63 results on '"Lê MP"'
Search Results
2. Sialolithiasis in an HIV-1-infected patient treated with atazanavir/ritonavir monotherapy.
- Author
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Lê MP, Stitou H, Soulie C, Katlama C, and Peytavin G
- Published
- 2013
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3. Pharmacokinetic interaction between maraviroc and etravirine in HIV-infected patients receiving regimens containing both drugs and no ritonavir-boosted protease inhibitor.
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Lê MP, Solas C, Garraffo R, Gagnieu MC, Muret P, Yeni P, Dhiver C, Katlama C, Poizot-Martin I, Durant J, and Peytavin G
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- 2012
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4. Therapeutic drug monitoring and virological response at week 48 in a cohort of HIV-1-infected patients switching to dolutegravir/rilpivirine dual maintenance therapy (ANRS-MIE-BIRIDER study).
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Lemaitre F, Lagoutte-Renosi J, Gagnieu MC, Parant F, Venisse N, Grégoire M, Bouchet S, Garraffo R, Lê MP, Muret P, Comets E, Solas C, and Peytavin G
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- Humans, Retrospective Studies, Bayes Theorem, Drug Monitoring, Rilpivirine therapeutic use, Oxazines, Pyridones therapeutic use, Heterocyclic Compounds, 3-Ring adverse effects, Viral Load, HIV Infections, HIV-1, Anti-HIV Agents therapeutic use, Acquired Immunodeficiency Syndrome drug therapy
- Abstract
Aims: Dolutegravir (DTG) and rilpivirine (RPV) dual therapy is now recommended as a switch option in virologically suppressed HIV patients. Literature suggests that virological failure with dual therapy could possibly relate to subtherapeutic drug concentrations. In this study, we aimed at describing the DTG and RPV trough plasma concentrations (Cmin) and plasma HIV-1 RNA viral load (VL) during maintenance dual therapy., Methods: We performed a retrospective analysis of DTG and RPV therapeutic drug monitoring in people living with HIV/AIDS (PLWHA) with dual therapy in 9 French centres. DTG and RPV trough plasma concentrations were estimated using a Bayesian approach to predict Cmin. The relationship between the pharmacokinetics of DTG and RPV and VL > 50 copies (cp)/mL was explored using joint nonlinear mixed models. The frequency of subtherapeutic threshold (DTG Cmin below 640 ng/mL and RPV Cmin below 50 ng/mL) were compared between PLWHA presenting VL > 50 cp/mL or not during the study., Results: At baseline, 209 PLWHA were enrolled in the study. At week 48, 19 people living with HIV/AIDS (9.1%) discontinued their treatment and 15 PLWHA (7.1%) exhibited VL > 50 cp/mL. Six PLWHA out of 15 (40.0%) with VL > 50 cp/mL during the follow-up had at least 1 Cmin below the respective thresholds while only 26/194 patients (13.4%) without virological replication had at least 1 concentration below the threshold (P = .015)., Conclusion: A majority of PLWHA receiving DTG/RPV maintenance dual therapy demonstrated VL < 50 cp/mL but virological replication was more frequent in people living with HIV/AIDS with subtherapeutic Cmin., (© 2023 The British Pharmacological Society.)
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- 2024
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5. Dabigatran-reversal failure using standard dose of idarucizumab: a systematic review and meta-analysis of cases.
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Melicine S, Billoir P, Faille D, Grove EL, Lê MP, Ajzenberg N, Smadja DM, and Gendron N
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- 2023
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6. [Human immunodeficiency virus and venous thromboembolism: Role of direct oral anticoagulants].
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Bentounes NK, Le Hingrat Q, Planquette B, Darnige L, Khider L, Sanchez O, Smadja DM, Mauge L, Lê MP, Mirault T, and Gendron N
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- Humans, Anticoagulants adverse effects, HIV, Hemorrhage, Administration, Oral, Venous Thromboembolism epidemiology, Venous Thromboembolism prevention & control, Venous Thromboembolism drug therapy, Thrombosis etiology
- Abstract
Nowadays, thanks to highly active antiretroviral therapy (HAART), human immunodeficiency virus (HIV) infection is transforming into a chronic disease. The life expectancy of people living with HIV (PWH) has increased, as well as their risk of developing several co-morbidities, in particular cardiovascular diseases. In addition, the incidence of venous thromboembolism (VTE) is increased in PWH with a 2 to 10 times higher incidence when compared to the general population. Over the last decade, direct oral anticoagulants (DOACs) have been widely used in the treatment and prevention of VTE and non-valvular atrial fibrillation. DOACs are characterized by a rapid onset of activity, a predictable response and a relatively wide therapeutic window. Nevertheless, drug interactions exist between HAART and DOACs, exposing PWH to a theoretically increased bleeding or thrombotic risk. DOACs are substrates of the transport protein P-glycoprotein and/or of isoforms of cytochromes P450 pathway, which can be affected by some antiretroviral drugs. Limited guidelines are available to assist physicians with the complexity of those drug-drug interactions. The aim of this paper is to provide an updated review on the evidence of the high risk of VTE in PWH and the place of DOAC therapy in this population., (Copyright © 2023 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier Masson SAS. All rights reserved.)
- Published
- 2023
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7. Doravirine Exposure Decreased by Dialysis in a HIV Patient: A Grand Round.
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Fromage Y, Codde C, Monchaud C, Labriffe M, Lê MP, Faucher JF, and Woillard JB
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- Male, Humans, Aged, Renal Dialysis, Pyridones therapeutic use, Anti-HIV Agents therapeutic use, Teaching Rounds, HIV Infections drug therapy
- Abstract
Background: The authors report the case of a 66-year-old male patient who was hemodialyzed 3 times per week for chronic renal failure and treated with 100 mg of doravirine once daily in combination with dolutegravir for HIV-1. No dose adjustment is required for doravirine in cases of severe renal injury, but the effect of dialysis on its exposure is poorly understood., Methods Results: Two series of 2 samples were drawn before and after 4-hour hemodialysis and showed an average doravirine concentration decrease of 48.1 ± 6.7%. The effects of hemodialysis were important, contrary to what was expected and has been previously reported. In addition, intraindividual variability was low. Nevertheless, because the concentrations reported were largely above the inhibitory concentration 50 (IC 50 ), no dose adjustment was required., Conclusions: The decrease in doravirine concentration due to hemodialysis observed in this case report was quite significant. Therefore, therapeutic drug monitoring might be recommended in certain patients undergoing doravirine treatment also on hemodialysis., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)
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- 2023
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8. Comment on: Population pharmacokinetics of the rilpivirine long-acting formulation after intramuscular dosing in healthy subjects and people living with HIV.
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Benaboud S, Solas C, Bouchet S, Gregoire M, Lemaitre F, Venisse N, Lê MP, Muret P, Parant F, Neant N, Boujafaar S, Lagoutte-Renosi J, Garraffo R, and Peytavin G
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- Humans, Rilpivirine therapeutic use, Healthy Volunteers, Anti-HIV Agents therapeutic use, HIV Infections drug therapy
- Published
- 2023
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9. Pharmaco-virological algorithm to target risk of drug resistance among a population of HIV-infected key populations in Togo.
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Ferré VM, Bitty-Anderson AM, Peytavin G, Lê MP, Dagnra CA, Coppée R, Gbeasor-Komlanvi FA, Descamps D, Charpentier C, and Ekouevi DK
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- Male, Humans, Female, Homosexuality, Male, Togo epidemiology, Cross-Sectional Studies, Anti-Retroviral Agents therapeutic use, Viral Load, Drug Resistance, Viral genetics, HIV Infections, Sexual and Gender Minorities, Sex Workers, Anti-HIV Agents therapeutic use
- Abstract
No data about antiretroviral (ARV) treatment coverage and virological response are available among key populations (female sex workers [FSW] and Men having Sex with Men [MSM]) in Togo. This study aimed to both describe Human Immunodeficiency Virus (HIV) immunovirological status and evaluate the pertinence of an original algorithm combining pharmacology (PK) and viral load (VL) to identify subjects at risk of ARV drug resistance. A cross-sectional multicentric study was conducted in 2017 in Togo. Our PK-virological algorithm (PK-VA) defines subjects at risk of resistance when exhibiting both detectable plasma drug concentrations and VL > 200 c/mL. Among the 123 FSW and 136 MSM included, 50% and 66% were receiving ARV, with 69% and 80% of them successfully-treated, respectively. Genotypes showed drug-resistance mutation in 58% and 63% of nonvirologically controlled (VL > 200 c/mL) ARV-treated FSW and MSM, respectively. PK-VA would have enabled to save 75% and 72% of genotypic tests, for FSW and MSM, respectively. We reported first data about HIV care cascade among key populations in Togo, highlighting they are tested for HIV but linkage to care remains a concern. Furthermore, 70%-80% of ARV-treated participants experienced virological success. In limited resources settings, where genotyping tests are beyond reach, PK-VA might be an easiest solution to sort out patients needing ARV adaptation due to resistance., (© 2023 The Authors. Journal of Medical Virology published by Wiley Periodicals LLC.)
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- 2023
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10. Current Advances in Lung Ultrasound in COVID-19 Critically Ill Patients: A Narrative Review.
- Author
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Lê MP, Jozwiak M, and Laghlam D
- Abstract
Lung ultrasound (LUS) has a relatively recent democratization due to the better availability and training of physicians, especially in intensive care units. LUS is a relatively cheap and easy-to-learn and -use bedside technique that evaluates pulmonary morphology when using simple algorithms. During the global COVID-19 pandemic, LUS was found to be an accurate tool to quickly diagnose, triage and monitor patients with COVID-19 pneumonia. This paper aims to provide a comprehensive review of LUS use during the COVID-19 pandemic. The first section of our work defines the technique, the practical approach and the semeiotic signs of LUS examination. The second section exposed the COVID-19 pattern in LUS examination and the difference between the differential diagnosis patterns and the well-correlation found with computer tomography scan findings. In the third section, we described the utility of LUS in the management of COVID-19 patients, allowing an early diagnosis and triage in the emergency department, as the monitoring of pneumonia course (pneumonia progression, alveolar recruitment, mechanical ventilation weaning) and detection of secondary complications (pneumothorax, superinfection). Moreover, we describe the usefulness of LUS as a marker of the prognosis of COVID-19 pneumonia in the fourth section. Finally, the 5th part is focused on describing the interest of the LUS, as a non-ionized technique, in the management of pregnant COVID-19 women.
- Published
- 2022
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11. Viral suppression and HIV-1 drug resistance 1 year after pragmatic transitioning to dolutegravir first-line therapy in Malawi: a prospective cohort study.
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Schramm B, Temfack E, Descamps D, Nicholas S, Peytavin G, Bitilinyu-Bangoh JE, Storto A, Lê MP, Abdi B, Ousley J, Kalua T, Calvez V, Jahn A, Marcelin AG, and Szumilin E
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- Adult, Anti-Retroviral Agents therapeutic use, Drug Resistance, Heterocyclic Compounds, 3-Ring therapeutic use, Humans, Lamivudine pharmacology, Lamivudine therapeutic use, Malawi, Oxazines, Piperazines, Prospective Studies, Pyridones, Retrospective Studies, Reverse Transcriptase Inhibitors therapeutic use, Tenofovir therapeutic use, Viral Load, Anti-HIV Agents pharmacology, Anti-HIV Agents therapeutic use, HIV Infections drug therapy, HIV Seropositivity drug therapy, HIV-1 genetics
- Abstract
Background: Many countries are now replacing non-nucleoside reverse transcriptase inhibitor (NNRTI)-based first-line antiretroviral therapy (ART) with a regimen containing tenofovir disoproxil fumarate, lamivudine, and dolutegravir (TLD). Recognising laboratory limitations, Malawi opted to transition those on NNRTI-based first-line ART to TLD without viral load testing. We aimed to assess viral load and HIV drug resistance during 1 year following transition to TLD without previous viral load testing., Methods: In this prospective cohort study, we monitored 1892 adults transitioning from NNRTI-based first-line ART to the TLD regimen in the Médecins Sans Frontières-supported decentralised HIV programme in Chiradzulu District, Malawi. Eligible adults were enrolled between Jan 17 and May 11, 2019, at Ndunde and Milepa health centres, and between March 8 and May 11, 2019, at the Boma clinic. Viral load at the start of the TLD regimen was assessed retrospectively and measured at month 3, 6, and 12, and additionally at month 18 for those ever viraemic (viral load ≥50 copies per mL). Dolutegravir minimal plasma concentrations (C
min ) were determined for individuals with viraemia. Drug-resistance testing was done at the start of TLD regimen and at viral failure (viral load ≥50 copies per mL, followed by viral load ≥500 copies per mL; resistance defined as Stanford score ≥15)., Findings: Of 1892 participants who transitioned to the TLD regimen, 101 (5·3%) were viraemic at TLD start. 89 of 101 had drug-resistance testing with 31 participants (34·8%) with Lys65Arg mutation, 48 (53·9%) with Met184Val/Ile, and 42 (40·4%) with lamivudine and tenofovir disoproxil fumerate dual resistance. At month 12 (in the per-protocol population), 1725 (97·9% [95% CI 97·1-98·5]) of 1762 had viral loads of less than 50 copies per mL, including 83 (88·3% [80·0-94·0]) of 94 of those who were viraemic at baseline. At month 18, 35 (97·2% [85·5-99·9]) of 36 who were viraemic at TLD start with lamivudine and tenofovir disoproxil fumarate resistance and 27 (81·8% [64·5-93·0]) of 33 of those viraemic at baseline without resistance had viral load suppression. 14 of 1838 with at least two viral load tests upon transitioning had viral failure (all with at least one dolutegravir Cmin value <640 ng/mL; active threshold), suggesting suboptimal adherence. High baseline viral load was associated with viral failure (adjusted odds ratio [aOR] 14·1 [2·3-87·4] for 1000 to <10 000 copies per mL; aOR 64·4 [19·3-215·4] for ≥10 000 copies per mL). Two people with viral failure had dolutegravir resistance at 6 months (Arg263Lys or Gly118Arg mutation), both were viraemic with lamivudine and tenofovir disoproxil fumarate resistance at baseline., Interpretation: High viral load suppression 1 year after introduction of the TLD regimen supports the unconditional transition strategy in Malawi. However, high pre-transition viral load, ongoing adherence challenges, and possibly existing nucleoside reverse transcriptase inhibitor resistance can lead to rapid development of dolutegravir resistance in a few individuals. This finding highlights the importance of viral load monitoring and dolutegravir-resistance surveillance after mass transitioning to the TLD regimen., Funding: Médecins Sans Frontières., Translations: For the French and Portuguese translations of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests DD reports honoraria for attending symposia, research grants, and support for attending meetings or travel from Gilead Sciences, MSD, Janssen-Cilag, and Merck Sharp and Dohme. A-GM reports funds for attending symposia, speaking, and research grants from ViiVHealthcare, Gilead Sciences, Theratechnologies, and Merck Sharp & Dohme. GP reports consulting fees from Gilead Sciences, ViiVHealthcare, Merck, Takeda, Pfizer, and TheraTechnologies; and honoraria from Gilead Sciences, ViiVHealthcare, and Merck. VC reports consulting fees and payment or honoraria from Gilead Sciences, ViiVHealthcare, and MSD; he is founder and member of the board of SkinDermic. All other authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)- Published
- 2022
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12. Bictegravir pharmacokinetics in a late-presenting HIV-1-infected pregnant woman: a case report.
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Lê MP, Ferré VM, Mazy F, Bourgeois-Moine A, Damond F, Matheron S, Descamps D, Ghosn J, and Peytavin G
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- Amides, Female, Heterocyclic Compounds, 3-Ring therapeutic use, Humans, Piperazines, Pregnancy, Pregnant Women, Pyridones, HIV-1
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- 2022
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13. Remdesivir plus standard of care versus standard of care alone for the treatment of patients admitted to hospital with COVID-19 (DisCoVeRy): a phase 3, randomised, controlled, open-label trial.
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Ader F, Bouscambert-Duchamp M, Hites M, Peiffer-Smadja N, Poissy J, Belhadi D, Diallo A, Lê MP, Peytavin G, Staub T, Greil R, Guedj J, Paiva JA, Costagliola D, Yazdanpanah Y, Burdet C, and Mentré F
- Subjects
- Adenosine Monophosphate therapeutic use, Aged, Alanine therapeutic use, COVID-19 mortality, Europe, Extracorporeal Membrane Oxygenation, Female, Hospitalization, Humans, Male, Middle Aged, Oxygen administration & dosage, Respiration, Artificial, COVID-19 Drug Treatment, Adenosine Monophosphate analogs & derivatives, Alanine analogs & derivatives, Antiviral Agents therapeutic use, COVID-19 therapy, Standard of Care
- Abstract
Background: The antiviral efficacy of remdesivir against SARS-CoV-2 is still controversial. We aimed to evaluate the clinical efficacy of remdesivir plus standard of care compared with standard of care alone in patients admitted to hospital with COVID-19, with indication of oxygen or ventilator support., Methods: DisCoVeRy was a phase 3, open-label, adaptive, multicentre, randomised, controlled trial conducted in 48 sites in Europe (France, Belgium, Austria, Portugal, Luxembourg). Adult patients (aged ≥18 years) admitted to hospital with laboratory-confirmed SARS-CoV-2 infection and illness of any duration were eligible if they had clinical evidence of hypoxaemic pneumonia, or required oxygen supplementation. Exclusion criteria included elevated liver enzymes, severe chronic kidney disease, any contraindication to one of the studied treatments or their use in the 29 days before random assignment, or use of ribavirin, as well as pregnancy or breastfeeding. Participants were randomly assigned (1:1:1:1:1) to receive standard of care alone or in combination with remdesivir, lopinavir-ritonavir, lopinavir-ritonavir and interferon beta-1a, or hydroxychloroquine. Randomisation used computer-generated blocks of various sizes; it was stratified on severity of disease at inclusion and on European administrative region. Remdesivir was administered as 200 mg intravenous infusion on day 1, followed by once daily, 1-h infusions of 100 mg up to 9 days, for a total duration of 10 days. It could be stopped after 5 days if the participant was discharged. The primary outcome was the clinical status at day 15 measured by the WHO seven-point ordinal scale, assessed in the intention-to-treat population. Safety was assessed in the modified intention-to-treat population and was one of the secondary outcomes. This trial is registered with the European Clinical Trials Database, EudraCT2020-000936-23, and ClinicalTrials.gov, NCT04315948., Findings: Between March 22, 2020, and Jan 21, 2021, 857 participants were enrolled and randomly assigned to remdesivir plus standard of care (n=429) or standard of care only (n=428). 15 participants were excluded from analysis in the remdesivir group, and ten in the control group. At day 15, the distribution of the WHO ordinal scale was: (1) not hospitalised, no limitations on activities (61 [15%] of 414 in the remdesivir group vs 73 [17%] of 418 in the control group); (2) not hospitalised, limitation on activities (129 [31%] vs 132 [32%]); (3) hospitalised, not requiring supplemental oxygen (50 [12%] vs 29 [7%]); (4) hospitalised, requiring supplemental oxygen (76 [18%] vs 67 [16%]); (5) hospitalised, on non-invasive ventilation or high flow oxygen devices (15 [4%] vs 14 [3%]); (6) hospitalised, on invasive mechanical ventilation or extracorporeal membrane oxygenation (62 [15%] vs 79 [19%]); (7) death (21 [5%] vs 24 [6%]). The difference between treatment groups was not significant (odds ratio 0·98 [95% CI 0·77-1·25]; p=0·85). There was no significant difference in the occurrence of serious adverse events between treatment groups (remdesivir, 135 [33%] of 406 vs control, 130 [31%] of 418; p=0·48). Three deaths (acute respiratory distress syndrome, bacterial infection, and hepatorenal syndrome) were considered related to remdesivir by the investigators, but only one by the sponsor's safety team (hepatorenal syndrome)., Interpretation: No clinical benefit was observed from the use of remdesivir in patients who were admitted to hospital for COVID-19, were symptomatic for more than 7 days, and required oxygen support., Funding: European Union Commission, French Ministry of Health, Domaine d'intérêt majeur One Health Île-de-France, REACTing, Fonds Erasme-COVID-Université Libre de Bruxelles, Belgian Health Care Knowledge Centre, Austrian Group Medical Tumor, European Regional Development Fund, Portugal Ministry of Health, Portugal Agency for Clinical Research and Biomedical Innovation., Translation: For the French translation of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests DC reports grants and lecture fees from Janssen and lecture fees from Gilead, outside the submitted work. FM reports grants and consulting fees from Da Volterra, grants from Sanofi, and consulting fees from Ipsen, outside the submitted work. MH reports grants from The Belgian Center for Knowledge (KCE), the Fonds Erasme-COVID-Université Libre de Bruxelles and the EU-Horizon programme, for the submitted work; and has received support for attending meetings from Pfizer; support for participation on an advisory board for therapeutics on COVID-19; and support for leadership for the Belgian guidelines on therapeutics for COVID-19 and acting as a treasurer for the Belgian Society of Clinical Microbiology and Infectious Diseases. JP reports lecture fees from Gilead; support for attending meetings from Gilead, Eumedica, Merck Sharp & Dohme, outside the submitted work. GP reports grants or contracts from Gilead Sciences, Merck France, Takeda, TheraTechnologies, and ViiV Healthcare; consulting fees from Gilead Sciences, Merck France, Takeda, TheraTechnologies, and ViiV Healthcare; lecture fees from Gilead Sciences, Merck France, and ViiV Healthcare; support for attending meetings from Gilead Sciences; and participation in a Data Safety and Monitoring Board for Gilead Sciences, Merck France, and ViiV Healthcare, outside the submitted work. CB reports participation in a Data Safety and Monitoring Board for 4Living Biotech; and consulting fees from Da Volterra and Mylan Pharmaceuticals, outside the submitted work. RG reports consulting fees from Celgene, Novartis, Roche, Bristol Myers Squibb, Takeda, Abbvie, AstraZeneca, Janssen, Merck Sharp & Dohme, Merck, Gilead, and Daiichi Sankvo; lecture fees from Celgene, Roche, Merck, Takeda, AstraZeneca, Novartis, Amgen, Bristol Myers Squibb, Merck Sharp & Dohme, Sandoz, Abbvie, Gilead, and Daiichi Sankvo; support for attending meetings from Roche, Amgen, Janssen, AstraZeneca, Novartis, Merck Sharp & Dohme, Celgene, Gilead, Bristol Myers Squibb, Abbvie, and Daiichi Sankvo; participation in a Data Safety and Monitoring Board for Celgene, Novartis, Roche, Bristol Myers Squibb, Takeda, Abbvie, AstraZeneca, Janssen, Merck Sharp & Dohme, Merck, Gilead, and Daiichi Sankyo; research grants from Celgene, Roche, Merck, Takeda, AstraZeneca, Novartis, Amgen, Bristol Myers Squibb, Merck Sharp & Dohme, Sandoz, Abbvie, Gilead, and Daiichi Sankyo. J-AP reports consulting fees from Pfizer, Merck Sharp & Dohme, and Janssen-Cilag; lecture fees from Pfizer; and support for attending meetings from Pfizer. All other authors decalre no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)
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- 2022
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14. An open-label randomized controlled trial of the effect of lopinavir/ritonavir, lopinavir/ritonavir plus IFN-β-1a and hydroxychloroquine in hospitalized patients with COVID-19.
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Ader F, Peiffer-Smadja N, Poissy J, Bouscambert-Duchamp M, Belhadi D, Diallo A, Delmas C, Saillard J, Dechanet A, Mercier N, Dupont A, Alfaiate T, Lescure FX, Raffi F, Goehringer F, Kimmoun A, Jaureguiberry S, Reignier J, Nseir S, Danion F, Clere-Jehl R, Bouiller K, Navellou JC, Tolsma V, Cabié A, Dubost C, Courjon J, Leroy S, Mootien J, Gaci R, Mourvillier B, Faure E, Pourcher V, Gallien S, Launay O, Lacombe K, Lanoix JP, Makinson A, Martin-Blondel G, Bouadma L, Botelho-Nevers E, Gagneux-Brunon A, Epaulard O, Piroth L, Wallet F, Richard JC, Reuter J, Staub T, Lina B, Noret M, Andrejak C, Lê MP, Peytavin G, Hites M, Costagliola D, Yazdanpanah Y, Burdet C, and Mentré F
- Subjects
- Adult, Drug Combinations, Female, Humans, Male, Middle Aged, Treatment Outcome, Antiviral Agents therapeutic use, Hydroxychloroquine therapeutic use, Interferon beta-1a therapeutic use, Lopinavir therapeutic use, Ritonavir therapeutic use, COVID-19 Drug Treatment
- Abstract
Objectives: We evaluated the clinical, virological and safety outcomes of lopinavir/ritonavir, lopinavir/ritonavir-interferon (IFN)-β-1a, hydroxychloroquine or remdesivir in comparison to standard of care (control) in coronavirus 2019 disease (COVID-19) inpatients requiring oxygen and/or ventilatory support., Methods: We conducted a phase III multicentre, open-label, randomized 1:1:1:1:1, adaptive, controlled trial (DisCoVeRy), an add-on to the Solidarity trial (NCT04315948, EudraCT2020-000936-23). The primary outcome was the clinical status at day 15, measured by the WHO seven-point ordinal scale. Secondary outcomes included quantification of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in respiratory specimens and pharmacokinetic and safety analyses. We report the results for the lopinavir/ritonavir-containing arms and for the hydroxychloroquine arm, trials of which were stopped prematurely., Results: The intention-to-treat population included 583 participants-lopinavir/ritonavir (n = 145), lopinavir/ritonavir-IFN-β-1a (n = 145), hydroxychloroquine (n = 145), control (n = 148)-among whom 418 (71.7%) were male, the median age was 63 years (IQR 54-71), and 211 (36.2%) had a severe disease. The day-15 clinical status was not improved with the investigational treatments: lopinavir/ritonavir versus control, adjusted odds ratio (aOR) 0.83, (95% confidence interval (CI) 0.55-1.26, p 0.39), lopinavir/ritonavir-IFN-β-1a versus control, aOR 0.69 (95%CI 0.45-1.04, p 0.08), and hydroxychloroquine versus control, aOR 0.93 (95%CI 0.62-1.41, p 0.75). No significant effect of investigational treatment was observed on SARS-CoV-2 clearance. Trough plasma concentrations of lopinavir and ritonavir were higher than those expected, while those of hydroxychloroquine were those expected with the dosing regimen. The occurrence of serious adverse events was significantly higher in participants allocated to the lopinavir/ritonavir-containing arms., Conclusion: In adults hospitalized for COVID-19, lopinavir/ritonavir, lopinavir/ritonavir-IFN-β-1a and hydroxychloroquine improved neither the clinical status at day 15 nor SARS-CoV-2 clearance in respiratory tract specimens., (Copyright © 2021 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)
- Published
- 2021
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15. A case of tuberculosis and black-grain eumycetoma co-infection in a non-endemic country: clinical presentation and therapeutic management.
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Vu S, Belaube N, Canestri A, Develoux M, Moreno A, Fourniols E, Lê MP, Lassel L, Pialoux G, and Calin R
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- Antifungal Agents therapeutic use, Humans, Spine, Coinfection diagnosis, Coinfection drug therapy, Mycetoma diagnosis, Mycetoma drug therapy, Tuberculosis complications, Tuberculosis diagnosis, Tuberculosis drug therapy
- Abstract
We report a case of black-grain eumycetoma co-localized with Mycobacterium tuberculosis infection, presenting as a painless leg abscess and associated with vertebral tuberculosis. The rare association of these two pathogens raises several challenges regarding foreseeable drug interactions, side effects, the most appropriate management, and the potential link between these two diseases., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)
- Published
- 2021
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16. Diaphragm Dysfunction After Cardiac Surgery: Reappraisal.
- Author
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Laghlam D, Lê MP, Srour A, Monsonego R, Estagnasié P, Brusset A, and Squara P
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- Coronary Artery Bypass, Humans, Length of Stay, Postoperative Complications diagnostic imaging, Postoperative Complications epidemiology, Retrospective Studies, Cardiac Surgical Procedures adverse effects, Diaphragm diagnostic imaging
- Abstract
Objectives: The aim of this study was to re-investigate the incidence, risk factors, and outcomes of postoperative diaphragmatic dysfunction (DD) with actual cardiac surgery procedures., Design: Single-center, retrospective, observational study based on a prospectively collected database., Setting: Tertiary care cardiac surgery center., Participants: Patients who underwent cardiac surgery between January 2016 and September 2019., Interventions: None., Measurements and Main Results: The DD group included patients with clinically perceptible diaphragmatic paralysis, which was confirmed by chest ultrasound (amplitude of the diaphragm movement in time-motion mode at rest, after a sniff test). The primary endpoint was the incidence of DD. Among 3,577 patients included, the authors found 272 cases of DD (7.6%). Individuals with DD had more arterial hypertension (64.3% v 52.6%; p < 0.0001), higher body mass index (BMI) (28 [25-30] kg/m
2 v 26 [24-29] kg/m2 ; p < 0.0002), and higher incidence of coronary bypass grafting (CABG) (58.8% v 46.6%; p = 0.0001). DD was associated with more postoperative pneumonia (23.9% v 8.7%; p < 0.0001), reintubation (8.8% v 2.9%; p < 0.0001), tracheotomy (3.3% v 0.3%; p < 0.0001), noninvasive ventilation (45.6% v 5.4%; p < 0.0001), duration of mechanical ventilation (five [four-11] hours v four [three-six] hours; p < 0.0001), and intensive care unit and hospital stays (14 [11-17] days v 13 [11-16] days; p < 0.0001). In multivariate analysis, DD was associated with CABG (odds ratio [OR] 1.9 [1.5-2.6]; p = 0.0001), arterial hypertension (OR 1.4 [1.1-1.9]; p = 0.008), and BMI (OR per point 1.04 [1.01-1.07] kg/m2 ; p = 0.003)., Conclusions: The incidence of symptomatic DD after cardiac surgery was 7.6%, leading to respiratory complications and increased ICU stay. CABG was the principal factor associated with DD., (Copyright © 2021 Elsevier Inc. All rights reserved.)- Published
- 2021
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17. Placental transfer of doravirine, a recent HIV-1 NNRTI in the ex vivo human cotyledon perfusion model.
- Author
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Lê MP, Pencolé L, Peytavin G, Bouchet-Crivat F, and Mandelbrot L
- Subjects
- Humans, Pregnancy, HIV-1, Perfusion, HIV Infections drug therapy, Female, Maternal-Fetal Exchange, Placenta metabolism, Pyridones pharmacokinetics, Triazoles pharmacokinetics
- Abstract
Background: The recent HIV-1 NNRTI doravirine is likely to be used in pregnant women despite the complete lack of data on safety and exposure in the fetus. The objective of this study was to determine its placental transfer., Methods: Maternal-to-fetal transfer was investigated using the open-circuit ex vivo dually perfused human cotyledon model. Doravirine was added to a maternal perfusate (theoretical doravirine concentration of 250 ng/mL) containing 2 g/L human albumin and 20 g/L antipyrine, a marker to validate the cotyledon's viability, and cotyledons were dually perfused for up to 90 min., Results: In five experiments, the median (IQR) doravirine concentrations in the maternal and fetal compartments were, respectively, 303 (178-420) and 40 (30-54) ng/mL, the fetal-to-maternal ratio was 16% (12%-18%) and the clearance index (in comparison with antipyrine transfer) was 48% (35%-64%). The median accumulation index in cotyledon tissue was 39% (range 10%-66%)., Conclusions: Doravirine both crosses and accumulates in the placenta. This may be useful as pre/post-exposure prophylaxis to reduce the risk of vertical HIV transmission but carries the potential for fetal toxicities. Further investigation is required to determine the safety and efficacy of this new antiretroviral agent in pregnancy., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.)
- Published
- 2021
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18. Once-daily etravirine/raltegravir (400/800 mg q24h) dual therapy maintains viral suppression over 48 weeks in HIV-infected patients switching from a twice-daily etravirine/raltegravir (200/400 mg q12h) regimen.
- Author
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Palich R, Allavena C, Peytavin G, Soulie C, Tubiana R, Weiss L, Montoya Ferrer A, Duvivier C, Bouchaud O, Bottero J, Durand A, Lê MP, Marcelin AG, Dudoit Y, Assoumou L, and Katlama C
- Subjects
- Humans, Middle Aged, Nitriles, Prospective Studies, Pyrimidines, Raltegravir Potassium therapeutic use, Treatment Outcome, Viral Load, Anti-HIV Agents therapeutic use, HIV Infections drug therapy, HIV-1
- Abstract
Background: Etravirine/raltegravir dual therapy has been shown to be highly effective as a twice-daily (q12h) regimen in suppressed HIV-infected patients enrolled in the ANRS-163 study., Objectives: As a once-daily (q24h) regimen is easier for daily life, we aimed to evaluate the capacity of etravirine/raltegravir (400/800 mg) q24h to maintain viral suppression in patients on etravirine/raltegravir q12h., Methods: Patients on a suppressive etravirine/raltegravir q12h regimen for at least 96 weeks were switched to etravirine/raltegravir q24h in this prospective, multicentre, open-label, single-arm study. Primary outcome was the rate of virological failure (VF: confirmed pVL >50 copies/mL, single pVL >400 copies/mL or single pVL >50 copies/mL with ART change) at Week 48 (W48). Secondary outcomes included treatment strategy success rate (no VF and no treatment discontinuation), regimen tolerability, plasma drug concentrations and resistance profile in the case of VF., Results: A total of 111 patients were enrolled, with a median (IQR) age of 57 years (52-62), CD4 count of 710 cells/mm3 (501-919) and viral suppression for 7.9 years (5.9-10.7). Two patients experienced viral rebound at W24 and W48, leading to a VF rate of 2.0% (95% CI 0.5-7.8) at W48, associated with INSTI resistance in one case. Both had past NNRTI mutations. Ten patients discontinued treatment for adverse events (n = 2), investigator or patient decisions (n = 3), lost to follow-up (n = 3), death (n = 1) or pregnancy (n = 1). Overall, the strategy success rate was 89% (95% CI 81.5-93.6) at W48. In a subgroup of 64 patients, median (IQR) plasma C24h concentrations were 401 ng/mL (280-603) for etravirine and 62 ng/mL (31-140) for raltegravir., Conclusions: Switching patients virally suppressed on etravirine/raltegravir q12h to the same regimen but given q24h was highly effective in maintaining virological suppression in HIV-infected patients., (© The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.)
- Published
- 2021
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19. Early administration of ritonavir-boosted lopinavir could prevent severe COVID-19.
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Klement-Frutos E, Burrel S, Peytavin G, Marot S, Lê MP, Godefroy N, Calvez V, Marcelin AG, Caumes E, Pourcher V, and Boutolleau D
- Subjects
- Disease Outbreaks, Humans, Lopinavir therapeutic use, Prospective Studies, Ritonavir therapeutic use, SARS-CoV-2, Viral Load, Antiviral Agents therapeutic use, COVID-19, Pneumonia drug therapy, Severe Acute Respiratory Syndrome
- Published
- 2021
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20. Rationale of a loading dose initiation for hydroxychloroquine treatment in COVID-19 infection in the DisCoVeRy trial-authors' response.
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Lê MP, Peiffer-Smadja N, Guedj J, Neant N, Mentré F, Ader F, Yazdanpanah Y, and Peytavin G
- Subjects
- Humans, Hydroxychloroquine, Pandemics, SARS-CoV-2, COVID-19, Coronavirus Infections epidemiology, Pneumonia, Viral
- Published
- 2021
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21. Identifying lithium-poisoned patients who may benefit from haemodialysis remains highly challenging.
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Vodovar D, Lê MP, Labat L, and Mégarbane B
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- Antidepressive Agents, Humans, Renal Dialysis, Lithium, Poisons
- Published
- 2020
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22. Usefulness of therapeutic drug monitoring of rilpivirine and its relationship with virologic response and resistance in a cohort of naive and pretreated HIV-infected patients.
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Néant N, Lê MP, Bouazza N, Gattacceca F, Yazdanpanah Y, Dhiver C, Bregigeon S, Mokhtari S, Peytavin G, Tamalet C, Descamps D, Lacarelle B, and Solas C
- Subjects
- Adult, Aged, Cohort Studies, Emtricitabine, Female, Humans, Male, Middle Aged, Retrospective Studies, Tenofovir therapeutic use, Viral Load, Young Adult, Anti-HIV Agents therapeutic use, Drug Monitoring, HIV Infections drug therapy, HIV-1, Rilpivirine therapeutic use
- Abstract
Aims: The purpose of this study was to assess the antiviral activity of the rilpivirine/emtricitabine/tenofovir disoproxil fumarate combination and to describe the pharmacokinetics of rilpivirine and its association with resistance in clinical routine., Methods: A retrospective multicentre cohort study was performed in both naive and pretreated HIV patients receiving the once-daily rilpivirine/emtricitabine/tenofovir disoproxil fumarate regimen. Immuno-virologic and resistance data, and rilpivirine plasma trough concentrations were collected over the follow-up. Statistical analyses were performed to evaluate the relationship between rilpivirine pharmacokinetics and virological response. Receiver operating characteristic (ROC) curve analysis was performed to determine the best target rilpivirine trough concentration., Results: Overall, 379 patients were included. After a median follow-up of 28 months, 26% of patients discontinued mainly due to toxicity and the virological success rate was 65.7%. Virological failure occurred in 5% of patients. A significant proportion of patients with HIV-RNA > 40 copies/mL displayed rilpivirine plasma trough concentrations below the currently used 50 ng/mL efficacy threshold at both M6 (28%) and M12 (31%), in agreement with a significant lower median rilpivirine plasma trough concentration compared with patients virologically suppressed. Half of the patients with virologic failure who acquired rilpivirine resistance mutations had at least one suboptimal rilpivirine trough concentration. The optimal target for rilpivirine trough concentration was 70 ng/mL (sensitivity 75.4%; specificity 61.5%)., Conclusions: This study shows the impact of rilpivirine plasma trough concentration on both virological response and the emergence of rilpivirine mutations. Moreover, our results suggest that a higher target of rilpivirine trough concentration could be proposed in clinical practice., (© 2020 The British Pharmacological Society.)
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- 2020
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23. Reply to Yan and Muller, "Captisol and GS-704277, but Not GS-441524, Are Credible Mediators of Remdesivir's Nephrotoxicity".
- Author
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Lê MP, Le Beller C, Le Hingrat Q, Jaquet P, Wicky PH, Bunel V, Massias L, Visseaux B, Messika J, Descamps D, Mal H, Timsit JF, and Peytavin G
- Subjects
- Adenosine analogs & derivatives, Adenosine Monophosphate analogs & derivatives, Alanine analogs & derivatives, Furans, Humans, Neuroglia, Pandemics, Pyrroles, SARS-CoV-2, Transplant Recipients, Triazines, beta-Cyclodextrins, COVID-19, Lung Transplantation, Renal Dialysis
- Published
- 2020
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24. Impact of Loading Dose of Caspofungin in Pharmacokinetic-Pharmacodynamic Target Attainment for Severe Candidiasis Infections in Patients in Intensive Care Units: the CASPOLOAD Study.
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Bailly S, Gautier-Veyret E, Lê MP, Bouadma L, Andremont O, Neuville M, Mourvillier B, Sonneville R, Magalhaes E, Lebut J, Radjou A, Smonig R, Wolff M, Massias L, Dupuis C, and Timsit JF
- Subjects
- Antifungal Agents therapeutic use, Caspofungin, Humans, Intensive Care Units, Lipopeptides, Microbial Sensitivity Tests, Monte Carlo Method, Candidiasis drug therapy, Echinocandins
- Abstract
This study evaluated the impact of a high loading dose of caspofungin (CAS) on the pharmacokinetics of CAS and the pharmacokinetic-pharmacodynamic (PK-PD) target attainment in patients in intensive care units (ICU). ICU patients requiring CAS treatment were prospectively included to receive a 140-mg loading dose of CAS. Plasma CAS concentrations (0, 2, 3, 5, 7, and 24 h postinfusion) were determined to develop a two-compartmental population PK model. A Monte Carlo simulation was performed and the probabilities of target attainment (PTAs) were computed using previously published MICs. PK-PD targets were ratios of area under the concentration-time curve from 0 to 24 h (AUC
0-24h ) divided by the MIC (AUC0-24h /MIC) of 250, 450, and 865 and maximal concentration ( Cmax ) divided by the MIC ( Cmax /MIC) of 5, 10, 15, and 20. Among 13 included patients, CAS clearance was 0.98 ± 0.13 liters/h and distribution volumes were V1 = 9.0 ± 1.2 liters and V2 = 11.9 ± 2.9 liters. Observed and simulated CAS AUC0-24h were 79.1 (IQR 55.2; 108.4) and 81.3 (IQR 63.8; 102.3) mg · h/liter during the first 24 h of therapy, which is comparable to values usually observed in ICU patients at day 3 or later. PTAs were >90% for MICs of 0.19 and 0.5 mg/liter, considering AUC/MIC = 250 and Cmax /MIC = 10 as PK-PD targets, respectively. Thus, a high loading dose of CAS (140 mg) increased CAS exposure in the first 24 h of therapy, allowing early achievement of PK-PD targets for most Candida strains. Such a strategy seems to improve treatment efficacy, though further studies are needed to assess the impact on clinical outcomes. (This study has been registered at ClinicalTrials.gov under identifier NCT02413892.)., (Copyright © 2020 American Society for Microbiology.)- Published
- 2020
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25. Placental transfer of the integrase strand inhibitors cabotegravir and bictegravir in the ex-vivo human cotyledon perfusion model.
- Author
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Pencolé L, Lê MP, Bouchet-Crivat F, Duro D, Peytavin G, and Mandelbrot L
- Subjects
- Female, Humans, Pregnancy, Amides, Fetus blood supply, Heterocyclic Compounds, 3-Ring, In Vitro Techniques, Models, Biological, Perfusion, Piperazines, Heterocyclic Compounds, 4 or More Rings pharmacokinetics, Heterocyclic Compounds, 4 or More Rings therapeutic use, HIV Infections drug therapy, HIV Integrase Inhibitors therapeutic use, Maternal-Fetal Exchange, Placenta blood supply, Placenta metabolism, Pyridones pharmacokinetics, Pyridones therapeutic use
- Abstract
: Data on placental transfer is lacking for the recent HIV integrase inhibitors, bictegravir and cabotegravir, although their future use in pregnancy is to be expected. The objective of this study was to determine their transplacental pharmacokinetics. Maternal-to-fetal transfer was investigated using the open-circuit ex-vivo dually perfused human cotyledon model. Cabotegravir or bictegravir was added to a maternal perfusate containing 2 g/l of human albumin and antipyrine, a marker to validate the cotyledon's viability, and cotyledons were dually perfused for up to 90 min. For cabotegravir, in five experiments, the median (IQR 25-75) concentrations in the maternal and in the fetal compartments were, respectively, 550 ng/ml (344-788) and 48 ng/ml (37-54), with a maternal-to-fetal ratio of 10% (5-16) and a clearance index (in comparison with antipyrine transfer) of 22% (19-28). The median cotyledon accumulation index was 10% (2-21). For bictegravir, in six experiments, the median (IQR 25-75) concentrations in the maternal and in the fetal compartments were, respectively, 1650 ng/ml (1455-1960) and 126 ng/ml (112-142), with a maternal-to-fetal ratio of 7% (6-9.5) and a clearance index (in comparison with antipyrine transfer) of 21% (17-29). The median cotyledon accumulation index was 4% (3-5). Placental transfer of cabotegravir and bictegravir were low. This may not only limit the potential for fetal toxicities but also be a limit to their usefulness at the time of labor and delivery to reduce the risk of vertical HIV transmission. The safety and efficacy of these new integrase inhibitors in pregnancy require more investigation.
- Published
- 2020
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26. A Simple Approach for Gas Blender on Extracorporeal Membrane Oxygenation in Resource Shortage Context.
- Author
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De Roux Q, Delage M, Lê MP, Vincent T, and Mongardon N
- Subjects
- Betacoronavirus, COVID-19, Humans, Pandemics, SARS-CoV-2, Coronavirus Infections therapy, Extracorporeal Membrane Oxygenation instrumentation, Oxygenators, Membrane supply & distribution, Pneumonia, Viral therapy
- Abstract
With the massive influx of patients during COVID-19 pandemic into intensive care unit, resources have quickly been stretched to the limit, including extracorporeal membrane oxygenation (ECMO). Gas blender attached to ECMO is used to allow precise adjustment of characteristics of fresh gas flow, that is, blood oxygen delivery and carbon dioxide removal. To cope with the gas blender shortage, we describe a back-up system set up in our French tertiary referral ECMO center using air and oxygen flowmeters. A table has been created to facilitate medical prescription but also nurse monitoring. This extraordinary situation forces physicians to adapt medical devices, and that could be useful in future viral pandemics.
- Published
- 2020
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27. Removal of Remdesivir's Metabolite GS-441524 by Hemodialysis in a Double Lung Transplant Recipient with COVID-19.
- Author
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Lê MP, Le Hingrat Q, Jaquet P, Wicky PH, Bunel V, Massias L, Visseaux B, Messika J, Descamps D, Mal H, Timsit JF, and Peytavin G
- Subjects
- Adenosine analogs & derivatives, Adenosine Monophosphate administration & dosage, Adenosine Monophosphate adverse effects, Adenosine Monophosphate chemistry, Adenosine Monophosphate metabolism, Alanine administration & dosage, Alanine adverse effects, Alanine chemistry, Alanine metabolism, Antiviral Agents adverse effects, Antiviral Agents chemistry, Antiviral Agents metabolism, COVID-19, Coronavirus Infections drug therapy, Coronavirus Infections surgery, Coronavirus Infections virology, Drug Interactions, Furans adverse effects, Furans chemistry, Humans, Intensive Care Units, Lung Transplantation, Multiple Organ Failure, Pandemics, Pneumonia, Viral surgery, Pneumonia, Viral virology, Pyrroles adverse effects, Pyrroles chemistry, Renal Dialysis, SARS-CoV-2, Transplant Recipients, Triazines adverse effects, Triazines chemistry, beta-Cyclodextrins adverse effects, beta-Cyclodextrins chemistry, COVID-19 Drug Treatment, Adenosine Monophosphate analogs & derivatives, Alanine analogs & derivatives, Antiviral Agents administration & dosage, Betacoronavirus drug effects, Coronavirus Infections therapy, Furans urine, Pneumonia, Viral therapy, Pyrroles urine, Triazines urine, beta-Cyclodextrins urine
- Abstract
Remdesivir has reported efficacy against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in vitro and in vivo Drug-drug interactions limit therapeutic options in transplant patients. Remdesivir and its metabolite GS-441524 are excreted principally in urine. In intensive care unit (ICU) settings, in which multiple-organ dysfunctions can occur rapidly, hemodialysis may be a viable option for maintaining remdesivir treatment, while improving tolerance, by removing both remdesivir's metabolite (GS-441524) and sulfobutylether β-cyclodextrin sodium (SEBCD). Additional studies may prove informative, particularly in the evaluations of therapeutic options for coronavirus disease 2019 (COVID-19)., (Copyright © 2020 American Society for Microbiology.)
- Published
- 2020
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28. Management of oral antiretroviral administration in patients with swallowing disorders or with an enteral feeding tube.
- Author
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San C, Lê MP, Matheron S, Mourvillier B, Caseris M, Timsit JF, Wolff M, Yazdanpanah Y, Descamps D, and Peytavin G
- Subjects
- Administration, Oral, Humans, Anti-Retroviral Agents administration & dosage, Deglutition Disorders complications, Enteral Nutrition instrumentation, HIV Infections complications, HIV Infections drug therapy
- Abstract
HIV infection has evolved into a chronic disease with comorbidities since the combination antiretroviral therapy era. Complications still occur and patients may need to be admitted to an intensive care unit. Acute respiratory failure is the first cause of these admissions, questioning the administration of solid oral dosage formulations. This issue is also observed in geriatric units where the prevalence of dysphagia is high and underestimated. The problem of antiretroviral administration is critical: altered solid oral dosage formulations and/or administration via enteral feeding tubes are sometimes the only option. The aim is to help manage antiretroviral treatment in unconscious or intubated patients and those with swallowing disorders who are hospitalized in intensive care units or geriatric units. This review provides information on the main antiretroviral regimens and on practical and legal aspects of manipulating solid oral dosage formulations and administration via enteral feeding tubes. Alternatives to the solid formulation are available for most of the 27 oral antiretrovirals available, or manufacturers provide recommendations for patients who are unable to swallow. Manipulation of solid oral dosage formulations such as crushing tablets or opening capsules and administration via feeding tubes are frequently reported but should be the last option for safety and liability issues. Before any off-label administration of a drug, physicians should consider alternatives to the solid oral dosage formulation and check whether the drug can be altered. Therapeutic monitoring is important in this particular setting as the pharmacokinetic profile of drugs is difficult to predict., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)
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- 2020
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29. Persistent low-level viraemia in antiretroviral treatment-experienced patients is not linked to viral resistance or inadequate drug concentrations.
- Author
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Palich R, Wirden M, Peytavin G, Lê MP, Seang S, Abdi B, Schneider L, Tubiana R, Valantin MA, Paccoud O, Soulié C, Calvez V, Katlama C, and Marcelin AG
- Subjects
- Anti-Retroviral Agents therapeutic use, Antiretroviral Therapy, Highly Active, CD4 Lymphocyte Count, Drug Resistance, Viral, Humans, Middle Aged, Viral Load, Viremia drug therapy, Anti-HIV Agents therapeutic use, HIV Infections drug therapy, HIV-1 genetics, Pharmaceutical Preparations
- Abstract
Objectives: To assess genotypic sensitivity scores (GSSs), plasma antiretroviral concentrations (PACs) and immunovirological outcomes at Week 96 (W96) in patients with persistent low-level viraemia (LLV)., Methods: On 1 January 2017, we analysed data from patients on three-drug regimens with persistent LLV defined as at least two consecutive plasma viral loads (pVLs) between 21 and 200 copies/mL (including one pVL of ≥50 copies/mL), at the Pitié-Salpêtrière Hospital. Outcomes were: GSS, PACs and HIV-DNA load at study entry; and virological status and proportion of patients with resistance-associated mutations (RAMs) at W96., Results: Fifty-seven patients were included, with median age of 52.6 years (IQR 45.2-57.9), last CD4 count of 658 cells/mm3 (IQR 462-909) and total ART duration of 10.2 years (IQR 5.7-15.2). LLV duration was 14.0 months (IQR 5.5-22.3). GSS was 3 in 46/57 (81%) patients and PACs were adequate in 53/57 (93%) patients. Median total HIV-DNA was 2.65 log10 copies/106 cells (IQR 2.44-2.86). During follow-up, 26/57 (46%) had experienced ART modifications. At W96, 38/57 (67%) patients remained with LLV, 15/60 (26%) had achieved confirmed pVL of <20 copies/mL and 4/57 (7%) had virological failure. The four virological failures were due to three ART interruptions and one incomplete adherence (selection of Y181C RAM). No factors (patient characteristics at study entry, GSS, PACs, total HIV-DNA load and ART modification) were associated with W96 viral outcome, except for time from HIV diagnosis and the LLV duration at study entry., Conclusions: A substantial number of patients harbouring LLV had no resistance to ART and adequate PACs. Two-thirds of these patients remained with this LLV status., (© The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.)
- Published
- 2020
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30. Pharmacokinetics of lopinavir/ritonavir oral solution to treat COVID-19 in mechanically ventilated ICU patients.
- Author
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Lê MP, Jaquet P, Patrier J, Wicky PH, Le Hingrat Q, Veyrier M, Kauv J, Sonneville R, Visseaux B, Laouénan C, Bouadma L, Descamps D, de Montmollin E, Peytavin G, and Timsit JF
- Subjects
- Administration, Oral, COVID-19, Coronavirus Infections drug therapy, Cytochrome P-450 CYP3A Inhibitors administration & dosage, Cytochrome P-450 CYP3A Inhibitors blood, Drug Therapy, Combination, Female, Humans, Lopinavir administration & dosage, Male, Middle Aged, Pandemics, Pharmaceutical Solutions administration & dosage, Pharmaceutical Solutions pharmacokinetics, Pneumonia, Viral drug therapy, Prospective Studies, Ritonavir administration & dosage, SARS-CoV-2, Betacoronavirus, Coronavirus Infections blood, Intensive Care Units trends, Lopinavir blood, Pneumonia, Viral blood, Respiration, Artificial trends, Ritonavir blood
- Abstract
Background: The combination lopinavir/ritonavir is recommended to treat HIV-infected patients at the dose regimen of 400/100 mg q12h, oral route. The usual lopinavir trough plasma concentrations are 3000-8000 ng/mL. A trend towards a 28 day mortality reduction was observed in COVID-19-infected patients treated with lopinavir/ritonavir., Objectives: To assess the plasma concentrations of lopinavir and ritonavir in patients with severe COVID-19 infection and receiving lopinavir/ritonavir., Patients and Methods: Mechanically ventilated patients with COVID-19 infection included in the French COVID-19 cohort and treated with lopinavir/ritonavir were included. Lopinavir/ritonavir combination was administered using the usual adult HIV dose regimen (400/100 mg q12h, oral solution through a nasogastric tube). A half-dose reduction to 400/100 mg q24h was proposed if lopinavir Ctrough was >8000 ng/mL, the upper limit considered as toxic and reported in HIV-infected patients. Lopinavir and ritonavir pharmacokinetic parameters were determined after an intensive pharmacokinetic analysis. Biological markers of inflammation and liver/kidney function were monitored., Results: Plasma concentrations of lopinavir and ritonavir were first assessed in eight patients treated with lopinavir/ritonavir. Median (IQR) lopinavir Ctrough reached 27 908 ng/mL (15 928-32 627). After the dose reduction to 400/100 mg q24h, lopinavir/ritonavir pharmacokinetic parameters were assessed in nine patients. Lopinavir Ctrough decreased to 22 974 ng/mL (21 394-32 735)., Conclusions: In mechanically ventilated patients with severe COVID-19 infections, the oral administration of lopinavir/ritonavir elicited plasma exposure of lopinavir more than 6-fold the upper usual expected range. However, it remains difficult to safely recommend its dose reduction without compromising the benefit of the antiviral strategy, and careful pharmacokinetic and toxicity monitoring are needed., (© The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.)
- Published
- 2020
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31. Failure of hydroxychloroquine pre-exposure prophylaxis in COVID-19 infection? A case report.
- Author
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Kauv J, Lê MP, Veyrier M, Le Hingrat Q, Visseaux B, Massias L, Chauveheid MP, Descamps D, Ghosn J, and Peytavin G
- Subjects
- Aged, Antiviral Agents administration & dosage, Antiviral Agents blood, COVID-19, Coronavirus Infections blood, Drug Therapy, Combination, Humans, Hydroxychloroquine blood, Male, Pneumonia, Viral blood, SARS-CoV-2, Betacoronavirus, Coronavirus Infections diagnosis, Coronavirus Infections prevention & control, Hydroxychloroquine administration & dosage, Pandemics prevention & control, Pneumonia, Viral diagnosis, Pneumonia, Viral prevention & control, Pre-Exposure Prophylaxis methods, Treatment Failure
- Published
- 2020
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32. Rationale of a loading dose initiation for hydroxychloroquine treatment in COVID-19 infection in the DisCoVeRy trial.
- Author
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Lê MP, Peiffer-Smadja N, Guedj J, Néant N, Mentré F, Ader F, Yazdanpanah Y, and Peytavin G
- Subjects
- COVID-19, Coronavirus Infections metabolism, Drug Administration Schedule, Humans, Pandemics, Pneumonia, Viral metabolism, SARS-CoV-2, Betacoronavirus, Clinical Trials as Topic methods, Coronavirus Infections drug therapy, Hydroxychloroquine administration & dosage, Pneumonia, Viral drug therapy
- Abstract
Around the world, several dose regimens of hydroxychloroquine have been used for COVID-19 infection treatment, with the objective of identifying a short-term course. Hydroxychloroquine was found to decrease the viral replication in a concentration-dependent manner in vitro and to be more active when added prior to the viral challenge. A loading dose is used to rapidly attain a target drug concentration, which is usually considered as approximately the steady-state concentration. With a loading dose, the minimum effective concentration is reached much more rapidly than when using only the maintenance dose from the start. Thus, we propose a hydroxychloroquine sulphate dose regimen of 400 mg twice daily at Day 1 then 400 mg once daily from Day 2 to Day 10. We aim to evaluate this in the C-20-15 DisCoVeRy trial., (© The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.)
- Published
- 2020
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33. Pharmacovirological analyses of blood and male genital compartment in patients receiving dolutegravir + lamivudine dual therapy as a switch strategy (ANRS 167 LAMIDOL trial).
- Author
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Charpentier C, Peytavin G, Raffi F, Burdet C, Landman R, Lê MP, Katlama C, Collin G, Benalycherif A, Cabie A, Mentré F, Yazdanpanah Y, Descamps D, and Joly V
- Subjects
- Chromatography, Liquid, Genitalia, Male, Heterocyclic Compounds, 3-Ring therapeutic use, Humans, Lamivudine therapeutic use, Leukocytes, Mononuclear, Male, Oxazines, Piperazines therapeutic use, Pyridones, Tandem Mass Spectrometry, Viral Load, Anti-HIV Agents therapeutic use, HIV Infections drug therapy, HIV-1
- Abstract
Objectives: To describe plasma residual HIV viraemia, cellular HIV reservoir size, blood plasma drug concentrations and their male genital tract penetration during the maintenance dual therapy dolutegravir + lamivudine., Patients and Methods: ANRS167 LAMIDOL enrolled 104 virologically suppressed patients to switch to dolutegravir + lamivudine. In this pharmacovirological substudy, ultrasensitive plasma viral load (USpVL) and plasma drug concentrations were measured at Day 0 (D0), Week 24 (W24) and W48 of dolutegravir + lamivudine, and HIV-DNA was measured at W-8 and W48. Semen samples were collected at D0 and W24 from 18 participants. Total and unbound blood and seminal plasma drug concentrations were measured using UPLC-MS/MS., Results: Median HIV-DNA was 2.5 log10 copies/106 PBMC (IQR = 2.2-3.0, n = 100) at W-8 and 2.4 log10 copies/106 PBMC (IQR = 2.1-2.9, n = 100) at W48 (P = 0.17). The proportion of patients with undetected USpVL was 38% (n = 98), 43% (n = 98) and 49% (n = 97) at D0, W24 and W48, respectively (P = 0.08). Total and unbound plasma dolutegravir concentrations were stable between timepoints (P = 0.13) and all total plasma dolutegravir concentrations except one were adequate. Median free fraction of dolutegravir in plasma was 0.21%. Median blood plasma and seminal plasma concentrations of total dolutegravir at 24 h were 1812 ng/mL and 206 ng/mL, respectively. Median seminal plasma/blood plasma total concentration ratios were 11.6% and 2478% for dolutegravir and lamivudine, respectively. HIV-RNA (365 to 475 copies/mL) was detected in seminal plasma of one patient at D0 (5.9%) and of two patients at W24 (11.8%)., Conclusions: These findings add further important information regarding the effectiveness of dolutegravir + lamivudine maintenance dual therapy in terms of plasma residual viraemia, cellular reservoir size and drug penetration in the male genital tract., (© The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.)
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- 2020
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34. M184V/I does not impact the efficacy of abacavir/lamivudine/dolutegravir use as switch therapy in virologically suppressed patients.
- Author
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Jary A, Marcelin AG, Charpentier C, Wirden M, Lê MP, Peytavin G, Descamps D, and Calvez V
- Subjects
- Dideoxynucleosides therapeutic use, Heterocyclic Compounds, 3-Ring, Humans, Lamivudine therapeutic use, Oxazines, Piperazines, Pyridones, Retrospective Studies, Viral Load, Anti-HIV Agents therapeutic use, HIV Infections drug therapy
- Abstract
Background: M184V/I NRTI resistance mutations can be selected by either lamivudine/emtricitabine or abacavir. There are controversies about the use of abacavir/lamivudine/dolutegravir combinations in HIV-1-infected treatment-experienced patients with a fully suppressed HIV viral load (VL) and harbouring M184V/I., Objectives: We assessed the efficacy of abacavir/lamivudine/dolutegravir when used in HIV-infected pretreated patients with an undetectable VL who previously harboured M184V/I as a unique NRTI resistance mutation in a genotypic resistance test and had no resistance to integrase inhibitors., Patients and Methods: A total of 154 patients with a fully suppressed HIV-1 plasma VL (<50 copies/mL) treated with tenofovir disoproxil fumarate/emtricitabine/boosted PI or abacavir/lamivudine/boosted PI who switched to an abacavir/lamivudine/dolutegravir regimen and had M184V/I as a unique NRTI resistance mutation in their therapeutic history were retrospectively analysed up to 12 months after the switch to abacavir/lamivudine/dolutegravir. Assessment of residual viraemia was performed at Months 1, 3, 6 and 12. Plasma VL with undetectable HIV-1 RNA corresponded to an absence of residual viraemia., Results: During the 12 months of follow-up, three patients had a blip of VL (53, 62 and 106 copies/mL) at Month 3 followed by a subsequent VL <50 copies/mL. No patient harboured a virological failure during the follow-up. Moreover, there was no change in residual viraemia during the follow-up., Conclusions: M184V/I as a unique NRTI resistance mutation, regardless of possible selection by regimens containing lamivudine/emtricitabine or abacavir, does not affect the virological response of well-controlled patients who switched to abacavir/lamivudine/dolutegravir for at least 12 months., (© The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.)
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- 2020
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35. Placental transfer of Letermovir & Maribavir in the ex vivo human cotyledon perfusion model. New perspectives for in utero treatment of congenital cytomegalovirus infection.
- Author
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Faure Bardon V, Peytavin G, Lê MP, Guilleminot T, Elefant E, Stirnemann J, Leruez-Ville M, and Ville Y
- Subjects
- Acetates pharmacology, Adult, Antiviral Agents pharmacology, Benzimidazoles pharmacology, Chromatography, Liquid methods, Female, Humans, Kinetics, Models, Biological, Perfusion, Pregnancy, Quinazolines pharmacology, Ribonucleosides pharmacology, Tandem Mass Spectrometry methods, Cytomegalovirus Infections drug therapy, Maternal-Fetal Exchange drug effects, Placenta drug effects
- Abstract
Background: Congenital cytomegalovirus infection can lead to severe sequelae. When fetal infection is confirmed, we hypothesize that fetal treatment could improve the outcome. Maternal oral administration of an effective drug crossing the placenta could allow fetal treatment. Letermovir (LMV) and Maribavir (MBV) are new CMV antivirals, and potential candidates for fetal treatment., Methods: The objective was to investigate the placental transfer of LMV and MBV in the ex vivo method of the human perfused cotyledon. Term placentas were perfused, in an open-circuit model, with LMV or MBV at concentrations in the range of clinical peak plasma concentrations. Concentrations were measured using ultraperformance liquid chromatography coupled with tandem mass spectrometry. Mean fetal transfer rate (FTR) (fetal (FC) /maternal concentration), clearance index (CLI), accumulation index (AI) (retention of each drug in the cotyledon tissue) were measured. Mean FC were compared with half maximal effective concentrations of the drugs (EC50(LMV) and EC50(MBV))., Results: For LMV, the mean FC was (± standard deviation) 1.1 ± 0.2 mg/L, 1,000-fold above the EC50(LMV). Mean FTR, CLI and AI were 9 ± 1%, 35 ± 6% and 4 ± 2% respectively. For MBV, the mean FC was 1.4 ± 0.2 mg/L, 28-fold above the EC50(MBV). Mean FTR, CLI and AI were 10 ± 1%, 50 ± 7% and 2 ± 1% respectively., Conclusions: Drugs' concentrations in the fetal side should be in the range for in utero treatment of fetuses infected with CMV as the mean FC was superior to the EC50 for both molecules., Competing Interests: - Valentine Faure Bardon: No conflict - Gilles Peytavin has received travel grants, consultancy fees, honoraria or study grants from various pharmaceutical companies, including Bristol-Myers Squibb, Gilead Sciences, Janssen, Merck and ViiV Healthcare. - Minh Patrick Lê has received travel grants from Bristol-Myers Squibb and Janssen. - Tiffany Guilleminot: No conflict - Elisabeth Elefant: No conflict - Julien Stirnemann: No conflict - Marianne Leruez-Ville declares receiving financial support for meeting expenses from BioMerieux outside the submitted work. - Yves Ville: reports non-financial support from Ferring SAS, non-financial support from Siemens Health Care, non-financial support from GE medical, outside the submitted work. This does not alter our adherence to PLOS ONE policies on sharing data and materials.
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- 2020
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36. Plasma pharmacokinetics of bedaquiline administered by nasogastric tube in an intensive care unit.
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Dang E, Sayagh F, Lê MP, Neuville M, Sinnah F, Timsit JF, and Peytavin G
- Subjects
- Adult, Antitubercular Agents therapeutic use, Diarylquinolines, Humans, Intensive Care Units, Male, Plasma, Young Adult, Pharmaceutical Preparations, Tuberculosis, Multidrug-Resistant drug therapy
- Abstract
We present the case of a 21-year-old man admitted to the intensive care unit with multi-organ failure due to multidrug-resistant tuberculosis (TB). TB treatment initially comprised moxifloxacin, ethambutol, linezolid and amikacin administered intravenously. Due to suspected moxifloxacin-induced liver injury, we stopped all fluoroquinolones and switched to bedaquiline (BDQ), which is only available in tablets for oral administration. Since our patient had to be fed through a nasogastric tube (NGT), BDQ was administered after being crushed and dissolved in water; drug pharmacokinetics were studied using repeated blood sampling. Therapeutic drug monitoring showed that BDQ was detectable in blood plasma with a trough concentration above the supposed efficacy threshold, suggesting that this molecule could be administered through NGT.
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- 2020
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37. Concentration-response model of rilpivirine in a cohort of HIV-1-infected naive and pre-treated patients.
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Néant N, Solas C, Bouazza N, Lê MP, Yazdanpanah Y, Dhiver C, Bregigeon S, Mokhtari S, Peytavin G, Tamalet C, Descamps D, Lacarelle B, and Gattacceca F
- Subjects
- Adult, Aged, Algorithms, Anti-HIV Agents therapeutic use, CD4 Lymphocyte Count, Computer Simulation, Disease Management, Drug Monitoring, Female, HIV Infections immunology, Humans, Male, Middle Aged, Rilpivirine therapeutic use, Viral Load, Young Adult, Anti-HIV Agents pharmacokinetics, HIV Infections drug therapy, HIV Infections virology, HIV-1 drug effects, Models, Theoretical, Rilpivirine pharmacokinetics
- Abstract
Background: Rilpivirine is widely prescribed in people living with HIV. Although trough plasma concentrations have been associated with virological response, the drug pharmacodynamics remain incompletely characterized., Objectives: To develop the first pharmacodynamic model of rilpivirine in order to establish the rilpivirine concentration-response relationship for future treatment optimization., Methods: A retrospective observational study was conducted in patients receiving the once-daily rilpivirine/tenofovir disoproxil fumarate/emtricitabine regimen. Individual rilpivirine trough plasma concentrations over time were predicted using a previous pharmacokinetic model. An established susceptible, infected, recovered model was used to describe HIV dynamics without assuming disease steady-state. Population analysis was performed with MONOLIX 2018 software. Simulations of the viral load evolution as a function of time and rilpivirine trough plasma concentration were performed., Results: Overall, 60 naive and 39 pre-treated patients were included with a follow-up ranging from 2 to 37 months. The final model adequately described the data and the pharmacodynamic parameters were estimated with a good precision. The population typical value of rilpivirine EC50 was estimated at 65 ng/mL. A higher infection rate constant of CD4 cells for HIV-1 was obtained in pre-treated patients. Consequently, the time to obtain virological suppression was longer in pre-treated than in naive patients., Conclusions: The concentration-response relationship of rilpivirine was satisfactorily described for the first time using an original population pharmacodynamic model. Simulations performed using the final model showed that the currently used 50 ng/mL rilpivirine trough plasma concentration efficacy target might need revision upwards, particularly in pre-treated patients., (© The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.)
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- 2019
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38. Lack of a Clinically Significant Pharmacokinetic Interaction between Etravirine and Raltegravir Using an Original Approach Based on Drug Metabolism, Protein Binding, and Penetration in Seminal Fluid: A Pharmacokinetic Substudy of the ANRS-163 ETRAL Study.
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Lê MP, Valantin MA, Assoumou L, Soulie C, Le Mestre S, Weiss L, Yazdanpanah Y, Molina JM, Bouchaud O, Raffi F, Reynes J, Calvez V, Marcelin AG, Costagliola D, Katlama C, and Peytavin G
- Subjects
- Anti-HIV Agents blood, Anti-HIV Agents therapeutic use, Drug Interactions, Drug Therapy, Combination, Female, HIV Infections blood, HIV-1 drug effects, Humans, Male, Middle Aged, Nitriles, Protein Binding, Pyridazines blood, Pyridazines therapeutic use, Pyrimidines, Raltegravir Potassium blood, Raltegravir Potassium therapeutic use, Semen metabolism, Anti-HIV Agents administration & dosage, Anti-HIV Agents pharmacokinetics, HIV Infections drug therapy, Pyridazines administration & dosage, Pyridazines pharmacokinetics, Raltegravir Potassium administration & dosage, Raltegravir Potassium pharmacokinetics, Semen drug effects
- Abstract
Study Objective: The ANRS163-ETRAL study showed that etravirine 200 mg/raltegravir 400 mg twice-daily dual therapy was highly effective in the treatment of human immunodeficiency virus (HIV)-infected patients older than 45 years, with virologic and therapeutic success rates at week 48 of 99.4% and 94.5%, respectively. The objective of this study was to determine whether a clinically significant pharmacokinetic interaction between etravirine and raltegravir exists by assessing steady-state total and unbound etravirine, raltegravir, and inactive raltegravir-glucuronide concentrations 12 hours after last intake (C
12h ) in blood plasma (BP) and seminal plasma (SP)., Design: Pharmacokinetic analysis of data from the ANRS163-ETRAL study., Patients: One hundred forty-six HIV-1-infected patients (of the 165 patients included in the ANRS-163 ETRAL study) who were receiving etravirine 200 mg and raltegravir 400 mg twice daily., Measurements and Main Results: Blood was collected from all 146 patients at weeks 2-4, 12, 24, and 48, and semen was collected from 21 patients at week 48. The extent of BP and SP protein binding was determined by using ultrafiltration assay. Total and unbound etravirine, raltegravir, and raltegravir-glucuronide C12h were determined by ultra high performance liquid chromatography coupled with tandem mass spectrometry and interpreted by using the in vitro calculated protein-bound 95% inhibitory concentration (PBIC95 ) for wild-type (WT) HIV: etravirine (116 ng/ml) and raltegravir (15 ng/ml). Median (interquartile range [IQR]) total BP etravirine C12h (536 ng/ml [376-719]) and raltegravir (278 ng/ml [97-690]) were adequate in 99% and 96% of patients, respectively. Median (IQR) SP:BP C12h ratio and BP unbound fraction were etravirine 0.3 (0.2-0.5) and < 1%, respectively, raltegravir 1.8 (1.3-3.3) and 12%, respectively, and raltegravir-glucuronide 12.0 (6.5-17.7) and > 99%, respectively. The BP raltegravir metabolic ratio (raltegravir glucuronide:raltegravir ratio) was 1.7, suggesting only weak induction of raltegravir glucuronidation by etravirine. Only three patients had etravirine and raltegravir C12h < PBIC95 simultaneously., Conclusion: No clinically significant pharmacokinetic interaction between etravirine and raltegravir was detected. Total etravirine and raltegravir BP concentrations were adequate in most patients, favoring virologic efficacy and confirming good treatment adherence (> 95%), despite twice-daily administration. The long half-life of etravirine and higher unbound fraction SP of raltegravir (57%) ensured adequate concentrations of dual therapy in genital compartments. Our results indicate that etravirine and raltegravir have good, complementary pharmacokinetic profiles, suggesting that they could be used in a dual-treatment strategy., (© 2019 Pharmacotherapy Publications, Inc.)- Published
- 2019
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39. Long-term plasma pharmacokinetics of bedaquiline for multidrug- and extensively drug-resistant tuberculosis.
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Perrineau S, Lachâtre M, Lê MP, Rioux C, Loubet P, Fréchet-Jachym M, Gonzales MC, Grall N, Bouvet E, Veziris N, Yazdanpanah Y, and Peytavin G
- Subjects
- Adult, Antitubercular Agents blood, Antitubercular Agents therapeutic use, Diarylquinolines blood, Diarylquinolines therapeutic use, Female, France, Humans, Male, Medication Adherence, Middle Aged, Retrospective Studies, Treatment Outcome, Young Adult, Antitubercular Agents pharmacokinetics, Diarylquinolines pharmacokinetics, Extensively Drug-Resistant Tuberculosis drug therapy, Tuberculosis, Multidrug-Resistant drug therapy
- Abstract
Setting: Bedaquiline (BDQ) has been approved for the treatment of multidrug- and extensively drug-resistant tuberculosis (MDR/XDR-TB). For many patients treatment is prolonged beyond the recommended 6 months. The long-term pharmacokinetics of BDQ have yet to be elucidated., Objective: To evaluate plasma concentrations of BDQ during treatment and its elimination after treatment discontinuation., Design: This was a retrospective study conducted in two units in France that provide treatment for MDR/XDR-TB. Sociodemographic, clinical, biological and therapeutic parameters were collected from patients currently or formerly treated with BDQ. Plasma concentrations of BDQ and its active M2 ( N -desmethyl) metabolite were determined using ultra-performance liquid chromatography with tandem mass spectrometry., Results: Thirteen patients were recruited (35 samples): 10 (31 samples) during BDQ treatment and 3 (4 samples) after BDQ discontinuation. The median duration of treatment with BDQ was 11 months (interquartile range [IQR] 8-14). During treatment, the median plasma BDQ concentrations and M2 were respectively 1264 ng/ml (IQR 910-2244) and 252 ng/ml (IQR 134-290). In one patient, BDQ was detected in the plasma 200 days after treatment discontinuation (528 ng/ml)., Conclusion: BDQ and M2 plasma concentrations were consistent with good drug efficacy/safety profiles, suggesting good treatment adherence with no relevant drug interactions. The long-term plasma detectability of BDQ after treatment discontinuation may raise the spectre of the emergence of resistance.
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- 2019
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40. Once-daily darunavir/ritonavir 400/100 mg in triple therapy: efficacy and penetration in seminal compartment in ANRS-165 DARULIGHT study.
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Lê MP, Chaix ML, Raffi F, Chevret S, Gallien S, Katlama C, Delobel P, Yazdanpanah Y, Saillard J, Molina JM, and Peytavin G
- Subjects
- Adult, Darunavir administration & dosage, Darunavir pharmacokinetics, Dose-Response Relationship, Drug, Drug Administration Schedule, Drug Combinations, Drug Therapy, Combination methods, HIV Infections blood, HIV Infections virology, HIV Protease Inhibitors administration & dosage, HIV-1 drug effects, HIV-1 genetics, HIV-1 isolation & purification, Humans, Male, Middle Aged, Prospective Studies, RNA, Viral isolation & purification, Reverse Transcriptase Inhibitors administration & dosage, Ritonavir administration & dosage, Ritonavir pharmacokinetics, Semen virology, Tissue Distribution, Virus Shedding drug effects, HIV Infections drug therapy, HIV Protease Inhibitors pharmacokinetics, Reverse Transcriptase Inhibitors pharmacokinetics, Semen metabolism
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- 2019
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41. Prevalence and clinical impact of minority resistant variants in patients failing an integrase inhibitor-based regimen by ultra-deep sequencing.
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Nguyen T, Fofana DB, Lê MP, Charpentier C, Peytavin G, Wirden M, Lambert-Niclot S, Desire N, Grude M, Morand-Joubert L, Flandre P, Katlama C, Descamps D, Calvez V, Todesco E, and Marcelin AG
- Subjects
- Adult, Female, Genotyping Techniques, HIV Infections epidemiology, HIV-1 genetics, HIV-1 isolation & purification, High-Throughput Nucleotide Sequencing, Humans, Male, Middle Aged, Paris epidemiology, Prevalence, Treatment Failure, Antiretroviral Therapy, Highly Active methods, Drug Resistance, Viral, HIV Infections drug therapy, HIV Infections virology, HIV Integrase Inhibitors pharmacology, HIV Integrase Inhibitors therapeutic use, HIV-1 drug effects
- Abstract
Background: Integrase strand transfer inhibitors (INSTIs) are recommended by international guidelines as first-line therapy in antiretroviral-naive and -experienced HIV-1-infected patients., Objectives: This study aimed at evaluating the prevalence at failure of INSTI-resistant variants and the impact of baseline minority resistant variants (MiRVs) on the virological response to an INSTI-based regimen., Methods: Samples at failure of 134 patients failing a raltegravir-containing (n = 65), an elvitegravir-containing (n = 20) or a dolutegravir-containing (n = 49) regimen were sequenced by Sanger sequencing and ultra-deep sequencing (UDS). Baseline samples of patients with virological failure (VF) (n = 34) and of those with virological success (VS) (n = 31) under INSTI treatment were sequenced by UDS. Data were analysed using the SmartGene platform, and resistance was interpreted according to the ANRS algorithm version 27., Results: At failure, the prevalence of at least one INSTI-resistant variant was 39.6% by Sanger sequencing and 57.5% by UDS, changing the interpretation of resistance in 17/134 (13%) patients. Among 53 patients harbouring at least one resistance mutation detected by both techniques, the most dominant INSTI resistance mutations were N155H (45%), Q148H/K/R (23%), T97A (19%) and Y143C (11%). There was no difference in prevalence of baseline MiRVs between patients with VF and those with VS. MiRVs found at baseline in patients with VF were not detected at failure either in majority or minority mutations., Conclusions: UDS is more sensitive than Sanger sequencing at detecting INSTI MiRVs at treatment failure. The presence of MiRVs at failure could be important to the decision to switch to other INSTIs. However, there was no association between the presence of baseline MiRVs and the response to INSTI-based therapies in our study.
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- 2018
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42. Pharmacokinetic modelling of darunavir/ritonavir dose reduction (800/100 to 400/100 mg once daily) in a darunavir/ritonavir-containing regimen in virologically suppressed HIV-infected patients: ANRS 165 DARULIGHT sub-study.
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Lê MP, Chaix ML, Chevret S, Bertrand J, Raffi F, Gallien S, El Abbassi EMB, Katlama C, Delobel P, Yazdanpanah Y, Saillard J, Molina JM, and Peytavin G
- Subjects
- Adult, Darunavir blood, Drug Therapy, Combination, HIV Protease Inhibitors administration & dosage, HIV Protease Inhibitors blood, HIV Protease Inhibitors pharmacokinetics, Humans, Male, Middle Aged, Plasma chemistry, Reverse Transcriptase Inhibitors blood, Reverse Transcriptase Inhibitors pharmacokinetics, Ritonavir blood, Semen chemistry, Therapeutic Equivalency, Darunavir administration & dosage, Darunavir pharmacokinetics, HIV Infections drug therapy, Ritonavir administration & dosage, Ritonavir pharmacokinetics
- Abstract
Background: In the ANRS 165 DARULIGHT study (NCT02384967) carried out in HIV-infected patients, the use of a darunavir/ritonavir-containing regimen with a switch to a reduced dose of darunavir maintained virological efficacy (≤50 copies/mL) for 48 weeks with a good safety profile., Objectives: To assess the total and unbound blood plasma pharmacokinetics of darunavir and associated antiretrovirals, and their penetration into semen before and after dose reduction., Patients and Methods: Patients receiving a darunavir/ritonavir (800/100 mg q24h)-containing regimen for >6 months with plasma HIV-RNA ≤50 copies/mL for >12 months were switched to 400/100 mg darunavir/ritonavir q24h at week 0. A 24 h intensive pharmacokinetic blood sampling and a trough seminal sampling were performed before (week 0) and after (week 12) dose reduction. Individual pharmacokinetic parameter estimates were obtained using non-linear mixed-effect modelling for darunavir/ritonavir in blood plasma and used to test for bioequivalence, whereas darunavir/ritonavir in seminal plasma and NRTIs were analysed using a non-compartmental approach., Results and Conclusions: Fifteen patients completed the intensive pharmacokinetic analysis. There was no significant decrease in total and unbound darunavir blood plasma exposure despite a 50% decrease in darunavir daily dose from 800 to 400 mg (AUC0-24 = 65 563 versus 52 518 ng·h/mL; P = 0.25). A decrease in apparent oral clearance (CL/F) of both darunavir and ritonavir at week 12 suggests a modification of the initial darunavir/ritonavir daily dose balance (800/100 to 400/100 mg), in favour of a reduced inducer effect of darunavir on cytochrome P450 and efflux transporters compared with the standard dose.
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- 2018
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43. High virological suppression regardless of the genotypic susceptibility score after switching to a dolutegravir-based regimen: week 48 results in an observational cohort.
- Author
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Charpentier C, Peytavin G, Lê MP, Joly V, Cabras O, Perrier M, Le Gac S, Phung B, Yazdanpanah Y, Descamps D, and Landman R
- Subjects
- Anti-HIV Agents blood, Antiretroviral Therapy, Highly Active, CD4 Lymphocyte Count, Cohort Studies, Drug Resistance, Viral genetics, Drug Substitution, Female, HIV-1 genetics, Heterocyclic Compounds, 3-Ring blood, Humans, Male, Middle Aged, Oxazines, Piperazines, Pyridones, RNA, Viral blood, Anti-HIV Agents therapeutic use, Genotype, HIV Infections drug therapy, HIV-1 drug effects, Heterocyclic Compounds, 3-Ring therapeutic use, Viral Load drug effects
- Abstract
Objectives: To assess, in a clinical cohort, the efficacy of switching current ART in virologically suppressed patients to a dolutegravir-based regimen, regardless of the genotypic susceptibility score (GSS)., Patients and Methods: This was an observational single-centre study assessing ART-treated patients with plasma viral load (pVL) <50 copies/mL who were switched to a dolutegravir-based regimen with 1 year of follow-up. PCR negative was defined as an undetected PCR signal. Trough plasma concentration (C24) was determined using UPLC-MS/MS., Results: Two hundred and thirty-nine patients initiated a dolutegravir-based regimen: 12%, 29% and 59% had a total GSS of 1 or 1.5 (group 1), 2 or 2.5 (group 2) and 3 (group 3), respectively. At switch initiation, the median time since first ART and the median duration with pVL <50 copies/mL were 13 years (IQR = 6-19) and 3 years (IQR = 1-6), respectively. Median times since last genotype were 9, 10 and 5 years for groups 1, 2 and 3, respectively. Twenty patients (8.4%) discontinued the dolutegravir-based regimen due to adverse events. During the study, 96.4% (n = 661/686) of all pVL were <50 copies/mL. Four patients (1.7%) experienced virological failure (two pVL >50 copies/mL) without emergence of resistance; these patients' GSSs were 2, 2.5, 3 and 3. The median dolutegravir C24 was 1545 ng/mL (IQR = 1150-2097). Of the patients with pVL <20 copies/mL, 72% were PCR negative during the follow-up, with no difference between the three groups of patients., Conclusions: This observational cohort study showed a high level of virological suppression maintenance in the first year following the switch to a dolutegravir-based regimen, even in patients with GSS ≤2.
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- 2018
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44. Population pharmacokinetics of Rilpivirine in HIV-1-infected patients treated with the single-tablet regimen rilpivirine/tenofovir/emtricitabine.
- Author
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Néant N, Gattacceca F, Lê MP, Yazdanpanah Y, Dhiver C, Bregigeon S, Mokhtari S, Peytavin G, Tamalet C, Descamps D, Lacarelle B, and Solas C
- Subjects
- Administration, Oral, Adult, Aged, Aged, 80 and over, Anti-HIV Agents administration & dosage, Anti-HIV Agents adverse effects, Area Under Curve, Chromatography, Liquid, Computer Simulation, Drug Dosage Calculations, Drug Monitoring methods, Emtricitabine, Rilpivirine, Tenofovir Drug Combination administration & dosage, Emtricitabine, Rilpivirine, Tenofovir Drug Combination adverse effects, Female, France, HIV Infections blood, HIV Infections virology, HIV-1 pathogenicity, Half-Life, Humans, Male, Metabolic Clearance Rate, Middle Aged, Nonlinear Dynamics, Retrospective Studies, Software, Tablets, Tandem Mass Spectrometry, Young Adult, Anti-HIV Agents pharmacokinetics, Emtricitabine, Rilpivirine, Tenofovir Drug Combination pharmacokinetics, HIV Infections drug therapy, HIV-1 drug effects, Models, Biological
- Abstract
Purpose: Rilpivirine, prescribed for the treatment of HIV infection, presents an important inter-individual pharmacokinetic variability. We aimed to determine population pharmacokinetic parameters of rilpivirine in adult HIV-infected patients and quantify their inter-individual variability., Methods: We conducted a multicenter, retrospective, and observational study in patients treated with the once-daily rilpivirine/tenofovir disoproxil fumarate/emtricitabine regimen. As part of routine therapeutic drug monitoring, rilpivirine concentrations were measured by UPLC-MS/MS. Population pharmacokinetic analysis was performed using NONMEM software. Once the compartmental and random effects models were selected, covariates were tested to explain the inter-individual variability in pharmacokinetic parameters. The final model qualification was performed by both statistical and graphical methods., Results: We included 379 patients, resulting in the analysis of 779 rilpivirine plasma concentrations. Of the observed trough individual plasma concentrations, 24.4% were below the 50 ng/ml minimal effective concentration. A one-compartment model with first-order absorption best described the data. The estimated fixed effect for plasma apparent clearance and distribution volume were 9 L/h and 321 L, respectively, resulting in a half-life of 25.2 h. The common inter-individual variability for both parameters was 34.1% at both the first and the second occasions. The inter-individual variability of clearance was 30.3%., Conclusions: Our results showed a terminal half-life lower than reported and a high proportion of patients with suboptimal rilpivirine concentrations, which highlights the interest of using therapeutic drug monitoring in clinical practice. The population analysis performed with data from "real-life" conditions resulted in reliable post hoc estimates of pharmacokinetic parameters, suitable for individualization of dosing regimen.
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- 2018
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45. Serious neuropsychiatric adverse effects related to interaction between itraconazole and darunavir/ritonavir in an HIV-infected patient with cerebral histoplasmosis.
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Le Meur L, Tantet C, Lê MP, Desselas E, Bonnal C, Lillo-Le-Louet A, Sonneville R, Massias L, Giraud J, Descamps D, Yazdanpanah Y, Lariven S, and Peytavin G
- Subjects
- Anti-HIV Agents administration & dosage, Antifungal Agents administration & dosage, Darunavir administration & dosage, HIV Infections complications, HIV Infections drug therapy, Histoplasmosis complications, Histoplasmosis drug therapy, Humans, Itraconazole administration & dosage, Male, Mental Disorders diagnosis, Mental Disorders pathology, Middle Aged, Plasma chemistry, Ritonavir administration & dosage, Anti-HIV Agents adverse effects, Antifungal Agents adverse effects, Darunavir adverse effects, Drug Interactions, Itraconazole adverse effects, Mental Disorders chemically induced, Ritonavir adverse effects
- Published
- 2018
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46. Darunavir/ritonavir monotherapy at a low dose (600/100 mg/day) in HIV-1-infected individuals with suppressed HIV viraemia.
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Seang S, Schneider L, Nguyen T, Lê MP, Soulie C, Calin R, Caby F, Valantin MA, Tubiana R, Assoumou L, Marcelin AG, Peytavin G, and Katlama C
- Subjects
- Drug Resistance, Viral, Female, Humans, Male, Middle Aged, Treatment Outcome, Anti-HIV Agents administration & dosage, Darunavir administration & dosage, HIV Infections drug therapy, HIV-1 isolation & purification, Ritonavir administration & dosage, Sustained Virologic Response, Viral Load
- Abstract
Background: Darunavir/ritonavir is a potent PI with a high genetic barrier and pharmacological robustness favourably investigated as monotherapy. Whether darunavir could be dose reduced in the context of monotherapy deserves investigation., Methods: Patients with HIV suppressed viraemia (plasma viral load <50 copies/mL for 12 months) under ART who had switched to darunavir/ritonavir monotherapy at 600/100 mg/day between 2013 and 2015 were included in this observational 48 week single-centre study. The primary outcome was the proportion of patients with virological success (defined as plasma viral load <50 copies/mL) at week 24. Secondary outcomes included treatment strategy success and resistance., Results: Thirty-one patients were included with the following baseline characteristics [median (IQR)]: age 52 years (47-57), CD4+ 649 cells/mm3 (463-813), ART duration 16.3 years (9.2-22.3), nadir CD4+ 195 cells/mm3 (144-261) and duration of HIV suppression 7.8 years (4.8-9.7). Prior to switch, ART consisted of PI monotherapy for 28 of 31 patients [darunavir/ritonavir 800/100 mg/day (n = 26), lopinavir/ritonavir (n = 1) and atazanavir/ritonavir (n = 1)] and a triple drug regimen for 3 of 31 patients. Within the 48 weeks of follow-up, no virological failure occurred and two patients discontinued 600/100 mg of darunavir/ritonavir due to side effects at week 16 and 40, leading to a virological suppression rate of 100% (95% CI = 89-100) at weeks 24 and 48. Strategy success rates were 96.8% (95% CI = 83.3-99.9) at week 24 and 93.5% (95% CI = 78.6-99.2) at week 48. Median (IQR) Ctrough values of 800/100 mg of darunavir/ritonavir and 600/100 mg of darunavir/ritonavir were 1537 ng/mL (1286-1724) and 1255 ng/mL (873-2161), respectively., Conclusions: A lower dose of darunavir/ritonavir used as monotherapy (600/100 mg/day) was highly effective in virologically suppressed HIV-infected patients. Further studies are needed to confirm these data., (© The Author 2017. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)
- Published
- 2018
- Full Text
- View/download PDF
47. Penetration and antiviral efficacy of total and unbound maraviroc, raltegravir and rilpivirine in both female and male genital fluids from HIV-positive patients receiving regimens containing these antiretrovirals.
- Author
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Lê MP, Belarbi L, Chaix ML, Dulioust E, Mahjoub N, Salmon D, Viard JP, Duvivier C, Peytavin G, Launay O, and Ghosn J
- Subjects
- Adult, Anti-HIV Agents administration & dosage, Cervix Uteri chemistry, Cervix Uteri virology, Cyclohexanes administration & dosage, Cyclohexanes pharmacokinetics, Cyclohexanes therapeutic use, Female, HIV Infections metabolism, HIV Infections transmission, HIV Infections virology, HIV-1 drug effects, Humans, Male, Maraviroc, Middle Aged, Prospective Studies, Raltegravir Potassium administration & dosage, Raltegravir Potassium pharmacokinetics, Raltegravir Potassium therapeutic use, Rilpivirine administration & dosage, Rilpivirine metabolism, Rilpivirine pharmacokinetics, Rilpivirine therapeutic use, Semen virology, Triazoles administration & dosage, Triazoles pharmacokinetics, Triazoles therapeutic use, Vagina chemistry, Vagina virology, Viral Load, Anti-HIV Agents pharmacokinetics, Anti-HIV Agents therapeutic use, Body Fluids chemistry, HIV Infections drug therapy, Semen chemistry
- Abstract
Background: Sub-optimal penetration of antiretroviral drugs in genital compartments might promote local HIV persistence and increase the risk of HIV transmission., Objectives: To describe the penetration of maraviroc, raltegravir, raltegravir glucuronide and rilpivirine in seminal plasma and cervico-vaginal secretions (CVS) and to assess local antiretroviral efficacy in HIV-1-positive patients., Methods: This was a prospective, multicentre study. Inclusion criteria were HIV-1 positive, age >18 years, receiving regimens containing maraviroc and/or raltegravir and/or rilpivirine for >1 month, and good self-reported adherence. Paired blood and genital samples were collected 12 h (raltegravir and maraviroc) or 24 h (rilpivirine) post-dose. These concentrations were determined (UPLC-MS/MS) in blood and seminal plasma (total and unbound) and CVS (total, dried spots) and HIV-RNA was quantified in paired blood and genital samples., Results: Among the 54 enrolled patients, 15 received maraviroc (6 men), 27 received raltegravir (14 men) and 20 received rilpivirine (10 men), corresponding to 54 total and 52 unbound plasma concentrations, 29 total CVS samples and 23 total and 18 unbound seminal plasma samples. Maraviroc and raltegravir displayed a ratio of genital fluids/plasma concentrations >0.5 in both male and female genital tracts. Conversely, rilpivirine displayed a low ratio. Antiretroviral free fractions were consistent with historical data. Nine patients had blood plasma HIV-RNA >50 copies/mL (2/9 had sub-optimal antiretroviral blood plasma exposure) and two other patients had detectable HIV-RNA in genital fluids., Conclusions: Maraviroc and raltegravir demonstrated good penetration in genital compartments, yielding good local virological response in genital compartments, whereas rilpivirine presented a low penetration profile but good local response., (© The Author 2017. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)
- Published
- 2017
- Full Text
- View/download PDF
48. Plasma concentrations of atovaquone given to immunocompromised patients to prevent Pneumocystis jirovecii.
- Author
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Robin C, Lê MP, Melica G, Massias L, Redjoul R, Khoudour N, Leclerc M, Beckerich F, Maury S, Hulin A, and Cordonnier C
- Subjects
- Aged, Antifungal Agents administration & dosage, Atovaquone administration & dosage, Atovaquone pharmacokinetics, Biological Availability, Female, HIV Infections complications, HIV Infections virology, Humans, Male, Middle Aged, Pneumonia, Pneumocystis complications, Pneumonia, Pneumocystis microbiology, Antifungal Agents blood, Atovaquone blood, Immunocompromised Host, Pneumocystis carinii drug effects, Pneumonia, Pneumocystis prevention & control
- Abstract
Objectives: Atovaquone is one of the alternatives to trimethoprim/sulfamethoxazole for prophylaxis of Pneumocystis jirovecii pneumonia (PCP) in immunocompromised patients. In volunteers, there was wide inter-individual variability in atovaquone bioavailability. The aim of this study was to assess the plasma concentrations of atovaquone in immunocompromised patients under PCP prophylaxis., Methods: Adult haematology or HIV-positive patients receiving atovaquone (750 mg oral suspension twice a day) for PCP prophylaxis were included. Plasma concentrations were assessed using UV-HPLC, around 12 h after the evening dose (Cmin) and 1-5 h after the morning dose (Cmax)., Results: A total of 82 measurements were performed in 33 patients. This included 19 HSCT recipients, 7 haematology non-transplant patients and 7 HIV-positive patients. The median Cmin (IQR) was 11.3 μg/mL (6.2-27.8) and the median Cmax was 13.4 μg/mL (6.0-28.3). The Cmin and Cmax of atovaquone were not different between HIV-negative and HIV-positive patients, or between HSCT and non-HSCT patients. Atovaquone concentrations were not influenced by the co-administration of valaciclovir (n = 20) or ciclosporin (n = 11), by gut graft-versus-host disease (n = 7) or by the intake of atovaquone with food. Nineteen of the 33 (58%) patients had Cmin <15 μg/mL, a threshold associated with a low rate of clinical response in PCP treatment., Conclusions: Atovaquone is poorly absorbed in more than half of immunocompromised patients and its bioavailability varies between individuals. These unpredictable variations raise the question of therapeutic drug monitoring, in order to identify patients with low concentrations and those who could benefit from regimen adaptation or from alternatives., (© The Author 2017. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)
- Published
- 2017
- Full Text
- View/download PDF
49. Reply to: "Therapeutic drug monitoring for sofosbuvir and daclatasvir in transplant recipients with chronic hepatitis C and advanced renal disease".
- Author
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Desnoyer A, Lê MP, Yazdanpanah Y, and Peytavin G
- Subjects
- Antiviral Agents, Carbamates, Drug Monitoring, Drug Therapy, Combination, Hepacivirus, Humans, Imidazoles, Pyrrolidines, Transplant Recipients, Treatment Outcome, Valine analogs & derivatives, Hepatitis C, Chronic, Sofosbuvir
- Published
- 2016
- Full Text
- View/download PDF
50. High efficacy of first-line ART in a West African cohort, assessed by dried blood spot virological and pharmacological measurements.
- Author
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de Truchis P, Lê MP, Daou M, Madougou B, Nouhou Y, Moussa Saley S, Sani A, Adehossi E, Rouveix E, Saidou M, Peytavin G, and Delaugerre C
- Subjects
- Adolescent, Adult, Anti-Retroviral Agents pharmacokinetics, Blood Chemical Analysis, Cross-Sectional Studies, Desiccation, Female, Genotyping Techniques methods, Humans, Male, Medication Adherence, Microbial Sensitivity Tests methods, Middle Aged, Niger, Nucleic Acid Amplification Techniques methods, Treatment Outcome, Young Adult, Anti-Retroviral Agents therapeutic use, Antiretroviral Therapy, Highly Active, Blood virology, HIV isolation & purification, HIV Infections drug therapy, Specimen Handling methods, Viral Load methods
- Abstract
Objectives: The objectives of this study were to determine the rate of viral success in HIV-infected patients on first-line ART by the assessment of dried blood spot (DBS) viral load (VL) and to assess the performance of DBS sampling for VL measurement, genotypic resistance and antiretroviral concentration determinations., Methods: HIV-infected patients treated for >1 year with first-line ART in Niamey, Niger were included. VL based on nucleic acid sequence-based amplification (NASBA) assay (limit of quantification <800 copies/mL) was measured on DBS capillary samples. Resistance genotype was assessed for all detectable VLs (limit of detection >100 copies/mL); antiretroviral concentrations were interpreted using standard plasma cut-offs after extrapolation of blood to plasma results. Median (IQR) results are presented., Results: Two hundred and eighteen patients (61% women), aged 41 (34-46) years, with 138 (56-235) CD4 cells/mm
3 at baseline were included. After 4 (2-6) years of follow-up under therapy, CD4 gain was +197 (98-372) cells/mm3 ; 81% had VL <800 copies/mL. Antiretroviral concentrations were adequate in 87% of patients and nevirapine/efavirenz concentrations were related to viral success (P < 0.001). DBS genotypic resistance amplification succeeded in 71% of failing patients: NRTI drug resistance mutations were identified in 73% including resistance to lamivudine/emtricitabine (67%), abacavir (30%) and tenofovir (21%); and NNRTI drug resistance mutations were identified in 82% including resistance to rilpivirine (39%) and etravirine (15%)., Conclusions: This study demonstrated a good response after 4 years of first-line ART in Niger. Adherence was high, according to antiretroviral concentrations, and the majority of failures were explained by selection of drug resistance mutations detected in the DBS genotype. Using DBS might improve the assessment of ART failure in HIV-infected patients in low-income countries., (© The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)- Published
- 2016
- Full Text
- View/download PDF
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