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To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.jsat.2006.03.006 Byline: Lawrence S. Brown (a)(b), Steven Kritz (a), Melissa Chu (a), Charles Madray (a) Keywords: HIV; Hepatitis C; Nelfinavir; Methadone maintenance Abstract: The safety, efficacy, and tolerability of nelfinavir (NFV)-containing antiretroviral therapy were evaluated in patients coinfected with HIV and hepatitis C undergoing methadone maintenance at an urban outpatient opioid treatment program serving a minority adult population. Eligibility covered methadone-maintained patients coinfected with HIV and hepatitis C who had received or were currently receiving NFV. The yield was 51 case patients. Parameters examined looked into safety, efficacy, and tolerability. Nelfinavir was discontinued in 2 patients for liver function abnormalities but resumed in 1 patient. One patient developed laboratory abnormalities during NFV therapy that were not present before NFV therapy; in 12 case patients, pre-NFV therapy liver function abnormalities resolved completely during NFV therapy. There was a statistically significant increase in CD4 count during NFV therapy. Viral load decreased or was unchanged in 10 case patients and increased in 8, of whom 5 had a CD4 count increase during NFV therapy. Three patients had diarrhea and 4 patients had constipation. Nelfinavir was not discontinued -- neither was dose adjusted -- in any of these patients. Patients who had received NFV [greater than or equal to]36 months had a smaller increase in mean methadone dose as compared with patients who had received NFV Author Affiliation: (a) Division of Medical Services, Evaluation and Research, Addiction Research and Treatment Corporation, Brooklyn, NY 11201, USA (b) Department of Public Health, Weill Medical College, Cornell University, New York, NY 10021, USA Article History: Received 17 January 2006; Accepted 13 March 2006

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. [ABSTRACT FROM AUTHOR]

Background Despite high hepatitis C virus (HCV) prevalence, opioid use disorder (OUD) patients on methadone rarely engage in HCV treatment. We investigated the effectiveness of HCV management via telemedicine in an opioid substitution therapy (OST) program. Methods OUD patients on methadone underwent biweekly telemedicine sessions between a hepatologist and physician assistant during the entire HCV treatment course. All pretreatment labs (HCV RNA, genotype, and noninvasive fibrosis assessments) were obtained onsite and direct-acting antivirals were coadministered with methadone using modified directly observed therapy. We used multiple correspondence analysis, least absolute shrinkage and selection operator, and logistic regression to identify variables associated with pursuit of HCV care. Results Sixty-two HCV RNA–positive patients (24% human immunodeficiency virus [HIV] infected, 61% male, 61% African American, 25.8% Hispanic) were evaluated. All patients were stabilized on methadone and all except 4 were HCV genotype 1 infected. Advanced fibrosis/cirrhosis was present in 34.5% of patients. Of the 45 treated patients, 42 (93.3%) achieved viral eradication. Of 17 evaluated patients who were not treated, 5 were discontinued from the drug treatment program or did not follow up after the evaluation, 2 had HIV adherence issues, and 10 had insurance authorization issues. Marriage and a mental health diagnosis other than depression were the strongest positive predictors of treatment pursuit, whereas being divorced, separated, or widowed was the strongest negative predictor. Conclusions HCV management via telemedicine integrated into an OST program is a feasible model with excellent virologic effectiveness. Psychosocial and demographic variables can assist in identification of subgroups with a propensity or aversion to pursue HCV treatment. [ABSTRACT FROM AUTHOR]

Introduction: Addiction treatment clients are more likely to die of tobacco-related diseases than of alcohol or illicit drug-related causes. We aimed to assess smoking behavior, and smoking-related attitudes and services, in New York addiction treatment programs before a statewide smoking ban in treatment facilities was implemented (2008), 1 year (2009) and 5 years after implementation (2013).Methods: We conducted surveys at each time point with clients (N = 329, 341, and 353, respectively) and staff (N = 202, 203, and 166, respectively) from five residential and two methadone maintenance programs in New York State. At each data collection wave, questionnaires measured smoking behavior as well as smoking-related knowledge, attitudes, and experiences with tobacco cessation services as part of addiction treatment.Results: Staff smoking prevalence decreased from 35.2% in 2008 to 21.8% in 2013 (P = .005) while client smoking prevalence over the same period was unchanged (68.1% vs. 66.0%, P = .564). Among clients who smoked, mean cigarettes per day decreased from 13.7 (SD = 8.38) to 10.2 (SD = 4.44; P < .001). There were significant time-by-treatment-type interactions for client tobacco-related attitudes and cessation services received; and for staff self-efficacy and cessation services provided. In residential programs, scores for most items decreased (became less positive) in 2009 followed by a partial rebound in 2013. Methadone program scores tended to rise (become more positive) throughout the study period.Conclusions: Staff and clients may respond differentially to tobacco-free policies depending on type of treatment program, and this finding may help to inform the implementation of tobacco-free policies in other statewide addiction treatment systems. [ABSTRACT FROM AUTHOR]

Objectives. We assessed changes in smoking prevalence and other measures associated with the July 2008 New York Office of Alcholism and Substance Abuse Services tobacco policy, which required that all publicly funded addiction treatment programs implement smoke-free grounds, have "no evidence" of smoking among staff, and make tobacco dependence treatment available for all clients. Methods. In a random sample of 10 programs, staff and clients were surveyed before the policy and 1 year later. Measures included tobacco-related knowledge, attitudes, and practices used by counselors and received by clients. Results. Client smoking decreased from 69.4% to 62.8% (P = .044). However, response to the policy differed by program type. Outpatient programs showed no significant changes on any of the staff and client survey measures. In methadone programs, staff use of tobacco-related practices increased (P < .01), client attitudes toward tobacco treatment grew more positive (P < .05), and clients received more tobacco-related services (P < .05). Residential clients were more likely to report having quit smoking after policy implementation (odds ratio = 4.7; 95% confidence interval = 1.53, 14.19), but they reported less favorable attitudes toward tobacco treatment (P < .001) and received fewer tobacco-related services from their program (P < .001) or their counselor (P < .001). Conclusions. If supported by additional research, the New York policy may offer a model that addiction treatment systems can use to address smoking in a population where it has been prevalent and intractable. Additional intervention or policy supports may be needed in residential programs, which face greater challenges to implementing tobacco-free grounds. [ABSTRACT FROM AUTHOR]