دورية أكاديمية
Real-world trough concentrations and effectiveness of long-acting cabotegravir and rilpivirine: a multicenter prospective observational study in Switzerland.
| العنوان: | Real-world trough concentrations and effectiveness of long-acting cabotegravir and rilpivirine: a multicenter prospective observational study in Switzerland. |
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| المؤلفون: | Thoueille P; Service and Laboratory of Clinical Pharmacology, Department of Laboratory Medicine and Pathology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland., Saldanha SA; Service and Laboratory of Clinical Pharmacology, Department of Laboratory Medicine and Pathology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland., Schaller F; Service and Laboratory of Clinical Pharmacology, Department of Laboratory Medicine and Pathology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland., Choong E; Service and Laboratory of Clinical Pharmacology, Department of Laboratory Medicine and Pathology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland., Munting A; Service of Infectious Diseases, Department of Medicine, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland., Cavassini M; Service of Infectious Diseases, Department of Medicine, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland., Braun D; Department of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, Zurich, Switzerland.; Institute of Medical Virology, University of Zurich, Zurich, Switzerland., Günthard HF; Department of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, Zurich, Switzerland.; Institute of Medical Virology, University of Zurich, Zurich, Switzerland., Kusejko K; Department of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, Zurich, Switzerland.; Institute of Medical Virology, University of Zurich, Zurich, Switzerland., Surial B; Department of Infectious Diseases, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland., Furrer H; Department of Infectious Diseases, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland., Rauch A; Department of Infectious Diseases, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland., Rougemont M; Primary Care Medicine Division, University Hospital Geneva, Geneva, Switzerland., Ustero P; Division of Infectious Diseases, Geneva University Hospitals, Faculty of Medicine, Geneva, Switzerland., Calmy A; Division of Infectious Diseases, Geneva University Hospitals, Faculty of Medicine, Geneva, Switzerland.; Department of Medicine, Faculty of Medicine, University of Geneva, Geneva, Switzerland., Stöckle M; Division of Infectious Diseases and Hospital Epidemiology, University Hospital Basel, University of Basel, Basel, Switzerland., Marzolini C; Service and Laboratory of Clinical Pharmacology, Department of Laboratory Medicine and Pathology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.; Division of Infectious Diseases and Hospital Epidemiology, University Hospital Basel, University of Basel, Basel, Switzerland.; Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool, UK., Di Benedetto C; Division of Infectious Diseases, Ente Ospedaliero Cantonale, Lugano, Switzerland., Bernasconi E; Division of Infectious Diseases, Ente Ospedaliero Cantonale, Lugano, Switzerland.; University of Geneva, University of Southern Switzerland, Lugano, Switzerland., Schmid P; Division of Infectious Diseases and Hospital Epidemiology, Cantonal Hospital St Gallen, St Gallen, Switzerland., Piso RJ; Department of Internal Medicine, Infectious Diseases and Hospital Epidemiology, Cantonal Hospital Olten, Switzerland., Andre P; Service and Laboratory of Clinical Pharmacology, Department of Laboratory Medicine and Pathology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland., Girardin FR; Service and Laboratory of Clinical Pharmacology, Department of Laboratory Medicine and Pathology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland., Guidi M; Service and Laboratory of Clinical Pharmacology, Department of Laboratory Medicine and Pathology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.; Centre for Research and Innovation in Clinical Pharmaceutical Sciences, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.; Institute of Pharmaceutical Sciences of Western Switzerland, University of Geneva, University of Lausanne, Geneva, Switzerland., Buclin T; Service and Laboratory of Clinical Pharmacology, Department of Laboratory Medicine and Pathology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland., Decosterd LA; Service and Laboratory of Clinical Pharmacology, Department of Laboratory Medicine and Pathology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland. |
| مؤلفون مشاركون: | Swiss HIV Cohort Study |
| المصدر: | The Lancet regional health. Europe [Lancet Reg Health Eur] 2023 Dec 13; Vol. 36, pp. 100793. Date of Electronic Publication: 2023 Dec 13 (Print Publication: 2024). |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: [Oxford] Country of Publication: England NLM ID: 101777707 Publication Model: eCollection Cited Medium: Internet ISSN: 2666-7762 (Electronic) Linking ISSN: 26667762 NLM ISO Abbreviation: Lancet Reg Health Eur Subsets: PubMed not MEDLINE |
| أسماء مطبوعة: | Original Publication: [Oxford] : Elsevier Ltd., [2020]- |
| مستخلص: | Background: The efficacy and tolerability of long-acting cabotegravir and rilpivirine were demonstrated in Phase III trials. However, low concentrations combined with other risk factors have been associated with an increased risk of virologic failure. This study aims to verify whether drug concentrations measured in a real-world setting are consistent with those previously reported. Methods: SHCS-879 is a nationwide observational study within the Swiss HIV Cohort Study for the monitoring of people with HIV (PWH) on long-acting cabotegravir plus rilpivirine. Samples were collected from March 2022 to March 2023. Findings: Overall, 725 samples were obtained from 186 PWH. Our data show a large inter-individual variability in cabotegravir and rilpivirine concentrations, with some individuals exhibiting repeatedly low concentrations. Rilpivirine trough concentrations were consistent with those from Phase III trials, while cabotegravir concentrations were lower. The first concentrations quartile was only slightly above the target of 664 ng/mL. Exploratory statistical analyses found 35% (p < 0·01) lower cabotegravir trough in males compared to females. Overall, 172 PWH (92%) remained suppressed and three experienced virologic failures (1·6%), of those, two had sub-optimal drug exposure. No association was found between low trough levels and detectable viral load. Interpretation: Real-world cabotegravir concentrations are substantially lower than previously reported. However, these concentrations appear sufficient to ensure sustained virological suppression in almost every PWH. These reassuring data challenge the rather conservative thresholds adopted to date, which may raise unnecessary concerns. Yet, our study reveals that some PWH have repeatedly very low drug levels, for reasons that remain to be elucidated. Funding: This work was funded by the Swiss National Science Foundation, grant number N ◦ 324730_192449. This study received no support from pharmaceutical industries. This study was performed within the framework of the Swiss HIV Cohort Study, supported by the Swiss National Science Foundation (grant #201369), by SHCS project #879, and by the SHCS research foundation. The SHCS data were gathered by the Five Swiss University Hospitals, two Cantonal Hospitals, 15 affiliated hospitals and 36 private physicians (listed in http://www.shcs.ch/180-health-care-providers). Competing Interests: M.C. reports grants and payment for expert testimony from Gilead, MSD and ViiV, and support for attending meetings from Gilead, paid to his institution outside of the submitted work. D.B. has received honoraria for advisory board from the companies Gilead, MSD, and ViiV, and support for attending meetings from ViiV and Gilead. H.F.G. has received unrestricted research grants from Gilead Sciences; fees for data and safety monitoring board membership from Merck; consulting/advisory board membership fees from Gilead Sciences, Johnson and Johnson, Janssen, Novartis, and ViiV Healthcare; and grants from the Swiss National Science Foundation, the Yvonne Jacob Foundation, from National Institutes of Health and unrestricted research grants from Gilead Sciences. B.S. reports support for travel grants and advisory boards from Gilead Sciences and ViiV, paid to his institution outside of the submitted work. The institution of H.F. received educational grants from ViiV, MSD, AbbVie, Gilead, and Sandoz paid to the institution. M.S. reports advisory board paid to his institution by Gilead, MSD, ViiV, Moderna and Pfizer. The institution of A.R. received grants from Gilead; support for attending meetings from Gilead and Pfizer; and advisory boards from MSD and Moderna. C.M. has received speaker honoraria from ViiV, MSD, and Gilead unrelated to this work. C.D.B. received travel grant for congress participation from Gilead. The institution of E.B. received grants from the Swiss National Science Foundation; grants from MSD; support for attending meetings from Gilead, MSD, ViiV and Pfizer; and advisory boards from Gilead, MSD, ViiV, Pfizer, Moderna, AstraZeneca, Abbvie and Lilly. The institution of P.S. received honoraria for advisory board and support for attending meetings from ViiV and Gilead. The other authors declare no conflict of interest. (© 2023 The Author(s).) |
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| فهرسة مساهمة: | Keywords: Drug concentration monitoring; Long-acting cabotegravir and rilpivirine; Real-world |
| تواريخ الأحداث: | Date Created: 20240101 Latest Revision: 20240103 |
| رمز التحديث: | 20240103 |
| مُعرف محوري في PubMed: | PMC10757247 |
| DOI: | 10.1016/j.lanepe.2023.100793 |
| PMID: | 38162253 |
| قاعدة البيانات: | MEDLINE |
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Full Text Finder | تدمد: | 2666-7762 |
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| DOI: | 10.1016/j.lanepe.2023.100793 |