Search

Competing Interests: Tracy Jansen Cheney: advisory board work for Gilead; Pierre Giguere: speaking honoraria and/or advisory board work for ViiV, Gilead, Merck, Pfizer; Deborah Kelly: speaking honoraria and/or advisory board work for ViiV, Gilead, Moderna; Dominic Martel: speaking honoraria and/or advisory board work for AbbVie, Gilead, Paladin and Pfizer; Carley Pozniak: speaking honoraria and advisory board work for Viiv, Gilead, Merck; Linda Robinson: speaker/educational honoraria, ViiV, Gilead, Merck; Jonathan Smith: advisory board work for ViiV; Alice Tseng: speaking honoraria and/or advisory board work for ViiV, Gilead, Merck, Pfizer.

PEP-In-Pocket (Post-Exposure Prophylaxis-In-Pocket, or "PIP") is a biobehavioural HIV prevention strategy wherein patients are proactively identified and given a prescription for HIV post-exposure prophylaxis (PEP) medications to self-initiate in case of high-risk exposures. We evaluated this strategy in a prospective observational study at two hospital-based clinics in Toronto, Canada. HIV-negative adults using PIP underwent chart review and completed quarterly electronic questionnaires over 12 months. The primary objective was to quantify appropriate PIP initiation, defined as starting PIP within 72 h of a high-risk exposure. Secondary objectives were to quantify HIV seroconversions, changes in sexual risk behaviour, sexual satisfaction, and satisfaction with the PIP strategy. From 11/2017 to 02/2020, 43 participants enrolled and completed ≥1 questionnaire. PIP was self-initiated on 27 occasions by 15 participants, of which 24 uses (89%) were appropriate, 2 were unnecessary, and 1 was for an unknown exposure. Chart review identified no inappropriate non-use. Over 32 person-years of testing follow-up, we observed zero HIV seroconversions. Sexual risk declined modestly over follow-up, with a HIRI-MSM (HIV Incidence Risk Index for MSM) change of -0.39 (95% CI = -0.58, -0.21 per 3 months, p < .001). Sexual satisfaction was stable over time. At 12 months, 31 (72%) remained on PIP, 8 (19%) had transitioned to pre-exposure prophylaxis and 4 (9%) were lost-to-follow-up. Among participants who remained on PIP and completed questionnaires at 12 months, 24/25 (96%) strongly/somewhat agreed that PIP decreased their anxiety about contracting HIV and 25/25 (100%) strongly/somewhat agreed that they would recommend PIP to a friend. PIP is a feasible HIV prevention strategy in carefully selected individuals at modest HIV risk., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: DHST’s institution has received support from Abbvie and Gilead for investigator-initiated research studies, and from Glaxo Smith Kline for participation in industry-sponsored clinical trials.

We developed a pharmacist-led one-month teaching rotation for medical residents to learn HIV pharmacotherapy. The postgraduate-year-3 residents found this interprofessional learning experience extremely valuable to their future practice in HIV care. The overarching concept of this rotation was for the medical trainee to "become-the-pharmacist," learning to recognize, prevent, and manage drug-related issues in HIV patients. To support medical training in other highly specialized pharmacotherapeutic areas we suggest considering a pharmacist-led interprofessional learning experience., Competing Interests: The authors have no conflicts of interest to declare., (© 2023 Naccarato, Yoong, Gough, Tseng, Arbess; licensee Synergies Partners.)

Abstract: In April 2021, the Japanese authorities' announcement of their decision to release processed wastewater from the damaged Fukushima Daiichi nuclear power plant into the Pacific Ocean over 30 y, beginning in 2023, triggered strong domestic and international opposition. Failure to handle this situation tactfully can lead to public disorder, civil disobedience, loss of trust in the authorities, and even diplomatic sanctions. In this article, we explain the underlying reasons behind this resistance, and we offer some strategic methods that the Japanese authorities can deploy to address opposing views and overcome the Fukushima wastewater crisis., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 Health Physics Society.)

Background: An optimal adherence to antiretroviral therapy (ART) is fundamental for suppression of HIV viral load and favourable treatment outcomes. Patient-reported outcomes (PROs) are effective tools for improving patient-provider communication and focusing providers' awareness on current health problems. The objectives of this analysis were (1) to determine the feasibility of implementing an electronic screening tool to measure PROs in a Canadian HIV clinic to obtain information on ART adherence and related factors and (2) to determine the factors related to sub-optimal adherence., Methods: This implementation research with a convenience sample of 600 people living with HIV (PLWH) was conducted in a busy, academic, urban HIV clinic in Toronto, Canada. PLWH were approached to participate in PRO assessments just prior to their in-clinic appointments, including health-related domains such as mental health, housing, nutrition, financial stress and medication adherence, and responses were summarized on a single sheet available for providers to review. Feasibility of implementing PROs was assessed by quantifying response rate, completion rate, time taken and participation rate. Medication adherence was elicited by self-report of the percentage of prescribed HIV medications taken in the last month. Unadjusted and adjusted odds ratios were estimated from logistic regression models to identify factors associated with adherence of <95%., Results: Of the 748 PLWH invited to participate, 692 (participation rate: 92.5%) completed the PRO assessments as standard of care in clinic. Of these, 600 consented to the use of their PRO results for research and were included in this analysis. The average response rate to the ART-related questions was 96.8% and mean completion rate was 95.5%. The median time taken to complete the assessment was 12.0 (IQR = 8.4-17.3) min, adjusted 8.7 (IQR = 7.2-10.8) min. 445 (74.9%) of participants were male, and 153 (26.2%) reported dissatisfaction with ART. 105 (19.7%) of the PLWH reported ART adherence of <95%. Multivariable logistic regression identified the following risk factors for sub-optimal adherence: dissatisfaction with ART (OR = 2.30, 95% CI 1.38-3.83), not having a family doctor or not visiting a family doctor in last year (OR = 1.69, 95% CI 1.02-2.79)., Conclusion: Collecting self-reported health information from PLWH through PROs in a busy urban clinic was feasible and can provide relevant information to healthcare providers on issues related to adherence. This has a potential to help in individualizing ambulatory care.

Antiretroviral medications are expensive, and people living with HIV often experience challenges accessing and paying for medication due to various obstacles. We used concept mapping to explore the challenges people living with HIV in Ontario, Canada, face when accessing medication. In brainstorming, 68 participants generated 447 statements in response to the focus prompt "Some people living with HIV have trouble getting and paying for prescription drugs because … ". These were consolidated into 77 statements, which were sorted ( n  =   30) and rated ( n  =   32) on importance and commonality. A ten-cluster concept map consisting of individual- and health system-related clusters was generated. Clusters included: (1) Stigma, (2) Medication-Related Issues, (3) Individual Challenges, (4) Basic Needs, (5) Immigration, (6) Coverage, (7) Trillium Drug Program, (8) Access to Services, (9) System-Level Issues and (10) Access to Professional Services. Statements in Coverage and Basic Needs were rated most important and common although there was variability by Ontario residence and drug coverage mechanisms. Strategies to address challenges were generated in Interpretation ( n  =   25 participants). Given that continuous access to antiretroviral therapy is necessary to fully realize treatment benefits, policies and interventions that address these challenges are needed.

Competing Interests: Declaration of Conflicting Interests:Christine Hughes reports personal fees from ViiV Healthcare, Merck and Gilead Sciences outside the submitted work. Deborah Yoong reports receiving honoraria for advisory board representation from Merck and Gilead Sciences. Pierre Giguère reports grants and personal fees from Gilead Sciences, ViiV Healthcare and Merck outside the submitted work. Mark Hull reports receiving honoraria for advisory board representation and speaking engagements regarding HIV and HCV from BMS, Gilead, Merck and ViiV Healthcare, paid to his institution. Darrell Tan reports personal fees from Gilead and ViiV Healthcare outside the submitted work, and his institution has received fees from GSK outside the submitted work.

Background: Antiretrovirals are expensive and people living with HIV may experience a range of financial burdens when accessing these medications. Our aim was to describe the policy of all Canadian public drug insurance programs for antiretroviral drugs and illustrated how these policies might affect patients' annual out-of-pocket expenditures., Methods: In December 2017, we reviewed public drug programs offering antiretroviral coverage in Canada using government websites to summarize eligibility criteria. We estimated the annual out-of-pocket costs incurred by people living with HIV by applying the cost-sharing rules to 2 hypothetical cases, a single man and a married woman with a net household income of $39 000 and $80 000, respectively, receiving identical prescriptions in different jurisdictions., Results: We observed substantial variation in the subsidy provided based mainly on geography, income and age. All 5 federal programs and 6 of 13 provincial and territorial jurisdictions offered universal coverage. In the remaining regions, patients spend up to several thousand dollars annually depending on income (Manitoba), age and income (Ontario, Saskatchewan) and age, income and drug costs (Quebec and Newfoundland and Labrador). We found the greatest variation for our higher income case, with out-of-pocket expenses ranging from 0 to over 50% of the antiretroviral cost., Interpretation: There is considerable inter- and intra-jurisdiction heterogeneity in the cost-sharing policies for antiretrovirals across Canada's public drug programs. Policy reforms that either eliminate or set national standards for copayments, deductibles or premiums would minimize variation and could reduce the risk of cost-associated non-adherence to HIV therapy., Competing Interests: Competing interests: Ahmed Bayoumi reports receiving personal fees from the Canadian Agency for Drugs and Technologies in Health, outside the submitted work. No other competing interests were declared., (Copyright 2018, Joule Inc. or its licensors.)

Introduction: The standard clinical approach to non-occupational HIV post-exposure prophylaxis (nPEP) focuses on biomedical aspects of the intervention, but may overlook co-occurring or 'syndemic' psychosocial problems that reinforce future vulnerability to HIV. We therefore sought to determine the prevalence of syndemic health problems in a cohort of Ontario nPEP patients, and explored the relationship between syndemic burden and HIV risk., Methods: Between 07/2013-08/2016, we distributed a self-administered questionnaire to patients presenting to three clinics in Toronto and Ottawa seeking nPEP for sexual HIV exposures. We used validated screening tools to estimate the prevalence of depression (CES-D score ≥16), harmful alcohol use (AUDIT ≥8), problematic drug use (DUDIT ≥6 men/≥2 women), and sexual compulsivity (SCS ≥24) among men who have sex with men (MSM) respondents. In exploratory analyses, we examined the relationships between syndemic conditions using univariable logistic regression models, and the relationship between syndemic count (total number of syndemic conditions per participant) and HIV risk, as estimated by the HIRI-MSM score, using linear regression models., Results: The 186 MSM included in the analysis had median age 31 (IQR = 26-36), including 87.6% having a college/undergraduate degree or higher. Overall, 53.8% screened positive for depression, 34.4% for harmful alcohol use, 30.1% for problematic drug use, and 16.1% for sexual compulsivity. Most participants (74.2%) had at least one syndemic condition and 46.8% had more than one. Exploratory analyses suggested positive associations between depression and harmful alcohol use (OR = 2.11, 95%CI = 1.13, 3.94) and between harmful alcohol use and problematic drug use (OR = 1.22, 95%CI = 0.65, 2.29). Syndemic count was associated with increased HIRI-MSM risk scores in univariable (2.2, 95%CI = 1.0, 3.3 per syndemic condition) and multivariable (2.1, 95%CI = 0.6, 3.6) linear regression models., Conclusions: The prevalence of syndemic conditions in MSM seeking nPEP for sexual exposure is alarmingly high, and is associated with underlying HIV risk. Routine screening for these conditions may identify opportunities for intervention and could alleviate future vulnerability to HIV., Competing Interests: We have read the journal's policy and the authors of this manuscript have the following competing interests: Deborah Yoong has received honoraria from Gilead, Janssen and Merck. Trevor A. Hart is supported by an Applied HIV Research Chair from the Ontario HIV Treatment Network. Paul MacPherson is supported by a Research Chair in Gay Men’s Health from the Ontario HIV Treatment Network. Isaac Bogoch and Darrell H. S. Tan are each supported by a New Investigator Award from the Canadian Institutes of Health Research and Ontario HIV Treatment Network. Darrell H. S. Tan reports receiving research grants from Gilead and Viiv, and being a site PI for industry-sponsored trials by GSK. No other authors have relevant competing interests to disclose. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Competing Interests: Competing interests: Darrell Tan reports grants from the Canadian Institutes of Health Research and Ontario HIV Treatment Network, during the conduct of the study, and personal fees from Merck and GSK and grants and personal fees from Gilead and ViiV Healthcare, outside the submitted work. Mark Hull reports receiving honoraria for advisory board representation and speaking engagements regarding HIV and the hepatitis C virus from BMS, Gilead, Merck and ViiV Healthcare, paid to his institution. Deborah Yoong reports personal fees from Merck and Gilead Science, outside the submitted work. Cécile Tremblay reports grants and personal fees from Gilead, Merck, ViiV Healthcare, the Canadian Institutes of Health Research and Fonds de recherche santé Québec, both during the conduct of the study and outside the submitted work. Réjean Thomas reports personal fees from Gilead, outside the submitted work. Jean-Guy Baril reports grants from Gilead, Merck and Glaxo, and personal fees from Gilead, Merck and ViiV Healthcare, outside the submitted work. Joseph Cox reports grants and personal fees from ViiV Healthcare, and grants from Merck and Gilead, outside the submitted work. Pierre Giguere reports grants and personal fees from Gilead Sciences, ViiV Healthcare and Merck outside the submitted work. Marianne Harris reports grants and personal fees from Gilead Sciences Canada and personal fees from Merck Canada and ViiV Healthcare, outside the submitted work. Christine Hughes reports grants and personal fees from ViiV Healthcare, and personal fees from Merck Canada and Gilead Sciences Canada, outside the submitted work. Stephen Shafran reports grants from AbbVie, Gilead and Janssen; grants and personal fees from Merck and BMS; and personal fees from Pfizer, outside the submitted work. No other competing interests were declared.

Pre-exposure prophylaxis (PrEP) has been shown to reduce the risk of HIV transmission but has the potential to cause harm if not used properly. Pharmacists are well-positioned to foster PrEP's efficacy but little is known whether they would endorse it as an HIV prevention tool. The objective of the study was to determine Canadian HIV pharmacists' support for PrEP and to identify current barriers to promoting PrEP. Canadian pharmacists with experience in HIV care were invited to complete an online survey about their experiences, opinions, and learning needs regarding PrEP from December 2012 to January 2013. Among the 59 surveys received, 48 met criteria for final analysis. Overall, 33 (69%) respondents would provide education positively supporting the use of PrEP and 26 (54%) believed Health Canada should approve PrEP for use in Canada. Familiarity with the concept of PrEP and practice characteristics examined did not appear to be significantly associated with support for PrEP in univariable analyses. The principal barriers to promoting PrEP included inadequate drug coverage and insufficient knowledge to educate others. Many Canadian HIV pharmacists would endorse PrEP for high-risk patients; however, wider dissemination of information and lower drug costs may be needed to make PrEP more widely promoted., (© The Author(s) 2015.)

Background: Without a national pharmacare plan in Canada, HIV-infected patients across the nation differ in their ability to obtain essential HIV therapy. Despite the fact there are public insurance programs in Ontario, patients are unable to access medication. The authors described how frequently patients in their urban clinic could not access medications and why they required a compassionate supply of HIV drugs, with the goals of minimizing treatment delays and avoiding interruptions., Methods: The authors conducted a retrospective review and collected information about demographic characteristics, current drug insurance and the challenges encountered., Results: Over one year, the authors provided 2,886 days of free HIV drugs to 42 patients who were predominantly citizens or permanent residents of Canada (88%). The most common obstacles were associated with the Trillium Drug Program and the total value of all drugs supplied was $134,860., Interpretation: This study suggests that Ontario's catastrophic drug insurance plan leaves some patients with significant gaps in drug coverage., (Copyright © 2015 Longwoods Publishing.)

Therapy for HIV often can make pharmacologic management of comorbidities challenging since many antiretroviral agents significantly modulate drug metabolism pathways. Amiodarone is commonly used to control cardiac arrhythmias; however, it is recognized as having a narrow therapeutic window with potential for significant drug toxicity. Amiodarone is metabolized by CYP3A4, CYP2C8 and CYP1A1 to an active metabolite and therefore may be affected by comedications that modulate these isoenzymes. Since amiodarone is frequently associated with toxicity, the Heart Rhythm Society (formerly the North American Society of Pacing and Electrophysiology) developed guidelines to minimize the potential for adverse events. However, recommendations for the management of situations where amiodarone must be given with a drug that significantly affects its metabolism are lacking. This paper will discuss our experience with a case of concurrent amiodarone and antiretroviral therapy, as well as provide a review of interactions that may lead to toxicity or potential treatment failure with amiodarone. Primary literature was identified through Medline (1946 to May 2013) and Embase (1980 to May 2013), using the following terms: amiodarone, antiretroviral, HIV, cytochrome P450 and drug interaction. Case reports, studies of xenobiotic interactions with amiodarone in healthy volunteers, and in vitro studies that investigated metabolic pathways of amiodarone were reviewed. Although clinical data was limited, several cases support the finding that potent inhibitors or inducers of cytochrome P450 may lead to amiodarone toxicity or lack of therapeutic effect, respectively. As well, several case reports, in vitro data and clinical investigations have associated some of the antiretrovirals with QT prolongation, which may result in additive cardiotoxicity in patients also receiving amiodarone. Therefore, to manage situations where amiodarone must be used with concurrent interacting antiretrovirals, we recommend a monitoring plan that follows the Heart Rhythm Society guidelines, however with the addition of serial therapeutic drug level monitoring and frequent electrocardiography to minimize potential toxicity and successfully manage both conditions.

Efavirenz (EFV) is primarily metabolized by cytochrome P450 (CYP) 2B6 and to a lesser extent by CYP3A4. Drugs that significantly inhibit or induce these enzymes would then be expected to increase or lower the levels of EFV potentially resulting in toxicity or therapeutic failure, respectively. The constituents of Ginkgo biloba extract have been demonstrated to induce gene expression of the CYP450 enzymes. We report a case in which a potential drug-herb interaction may have led to virological breakthrough in a patient that was maintained on the same regimen for 10 years. Therefore, a drug-herbal interaction may be expected when these agents are taken concurrently, and we advise clinicians to avoid this combination when possible.

The cytochrome P450 isoforms primarily involved in clobazam metabolism are CYP3A4 and 2C19. Drugs that modulate these enzymes would then be expected to alter the exposure of clobazam and its major metabolites. Etravirine, a second-generation non-nucleoside reverse transcriptase inhibitor has been shown to induce CYP3A4, while inhibiting CYP2C9 and CYP2C19. We report a case in which a potential drug interaction between clobazam and etravirine may have led to increased concentrations of clobazam and its pharmacologically active metabolite, N-desmethylclobazam, causing neurotoxic symptoms.

A 42-year-old man with human immunodeficiency virus (HIV) infection and a history of complex partial seizures developed severe anemia after the addition of valproic acid to his stable antiretroviral regimen of zidovudine, lamivudine, and abacavir. The inhibition of zidovudine glucuronidation by valproic acid and the resultant zidovudine hematologic toxicity is the proposed mechanism of the interaction.