Integrated Hepatitis C-Opioid Use Disorder Care Through Facilitated Telemedicine: A Randomized Trial.

Importance: Facilitated telemedicine may promote hepatitis C virus elimination by mitigating geographic and temporal barriers. Objective: To compare sustained virologic responses for hepatitis C virus among persons with opioid use disorder treated through facilitated telemedicine integrated into opioid treatment programs compared with off-site hepatitis specialist referral. Design, Setting, and Participants: Prospective, cluster randomized clinical trial using a stepped wedge design. Twelve programs throughout New York State included hepatitis C-infected participants (n = 602) enrolled between March 1, 2017, and February 29, 2020. Data were analyzed from December 1, 2022, through September 1, 2023. Intervention: Hepatitis C treatment with direct-acting antivirals through comanagement with a hepatitis specialist either through facilitated telemedicine integrated into opioid treatment programs (n = 290) or standard-of-care off-site referral (n = 312). Main Outcomes and Measures: The primary outcome was hepatitis C virus cure. Twelve programs began with off-site referral, and every 9 months, 4 randomly selected sites transitioned to facilitated telemedicine during 3 steps without participant crossover. Participants completed 2-year follow-up for reinfection assessment. Inclusion criteria required 6-month enrollment in opioid treatment and insurance coverage of hepatitis C medications. Generalized linear mixed-effects models were used to test for the intervention effect, adjusted for time, clustering, and effect modification in individual-based intention-to-treat analysis. Results: Among 602 participants, 369 were male (61.3%); 296 (49.2%) were American Indian or Alaska Native, Asian, Black or African American, multiracial, or other (ie, no race category was selected, with race data collected according to the 5 standard National Institutes of Health categories); and 306 (50.8%) were White. The mean (SD) age of the enrolled participants in the telemedicine group was 47.1 (13.1) years; that of the referral group was 48.9 (12.8) years. In telemedicine, 268 of 290 participants (92.4%) initiated treatment compared with 126 of 312 participants (40.4%) in referral. Intention-to-treat cure percentages were 90.3% (262 of 290) in telemedicine and 39.4% (123 of 312) in referral, with an estimated logarithmic odds ratio of the study group effect of 2.9 (95% CI, 2.0-3.5; P < .001) with no effect modification. Observed cure percentages were 246 of 290 participants (84.8%) in telemedicine vs 106 of 312 participants (34.0%) in referral. Subgroup effects were not significant, including fibrosis stage, urban or rural participant residence location, or mental health (anxiety or depression) comorbid conditions. Illicit drug use decreased significantly (referral: 95% CI, 1.2-4.8; P = .001; telemedicine: 95% CI, 0.3-1.0; P < .001) among cured participants. Minimal reinfections (n = 13) occurred, with hepatitis C virus reinfection incidence of 2.5 per 100 person-years. Participants in both groups rated health care delivery satisfaction as high or very high. Conclusions and Relevance: Opioid treatment program-integrated facilitated telemedicine resulted in significantly higher hepatitis C virus cure rates compared with off-site referral, with high participant satisfaction. Illicit drug use declined significantly among cured participants with minimal reinfections. Trial Registration: ClinicalTrials.gov Identifier: NCT02933970.

Hepatitis C Virus Elimination Programs in Louisiana and Washington: Importance of Screening and Surveillance Systems.

The US government has established a national goal of hepatitis C virus (HCV) elimination by 2030. To date, most HCV elimination planning and activity have been at the state level. Fifteen states presently have publicly available HCV elimination plans. In 2019, Louisiana and Washington were the first states to initiate 5-year funded HCV elimination programs. These states differ on motivation for pursuing HCV elimination and ranking on several indicators. Simultaneously, however, they have emphasized several similar elimination components including HCV screening promotion through public awareness, screening expansion, surveillance enhancement (including electronic reporting and task force development), and harm reduction. The 13 other states with published elimination plans have proposed the majority of the elements identified by Louisiana and Washington, but several have notable gaps. Louisiana's and Washington's comprehensive plans, funding approaches, and programs provide a useful framework that can move states and the nation toward HCV elimination.

Engaging people who use drugs in clinical research: integrating facilitated telemedicine for HCV into substance use treatment.

BACKGROUND: People who use drugs (PWUD) have difficulty participating in clinical research. We evaluated approaches to engage PWUD in clinical research, using facilitated telemedicine for hepatitis C virus (HCV) care as an example. METHODS: We analyzed stakeholder interview transcripts and study-related data (i.e., progress reports, meeting minutes) from interrelated studies to understand engagement experiences at the patient, site, and organizational levels. Stakeholders include patient-participants, opioid treatment program (OTP) staff and administrators, and research team members involved in HCV management through facilitated telemedicine integrated into OTPs. RESULTS: Three themes emerged. Initially, the research team sought understanding of the unique culture and community of each OTP (Theme 1). The team built trusting relationships through education, communication, and feedback (Theme 2). Finally, the research team enhanced collaborative care and incorporated the patients' voice to improve health outcomes (Theme 3). Patient-participants and OTP staff endorsed the integrated HCV care approach. Engagement practices are summarized as the CREATE framework (C = culture, R = respect, E = educate, A = advantage, T = trust, E = endorse). CONCLUSIONS: PWUD engagement in clinical research is maximized by building trusting relationships with open communication channels. Understanding the community, demonstrating respect, and augmenting knowledge are foundational for engaging PWUD in clinical research. These practices are transferable to engagement of PWUD in clinical research broadly.

People who use drugs rarely join clinical research studies for many reasons including mistrust of researchers and lack of access to healthcare. Their joining, however, is critical to understand how to address issues affecting their communities. For ten years, we have studied telemedicine (doctor visit through a computer) to increase healthcare access for people who use drugs with hepatitis C virus (HCV). HCV infection occurs commonly in people who use drugs and is curable in almost everyone who takes treatment. We place HCV treatment through facilitated telemedicine into drug treatment programs. A case manager who is familiar to patients oversees the telemedicine encounter with the doctor. We developed themes from interviews with patients, staff, and other involved people as well as from study documents. As a first step, researchers need to understand the culture and community of the drug treatment program. Knowing the culture permits researchers to connect the goals of the study with those of the drug treatment program. It also helps researchers build trust with the program staff. We have seen that trust between the researchers and the staff in the drug treatment program permits individuals with different jobs to work together to deliver HCV treatment resulting in a cure. During the entire process, a patient advisory committee made sure the patients were partners in the research. Based upon these results, we have developed a new approach, CREATE (C = Culture, R = respect, E = educate, A = advantage, T = trust, E = endorse), that explains each step in the process.

Facilitated telemedicine for hepatitis C virus: Addressing challenges for improving health and life for people with opioid use disorder.

BACKGROUND: People who use drugs (PWUD) frequently delay or avoid obtaining medical care in traditional healthcare settings. Through a randomized controlled trial, we investigated facilitated telemedicine for hepatitis C virus (HCV) integrated into opioid treatment programmes. We sought to understand the experiences and meanings of facilitated telemedicine and an HCV cure among PWUD. METHODS: We utilized purposive sampling to interview 25 participants, 6-40 months after achieving an HCV cure. We interpreted and explicated common meanings of participants' experiences of an HCV cure obtained through facilitated telemedicine. RESULTS: Participants embraced facilitated telemedicine integrated into opioid treatment programmes as patient-centred care delivered in 'safe spaces' (Theme 1). Participants elucidated their experiences of substance use and HCV while committing to treatment for both entities. Facilitated telemedicine integrated into opioid treatment programmes enabled participants to avoid stigma encountered in conventional healthcare settings (Theme 2). Participants conveyed facing negative perceptions of HCV and substance use disorder. Improved self-awareness, acquired through HCV and substance use treatment, enabled participants to develop strategies to address shame and stigma (Theme 3). An HCV cure, considered by PWUD as a victory over a lethal infectious disease, promotes self-confidence, enabling participants to improve their health and lives (Theme 4). CONCLUSIONS: Integrating facilitated telemedicine into opioid treatment programmes addresses several healthcare barriers for PWUD. Similarly, obtaining an HCV cure increases their self-confidence, permissive to positive lifestyle changes and mitigating the negative consequences of substance use. PATIENT AND PUBLIC CONTRIBUTION: In this study of patient involvement, we interviewed patient-participants to understand the meaning of an HCV cure through facilitated telemedicine. Participants from a facilitated telemedicine pilot study provided essential input on the design and outcomes of a randomized controlled trial. Pilot study participants endorsed facilitated telemedicine in a testimonial video. They attended site initiation meetings to guide trial implementation. A Patient Advisory Committee (PAC) ensured that patient participants were active members of the research team. The PAC represented patients' voices through feedback on study procedures. A Sustainability Committee supported public involvement in the research process, including educational opportunities, feedback on implementation, and future sustainability considerations.

Seroprevalence and Genotype Diversity of Hepatitis C Virus in the Caribbean-A Review.

Hepatitis C (HCV) continues to present a global public health challenge, with no vaccine available for prevention. Despite the availability of direct-acting antivirals (DAAs) to cure HCV, it remains prevalent in many regions including the Caribbean. As efforts are made to eliminate HCV from the region, existing barriers, such as the high cost of DAAs and lack of an established database of HCV cases within the Caribbean, must be addressed. This review seeks to assess epidemiologic trends (seroprevalence and genotypic diversity) of HCV in the Caribbean and identify gaps in surveillance of the disease. The literature for the period 1 January 2005 to October 2022 was reviewed to gather country-specific data on HCV across the Caribbean. References were identified through indexed journals accessed through established databases using the following keywords: Caribbean, genotype distribution, and general epidemiologic characteristics. The usage pattern of HCV drugs was determined from information obtained from pharmacists across the Caribbean including Jamaica. The prevalence of HCV in the Caribbean was 1.5%; the region should therefore be considered an area of moderate HCV prevalence. The prevalence of HCV among intravenous drug users (21.9-58.8%), persons living with HIV/AIDS (0.8 to 58.5%), prisoners (32.8-64%), and men who have sex with men (MSM) (0.8-6.9%) was generally higher than in the general population (0.8-2.3%). Genotype 1 (83%) was most prevalent followed by genotypes 2 (7.2%) and 3 (2.1%), respectively. Less than 50% of countries in the Caribbean have reliable or well-curated surveillance data on HCV. Drugs currently being used for treatment of HCV infections across the Caribbean include Epclusa (sofosbuvir/velpatasvir) and Harvoni (ledipasvir/sofosbuvir). Some of these drugs are only available in the private sector and are sourced externally whenever needed. While trends point to a potentially higher prevalence of HCV, it will require well-designed random surveys to obtain better estimates of the infection seroprevalence, supported by strong public health laboratory systems. DAAs that are pan-genotypic should translate into treatments that are affordable, accessible, and available to improve cure rates and reduce the HCV burden in the population.

Role of Dual-Contingency Management in Family-Based Obesity Therapy and the Effects of Weight Loss on Liver Transient Elastography Parameters in Youth: A Pilot Study.

The pilot study evaluated contingency management (CM) for family-based obesity therapy (FBT). The secondary outcome assessed the association of the hepatic transient electrography (TE) parameters, including the controlled attenuation parameter (CAP) and liver stiffness (LSM), and changes in liver function blood tests and BMI changes in youth involved in intensive FBT. It included youth-parent dyads from an urban pediatric center randomized to weekly behavioral therapy (BT, n= 4) who received fixed financial compensation for attendance, or BT+CM (n= 5) who received an escalating monetary reward for weight loss. At week 30, all youth and parents had weight-loss trends without significant differences between groups. While the TE measures and blood tests were normal in the youth at baseline and week 30, the CAP changes correlated with BMI changes (R2= 0.86, P< 0.001) and LSM changes with alanine aminotransferase changes (R2= 0.79, P=0.005). In conclusion, BT+CM did not significantly add to the BMI improvement seen with BT alone in youth and their parents. However, in youth with obesity and normal liver blood tests, TE may be useful for monitoring changes in fatty liver disease.

Scaling and Sustaining Facilitated Telemedicine to Expand Treatment Access Among Underserved Populations: A Qualitative Study.

Background: Opioid treatment programs are an essential component of the management of opioid use disorder (OUD). They have also been proposed as "medical homes" to expand health care access for underserved populations. We utilized telemedicine as a method to increase access for hepatitis C virus (HCV) care among people with OUD. Methods: We interviewed 30 staff and 15 administrators regarding the integration of facilitated telemedicine for HCV into opioid treatment programs. Participants provided feedback and insight for sustaining and scaling facilitated telemedicine for people with OUD. We utilized hermeneutic phenomenology to develop themes related to telemedicine sustainability in opioid treatment programs. Results: Three themes emerged on sustaining the facilitated telemedicine model: (1) Telemedicine as a Technical Innovation in Opioid Treatment Programs, (2) Technology Transcending Space and Time, and (3) COVID-19 Disrupting the Status Quo. Participants identified skilled staff, ongoing training, technology infrastructure and support, and an effective marketing campaign as key to maintaining the facilitated telemedicine model. Participants highlighted the study-supported case manager's role in managing the technology to transcend temporal and geographical challenges for HCV treatment access for people with OUD. COVID-19 fueled changes in health care delivery, including facilitated telemedicine, to expand the opioid treatment program's mission as a medical home for people with OUD. Conclusions: Opioid treatment programs can sustain facilitated telemedicine to increase health care access for underserved populations. COVID-19-induced disruptions promoted innovation and policy changes recognizing telemedicine's role in expanding health care access to underserved populations. ClinicalTrials.gov Identifier: NCT02933970.

Social determinants of health derived from people with opioid use disorder: Improving data collection, integration and use with cross-domain collaboration and reproducible, data-centric, notebook-style workflows.

Deriving social determinants of health from underserved populations is an important step in the process of improving the well-being of these populations and in driving policy improvements to facilitate positive change in health outcomes. Collection, integration, and effective use of clinical data for this purpose presents a variety of specific challenges. We assert that combining expertise from three distinct domains, specifically, medical, statistical, and computer and data science can be applied along with provenance-aware, self-documenting workflow tools. This combination permits data integration and facilitates the creation of reproducible workflows and usable (reproducible) results from the sensitive and disparate sources of clinical data that exist for underserved populations.

High Satisfaction with Patient-Centered Telemedicine for Hepatitis C Virus Delivered to Substance Users: A Mixed-Methods Study.

Background: While telemedicine may increase health care access for vulnerable populations, data are limited on whether people with opioid use disorder (PWOUD) are satisfied with telemedicine. We assessed PWOUD satisfaction with telemedicine and identified factors that increase telemedicine satisfaction. Methods: We conducted a mixed-methods study among hepatitis C virus (HCV)-infected persons enrolled at 12 opioid treatment programs (OTPs) throughout New York State. Participants successfully completed HCV treatment either through telemedicine integrated into OTPs (N = 238) or through offsite referral (N = 106). We evaluated Patient Satisfaction Questionnaire (PSQ) response scores at the initial and final health care encounters and subsequently interviewed telemedicine study participants (N = 25) to assess their experiences with telemedicine. Results: All participants (N = 344) successfully completed HCV treatment. We observed no differences in PSQ scores between telemedicine and in-person encounters (98.3% and 98.7% of telemedicine participants provided PSQ scores of satisfied or highly satisfied at each timepoint, respectively). Study participants indicated that attributes associated with high telemedicine encounter satisfaction included: (1) communicating study information, (2) gaining trust, and (3) delivering patient-centered care. Participants weighted "General Satisfaction" and "Time Spent with Doctor" higher than "Accessibility and Convenience," and female participants were significantly more satisfied than males. Satisfaction with health care delivery among all participants increased significantly comparing timepoints. Conclusions: Participants were highly satisfied with HCV telemedicine encounters equivalent to in-person encounters. Communication augments trust facilitating delivery of patient-centered care through telemedicine. Participants value empathy and trust with providers over accessibility and convenience. In summary, PWOUD are highly satisfied with the facilitated telemedicine model and value empathetic and trusting providers. ClinicalTrials.gov Identifier: NCT02933970.

Innovations in education: A prospective study of storytelling narratives to enhance hepatitis C virus knowledge among substance users.

BACKGROUND: Even though substance users have the highest hepatitis C virus (HCV) burden, many lack knowledge about the infection. Lack of knowledge is an important obstacle to pursuing HCV care. Although printed materials are conventionally utilized to disseminate HCV-related knowledge, narrative story-telling videos may be an alternative. Data are extremely limited, however, in the ability of storytelling videos to increase HCV knowledge among substance users. In this study, we hypothesized that a story-telling narrative video would increase substance user's immediate and 1-month HCV-related knowledge compared to a printed format. AIM: To assess immediate and 1-month HCV-related knowledge retention among substance users comparing education delivered via a storytelling narrative video compared to a printed format. METHODS: We conducted a prospective matched, case-control study among substance users actively prescribed buprenorphine enrolled from two sites. The intervention site received the video and the control site, the brochure. Participants (n = 176) were matched on age, gender, and race. We obtained extensive patient and stakeholder input on the video's design, validated the video's content, and developed a recruitment plan to guide participant enrollment. Knowledge was assessed by administration of a 25-item instrument immediately before, immediately after, or one month after the intervention. Data were analyzed using nonparametric and generalized linear mixed-effects models. RESULTS: We recruited a total of 176 substance users, 90 and 86 individuals, from each site, respectively. One-month follow up occurred in 92% and 94% of enrollees in the control and intervention groups, respectively. In comparison with the pre-intervention scores, immediate knowledge recall increased significantly for both the intervention (P < 0.0001) and control (P < 0.0001) groups. Multivariate modeling revealed a significant improvement in HCV-related knowledge and retention (P = 0.033) among participants who viewed the storytelling video. CONCLUSION: Storytelling narratives emphasizing HCV education appear to be an effective method to increase HCV-related knowledge among substance users. They should become an educational cornerstone to promote HCV management among this population.

Patient-centered HCV care via telemedicine for individuals on medication for opioid use disorder: Telemedicine for Evaluation, Adherence and Medication for Hepatitis C (TEAM-C).

BACKGROUND: Telemedicine has the potential to increase healthcare access especially for vulnerable populations. Telemedicine for Evaluation, Adherence, and Medication for Hepatitis C (TEAM-C) is comparing telemedicine access to specialty medical care to usual care for management of hepatitis C virus (HCV) infection among persons with opioid use disorder (PWOUD). PWOUD have the highest hepatitis C virus (HCV) prevalence and incidence, yet they infrequently receive HCV care. The study objectives are to compare access to specialty care via telemedicine to offsite specialty referral (usual care) on 1) treatment initiation, completion, and sustained virological response, 2) patient satisfaction with health care delivery, and 3) HCV reinfection after successful HCV cure. METHODS: TEAM-C is a multi-site, non-blinded, randomized pragmatic clinical trial conducted at 12 opioid treatment programs (OTP) throughout New York State that utilizes the stepped-wedge design. The unit of randomization is the OTP with a total sample size of 624 participants. HCV-infected PWOUD were treated via telemedicine or referral. Telemedicine encounters are conducted onsite in the OTP with co-administration of direct acting antivirals for HCV with medications for opioid use disorder. The primary outcome is undetectable HCV RNA obtained 12 weeks post-treatment cessation. We also follow participants for two years to assess for reinfection. CONCLUSIONS: The study utilizes a rigorous study design to evaluate the effectiveness and implementation of virtual treatment for HCV integrated into behavioral treatment. We demonstrate the feasibility, engagement principles and lessons learned from the initial prospective randomized trial of telemedicine targeted to a vulnerable population.

Facilitating engagement of persons with opioid use disorder in treatment for hepatitis C virus infection via telemedicine: Stories of onsite case managers.

Although hepatitis C virus (HCV) infection has high prevalence and incidence in persons with opioid use disorder (PWOUD), their engagement in HCV care has been limited due to a variety of factors. In an ongoing multisite study at 12 opioid treatment programs (OTPs) throughout New York State (NYS), we have been evaluating telemedicine accompanied by onsite administration of direct acting antiviral (DAA) medications compared with usual care including offsite referral to a liver specialist for HCV management. Each site has a case manager (CM) who is responsible for all study-related activities including participant recruitment, facilitating telemedicine interactions, retention in care, and data collection. Our overall objective is to analyze CM experiences of clients' stories and events to understand how the telemedicine model facilitates HCV treatment. Hermeneutic phenomenology was used to interpret and to explicate common meanings and shared practices of the phenomena of case management, and a focus group with CMs was conducted to reinforce and expand on key themes identified from the CMs' stories. We identified three themes: (1) building trust, (2) identification of multiple competing priorities, and (3) development of personalized care approaches. Our results illustrate that trust is a fundamental pillar on which the telemedicine system can be based. Participants' experiences at the OTP can reinforce trust. Understanding the specific competing priorities and routinizing dedicated personalized approaches to overcome them are key to increasing participation in HCV care among PWOUD.

A framework for patient-centered telemedicine: Application and lessons learned from vulnerable populations.

Virtual technologies can facilitate clinical monitoring, clinician-patient interactions, and enhance patient-centered approaches to healthcare delivery. Telemedicine, two-way communication between a healthcare provider and a patient not in the same physical location, emphasizes patient preference and convenience by substituting the transportation of patients with information transfer. We present a framework for implementation of a comprehensive, dynamic, patient-centered telemedicine network deployed in 12 opioid treatment programs (OTP) located throughout New York State (NYS). The program aims to effectively manage hepatitis C virus (HCV) infection via telemedicine with co-administration of HCV and substance use medications. We have found that the Sociotechnical System model with emphasis on patient-centered factors provides a framework for telemedicine deployment and implementation to a vulnerable population. The issue of interoperability between the telemedicine platform and the electronic health record (EHR) system as well as clinical information retrieval for medical decision-making are challenges with implementation of a comprehensive, dynamic telemedicine system. Targeting telemedicine to a vulnerable population requires additional consideration of trust in the security and confidentiality of the telemedicine system. Our contribution is the valuable lessons learned from implementing a comprehensive, dynamic, patient-centered telemedicine system among an OTP network throughout NYS as applied to a vulnerable population that can be generalized to other difficult-to-reach populations.

Age- and risk factor-based serologic screening for Hepatitis C virus among an Urban, high-risk population.

Hepatitis C virus (HCV) screening among individuals born between 1945 and 1965 (ie birth cohort) may augment risk factor-based screening. We assessed HCV seropositivity among injection drug users (IDUs) and birth cohort members from New York City. We assessed HCV risk factors and seropositivity in 7722 participants from community health, HIV prevention, syringe exchange and drug treatment programmes. A total of 26.6% were HCV seropositive, 55.8% were born between 1945 and 1965, and 82.2% had ever injected drugs. Among all participants, HCV seropositivity was higher among IDUs compared to non-IDUs (60.5% versus 7.7%, odds ratio (OR) = 18.5, 95% confidence interval (CI) [16.2, 21.1], P < .0001) and among birth cohort members compared to non-birth cohort members (31.3% versus 22.3%, OR = 1.6, 95%CI [1.4, 1.8], P < .0001). Within the birth cohort, HCV seroprevalence among IDUs was 68.5% versus 11.8%, OR = 16.2, 95%CI [13.7, 19.3]. After adjustment, HCV seroprevalence was higher in IDUs, previously incarcerated, whites (<42 years) and 'other races' (versus blacks), HIV-infected, those who snorted heroin, those with liver disease history, and those who had sex with an HCV-seropositive partner. HCV seroprevalence among IDU, birth cohort members, was considerably higher than among the general population. In this high-risk, urban population, the association between IDU and HCV seropositivity was approximately ten times that between birth cohort membership and HCV seropositivity.

Assessing routes of hepatitis C transmission in HIV-infected men who have sex with men using single genome sequencing.

The epidemic of hepatitis C virus (HCV) infection among HIV-infected men who have sex with men (MSM) is in its second decade, but the routes of transmission remain poorly understood. We hypothesized that by pairing single genome sequencing (SGS), to enumerate infecting HCV genomes (viruses), with detailed sexual and drug histories, we could gain insight into the routes of transmission among MSM. We used SGS to analyze blood specimens from eight HIV-infected MSM who had 10 episodes of acute (seronegative) or early HCV infections. Seven of eight men reported condomless receptive anal intercourse (CRAI), six with rectal exposure to semen, and all eight denied rectal trauma or bleeding. Of the 10 HCV infections, eight resulted from transmission of a single virus; one infection resulted from transmission of either one or a few (three or four) closely-related viruses; and one infection resulted from transmission of >10 distinct viruses. The participant infected by >10 viruses reported sharing injection equipment for methamphetamine during sex. Two other participants also injected methamphetamine during sex but they did not share injection equipment and were infected by a single virus. Conclusions: Most HCV infections of HIV-infected MSM without a history of either rectal trauma or bleeding or shared injection equipment were caused by a single virus. Intra-rectal exposure to semen during CRAI is therefore likely sufficient for HCV transmission among MSM. Conversely, rectal trauma or bleeding or shared injection equipment are not necessary for HCV transmission among MSM. These results help clarify routes of HCV transmission among MSM and can therefore help guide the design of much-needed behavioral and other interventions to prevent HCV transmission among MSM.

Toward precision prescribing for methadone: Determinants of methadone deposition.

BACKGROUND: Despite the World Health Organization listing methadone as an essential medication, effective dose selection is challenging, especially in racial and ethnic minority populations. Subtherapeutic doses can result in withdrawal symptoms while supratherapeutic doses can result in overdose and death. Although CYP3A4 was conventionally considered the principal methadone metabolizing enzyme, more recent data have identified CYP2B6 as the principal enzyme. CYP2B6 has ethnically-associated polymorphisms that affect the metabolic rate. Our objective was to investigate the effects of genetic and nongenetic factors on methadone metabolism. METHODS: We measured trough plasma methadone levels in 100 participants with opioid use disorder. We assessed methadone metabolism by calculating the metabolite ratio (major metabolite: 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine [EDDP] divided by methadone concentration). We assessed hepatic fibrosis and steatosis by transient elastography and CYP2B6 alleles, principally responsible for methadone metabolism. Mixed effects models modeled the data in 97 participants. RESULTS: Participants were largely male (58%), minority (61% African American) and non-Hispanic (68%). Forty percent were HCV mono-infected, 40% were uninfected, and 20% were HCV/HIV co-infected. Female sex had significant effects on (R)- and (S)-methadone metabolism (p = 0.016 and p = 0.044, respectively). CYP2B6 loss of function (LOF) alleles significantly affected (S)-methadone metabolism (p = 0.012). Body mass index (BMI) significantly affected (R)-methadone metabolism (p = 0.034). Methadone metabolism appeared to be lower in males, in individuals with LOF alleles, and elevated BMI. CONCLUSIONS: Genetic analysis, especially in minority populations, is essential to delivering individualized treatments. Although the principal methadone metabolizing enzyme remains controversial, our results suggest that sex, CYP2B6 genotype, and BMI should be incorporated into multivariate models to create methadone dosing algorithms. Methadone dosing algorithms should facilitate medication delivery, improve patient satisfaction, and diminish overdose potential.

Intrahepatic Viral Kinetics During Direct-Acting Antivirals for Hepatitis C in Human Immunodeficiency Virus Coinfection: The AIDS Clinical Trials Group A5335S Substudy.

BACKGROUND: Direct-acting antivirals (DAAs) targeting hepatitis C virus (HCV) have revolutionized outcomes in human immunodeficiency virus (HIV) coinfection. METHODS: We examined early events in liver and plasma through A5335S, a substudy of trial A5329 (paritaprevir/ritonavir, ombitasvir, dasabuvir, with ribavirin) that enrolled chronic genotype 1a HCV-infected persons coinfected with suppressed HIV: 5 of 6 treatment-naive enrollees completed A5335S. RESULTS: Mean baseline plasma HCV ribonucleic acid (RNA) = 6.7 log10 IU/mL and changed by -4.1 log10 IU/mL by Day 7. In liver, laser capture microdissection was used to quantify HCV. At liver biopsy 1, mean %HCV-infected cells = 25.2% (95% confidence interval [CI], 7.4%-42.9%), correlating with plasma HCV RNA (Spearman rank correlation r = 0.9); at biopsy 2 (Day 7 in 4 of 5 participants), mean %HCV-infected cells = 1.0% (95% CI, 0.2%-1.7%) (P < .05 for change), and DAAs were detectable in liver. Plasma C-X-C motif chemokine 10 (CXCL10) concentrations changed by mean = -160 pg/mL per day at 24 hours, but no further after Day 4. CONCLUSIONS: We conclude that HCV infection is rapidly cleared from liver with DAA leaving <2% HCV-infected hepatocytes at Day 7. We extrapolate that HCV eradication could occur in these participants by 63 days, although immune activation might persist. Single-cell longitudinal estimates of HCV clearance from liver have never been reported previously and could be applied to estimating the minimum treatment duration required for HCV infection.

Fine-Needle Aspiration for the Evaluation of Hepatic Pharmacokinetics of Vaniprevir: A Randomized Trial in Patients With Hepatitis C Virus Infection.

Fine-needle aspiration (FNA) for serial hepatic sampling may be an efficient and less invasive alternative to core needle biopsy (CNB), the current standard for liver tissue sampling. In this randomized, open-label trial in 31 participants with hepatitis C virus genotype 1 infection (NCT01678131/Merck protocol PN048), we evaluated the feasibility of using FNA to obtain human liver tissue samples appropriate for measuring hepatic pharmacokinetics (PK), using vaniprevir as a tool compound. The primary end point was successful retrieval of liver tissue specimens with measurable vaniprevir concentrations at two of three specified FNA time points. Twenty-nine patients met the primary end point and, therefore, were included in the PK analyses. Hepatic vaniprevir concentrations obtained with FNA were consistent with known vaniprevir PK properties. The shape of liver FNA and CNB concentration-time profiles were comparable. In conclusion, FNA may be effective for serial tissue sampling to assess hepatic drug exposure in patients with liver disease.

Influence of social determinants of health and substance use characteristics on persons who use drugs pursuit of care for hepatitis C virus infection.

BACKGROUND: Social determinants of health (SDOH), i.e., social, behavioral and environmental factors, are increasingly recognized for their important influence on health outcomes. Data are limited on the influence of SDOH, substance use characteristics, and their interactions on pursuit of hepatitis C virus (HCV) care among individuals with opioid use disorder (OUD). Linkage to HCV care remains low in this population despite high HCV prevalence and incidence. AIMS: To investigate the influence of SDOH, substance use factors, and their interactions on HCV treatment uptake among OUD patients in a methadone treatment program. METHODS: Information on patient demographics, SDOH, substance use characteristics, and co-morbid medical conditions were obtained from the paper and electronic medical records of OUD patients on methadone. We applied multiple correspondence analysis, k-means algorithm, and logistic regression with least absolute shrinkage and selection operator penalty to identify variables and clusters associated with pursuit of HCV care. RESULTS: Data from 161 patients (57% male, 60% Caucasian, mean age 45 years) were evaluated. Being employed, the absence of support systems, and a history of foster care were the strongest positive predictors of treatment pursuit. The use of crack/cocaine as the initial illicit substance, criminal activity without incarceration, and the absence of a family history of chemical dependency were the strongest negative predictors. We identified clusters among persons with OUD based upon their likelihood to pursue HCV management. CONCLUSION: Utilizing data from the medical record, we were able to identify factors positively and negatively associated with linkage-to-care for HCV. We were also able to divide patients into clusters of factors associated with linkage-to-care for HCV. These results could be used to identify individuals with OUD based upon their readiness for HCV care.