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AIMS: Trans/transfeminine women are disproportionally affected by HIV. Concerns regarding negative drug-drug interactions (DDIs) between ART drugs and gender-affirming hormone therapy (GAHT), specifically feminizing hormone therapy (FHT), may contribute to the lower ART uptake by trans women with HIV compared with their cis counterparts. The aim of this study is to investigate the bidirectional pharmacokinetic effects of components of FHT regimens (oral oestradiol and androgen-suppressing medications) with the ART regimen (bictegravir/emtricitabine/tenofovir alafenamide [B/F/TAF)]. METHODS: We present a protocol for a three-armed, parallel-group, longitudinal (6-month), DDI study. Group 1 includes 15 3trans women with HIV taking FHT and ART; group 2 includes 15 premenopausal cis women with HIV taking ART; group 3 includes 15 trans women without HIV taking FHT. Women with HIV must be on or switch to B/F/TAF at baseline and be virally suppressed for ≥3 months. Trans women must be taking a stable regimen of ≥2 mg daily oral oestradiol and an anti-androgen (pharmaceutical, and/or surgical, and/or medical) for ≥3 months. Plasma ART drug concentrations will be sampled at Month 2 and compared between groups 1 and 2. Serum oestradiol concentrations will be sampled at baseline and Month 2 visits and compared between groups 1 and 3. The primary outcomes are B/F/TAF pharmacokinetic parameters (Cmin, Cmax and AUC) and oestradiol concentrations (Cmin, C4h, Cmax and AUC) at month 2. DISCUSSION: This study is of global importance as it provides critical information regarding safe coadministration of B/F/TAF and FHT, both of which are life-saving therapies for trans women with HIV.
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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 (nâ=â8 with HIV, nâ=â7 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.
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Infecciones por VIH , Inhibidores de Integrasa VIH , VIH-1 , Humanos , Femenino , Adolescente , Adulto , Infecciones por VIH/tratamiento farmacológico , Proyectos Piloto , Emtricitabina/uso terapéutico , Estudios Transversales , Inhibidores de Integrasa VIH/uso terapéuticoRESUMEN
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.
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Fármacos Anti-VIH , Infecciones por VIH , Profilaxis Pre-Exposición , Minorías Sexuales y de Género , Masculino , Humanos , Femenino , Tenofovir/uso terapéutico , Emtricitabina/uso terapéutico , Homosexualidad Masculina , Infecciones por VIH/prevención & control , Infecciones por VIH/tratamiento farmacológico , Fármacos Anti-VIH/efectos adversos , Estudios TransversalesAsunto(s)
Tinturas para el Cabello , Hepatitis , Humanos , Tinturas para el Cabello/efectos adversos , Belleza , Piel , Enfermedad AgudaRESUMEN
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.
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Fármacos Anti-VIH/administración & dosificación , Cobicistat/administración & dosificación , Infecciones por VIH/tratamiento farmacológico , Ritonavir/administración & dosificación , Fármacos Anti-VIH/uso terapéutico , Sulfato de Atazanavir/administración & dosificación , Darunavir/administración & dosificación , Interacciones Farmacológicas , Humanos , Quinolonas/administración & dosificación , Ritonavir/uso terapéuticoRESUMEN
Background. Hepatitis C virus (HCV) coinfection occurs in 20-30% of Canadians living with HIV and is responsible for a heavy burden of morbidity and mortality. Purpose. To update national standards for management of HCV-HIV coinfected adults in the Canadian context with evolving evidence for and accessibility of effective and tolerable DAA therapies. The document addresses patient workup and treatment preparation, antiviral recommendations overall and in specific populations, and drug-drug interactions. Methods. A standing working group with HIV-HCV expertise was convened by The Canadian Institute of Health Research HIV Trials Network to review recently published HCV antiviral data and update Canadian HIV-HCV Coinfection Guidelines. Results. The gap in sustained virologic response between HCV monoinfection and HIV-HCV coinfection has been eliminated with newer HCV antiviral regimens. All coinfected individuals should be assessed for interferon-free, Direct Acting Antiviral HCV therapy. Regimens vary in content, duration, and success based largely on genotype. Reimbursement restrictions forcing the use of pegylated interferon is not acceptable if optimal patient care is to be provided. Discussion. Recommendations may not supersede individual clinical judgement. Treatment advances published since December 2015 are not considered in this document.
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The evolution of human immunodeficiency virus (HIV) treatment has improved our understanding and management of complex pharmacological issues that have driven improved outcomes and quality of life of the HIV-infected patient. These issues include adherence, long- and short-term toxicities, pharmacoenhancement, pharmacogenomics, therapeutic drug monitoring, differential penetration of drugs into sanctuary sites, such as the central nervous system, genital tract and small bowel, and drug-drug and drug-food interactions related to cytochrome P450 drug-metabolizing enzymes, uridine diphosphate glucuronyltransferases and drug transporters, to name a few. There is future promise, as an increased understanding of the immunopathogenesis of HIV and global public health initiatives are driving novel treatment approaches with goals to prevent, control and, ultimately, eradicate HIV.
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Fármacos Anti-VIH/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Calidad de Vida , Fármacos Anti-VIH/efectos adversos , Fármacos Anti-VIH/farmacocinética , Interacciones Farmacológicas , Monitoreo de Drogas , Interacciones Alimento-Droga , Salud Global , Humanos , Cooperación del Paciente , FarmacogenéticaRESUMEN
OBJECTIVE: To describe potential drug-drug interactions in the area of HIV/hepatitis C virus (HCV) coinfection and injection drug use, including those between antiretrovirals (ARVs), direct-acting antivirals (DAAs), and opioid-agonist therapy, and to supply a practical approach to their management. DATA SOURCES: We searched PubMed for relevant articles published up until February 2015 as well as conference reports and drug-drug-interaction Web sites. DATA SELECTION AND DATA EXTRACTION: We used the following search terms: pharmacokinetic and pharmacodynamic drug-drug interaction, opioid substitution, HIV, hepatitis and the individual names of the relevant agents of the following drug classes and the drug classes itself: reverse transcriptase inhibitors, nonnucleoside reverse transcriptase inhibitors, protease inhibitors, direct-acting antivirals, opioide, benzodiazepines, anticonvulsants, antidepressants and antipsychotics. Additional references were identified from a review of literature citations and drug-drug interaction Web sites. In our evaluation, we included German- and English-language studies and reports addressing drug-drug interactions between opioid agonist therapy and ARVs or DAAs. DATA SYNTHESIS: Pharmacokinetic data were available for all ARVs and DAAs except rilpivirine, indinavir, saquinavir, maraviroc, dolutegravir, and MK-8742 with buprenorphine as well as maraviroc with methadone Drug-drug interactions of potential clinical relevance are most likely to occur between opioid-replacement therapy and ARVs, particularly the nonnucleoside reverse transcriptase inhibitors, efavirenz and nevirapine, and HIV protease inhibitors. CONCLUSION: Integrase inhibitors may be safely coadministered with opioid-replacement therapy. With respect to HCV DAAs, most currently approved and late-stage investigational agents do not have clinically significant interactions with opioid-replacement therapy. ARV and DAAs may interact with other drug classes commonly used in the opioid-dependent population, including benzodiazepines, antidepressants, anticonvulsants, and antipsychotics.
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Analgésicos Opioides/uso terapéutico , Antivirales/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Hepatitis C/tratamiento farmacológico , Metadona/uso terapéutico , Abuso de Sustancias por Vía Intravenosa/tratamiento farmacológico , Analgésicos Opioides/efectos adversos , Antivirales/efectos adversos , Coinfección , Interacciones Farmacológicas , Infecciones por VIH/complicaciones , Inhibidores de la Proteasa del VIH/efectos adversos , Inhibidores de la Proteasa del VIH/uso terapéutico , Hepatitis C/complicaciones , Humanos , Metadona/efectos adversos , Tratamiento de Sustitución de Opiáceos , Inhibidores de la Transcriptasa Inversa/efectos adversos , Inhibidores de la Transcriptasa Inversa/uso terapéutico , Abuso de Sustancias por Vía Intravenosa/complicacionesRESUMEN
BACKGROUND: Hepatitis C virus (HCV) coinfection occurs in 20% to 30% of Canadians living with HIV and is responsible for a heavy burden of morbidity and mortality. Management of HIV-HCV coinfection is more complex due to the accelerated progression of liver disease, the timing and nature of antiretroviral and HCV therapy, mental health and addictions management, socioeconomic obstacles and drug-drug interactions between new HCV direct-acting antiviral therapies and antiretroviral regimens. OBJECTIVE: To update national standards for the management of HCV-HIV coinfected adults in the Canadian context. METHODS: A standing working group with specific clinical expertise in HIV-HCV coinfection was convened by The Canadian Institute of Health Research HIV Trials Network to review recently published data regarding HCV antiviral treatments and to update the Canadian HIV-HCV coinfection guidelines. RESULTS: Recent data suggest that the gap in sustained virological response rates between HCV monoinfection and HIV-HCV coinfection has been eliminated with newer HCV antiviral regimens. All HIV-HCV coinfected individuals should be assessed for HCV therapy. First-line treatment for genotypes 1 through 6 includes pegylated interferon and weight-based ribavirin dosing plus the nucleotide sofosbuvir for 12 weeks. Sofosbuvir in combination with the protease inhibitor simeprevir is another first-line consideration for genotype 1 infection. Sofosbuvir with ribavirin for 12 weeks (genotype 2) and 24 weeks (genotype 3) is also recommended as first-line treatment. DISCUSSION: Recommendations may not supersede individual clinical judgement.
HISTORIQUE: De 20 % à 30 % des Canadiens qui vivent avec le VIH sont co-infectés par le virus de l'hépatite C (VHC), lequel est responsable d'une morbidité et d'une mortalité importantes. La prise en charge du VIH et du VHC est plus complexe en raison de l'évolution accélérée de la maladie hépatique, du choix et des critères d'initiation de la thérapie antirétrovirale et du traitement anti-VHC, de la prise en charge de la santé mentale et des toxicomanies, des obstacles socioéconomiques et des interactions entre les nouvelles thérapies antivirales à action directe du VHC et les antirétroviraux. OBJECTIF: Mettre à jour les normes nationales pour la prise en charge des adultes co-infectés par le VHC et le VIH dans le contexte canadien. MÉTHODOLOGIE: Le Réseau canadien pour les essais VIH des Instituts de recherche en santé du Canada a réuni un groupe d'experts possédant des compétences cliniques en coinfection par le VIH et le VHC pour réviser les publications récentes sur les traitements antiviraux contre le VHC et mettre à jour les lignes directrices canadiennes sur la coinfection du VIH et du VHC. RÉSULTATS: Selon de récentes données, les nouvelles posologies antivirales ont éliminé la disparité entre le taux de réponse virologique soutenue de la monoinfection par le VIH et celui de la coinfection par le VIH et le VHC. Toutes les personnes co-infectées par le VIH et le VHC devraient subir une évaluation en vue de recevoir un traitement du VHC. Le traitement de première ligne du VHC des génotypes 1 à 6 inclut un régime composé d'interféron pégylé et de ribavirine dosée en fonction du poids, associé au sofosbuvir, un analogue des nucléotides, pendant 12 semaines. Le sofosbuvir combiné au siméprévir, un inhibiteur de la protéase, peut également constituer un traitement de première ligne pour l'infection par le génotype 1. Le sofosbuvir associé à de la ribavirine pendant 12 semaines (génotype 2) et 24 semaines (génotype 3) est également recommandé en première ligne. EXPOSÉ: Les recommandations ne se substituent pas nécessairement au jugement clinique personnel.
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Five long-acting (LA) antiretrovirals (ARVs) are currently available in a limited number of countries worldwide for HIV-1 prevention or treatment - cabotegravir, rilpivirine, lenacapavir, ibalizumab, and dapivirine. Implementing use of LA ARVs in routine clinical practice requires significant changes to the current framework of HIV-1 prevention, treatment, and service provision. Given the novelty, complexity, and interdisciplinary requirements of safe and optimal use of LA ARVs, consensus recommendations on the use of LA ARVs will assist clinicians in optimizing use of these agents. The purpose of these recommendations is to provide guidance for the clinical use of LA ARVs for HIV-1 treatment and prevention. In addition, future areas of research are identified and discussed.
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Fármacos Anti-VIH , Infecciones por VIH , VIH-1 , Humanos , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/prevención & control , VIH-1/efectos de los fármacos , Fármacos Anti-VIH/uso terapéutico , Fármacos Anti-VIH/administración & dosificación , Preparaciones de Acción Retardada , Consenso , Antirretrovirales/uso terapéutico , Antirretrovirales/administración & dosificaciónRESUMEN
Five long-acting (LA) antiretrovirals (ARVs) are currently available in a limited number of countries worldwide for HIV-1 prevention or treatment-cabotegravir, rilpivirine, lenacapavir, ibalizumab, and dapivirine. Implementing use of LA ARVs into routine clinical practice requires significant changes to the current framework of HIV-1 prevention, treatment, and service provision. Given the novelty, complexity, and interdisciplinary requirements needed to safely and optimally utilize LA ARVs, consensus recommendations on the use of LA ARVs will assist clinicians in optimizing use of these agents. The purpose of these recommendations is to provide guidance for the clinical use of LA ARVs for HIV-1 treatment and prevention. In addition, future areas of research are also identified and discussed.
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Fármacos Anti-VIH , Infecciones por VIH , VIH-1 , Humanos , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/prevención & control , VIH-1/efectos de los fármacos , Fármacos Anti-VIH/uso terapéutico , Fármacos Anti-VIH/administración & dosificación , Preparaciones de Acción Retardada , Consenso , Antirretrovirales/uso terapéutico , Antirretrovirales/administración & dosificaciónRESUMEN
BACKGROUND: Despite recent advances in hepatitis C (HCV) treatment, specifically the addition of direct acting antivirals (DAAs), pegylated interferon-alpha remains the backbone of HCV therapy. Therefore, the impact of DAAs on the management of co-morbid psychiatric illness and neuropsychiatric sequalae remains an ongoing concern during HCV therapy. This paper provides a review of the neuropsychiatric adverse effects of DAAs and drug-drug interactions (DDIs) between DAAs and psychiatric medications. METHODS: We conducted a Pubmed search using relevant search terms and hand searched reference lists of related review articles. In addition, we searched abstracts for major hepatology conferences and contacted respective pharmaceutical companies for additional studies. RESULTS: Limited data is available on the neuropsychiatric adverse effects of DAAs; however, data from major clinical trials suggest that DAAs have minimal neuropsychiatric risk. DAAs can potentially interact with a variety of psychotropic agents via cytochrome P450 and p-glycoprotein interactions. Triazolam, oral midazolam, St. John's Wort, carbamazepine and pimozide, are contraindicated with DAAs. DDIs between DAAs and antidepressants, anxiolytics, hypnotics, mood stabilizers, antipsychotics and treatments for opioid dependence are summarized. CONCLUSIONS: Although DAAs do not add significant neuropsychiatric risk, the potential for DDIs is high. Consideration of DDIs is paramount to improving medication adherence and mitigating adverse effects during HCV therapy.
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Antivirales/efectos adversos , Interacciones Farmacológicas , Hepatitis C/tratamiento farmacológico , Trastornos Mentales/tratamiento farmacológico , Psicotrópicos/uso terapéutico , Antivirales/uso terapéutico , Contraindicaciones , Hepatitis C/complicaciones , Humanos , Cumplimiento de la Medicación , Trastornos Mentales/inducido químicamente , Trastornos Mentales/complicaciones , Oligopéptidos/efectos adversos , Prolina/efectos adversos , Prolina/análogos & derivadosRESUMEN
BACKGROUND: Although some studies show higher antiretroviral concentrations in women compared to men, data are limited. We conducted a cross-sectional study of HIV-positive women to determine if protease inhibitor (PI) and non-nucleoside reverse transcriptase inhibitor (NNRTI) C(min) and Cmax values were significantly different than historical general population (predominantly male) averages and to evaluate correlates of higher concentrations. METHODS: HIV-positive women with virologic suppression (viral load < 50copies/mL) on their first antiretroviral regimen were enrolled. Timed blood samples for C(min) and Cmax were drawn weekly for 3 weeks. The ratio of each individual's median C(min) and Cmax to the published population mean values for their PI or NNRTI was calculated and assessed using Wilcoxon sign-rank. Intra- and inter-patient variability of antiretroviral drug levels was assessed using coefficient of variation and intra-class correlation. Linear regression was used to identify correlates of the square root-transformed C(min) and Cmax ratios. RESULTS: Data from 82 women were analyzed. Their median age was 41 years (IQR=36-48) and duration of antiretrovirals was 20 months (IQR=9-45). Median antiretroviral C(min) and Cmax ratios were 1.21 (IQR=0.72-1.89, p=0.003) (highest ratios for nevirapine and lopinavir) and 0.82 (IQR=0.59-1.14, p=0.004), respectively. Nevirapine and efavirenz showed the least and unboosted atazanavir showed the most intra- and inter-patient variability. Higher CD4+ count correlated with higher C(min). No significant correlates for Cmax were found. CONCLUSIONS: Compared to historical control data, C(min) in the women enrolled was significantly higher whereas Cmax was significantly lower. Antiretroviral C(min) ratios were highly variable within and between participants. There were no clinically relevant correlates of drug concentrations. TRIAL REGISTRATION: NCT00433979.
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Antirretrovirales/farmacocinética , Infecciones por VIH/metabolismo , Adulto , Alquinos , Antirretrovirales/sangre , Antirretrovirales/uso terapéutico , Sulfato de Atazanavir , Benzoxazinas/sangre , Benzoxazinas/farmacocinética , Benzoxazinas/uso terapéutico , Estudios Transversales , Ciclopropanos , Quimioterapia Combinada , Femenino , Infecciones por VIH/sangre , Infecciones por VIH/tratamiento farmacológico , Humanos , Modelos Lineales , Persona de Mediana Edad , Nevirapina/sangre , Nevirapina/farmacocinética , Nevirapina/uso terapéutico , Oligopéptidos/sangre , Oligopéptidos/farmacocinética , Oligopéptidos/uso terapéutico , Piridinas/sangre , Piridinas/farmacocinética , Piridinas/uso terapéutico , Factores de Riesgo , Carga ViralRESUMEN
BACKGROUND: Interactions between antiretroviral (ARV) therapy and medications to treat age-related comorbidities are a growing concern in the aging HIV population. OBJECTIVE: To investigate the association of age with potential drug-drug interactions (PDDIs) involving ARVs. METHODS: We studied ARV-treated patients attending a tertiary care center. PDDIs were classified as "red flag" (contraindicated) or "orange flag" (use with caution or dose adjustment). Logistic regression was used to determine the association of age with the occurrence of ≥1 PDDI. RESULTS: Of 914 patients (78% male, median age 49 years), older patients (age ≥50 years) were on more drugs than younger patients (total 9 vs 7; P < .0001) and were more likely to be on ritonavir-boosted protease inhibitors (PIs), integrase inhibitors, and non-ARV medications. Older patients were more likely to have ≥1 orange flag PDDI (71% vs 55%, P < .0001) and to have a red flag PDDI (5% vs 2%, P = .07), although the latter did not reach statistical significance. A 10-year increase in age was associated with an increased likelihood of ≥1 PDDI (odds ratio [OR] = 1.72; P < .0001) after adjusting for gender, race and number and class of ARVs. The effect of age was diminished after adjusting further for the number of non-ARV medications (OR = 1.28; P = .02) and use of cardiovascular drugs (OR = 1.16; P = .21). CONCLUSIONS: In our clinic population, older patients were more likely to have a PDDI because of the greater number of non-ARV medications, particularly cardiovascular agents.
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Antirretrovirales/efectos adversos , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Polifarmacia , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Antirretrovirales/administración & dosificación , Antirretrovirales/uso terapéutico , Comorbilidad , Estudios Transversales , Interacciones Farmacológicas , Femenino , Infecciones por VIH/epidemiología , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Ontario , Centros de Atención Terciaria , Adulto JovenRESUMEN
BACKGROUND: Hepatitis C virus (HCV) coinfection occurs in 20% to 30% of Canadians living with HIV, and is responsible for a heavy burden of morbidity and mortality. HIV-HCV management is more complex due to the accelerated progression of liver disease, the timing and nature of antiretroviral and HCV therapy, mental health and addictions management, socioeconomic obstacles and drug-drug interactions between new HCV direct-acting antiviral therapies and antiretroviral regimens. OBJECTIVE: To develop national standards for the management of HCV-HIV coinfected adults in the Canadian context. METHODS: A panel with specific clinical expertise in HIV-HCV co-infection was convened by The CIHR HIV Trials Network to review current literature, existing guidelines and protocols. Following broad solicitation for input, consensus recommendations were approved by the working group, and were characterized using a Class (benefit verses harm) and Level (strength of certainty) quality-of-evidence scale. RESULTS: All HIV-HCV coinfected individuals should be assessed for HCV therapy. Individuals unable to initiate HCV therapy should initiate antiretroviral therapy to slow liver disease progression. Standard of care for genotype 1 is pegylated interferon and weight-based ribavirin dosing plus an HCV protease inhibitor; traditional dual therapy for 24 weeks (for genotype 2/3 with virological clearance at week 4); or 48 weeks (for genotypes 2-6). Therapy deferral for individuals with mild liver disease may be considered. HIV should not be considered a barrier to liver transplantation in coinfected patients. DISCUSSION: Recommendations may not supersede individual clinical judgement.
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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 cÅur 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.
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Infecciones por VIH , Internado y Residencia , Humanos , Medicina Familiar y Comunitaria/educación , Farmacéuticos , Curriculum , Infecciones por VIH/tratamiento farmacológicoRESUMEN
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.
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COVID-19 , Humanos , Tratamiento Farmacológico de COVID-19 , Anticuerpos Monoclonales , Corticoesteroides/uso terapéuticoRESUMEN
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.
Asunto(s)
Fármacos Anti-VIH , Terapia Antirretroviral Altamente Activa , Infecciones por VIH , Testosterona , Personas Transgénero , Femenino , Humanos , Canadá/epidemiología , Estradiol/farmacocinética , Estradiol/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Testosterona/sangre , Interacciones Farmacológicas , Fármacos Anti-VIH/farmacocinética , Fármacos Anti-VIH/uso terapéuticoRESUMEN
Advances in antiretroviral therapy have turned HIV into a chronic, manageable disease. Patients often require treatment for co-morbid conditions as well as HIV, and consequently, pharmacokinetic interactions between antiretrovirals (ARVs) and other drug classes are an increasing concern. Protease inhibitors and non-nucleoside reverse transcriptase inhibitors are involved in the CYP450 or other transporter systems, and may be associated with higher risk of clinically significant drug interactions. One reverse transcriptase inhibitor, abacavir, has demonstrated weak inhibition of CYP3A4, 2D6 and 2C9 in vitro, but is not associated with any clinically significant interactions involving the CYP450 system. The integrase inhibitor raltegravir is not involved in the CYP450 system, and may be a suitable option to use when trying to minimize interactions with other drug classes. This review summarizes recently published data on clinically significant drug interactions between ARVs and other drug classes including antineoplastics, immunosuppressant transplant drugs, directly acting antivirals for hepatitis C, antifungals, antimalarials, corticosteroids, psychotropics, hormonal contraceptives, anticoagulants, drugs for pulmonary hypertension, and herbal products. In situations of suspected or potential interactions, close monitoring is warranted, and dose adjustments or substitutions may be required.