Opioid Use Disorder and Perinatal Outcomes.

OBJECTIVES: Evidence on the perinatal health of mother-infant dyads affected by opioids is limited. Elevated risks of opioid-related harms for people with opioid use disorder (OUD) increase the urgency to identify protective factors for mothers and infants. Our objectives were to determine perinatal outcomes after an OUD diagnosis and associations between opioid agonist treatment and birth outcomes. METHODS: We conducted a population-based retrospective study among all women with diagnosed OUD before delivery and within the puerperium period in British Columbia, Canada, between 2000 and 2019 from provincial health administrative data. Controlling for demographic and clinical characteristics, we determined associations of opioid agonist treatment on birth weight, gestational age, infant disorders related to gestational age and birth weight, and neonatal abstinence syndrome via logistic regression. RESULTS: The population included 4574 women and 6720 live births. Incidence of perinatal OUD increased from 166 in 2000 to 513 in 2019. Compared with discontinuing opioid agonist treatment during pregnancy, continuous opioid agonist treatment reduced odds of preterm birth (adjusted odds ratio: 0.6; 95% confidence interval: 0.4-0.8) and low birth weight (adjusted odds ratio: 0.4; 95% confidence interval: 0.2-0.7). Treatment with buprenorphine-naloxone (compared with methadone) reduced odds of each outcome including neonatal abstinence syndrome (adjusted odds ratio: 0.6; 95% confidence interval: 0.4-0.9). CONCLUSIONS: Perinatal OUD in British Columbia tripled in incidence over a 20-year period. Sustained opioid agonist treatment during pregnancy reduced the risk of adverse birth outcomes, highlighting the need for expanded services, including opioid agonist treatment to support mothers and infants.

In-hospital training in addiction medicine: A mixed-methods study of health care provider benefits and differences.

Background: Hospital-based clinical addiction medicine training can improve knowledge of clinical care for substance-using populations. However, application of structured, self-assessment tools to evaluate differences in knowledge gained by learners who participate in such training has not yet been addressed. Methods: Participants (n = 142) of an elective with the hospital-based Addiction Medicine Consult Team (AMCT) in Vancouver, Canada, responded to an online self-evaluation survey before and immediately after the structured elective. Areas covered included substance use screening, history taking, signs and symptoms examination, withdrawal treatment, relapse prevention, nicotine use disorders, opioid use disorders, safe prescribing, and the biology of substance use disorders. A purposefully selected sample of 18 trainees were invited to participate in qualitative interviews that elicited feedback on the rotation. Results: Of 168 invited trainees, 142 (84.5%) completed both pre- and post-rotation self-assessments between May 2015 and May 2017. Follow-up participants included medical students, residents, addiction medicine fellows, and family physicians in practice. Self-assessed knowledge of addiction medicine increased significantly post-rotation (mean difference in scores = 11.87 out of the maximum possible 63 points, standard deviation = 17.00; P < .0001). Medical students were found to have the most significant improvement in addiction knowledge (estimated mean difference = 4.43, 95% confidence interval = 0.76, 8.09; P = .018). Illustrative quotes describe the dynamics involved in the learning process among trainees. Conclusions: Completion of a hospital-based clinical elective was associated with improved knowledge of addiction medicine. Medical students appear to benefit more from the addiction elective with a hospital-based AMCT than other types of learners.

Impact of a brief addiction medicine training experience on knowledge self-assessment among medical learners.

BACKGROUND: Implementation of evidence-based approaches to the treatment of various substance use disorders is needed to tackle the existing epidemic of substance use and related harms. Most clinicians, however, lack knowledge and practical experience with these approaches. Given this deficit, the authors examined the impact of an inpatient elective in addiction medicine amongst medical trainees on addiction-related knowledge and medical management. METHODS: Trainees who completed an elective with a hospital-based Addiction Medicine Consult Team (AMCT) in Vancouver, Canada, from May 2015 to May 2016, completed a 9-item self-evaluation scale before and immediately after the elective. RESULTS: A total of 48 participants completed both pre and post AMCT elective surveys. On average, participants were 28 years old (interquartile range [IQR] = 27-29) and contributed 20 days (IQR = 13-27) of clinical service. Knowledge of addiction medicine increased significantly post elective (mean difference [MD] = 8.63, standard deviation [SD] = 18.44; P = .002). The most and the least improved areas of knowledge were relapse prevention and substance use screening, respectively. CONCLUSIONS: Completion of a clinical elective with a hospital-based AMCT appears to improve medical trainees' addiction-related knowledge. Further evaluation and expansion of addiction medicine education is warranted to develop the next generation of skilled addiction care providers.

A Needs Assessment of the Number of Comprehensive Addiction Care Physicians Required in a Canadian Setting.

OBJECTIVE: Medical professionals adequately trained to prevent and treat substance use disorders are in short supply in most areas of the world. Whereas physician training in addiction medicine can improve patient and public health outcomes, the coverage estimates have not been established. We estimated the extent of the need for medical professionals skilled in addiction medicine in a Canadian setting. METHODS: We used Monte-Carlo simulations to generate medians and 95% credibility intervals for the burden of alcohol and drug use harms, including morbidity and mortality, in British Columbia, by geographic health region. We obtained prevalence estimates for the models from the Medical Services Plan billing, the Discharge Abstract Database data, and the government surveillance data. We calculated a provider availability index (PAI), a ratio of the size of the labor force per 1000 affected individuals, for each geographic health region, using the number of American Board of Addiction Medicine certified physicians in each area. RESULTS: Depending on the data source used for population estimates, the availability of specialized addiction care providers varied across geographic health regions. For drug-related harms, we found the highest PAI of 23.72 certified physicians per 1000 affected individuals, when using the Medical Services Plan and Discharge Abstract Database data. Drawing on the surveillance data, the drug-related PAI dropped to 0.46. The alcohol-related PAI ranged between 0.10 and 86.96 providers, depending on data source used for population estimates. CONCLUSIONS: Our conservative estimates highlight the need to invest in healthcare provider training and to develop innovative approaches for more rural health regions.

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.

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 alpha-2b) or pegylated-interferon alpha-2b (PEG-IFN alpha-2b) and ribavirin (RBV) in injection drug users (IDU) enrolled in a directly observed therapy (DOT) program, as measured by sustained virologic response (SVR). METHODS: Viremic HCV-infected IDU, with alanine aminotransferase (ALT) >1.5x upper limit of normal (ULN) were offered 24-48 week (based on HCV genotype) therapy with RBV (800-1200 mg/day, based on weight) along with IFN alpha-2b (3 million IU thrice weekly) replaced by PEG-IFN alpha-2b (1.5 ìg/kg once weekly) as it became available. All injections were directly observed. The primary endpoint was SVR. RESULTS: Overall, 40 patients (33 males) received IFN alpha-2b (12) or PEG-IFN alpha-2b (28), 55% with HCV genotypes 2 or 3. Only 14 discontinued therapy, 5 due to toxicity, 6 due to illicit drug use and 3 did not achieve an early virologic response. In an intent-to-treat analysis, the overall SVR was 55% (22/40), 64% (14/22) in subjects with genotypes 2/3. There was no significant difference in response rates among those with >6 (50%) or

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.

The impact of ongoing illicit drug use on methadone adherence in illicit drug users receiving treatment for HIV in a directly observed therapy program.

INTRODUCTION: Studies evaluating the effectiveness of opioid agonist therapy programs typically evaluate drug abstinence or treatment retention as their primary outcomes. However, in many circumstances (e.g. directly observed therapy (DOT) programs within methadone maintenance programs), methadone adherence is an extremely relevant clinical outcome. We sought to evaluate the impact of ongoing illicit drug use on methadone adherence within a DOT program for the treatment of HIV-infection. METHODS: Patients were enrolled in a DOT program, where methadone and HIV medication are co-administered by a community pharmacist. Drug use (amphetamines, benzodiazepines, cocaine, and opiates) was assessed by repeated urinalysis results. Methadone adherence was calculated as the fraction of days methadone was administered. RESULTS: Ongoing drug use, and poly-substance use was common, with only 4 of 60 patients abstaining from all illicit drug use. Overall methadone adherence was 84.5%. Amphetamine use (without benzodiazepine and cocaine use), benzodiazepine use (without amphetamines) and higher methadone doses were associated with higher methadone adherence. When patients used benzodiazepines or cocaine, any positive effect associated with amphetamine use was negated. In addition, opiate use was associated with decreased methadone adherence. DISCUSSION: The effect of many illicit drugs on methadone adherence may differ from reports using other treatment outcomes.

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/mm(3) (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.

Directly observed therapy for the management of HIV-infected patients in a methadone program.

The objective of this prospective, observational clinical study was to evaluate the safety and efficacy of once-daily and twice-daily directly observed therapy (DOT) in human immunodeficiency virus (HIV)-infected patients undergoing methadone treatment. Methadone and highly active antiretroviral therapy (HAART) were dispensed daily as DOT, with patients in the twice-daily HAART group self-administering the second dose. Clinical and laboratory end points were monitored, along with the impact of ongoing cocaine use. We studied 54 patients coinfected with HIV and hepatitis C virus. At baseline, the median virus load was 111,000 copies/mL, and the median CD4+ cell count was 165 cells/mm3. After a median of 24 months, 17 of 29 patients in the once-daily HAART group and 18 of 25 in the twice-daily HAART group had virus loads of <400 copies/mL, regardless of ongoing cocaine use. Thirty-two patients required methadone dose adjustment, which was managed without modification of HAART. Treatment-limiting hepatic toxicity was rare. A DOT program of coadministered methadone and HAART can be implemented with good results, even for patients who continue to use cocaine.