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.

Oestradiol concentrations in trans women with HIV suppressed on unboosted integrase inhibitor regimens versus trans women without HIV taking oral oestradiol: a pilot study.

BACKGROUND: Feminizing hormone therapy (FHT) is essential to many trans women. Concern about negative drug interactions between FHT and ART can be an ART adherence barrier among trans women with HIV. OBJECTIVES: In this single-centre, parallel group, cross-sectional pilot study, we measured serum oestradiol concentrations in trans women with HIV taking FHT and unboosted integrase strand transfer inhibitor (INSTI)-based ART versus trans women without HIV taking FHT. METHODS: We included trans women with and without HIV, aged ≥18 years, taking ≥2 mg/day of oral oestradiol for at least 3 months plus an anti-androgen. Trans women with HIV were on suppressive ART ≥3 months. Serum oestradiol concentrations were measured prior to medication dosing and 2, 4, 6 and 8 h post-dose. Median oestradiol concentrations were compared between groups using Wilcoxon rank-sum tests. RESULTS: Participants (n = 8 with HIV, n = 7 without) had a median age of 32 (IQR: 28, 39) years. Among participants, the median oral oestradiol dose was 4 mg (range 2-6 mg). Participants had been taking FHT for a median of 4 years (IQR: 2, 8). Six trans women with HIV were taking bictegravir/emtricitabine/tenofovir alafenamide and two were taking dolutegravir/abacavir/lamivudine. All oestradiol concentrations were not significantly different between groups. Eleven (73%) participants had target oestradiol concentrations in the range 200-735 pmol/L at C4h (75% among women with HIV, 71% among those without HIV). CONCLUSIONS: Oestradiol concentrations were not statistically different in trans women with HIV compared with those without HIV, suggesting a low probability of clinically relevant drug-drug interactions between FHT and unboosted INSTI-based ART.

Feminizing hormone therapy in a Canadian cohort of transgender women with and without HIV.

BACKGROUND: Potential bidirectional drug-drug interactions between feminizing hormone therapy (FHT) and antiretroviral therapy (ART) are of concern for trans women with HIV and their healthcare providers. This study aimed to characterize patterns of FHT and ART among trans women with HIV and to compare serum hormone levels to trans women without HIV. METHODS: Charts of trans women were reviewed at seven HIV primary care or endocrinology clinics in Toronto and Montreal from 2018 to 2019. ART regimens, FHT use, serum estradiol, and serum testosterone levels were compared on the basis of HIV status (positive, negative, missing/unknown). RESULTS: Of 1495 trans women, there were 86 trans women with HIV, of whom 79 (91.8%) were on ART. ART regimens were most commonly integrase inhibitor-based (67.4%), many boosted with ritonavir or cobicistat (45.3%). Fewer (71.8%) trans women with HIV were prescribed FHT, compared to those without HIV (88.4%) and those with missing/unknown status (90.2%, p < 0.001). Among trans women on FHT with recorded serum estradiol (n = 1153), there was no statistical difference in serum estradiol between those with HIV (median: 203 pmol/L, IQR: 95.5, 417.5) and those with negative (200 mol/L [113, 407]) or missing/unknown HIV status (227 pmol/L [127.5, 384.5) (p = 0.633). Serum testosterone concentrations were also similar between groups. CONCLUSIONS: In this cohort, trans women with HIV were prescribed FHT less often than trans women with negative or unknown HIV status. There was no difference in serum estradiol or testosterone levels of trans women on FHT regardless of HIV status, providing reassurance regarding potential drug-drug interactions between FHT and ART.

Use and safety of appearance and performance enhancing supplements in gay, bisexual, and other men who have sex with men receiving daily tenofovir disoproxil fumarate/emtricitabine as HIV pre-exposure prophylaxis.

Appearance- and performance-enhancing supplements (APES) may be associated with liver and renal toxicity, but use is often under-reported. This study describes the use and safety of APES among gay, bisexual, and other men-who-have-sex with men (gbMSM) attending an urban HIV pre-exposure prophylaxis (PrEP) clinic. A cross-sectional study was conducted between February 2018 to September 2018 to assess APES usage in gbMSM taking daily tenofovir disoproxil fumarate/emtricitabine for PrEP. Renal and liver function were assessed from electronic medical records. Among 50 participants (98% male, median 32 years, 52% White, on PrEP for a median 4.4 years), 72% reported lifetime APES use, with 52% currently using APES (median 1.5 products/person) and 28% never used APES. The most common products included whey protein, creatine supplements and anabolic steroids. The primary reason for APES use was to increase muscle mass. Three (12%) current APES users had elevated serum creatinine (stage 1) versus zero (0%) in the non-APES group. Two (8%) current APES users experienced grade 3-4 ALT/AST elevations versus zero (0%) in the non-APES group. APES usage among gbMSM taking PrEP was high and may be associated with liver/renal lab abnormalities. Increased awareness of APES use and potential toxicity is encouraged to enhance safety.

COVID-19: A Review of Potential Treatments (Corticosteroids, Remdesivir, Tocilizumab, Bamlanivimab/Etesevimab, and Casirivimab/Imdevimab) and Pharmacological Considerations.

Objectives: In light of the ongoing global pandemic, this paper reviews data on a number of potential and approved agents for COVID-19 disease management, including corticosteroids, remdesivir, tocilizumab, and monoclonal antibody combinations. Dose considerations, potential drug-drug interactions, and access issues are discussed. Key findings: Remdesivir is the first antiviral agent approved for the treatment of COVID-19, based on results from large clinical trials showing reduction in recovery time, faster clinical improvement, and decrease in time to discharge with remdesivir. Dexamethasone and tocilizumab have demonstrated mortality benefits in large, randomized controlled trials. Consequently, the use of corticosteroids has become the standard of care for hospitalized patients with severe or critical COVID-19, while tocilizumab is recommended for use in combination with a corticosteroid in certain hospitalized patients. Recently, monoclonal antibody combinations bamlanivimab/etesevimab and casirivimab/imdevimab received emergency use authorizations for use in non-hospitalized patients with mild-to-moderate COVID-19 at high risk of disease progression. Summary: As data from large clinical trials emerge, the paradigm of COVID-19 treatments has shifted significantly. The use of corticosteroids, remdesivir, and tocilizumab depend on disease severity. Emerging data on monoclonal antibody combinations are promising, but further data are required. Pharmacists can play a role in ensuring appropriate access, correct administration, and safe use of COVID-19 treatments and are encouraged to stay abreast of new developments.

Polypharmacy-associated risk of hospitalisation among people ageing with and without HIV: an observational study.

BACKGROUND: Polypharmacy, defined as use of five or more medications concurrently, is associated with adverse health outcomes and people ageing with HIV might be at greater risk than similar uninfected individuals. We aimed to determine whether known pairwise drug interactions (KPDIs) were associated with risk of admission to hospital (hereafter referred to as hospitalisation) and medication count among people ageing with and without HIV after accounting for physiological frailty. METHODS: In this observational study, we collected individual-level data for participants of the Veterans Aging Cohort Study (VACS) with HIV on antiretroviral therapy (ART) and with supressed HIV-1 RNA and people without HIV who were receiving at least one prescription medication, based on active medications in the 2009 fiscal year (ie, Oct 1, 2008, to Sept 30, 2009). We identified KPDIs among these patients by linking prescription fill and refill data with data from DrugBank (version 5.0.11). We collected data on all-cause mortality and hospitalisations between Oct 1, 2009, and March 31, 2019. We compared KPDI counts using random selection and actual patterns of use across medication counts from two to 12. We created a weighted KPDI Index on the basis of the average association of each KPDI with mortality among people ageing without HIV and used nested Cox models stratified by HIV status to estimate the association between medication count and hospitalisation, with incremental adjustments for demographics, physiological frailty, and KPDI Index. FINDINGS: We collected data for 9186 people ageing with HIV and 37 930 individuals without HIV. 45 913 (97·4%) of 47 116 patients were men and the sample was predominantly aged 50-64 years (30 413 [64·6%]). Compared with a random sample of medications, real-world pattern of medication counts and combinations were associated with five-to-six times more KPDIs (eg, for a combination of six medications, KPDI count was 1·09 in the random sample, 5·49 in the HIV-negative population, and 7·13 in the HIV-positive population). For each additional observed medication, people ageing with HIV had approximately 2·94 additional KPDIs and comparators had approximately 2·67 additional KPDIs. Adjustment for demographics, physiological frailty, and KPDI Index reduced the association between medication count and risk of hospitalisation for people ageing with HIV (hazard ratio 1·08 [95% CI 1·07-1·09] reduced to 1·06 [1·05-1·07]) and those without HIV (1·08 [1·07-1·08] reduced to 1·04 [1·03-1·05]). INTERPRETATION: For each additional medication, people ageing with HIV have more drug-drug interactions than those without HIV. Adjusting for known non-ART drug-drug interactions, each additional non-ART medication confers excess risk of hospitalisation for people ageing with HIV. Randomised trials will be needed to determine whether reducing these interactions improves outcomes. FUNDING: National Institutes of Health, National Institute on Alcohol Abuse and Alcoholism, Department of Veterans Affairs Health Services Research & Development, and Office of Research and Development.

An update on neuropsychiatric adverse effects with second-generation integrase inhibitors and nonnucleoside reverse transcriptase inhibitors.

PURPOSE OF REVIEW: Neuropsychiatric adverse effects (NPAE) associated with integrase strand transfer inhibitors (INSTIs) and nonnucleoside reverse transcriptase inhibitors (NNRTIs) are a growing concern, with higher rates in the real-world compared to phase III trials. This paper reviews the incidence, risk factors, and management of NPAE with second-generation INSTIs, INSTI/rilpivirine dual therapy, and doravirine. RECENT FINDINGS: Recent cohort data confirm up to 8% NPAE-associated discontinuations for dolutegravir; NPAE with dolutegravir/rilpivirine therapy are higher than with dolutegravir alone, whereas bictegravir appears similar to dolutegravir. In contrast, NPAE with cabotegravir alone or with rilpivirine appears to be low. Doravirine has NPAE rates similar to rilpivirine and lower than efavirenz. Risk factors for NPAE include female gender, concurrent abacavir use, Sub-Saharan African descent, and age, whereas underlying psychiatric conditions do not appear to increase risk. Strategies to manage NPAE include changing administration time, therapeutic drug monitoring, or regimen modification including within-class INSTI changes. People experiencing NPAE with dolutegravir may tolerate bictegravir. SUMMARY: Overall, mild to moderate NPAE are associated with INSTIs and newer NNRTIs. Rarely, more severe symptoms may occur and lead to treatment discontinuation. Clinicians should be aware of NPAE to identify and manage drug-related adverse effects.

The intersection of drug interactions and adverse reactions in contemporary antiretroviral therapy.

PURPOSE OF REVIEW: Advances in antiretroviral therapy (ART) have transformed HIV infection into a chronic and manageable condition. The introduction of potent and more tolerable antiretrovirals (ARVs) with favorable pharmacokinetic profiles has changed the prevalence and nature of drug-drug interactions (DDIs). Here, we review the relevance of DDIs in the era of contemporary ART. RECENT FINDINGS: Management of DDIs remains an important challenge with modern ART, primarily due to increased polypharmacy in older persons living with HIV. Significant DDIs exist between boosted ARVs or older nonnucleoside reverse transcriptase inhibitors and comedications for chronic comorbidities (e.g., anticoagulants, antiplatelets, statins) or complex conditions (e.g., anticancer agents, immunosuppressants). Newer ARVs such as unboosted integrase inhibitors, doravirine, and fostemsavir have reduced DDI potential, but there are clinically relevant DDIs that warrant consideration. Potential consequences of DDIs include increased toxicity and/or reduced efficacy of ARVs and/or comedications. Management approaches include switching to an ARV with less DDI potential, changing comedications, or altering medication dosage or dosing frequency. Deprescribing strategies can reduce DDIs and polypharmacy, improve adherence, minimize unnecessary adverse effects, and prevent medication-related errors. SUMMARY: Management of DDIs requires close interdisciplinary collaboration from multiple healthcare disciplines (medicine, nursing, pharmacy) across a spectrum of care (community, outpatient, inpatient).

A practical clinical guide to counselling on and managing contraception, pre-conception planning, and menopause for women living with HIV.

Background: Women represent one quarter of the population living with HIV in Canada and are an increasingly important sector of the HIV community. While some women's health issues such as cervical cancer screening and management are well addressed in HIV management guidelines, others are not. These include sexual and reproductive health factors such as contraception, pre-conception planning, and menopause. Existing literature has shown that while women living with HIV in Canada receive good HIV care based on HIV care cascade indicators, their women's health and sexual and reproductive health care needs are not being met. Methods: In this article, we present a clinical guide for clinicians providing care for women living with HIV on three key women's health topics that are under-discussed during HIV care visits: (1) contraception, (2) pre-conception planning, and (3) menopause. Results: We have summarized the most pertinent clinical factors on each topic to support straightforward counselling and present important considerations in the context of HIV-related diseases and treatment. Finally, when relevant, we have provided practical stepwise approaches for addressing each of these women's health care topics when seeing a patient during a visit. Conclusions: It is important that HIV specialists stay well-versed in the complex clinical interactions between HIV treatment and management of women's health issues.

Historique: Les femmes forment le quart de la population qui vit avec le VIH au Canada et un segment croissant de la communauté du VIH. Certains problèmes de santé des femmes, comme le dépistage et la prise en charge du cancer du col de l'utérus, sont bien couverts dans les directives sur la prise en charge du VIH, mais d'autres non. Des facteurs liés à la santé sexuelle et reproductive, tels que la contraception, la planification avant la conception et la ménopause, en font partie. Les publications scientifiques ont démontré que les femmes qui vivent avec le VIH au Canada reçoivent de bons soins du VIH en fonction des indicateurs de soins du VIH ventilés en cascade, mais que leurs besoins en matière de santé des femmes, de santé sexuelle et de santé reproductive ne sont pas respectés. Méthodologie: Dans le présent article, les auteurs proposent un guide clinique à l'intention des cliniciens qui soignent des femmes atteintes du VIH, à l'égard de trois sujets en santé des femmes qui ne sont pas assez abordés pendant les rendez-vous sur les soins du VIH : 1) la contraception, 2) la planification avant la conception et 3) la ménopause. Résultats: Les auteurs ont résumé les facteurs cliniques les plus appropriés relatifs à chaque sujet pour favoriser un counseling franc et présentent des points de vue importants dans le contexte des maladies et des traitements liés au VIH. Enfin, lorsque c'est approprié, ils ont fourni une démarche pratique graduelle pour aborder chacun de ces sujets en santé des femmes lors d'un rendez-vous. Conclusions: Il est important que les spécialistes du VIH demeurent bien informés des interactions cliniques complexes entre le traitement du VIH et la prise en charge des problèmes de santé des femmes.

Drug Interactions with Gender-Affirming Hormone Therapy: Focus on Antiretrovirals and Direct Acting Antivirals.

INTRODUCTION: Gender-affirming care may include hormonal therapy to attain desired health outcomes in transgender (trans) individuals. To provide safe, affirming medical care for trans patients, health care providers must identify and manage drug-drug interactions (DDIs) between gender affirming hormonal therapy (GAHT) and other medication therapies. AREAS COVERED: This review summarizes available data on DDIs between GAHT and antiretrovirals (ARVs) or hepatitis C direct acting antivirals (DAAs). Potential pharmacokinetic and pharmacodynamic DDIs are predicted based on GAHT, ARV, and DAA pharmacology and adverse event profiles. Clinical management strategies are discussed. EXPERT OPINION: GAHT may be involved in pharmacokinetic and/or pharmacodynamic DDIs. Certain ARV classes (non-nucleoside reverse transcriptase inhibitors, protease inhibitors) may alter GAHT disposition, whereas selected ARVs (unboosted integrase inhibitors, doravirine, or rilpivirine) may have less impact on GAHT. DAAs may interact with GAHT, but the clinical relevance is unclear. ARV- and/or DAA-associated side effects (including depression, cardiovascular disease, hyperlipidemia) are important to consider in the clinical management of trans patients. Clinicians must evaluate potential DDIs and overlapping side effects between ARVs, DAAs and GAHT when providing care for trans patients.

Getting to the Heart of the Matter: A Review of Drug Interactions Between HIV Antiretrovirals and Cardiology Medications.

The past 20 years have seen remarkable advances in the treatment of HIV such that most people diagnosed with HIV today can live long, healthy lives by taking antiretrovirals which are usually life-long. Advancements in antiretroviral therapy include the availability of well tolerated, single tablet regimens that are associated with a lower risk of drug-drug interactions. Despite this, many people living with HIV infection might be taking antiretroviral agents that are associated with significant drug-drug interactions. Because HIV infection itself is associated with cardiovascular complications and this population is living longer, concomitant use of antiretrovirals and medications to treat cardiovascular-related diseases is often required. For this reason, it is imperative that clinicians are aware of the potential for clinically significant drug-drug interactions between antiretroviral agents and cardiac medications as well as the useful HIV drug interaction resources that might provide guidance. Available data on significant interactions are summarized and suggested guidance regarding management is discussed.

Therapeutic drug monitoring in treatment-experienced HIV-infected patients receiving darunavir-based salvage regimens: A case series.

Therapeutic drug monitoring (TDM) constitutes a compelling approach for the optimization of antiretroviral therapy in treatment-experienced HIV-1 patients. While various inhibitory indices have been proposed to predict virologic outcome, there is a lack of consensus on the clinical value of TDM. Here, we report the comparative results of TDM in 14 HIV-1-infected patients who had previously received at least two different PI-based regimens and who initiated darunavir (DRV)-based salvage therapy. Pharmacokinetic/pharmacodynamics (PK/PD) parameters were calculated for each subject. Seventy-nine percent of subjects had a viral load <50 copies/mL at 48 weeks. The only subject with two consecutive viral loads >50 copies/mL at the end of the study period was the patient with the lowest instantaneous inhibitory potential (IIP). The sample size was insufficient to show an association between any of the PK/PD parameters and virologic response. Based on our observations, we suggest that the utility of IIP for antiretroviral combinations for the prediction of virologic outcome in HIV-1 drug-experienced patients should be studied further.

Cobicistat Versus Ritonavir: Similar Pharmacokinetic Enhancers But Some Important Differences.

OBJECTIVE: To describe properties of cobicistat and ritonavir; compare boosting data with atazanavir, darunavir, and elvitegravir; and summarize antiretroviral and comedication interaction studies, with a focus on similarities and differences between ritonavir and cobicistat. Considerations when switching from one booster to another are discussed. DATA SOURCES: A literature search of MEDLINE was performed (1985 to April 2017) using the following search terms: cobicistat, ritonavir, pharmacokinetic, drug interactions, booster, pharmacokinetic enhancer, HIV, antiretrovirals. Abstracts from conferences, article bibliographies, and product monographs were reviewed. STUDY SELECTION AND DATA EXTRACTION: Relevant English-language studies or those conducted in humans were considered. DATA SYNTHESIS: Similar exposures of elvitegravir, darunavir, and atazanavir are achieved when combined with cobicistat or ritonavir. Cobicistat may not be as potent a CYP3A4 inhibitor as ritonavir in the presence of a concomitant inducer. Ritonavir induces CYP1A2, 2B6, 2C9, 2C19, and uridine 5'-diphospho-glucuronosyltransferase, whereas cobicistat does not. Therefore, recommendations for cobicistat with comedications that are extrapolated from studies using ritonavir may not be valid. Pharmacokinetic properties of the boosted antiretroviral can also affect interaction outcome with comedications. Problems can arise when switching patients from ritonavir to cobicistat regimens, particularly with medications that have a narrow therapeutic index such as warfarin. CONCLUSIONS: When assessing and managing potential interactions with ritonavir- or cobicistat-based regimens, clinicians need to be aware of important differences and distinctions between these agents. This is especially important for patients with multiple comorbidities and concomitant medications. Additional monitoring or medication dose adjustments may be needed when switching from one booster to another.