Milan Khara

Directly observed therapy for the treatment of hepatitis C virus infection in current and former injection drug users.

Background and Aim:  There are few studies investigating the treatment of hepatitis C virus (HCV) infection in current and former drug users. With this in mind, we sought to evaluate the antiviral efficacy of interferon alpha‐2b (IFN α‐2b) or pegylated‐interferon alpha‐2b (PEG‐IFN α‐2b) and ribavirin (RBV) in injection drug users (IDU) enrolled in a directly observed therapy (DOT) program, as measured by sustained virologic response (SVR).

Smoking cessation interventions among individuals in methadone maintenance: A brief review

BACKGROUND Individuals in methadone maintenance treatment are motivated to quit smoking and are interested in smoking cessation treatment. However, few studies have assessed the efficacy of smoking cessation treatment for individuals undergoing methadone maintenance. The purpose of this article is to review interventions for tobacco use cessation among individuals in methadone maintenance with a particular emphasis on the components of such interventions and their effect on smoking cessation/reduction and drug use. METHODS A comprehensive search of six databases in June 2008 retrieved 584 research studies, which addressed smoking cessation interventions among individuals in substance use treatment. Of the retrieved articles, eight studies addressed smoking cessation among individuals undergoing methadone maintenance treatment. These studies were examined for effect of intervention on smoking cessation/reduction, gender differences in treatment outcomes, and the effect of the smoking cessation intervention on substance use behaviors. RESULTS Few studies demonstrated successful smoking abstinence among individuals in methadone maintenance treatment. Most interventions were associated with significant smoking reduction from baseline. Few studies assessed differences between men and women in smoking cessation treatment outcome. Smoking cessation treatment was not associated with increased substance use. CONCLUSIONS To date, interventions among individuals in methadone treatment have been largely unsuccessful in achieving sustained smoking abstinence. However, smoking cessation treatment does not worsen substance use. Future studies are necessary to determine intervention designs and components that can enhance smoking cessation among individuals in methadone maintenance.

Methadone dosing strategies in HIV-infected injection drug users enrolled in a directly observed therapy program.

Objectives:We have measured methadone dose adjustments and treatment responses after nevirapine (NVP)-, efavirenz (EFV)-, ritonavir-boosted lopinavir (LPV/r), or atazanavir (ATV; with or without ritonavir)-based highly active antiretroviral therapy (HAART) was initiated in injection drug users (IDUs). Methods:We identified 120 IDUs receiving HAART and methadone within a directly observed therapy (DOT) program. Follow-up was according to clinical standards, with changes in methadone dose being made as required to achieve clinical stabilization within the first 3 months of HAART. Results:The observed median methadone dose changes from baseline were 20 mg/d (P < 0.001) in patients on NVP, with 32 (86%) of 37 patients requiring daily dose increases, and 7.5 mg/d (P = 0.004) in patients on EFV, with 11 (61%) of 18 patients requiring daily dose increases. Conversely, median changes were 0 mg/d for patients on LPV/r (P = 0.56) or ATV (P = 0.95). Virologic suppression (HIV RNA <400 copies/mL) was achieved in 26 (70%) of 37, 12 (67%) of 18, 25 (76%) of 33, and 24 (75%) of 32 patients receiving NVP-, EFV-, LPV/r-, and ATV-based regimens, respectively (P = 0.89). Conclusions:Although methadone-based DOT can be a successful tool for the coadministration of HAART, careful monitoring is required to ensure that methadone withdrawal does not adversely affect the goals of treatment, particularly when nonnucleoside reverse transcriptase inhibitors are used.

Primary drug resistance in antiretroviral-naïve injection drug users

OBJECTIVES We evaluated the prevalence of primary HIV drug resistance in a population of 128 injection drug users (48 female) prior to initiating antiretroviral therapy. METHODS Genotypic and phenotypic profiles were obtained retrospectively for the period June 1996 to February 2007. Genotypic drug resistance was defined as the presence of a major mutation (IAS-USA table, 2007 revision), adding revertants at reverse transcriptase (RT) codon 215. Phenotypic drug resistance was defined as the fold change associated with >or=80% loss of the wild type virologic response due to viral resistance based on virtual phenotype analysis. RESULTS Genotypic drug resistance was uncommon, and was only identified in six (4.7%) cases, all in the RT gene (L100I, K103N, Y181C, M184V, Y188L, and T215D). There were no cases of multi-class or protease inhibitor (PI) resistance. However, polymorphisms in the protease and RT genes were extremely common. Phenotypic drug resistance was also identified in six (4.7%) patients, four in the RT gene (in patients with mutations K103N, Y181C, M184V and Y188L) and two the protease gene (in two patients with minor PI mutations). In addition, 25 (19.5%) of the patients had reduced susceptibility to PIs, defined as resistance>20% but <80% of the wild type virologic response, with no primary PI mutations detected in all these patients. CONCLUSION The prevalence of primary HIV drug resistance was low in this population of injection drug users.

Smoking Cessation Outcomes and Predictors Among Individuals With Co-occurring Substance Use and/or Psychiatric Disorders

Objective: Individuals with substance use and psychiatric disorders have a high prevalence of tobacco use disorders and are disproportionately affected by tobacco-related morbidity and mortality. However, it is unclear how having co-occurring disorders affects tobacco cessation. Our aim was to examine smoking cessation outcomes and relevant predictors of smoking cessation among smokers with substance use and/or psychiatric disorders. Methods: Data from medical records of 674 participants in a tobacco treatment program within mental health and addictions services in Vancouver, Canada, were analyzed. The 26-week treatment program included an 8-week structured behavioral counseling group, an 18-week support group, and 26 weeks of no-cost pharmacotherapy. Information on demographics, tobacco use and history, type of pharmacotherapy received, nicotine dependence, importance of and confidence in quitting smoking, expired carbon monoxide level, substance use and psychiatric disorder history, and total program visits were gathered. Results: Approximately 67% (n = 449) of participants had co-occurring substance use and psychiatric disorders, while 20% (n = 136) had substance use disorder only, 10% (n = 67) had psychiatric disorder only, and 3% (n = 22) had tobacco dependence only. Rates of tobacco cessation (i.e., 7-day point prevalence of abstinence verified by expired carbon monoxide of ≤8 ppm) by group in the 522 people who completed treatment were as follows: 38.2% for those with co-occurring disorders, 47.1% for those with tobacco dependence only, 47.1% for those with substance use disorder only, and 41.8% for those with psychiatric disorder only. Length of treatment was a significant predictor of smoking cessation for those with co-occurring disorders and substance use disorder only. In the final stratified multivariate analysis, for individuals with co-occurring disorders, having an opiate use disorder (as compared to an alcohol use disorder) and higher nicotine dependence scores at baseline were predictive of poor cessation outcomes, while greater length of treatment was predictive of successful smoking cessation. Conclusions: Tobacco cessation treatment for individuals with co-occurring substance use and psychiatric disorders is likely to be as effective as for smokers with either disorder alone. Treatment duration predicts success among these smokers so strategies to enhance engagement and retention are needed.

Sex differences in smoking cessation outcomes of a tailored program for individuals with substance use disorders and mental illness

Tobacco use is highly prevalent among individuals with a history of substance use disorders (SUD) and/or mental illness (MI). Despite evidence of differences in smoking cessation (SC) outcomes between women and men, few studies have formally evaluated sex differences among SUD and/or MI populations. For 258 participants (62% male, mean age=48.6 years) with an SUD and/or MI enrolled in a tobacco dependence clinic (TDC) program, we examined SC outcomes and compared mens and womens predictors of end-of-treatment abstinence. Individuals with an MI, social support for quitting, and a greater number of visits to the TDC program were more likely to be female; whereas males were characterized by having an SUD, older age, smoking a greater number of cigarettes per day, and having higher confidence in quitting smoking. In the intent-to-treat analysis, end-of-treatment smoking cessation was 32.2% (females=35.4% vs males=30.2, χ(2)=0.74, df=1, p=.390). Among females, baseline expired carbon monoxide (CO) level and a greater number of visits to the program were significantly predictive of SC; among males, having a history of alcohol, heroin and other opioids, and marijuana use were predictive of unsuccessful SC, whereas baseline expired CO level and a greater number of visits to the program were predictive of SC. These factors may be important in the design of enhanced tailored treatments and development of future SC programs for individuals with SUD and MI.

Correlates of Secondhand Tobacco Smoke Exposure Among Individuals with a History of Substance Use and/or Psychiatric Disorders Participating in a Tobacco Treatment Program in Vancouver, Canada

Individuals with substance use (SUD) and/or psychiatric disorders (PD) are disproportionately affected by tobacco use; yet, little is known about secondhand tobacco smoke (SHS) exposure in these populations. An analysis of existing data examined SHS exposure among 497 smokers in community clinics in Vancouver, Canada. Seventy-percent of the participants reported SHS exposure. In sex-stratified multivariate logistic regression analyses correlates of SHS exposure among women were not having a history of using evidence-based smoking cessation treatment and using a single substance (as compared to a polysubstance use history); whereas among men, a history of a respiratory illness and higher nicotine dependence were associated with SHS exposure. Despite limitations about the measures of SHS exposure used in the study, these findings suggest a need to further determine the risks associated with SHS exposure and tobacco use among individuals with SUD and/or PD within mental health and addictions treatment settings.

Sex differences in nicotine dependence among addictions clients accessing a smoking cessation programme in Vancouver, British Columbia, Canada

Most individuals in drug treatment programmes use tobacco and are dependent on nicotine. For 323 participants (65% men, mean age = 49.3 years) with a history of substance use disorder (SUD) and/or psychiatric disorders (PD) enrolled in a tobacco dependence clinic programme, we compared baseline characteristics among women and men and examined factors associated with nicotine dependence (ND). Individuals with mood, anxiety and psychotic disorders were more likely to be female, whereas men were more likely to be characterized by alcohol, cocaine and marijuana use, older age, older age at smoking initiation and higher confidence in quitting smoking scores. In stratified multivariate analyses, among women, history of an anxiety disorder and a greater number of cigarettes smoked per day were associated with higher ND scores; among men, a greater number of cigarettes smoked per day and higher confidence in quitting scores were associated with higher ND scores. Given the differences in smoking, SUD and PD histories between women and men accessing addiction treatment, and differential associations with ND, it is important to further explore factors that may enhance tailored treatments and inform future studies examining biological and psychosocial factors for tobacco use in SUD and PD treatment populations.

Clinical Implications of Mutations at Reverse Transcriptase Codon 135 on Response to NNRTI-Based Therapy

To evaluate the impact of mutations at reverse transcriptase codon 135 on treatment outcomes in patients receiving NNRTI-based antiretroviral therapy, a total of 68 patients (30 with and 38 without baseline mutations at codon 135) were evaluated. Median increases in CD4 counts were 135 and 90 cells/mm3 (p=0.32), virologic suppression (HIV RNA < 400 copies/mL) was achieved in 16 (53%) and 16 (42%) patients (p=0.50), while NNRTI resistance was detected in 10/14 (71%) and 16/22 (73%) in patients with and without mutations at codon 135, respectively. Patients who experienced a virologic breakthrough and had a baseline mutation at codon 135 were more likely to evolve a single NNRTI resistance mutation (8/14 vs 4/22, p=0.029) but less likely to evolve multiple NNRTI resistance mutations (2/14 vs 12/22, p = 0.033). Mutations at codon 135 do not affect response rates, but affect the pattern of development of NNRTI resistance mutations. This has important implications for the subsequent use of newer NNRTIs such as etravirine in salvage therapy.

Smoking Cessation Outcomes among Individuals with Substance Use and/or Psychiatric Disorders

Objectives: The population of individuals with substance use (SUD) and/or psychiatric disorders (PD) has a high prevalence of smoking and a consequent increase in tobacco-related morbidity and mortality when compared to the general population. The aim of this study is to examine the outcomes of a program in a real-life setting which takes a tailored approach to smoking cessation among individuals with SUD and/or PD. Methods: A retrospective chart review of tailored tobacco dependence treatment was performed on individuals with histories of SUD and/or PD attending a Tobacco Dependence Clinic (TDC) program in Vancouver, British Columbia, Canada. Participants of the TDC received a combination of behavioural counselling and pharmacotherapy for smoking cessation. Data from 540 participants enrolled in the TDC between September 2007 and May 2011 was reviewed. Outcome measures included seven-day point-prevalence abstinence (validated by expired carbon monoxide) and program completion rates. Results: For individuals who completed the program the abstinence rate was 41.1% (167/406). Significant predictors of successful smoking cessation were: a) a lower expired carbon monoxide level at baseline (OR=.98, 95%CI=.96-1.00), and b) a longer duration of treatment (OR=1.09, 95%CI=1.05-1.12). Significant predictors of program completion were: a) being female (OR=1.86, 95%CI=1.21-2.87). Discussion: Tailored smoking cessation among individuals with SUD and/or PD yields modest end-of-treatment smoking cessation rates and can be an effective approach to reducing the burden of tobacco use in substance use and mental health treatment settings.