A pharmacist-led interprofessional learning experience for family practice medical residents specializing in HIV care.

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.

Nous avons développé un stage d'enseignement sur la pharmacothérapie du VIH guidé par un pharmacien pour les résidents en médecine de troisième année. Ces derniers ont trouvé cette expérience d'apprentissage interprofessionnel extrêmement enrichissante pour leur pratique future en lien avec le traitement du VIH. Le concept au cœur de ce stage d'une durée d'un mois était de mettre les apprenants dans la peau du pharmacien pour qu'ils apprennent à reconnaître, à prévenir et à prendre en charge les problèmes liés à la prise de médicaments chez les patients séropositifs. Nous recommandons des opportunités d'apprentissage interprofessionnel mené par un pharmacien pour appuyer la formation médicale dans d'autres domaines hautement spécialisés de la pharmacothérapie.

Appropriate usage of post-exposure prophylaxis-in-pocket for HIV prevention by individuals with low-frequency exposures.

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.

Treatment-emergent reverse transcriptase resistance during antiretroviral therapy with bictegravir, tenofovir alafenamide, and emtricitabine: A case series.

OBJECTIVES: Bictegravir/tenofovir alafenamide/emtricitabine (BIC/TAF/FTC) is a complete regimen for the treatment of HIV with a high barrier to resistance and few reported cases of treatment failure. We present three cases of treatment-emergent resistance to nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) in patients with suboptimal treatment adherence and assess whether the resistance-associated mutations were present before BIC/TAF/FTC initiation or emerged during therapy. METHODS: We used genotypic drug resistance testing by Sanger sequencing to identify emergent resistance mutations in plasma viral load specimens collected after combination antiretroviral therapy initiation in all participants. Additionally, we performed ultra-deep sequencing by Illumina MiSeq on the earliest available plasma HIV-1 viral load specimen and on any available specimens closest in time to the initiation of BIC/TAF/FTC therapy to identify low-abundance resistance mutations present in the viral quasispecies. RESULTS: All three participants developed NRTI resistance after prolonged exposure and incomplete adherence to BIC/TAF/FTC. The T69N, K70E, M184I, and/or T215I mutations identified in clinical samples at the time of virological failure were not present on deep sequencing of either baseline samples or samples collected before BIC/TAF/FTC initiation. CONCLUSIONS: Despite a generally high genetic barrier to resistance, NRTI resistance-associated mutations may emerge during therapy with BIC/TAF/FTC in the setting of suboptimal adherence.

Feasibility of implementing a same-day electronic screening tool for clinical assessment to measure patient-reported outcomes for eliciting actionable information on adherence to HIV medication and related factors in a busy Canadian urban HIV clinic.

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.

The PrEP You Want: A Web-Based Survey of Online Cross-Border Shopping for HIV Prophylaxis Medications.

BACKGROUND: In response to the high cost of HIV pre-exposure prophylaxis (PrEP) medications in Canada, community organizations have created internet-based guides detailing how to legally order generic medications online and travel to collect them in the United States. However, little is known about the patients following these guides. OBJECTIVE: Our primary objective was to measure the proportion of Ontario gay, bisexual, and other men who have sex with men (GBMSM) accessing these online guides who intended to use the border-crossing approach. Our secondary objectives were to explore their demographic characteristics, their completion of the steps in the border-crossing approach, and the barriers they perceived. METHODS: Between July 20, 2017, and May 18, 2018, we administered two online surveys of GBMSM accessing an online border-crossing guide posted by a gay men's health organization in Ontario. Participants completed an open baseline survey posted on the border-crossing guide's Web page and a follow-up survey 3 months later. The data were analyzed using descriptive statistics. We used multivariable logistic regression to identify characteristics associated with the intention to use the border-crossing approach. RESULTS: Most of the 141 participants were young (median age 23, interquartile range 22-25 years) and black (79.4%; 112/141) GBMSM who had completed a college or an undergraduate degree (62.4%; 88/141). In addition, 19.9% (28/141) of them reported a total family income less than Can $30,000 and another 53.9% (76/141) reported income between Can $30,000 and Can $60,000. 54.6% (76/141) paid for medications entirely out of pocket. Most participants indicated that they were likely to complete a border-crossing approach: 80.1% (113/141) at baseline and 79.1% (87/110) at follow-up. The characteristics associated with the intention to use the approach included being black (adjusted odds ratio [aOR] 5.73, 95% CI 2.06-16.61), paying for medications out of pocket (aOR 5.18, 95% CI 1.82-17.04), and having a provider who was thought to be willing to prescribe PrEP (aOR 4.42, 95% CI 1.63-12.41). Comparing baseline and follow-up for the 110 participants who completed both surveys, 65.4% (72/110) and 80.0% (88/110) had discussed PrEP with a health care provider, 18.1% (20/110) and 25.4% (28/110) had obtained a PrEP prescription, and 8.2% (9/110) and 5.5% (6/110) had ordered medications to that mailbox, whereas only 1.0% (1/110) and 0.0% (0/110) had crossed the border to collect them at baseline and follow-up, respectively. Reported barriers included perceived concerns about the approach's legality (56.0%; 79/141), the security of personal health information (39.0%; 55/141), and the safety of online vendors (38.3%; 54/141). CONCLUSIONS: Despite high interest in pursuing an online border-crossing approach to get PrEP medications, such an approach may not be a viable option for PrEP scale-up among interested GBMSM because of logistical challenges and perceptions of safety and legitimacy.

High prevalence of syndemic health problems in patients seeking post-exposure prophylaxis for sexual exposures to HIV.

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.

Combination Therapy with Tenofovir Disoproxil Fumarate/Emtricitabine/Elvitegravir/Cobicistat Plus Darunavir Once Daily in Antiretroviral-Naive and Treatment-Experienced Patients: A Retrospective Review.

BACKGROUND: Patients with drug-resistant HIV often require complex antiretroviral regimens. However, combining fixed-dose combination tablets such as tenofovir-disoproxil-fumarate, emtricitabine, and cobicistat-boosted elvitegravir (TDF/FTC/EVG/cobi) with darunavir (DRV) can provide a simple, once-daily (QD), 2-tablet regimen for patients with drug-resistant HIV. Primary objective was to determine the percentage of patients with HIV-1 RNA <40 copies/mL at 48 weeks. METHODS: We performed a retrospective chart review of patients initiated on TDF/FTC/EVG/cobi plus DRV. RESULTS: Among the 21 included patients, prior resistance showed a median of 2 nucleoside reverse transcriptase inhibitor mutations, 1 nonnucleoside reverse transcriptase mutation, and 1 protease inhibitor mutation. At week 48, 14 (67%) patients achieved HIV-1 RNA <40 copies/mL, 1 patient experienced viral rebound, and 6 (29%) had missing data or discontinued therapy. No patient discontinued for adverse events. CONCLUSION: According to this observational study, QD TDF/FTC/EVG/cobi plus DRV is considered safe, well tolerated, and generally effective in suppressing HIV drug-resistant virus.

A case of a probable drug interaction between lurasidone and atazanavir-based antiretroviral therapy.

The cytochrome P450 isoform that is primarily involved in the metabolism of the antipsychotic lurasidone is CYP3A4. Drugs that inhibit or induce this enzyme would then be expected to increase or decrease serum concentrations of lurasidone, respectively. Atazanavir, an HIV-1 protease inhibitor, has demonstrated to be an inhibitor of CYP3A4 and would be expected to increase the exposure of any drug metabolized by this enzyme. We report a case of an atazanavir-precipitated drug-drug interaction that led to elevated serum concentrations of lurasidone and associated clinical symptoms of drug toxicity.

Preparing for pre-exposure prophylaxis: perceptions and readiness of Canadian pharmacists for the implementation of HIV pre-exposure prophylaxis.

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.

Use of Compassionate Supply of Antiretroviral Drugs to Avoid Treatment Interruptions or Delayed Treatment Initiation among HIV-Positive Patients Living in Ontario: A Retrospective Review.

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.

Amiodarone and concurrent antiretroviral therapy: a case report and review of the literature.

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.

Erythema annulare centrifugum-like eruption associated with pegylated interferon treatment for hepatitis C.

Current standard of treatment for chronic hepatitis C virus infection requires the use of pegylated interferon plus ribavirin. Treatment with these two agents has been associated with numerous side effects, which frequently include dermatologic eruptions. We report a cutaneous eruption associated with interferon having clinical presentation of erythema annulare centrifugum. The eruption occurred within days of the first interferon injection and repeatedly flared following subsequent injections. Our patient was able to continue therapy without interruption, while managing the reaction with topical corticosteroid and oral antihistamine. We conclude that this is a benign cutaneous eruption associated with interferon which can be managed without discontinuing treatment for hepatitis C.

A case of a potential drug interaction between clobazam and etravirine-based antiretroviral therapy.

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 potential drug-herbal interaction between Ginkgo biloba and efavirenz.

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.