 of 258 participants (9.7%) were incarcerated or sent to compulsory rehabilitation at least once and completed the month 9 assessment. Of those, 19 (76.0%) did not receive MOUD in months 9 through 12. Both incarceration and compulsory rehabilitation were negatively associated with subsequent receipt of MOUD (aOR = 0.05, 95% CI = (0.01, 0.24); 0.14 (0.04, 0.50), respectively) and HIV clinic engagement (aOR = 0.13, 95% CI = (0.03, 0.71); 0.09 (0.02, 0.39), respectively). In the final three months of the study, participants who were incarcerated had 42.5 fewer days of MOUD (95% CI = 23.1, 61.9), and participants in compulsory rehabilitation had 46.1 fewer days of MOUD (95% CI = 33.8, 58.4) than those not incarcerated or in compulsory rehabilitation. CONCLUSION: Our findings suggest that both incarceration and compulsory rehabilitation disrupt MOUD and HIV treatment among people with HIV and Opioid Use Disorder in Vietnam. Prioritization of evidence-based strategies to support engagement in care for people who use drugs could potentially expand HIV and Opioid Use Disorder treatment access and curb substance use more effectively than reliance on incarceration or compulsory rehabilitation.

Correlates of days of medication for opioid use disorder exposure among people living with HIV in Northern Vietnam.

BACKGROUND: In Vietnam, access to medications for opioid use disorder (MOUD) for people living with HIV has rapidly expanded, but MOUD use over time remains low. We sought to assess factors associated with days of MOUD treatment exposure. METHODS: From 2015 to 2019, patients with OUD in six Northern Vietnamese HIV clinics were randomized to receive HIV clinic-based buprenorphine (BUP/NX) or referral for methadone maintenance therapy (MMT) and followed for 12 months. All MOUD doses were directly observed and abstracted from dosing logs. The primary outcome was days of MOUD treatment exposure (buprenorphine or methadone) received over 12 months. Negative binomial regression modelled associations with days of MOUD exposure. RESULTS: Of 281 participants, 264 (94%) were eligible for analysis. Participants were primarily male (97%), unmarried (61%), employed (54%), and previously arrested (83%). Participants had a mean 187 (SD 150) days of MOUD exposure with 134 (51%) having at least 180 days, and 35 (13.2%) having at least 360 days of MOUD exposure. Age (IRR 1.26, 95% CI 1.02-1.55), income (IRR 0.96, 95% CI 0.93-1.001), and methadone (IRR 1.88, 95% CI 1.51-2.42) were associated with MOUD exposure in multivariate models. Multivariate models predicted 127 (95% CL 109-147) days of MOUD exposure for HIV clinic based-buprenorphine vs 243 (95% CL 205-288) for MMT. CONCLUSION: MOUD treatment exposure was suboptimal among patients with HIV and OUD in Northern Vietnam and was influenced by several factors. Interventions to support populations at risk of lower MOUD exposure as well programs administering MOUD should be considered in countries seeking to expand access to MOUD.

HIV and STI prevalence and testing history among men who have sex with men in Hanoi, Vietnam.

BACKGROUND: HIV and other sexually transmitted infections (STIs) have disproportionately affected communities of men who have sex with men (MSM). We describe HIV and STI prevalence and testing patterns among urban Vietnamese MSM. METHODS: We conducted a cross-sectional community-based study of MSM in Hanoi, Vietnam in 2016. Participants self-reported experiences of social stigma in healthcare settings and previous HIV and STI testing. STI testing included HIV, herpes simplex virus-2 (HSV-2), syphilis, gonorrhea, and chlamydia. RESULTS: 205 MSM participated in the study. STI prevalence was HIV (10%), HSV-2 (4%), syphilis (13%), gonorrhea (34%), and chlamydia (19%). More than half (55%) of participants tested positive for at least one STI. Most participants had been previously tested for HIV or another STI (72%), with 24% previously receiving a positive result. Perceived and enacted social stigma in healthcare contexts was negatively associated with previous HIV or STI testing (adjusted prevalence odds ratio (aPOR): 0.22; 95% confidence interval (CI): 0.10-0.48). DISCUSSION: High prevalence of STIs was observed among Vietnamese MSM, and perceived and enacted stigma was related to HIV and STI testing. Our findings reaffirm the importance of regular STI screening among this population as well as additional outreach to promote safe HIV and STI healthcare engagement.

Effect of HIV, antiretrovirals, and genetics on methadone pharmacokinetics: Results from the methadone antiretroviral pharmacokinetics study.

BACKGROUND: Methadone treatment of opioid use disorder in HIV-infected individuals is complicated by drug-drug interactions. Genetic and other cofactors further contribute to interindividual variability in methadone pharmacokinetics. We used population pharmacokinetics to estimate the effect of drug-drug interactions, genetics, and other cofactors on methadone pharmacokinetics in a methadone maintained population in Vietnam. METHODS: Plasma R- and S-methadone levels were measured in 309 methadone maintained individuals just before and 2-5 h following methadone dosing. A linear one-compartment population pharmacokinetic model with first-order conditional estimation with interaction was used to evaluate methadone clearance (CL/F) and volume of distribution (V/F). The influence of covariates on parameter estimates was evaluated using stepwise covariate modeling. Covariates included HIV status, antiretroviral use (efavirenz or nevirapine), weight, BMI, age, methadone dose, and 8 single nucleotide polymorphisms in across the CYP2B6, ABCB1, and NR1I3 genes. RESULTS: Taking either efavirenz or nevirapine increased R-methadone CL/F 220%. Nevirapine and efavirenz increased S-methadone CL/F by 404% and 273%, respectively. Variants in NR1I3 increased R- and S-methadone CL/F by approximately 20% only in patients taking efavirenz. Different alleles in ABCB1 rs2032582 either increased or decreased R-methadone CL/F by 10%. The CYP 2B6*4 variant decreased S-methadone CL/F by 18%. HIV-infection increased R- and S-methadone CL/F and V/F by 24%-39%. CONCLUSIONS: The HIV antiretrovirals nevirapine and efavirenz significantly increase methadone clearance. Variants inNR1I3 increased the effect of efavirenz on methadone clearance. Other variants affecting methadone CL/F were also confirmed. To our knowledge, this is the first report of HIV itself affecting methadone pharmacokinetics.

Use of methamphetamine and alcohol among people with opioid use disorder and HIV in Vietnam: a qualitative study.

BACKGROUND: Heroin use continues to drive HIV transmission in Vietnam, but methamphetamine and alcohol use are growing rapidly and, as in other countries, polysubstance use is widespread. The objective of this study was to understand the interplay between heroin, methamphetamine, and alcohol use among people with opioid use disorder (OUD) and HIV in Vietnam. METHODS: We conducted 44 in-depth, face-to-face qualitative interviews with people with OUD and HIV who participated in the BRAVO trial of buprenorphine versus methadone in five Vietnam HIV clinics. Interviews probed participants' experiences of heroin, methamphetamine, and alcohol use and their interplay with HIV/OUD treatment. Interviews were professionally transcribed and analyzed using a thematic analysis approach. RESULTS: Of 44 participants interviewed 42 were male, on average 38.8 years of age, with 30 reporting a history of methamphetamine use and 33 reporting a history of alcohol use. Several themes emerged: 1) Methamphetamine and alcohol were perceived to have lower addiction potential than heroin 2) Social settings were key facilitators of alcohol and methamphetamine use 3) Some participants, but not all, used methamphetamine to help quit heroin 4) Consuming alcohol blunted the effects of heroin, while paradoxically serving as a catalyst for heroin use 5) Use of methamphetamine was perceived by many participants to be incompatible with treatment for HIV. CONCLUSIONS: Participant experiences reflected a significant impact of polysubstance use on treatment of HIV and OUD. Patterns of polysubstance use are subject to common preconceptions of alcohol and methamphetamine as having a low addictive potential, and these substances are deeply enmeshed in the social life of many people with OUD in Vietnam. Interventions to address complex social norms and potential harms of polysubstance use are urgently needed as the population of people receiving medication for OUD (MOUD) increases in Vietnam and globally. TRIAL REGISTRATION: BRAVO - NCT01936857 , September 2013.

Mental health in HIV prevention and care: A qualitative study of challenges and facilitators to integration in Vietnam.

INTRODUCTION: Globally, men who have sex with men (MSM) experience a disproportionate burden of mental health issues. While HIV service providers may possess the skills and relationships to provision mental health and psychosocial support (MHPSS) to this population, task-sharing models that integrate MHPSS into HIV contexts remain limited. The aim of this study was to explore the sociodemographic, psychological, and structural factors operant at the client and HIV service provider levels that shape MHPSS access and burden among MSM and opportunities for integration in Vietnam. METHODS: Between June and August 2018, semi-structured interviews were conducted with 20 MSM and 13 service providers at out-patient clinics (OPCs) and community-based organizations (CBOs) in Hanoi, Vietnam. Interviews explored participants' understandings of and experiences with the signs, causes, and appropriate treatments for mental health concerns; and perceived barriers to MHPSS integration in HIV contexts. Data were coded thematically and analyzed in MAXQDA. RESULTS: Most MSM did not view their mental distress as constituting illness or as warranting clinical attention. Specifically, terms like "mental illness" were often associated with being "crazy" or immoral, while symptoms of distress were interpreted as having to do with everyday difficulties associated with being MSM and/or HIV-positive. Due to mental health stigma, MSM were reluctant to access services while service providers were similarly reluctant to query about needs. Few service providers knew where to refer patients for MHPSS, and none had done so previously. Most service providers reported lacking the human capital, expertise, and funding to address MHPSS needs. CONCLUSIONS: Our findings suggest that aside from mental health stigma, future integration strategies must address competing demands and incentivization structures, limitations in existing mental health infrastructure and funding, misperceptions around MHPSS needs and symptoms, and opportunities to streamline MHPSS with existing CBO activities to strengthen community wellbeing.

HIV clinic-based buprenorphine plus naloxone versus referral for methadone maintenance therapy for treatment of opioid use disorder in HIV clinics in Vietnam (BRAVO): an open-label, randomised, non-inferiority trial.

BACKGROUND: UNAIDS recommends integrating methadone or buprenorphine treatment of opioid use disorder with HIV care to improve HIV outcomes, but buprenorphine adoption remains limited in many countries. We aimed to assess whether HIV clinic-based buprenorphine plus naloxone treatment for opioid use disorder was non-inferior to referral for methadone maintenance therapy in achieving HIV viral suppression in Vietnam. METHODS: In an open-label, non-inferiority trial (BRAVO), we randomly assigned people with HIV and opioid use disorder (1:1) by computer-generated random number sequence, in blocks of ten and stratified by site, to receive HIV clinic-based buprenorphine plus naloxone treatment or referral for methadone maintenance therapy in six HIV clinics in Vietnam. The primary outcome was HIV viral suppression at 12 months (HIV-1 RNA ≤200 copies per mL on PCR) by intention to treat (absolute risk difference [RD] margin ≤13%), compared by use of generalised estimating equations. Research staff actively queried treatment-emergent adverse events during quarterly study visits and passively collected adverse events reported during HIV clinic visits. This study is registered with ClinicalTrials.gov, NCT01936857, and is completed. FINDINGS: Between July 27, 2015, and Feb 12, 2018, we enrolled 281 patients. At baseline, 272 (97%) participants were male, mean age was 38·3 years (SD 6·1), and mean CD4 count was 405 cells per µL (SD 224). Viral suppression improved between baseline and 12 months for both HIV clinic-based buprenorphine plus naloxone (from 97 [69%] of 140 patients to 74 [81%] of 91 patients) and referral for methadone maintenance therapy (from 92 [66%] of 140 to 99 [93%] of 107). Buprenorphine plus naloxone did not demonstrate non-inferiority to methadone maintenance therapy in achieving viral suppression at 12 months (RD -0·11, 95% CI -0·20 to -0·02). Retention on medication at 12 months was lower for buprenorphine plus naloxone than for methadone maintenance therapy (40% vs 65%; RD -0·53, 95% CI -0·75 to -0·31). Participants assigned to buprenorphine plus naloxone more frequently experienced serious adverse events (ten [7%] of 141 vs four of 140 [3%] assigned to methadone maintenance therapy) and deaths (seven of 141 [5%] vs three of 141 [2%]). Serious adverse events and deaths typically occurred in people no longer taking ART or opioid use disorder medications. INTERPRETATION: Although integrated buprenorphine and HIV care may potentially increase access to treatment for opioid use disorder, scale-up in middle-income countries might require enhanced support for buprenorphine adherence to improve HIV viral suppression. The strength of our study as a multisite randomised trial was offset by low retention of patients on buprenorphine. FUNDING: National Institute on Drug Abuse (US National Institutes of Health).

Provider Perspectives on Integration of Substance Use Disorder and HIV Care in Vietnam: A Qualitative Study.

UNAIDS recommends integration of medications for substance use disorders (SUD) with HIV care to improve HIV outcomes. Yet, integration of HIV and SUD services remains limited in many countries. The objective of this study was to assess provider perceptions of care integration in Vietnam. Qualitative interviews were conducted with 43 providers (nurses, physicians, counselors, pharmacists, and clinic managers) in 8 HIV clinics in northern Vietnam, 2013-2015. Providers identified five themes informing HIV and SUD treatment integration: (1) treatment for alcohol use disorder is often neglected compared to other SUD treatment; (2) structural challenges must be addressed to increase integration feasibility; (3) workforce limitations; (4) societal and healthcare stigmatization of SUD; and (5) providers' conflicting views regarding integration challenges. The experience of providers in Vietnam may be useful to other countries attempting to integrate HIV and SUD services.