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13 results on '"Saadia Mokhtari"'

1. Risk of Progressive Multifocal Leukoencephalopathy in the Combination Antiretroviral Therapy Era in the French Hospital Database on Human Immunodeficiency Virus (ANRS-C4)

Author

Jacques Gasnault, Hugues Melliez, Olivier Robineau, Véronique Joly, Pierre de Truchis, Murielle Mary-Krause, Karine Risso, Dominique Costagliola, Marie-Aude Khuong-Josses, Nathalie De Castro, Anna Canestri, Matthieu Revest, Marguerite Guiguet, Saadia Mokhtari, Guillaume Martin-Blondel, Aurelia Henn, Sophie Abgrall, Christine Katlama, and Laurence Bocket

Subjects
Adult, Male, 0301 basic medicine, Microbiology (medical), Cart, Databases, Factual, Anti-HIV Agents, Hepatitis C virus, HIV Infections, computer.software_genre, medicine.disease_cause, Men who have sex with men, Sexual and Gender Minorities, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, medicine, Humans, Prospective Studies, Homosexuality, Male, Substance Abuse, Intravenous, Prospective cohort study, Proportional Hazards Models, Database, business.industry, Incidence, Progressive multifocal leukoencephalopathy, Incidence (epidemiology), Hazard ratio, Leukoencephalopathy, Progressive Multifocal, virus diseases, medicine.disease, Hepatitis C, Hospitals, 030104 developmental biology, Infectious Diseases, Cohort, HIV-1, Drug Therapy, Combination, Female, France, business, computer, 030217 neurology & neurosurgery
Abstract

Background Risk factors for progressive multifocal leukoencephalopathy (PML) in individuals with human immunodeficiency virus (HIV) infection are poorly documented in the era of combination antiretroviral therapy (cART). Methods We studied HIV-1-infected individuals aged ≥15 years who had no history of PML and were prospectively followed up between 1997 and 2011 in the French Hospital Database on HIV (FHDH-ANRS CO4) cohort. Cox models were used to calculate adjusted hazard ratios (HRs), focusing on sub-Saharan origin, suggested to be protective, and recent cART initiation, potentially associated with an increased risk of PML. Results PML developed in 555 individuals, in 57 during the first 6 months of cART. From 1997-2000 to 2009-2011, the incidence fell from 1.15 (95% confidence interval [CI], .98-1.31) to 0.49 (.37-.61) per 1000 person-years. Sub-Saharan African origin had no clear influence (HR, 0.80; 95% CI, .58-1.11). Compared with men who have sex with men, injection drug users (IDUs) were at higher risk (HR, 1.80 [95% CI, 1.32-2.45] for male and 1.68 [1.13-2.48] for female IDUs). When IDUs were excluded, hepatitis C virus seropositivity was associated with an increased risk (HR, 1.40; 95% CI, 1.02-1.93). Compared with no cART initiation, initiation

Published
2018

2. Concentration–response model of rilpivirine in a cohort of HIV-1-infected naive and pre-treated patients

Author

Florence Gattacceca, Nadège Néant, Caroline Solas, Gilles Peytavin, Diane Descamps, Catherine Dhiver, Yazdan Yazdanpanah, Bruno Lacarelle, Naïm Bouazza, Minh Patrick Lê, Catherine Tamalet, Saadia Mokhtari, Sylvie Bregigeon, Centre de Recherche en Cancérologie de Marseille (CRCM), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Microbes évolution phylogénie et infections (MEPHI), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Service d'Immuno-hématologie clinique [Hôpital Sainte Marguerite - APHM], Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital Sainte-Marguerite [CHU - APHM] (Hôpitaux Sud ), Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC), Pharmacocinétique Toxicocinétique - [Hôpital de la Timone - APHM], Hôpital de la Timone [CHU - APHM] (TIMONE)-Assistance Publique - Hôpitaux de Marseille (APHM), Université de Montpellier (UM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)

Subjects
Microbiology (medical), Oncology, Adult, Male, medicine.medical_specialty, Anti-HIV Agents, [SDV]Life Sciences [q-bio], Population, HIV Infections, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Emtricitabine, 030226 pharmacology & pharmacy, 03 medical and health sciences, chemistry.chemical_compound, Young Adult, 0302 clinical medicine, Pharmacokinetics, Internal medicine, medicine, Humans, Pharmacology (medical), Trough Concentration, Computer Simulation, 030212 general & internal medicine, education, Aged, Pharmacology, education.field_of_study, business.industry, Rilpivirine, Disease Management, Middle Aged, Models, Theoretical, Viral Load, 3. Good health, CD4 Lymphocyte Count, Regimen, Infectious Diseases, chemistry, Pharmacodynamics, HIV-1, Female, Drug Monitoring, business, Viral load, Algorithms, medicine.drug
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.

Published
2019

3. 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

Author

Bruno Lacarelle, Florence Gattacceca, Saadia Mokhtari, Gilles Peytavin, Caroline Solas, Naïm Bouazza, Catherine Dhiver, Diane Descamps, Minh Patrick Lê, Sylvie Bregigeon, Yazdan Yazdanpanah, Catherine Tamalet, and Nadège Néant

Subjects
Adult, Male, medicine.medical_specialty, Anti-HIV Agents, HIV Infections, Emtricitabine, 030226 pharmacology & pharmacy, Gastroenterology, Cohort Studies, 03 medical and health sciences, chemistry.chemical_compound, Young Adult, 0302 clinical medicine, Pharmacokinetics, Internal medicine, medicine, Humans, Pharmacology (medical), Trough Concentration, 030212 general & internal medicine, Tenofovir, Aged, Retrospective Studies, Pharmacology, medicine.diagnostic_test, business.industry, Rilpivirine, Original Articles, Middle Aged, Viral Load, Regimen, chemistry, Therapeutic drug monitoring, Pharmacodynamics, Cohort, HIV-1, Female, Drug Monitoring, business, medicine.drug
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.

Published
2019

4. Safety study and therapeutic drug monitoring of the oral tablet formulation of posaconazole in patients with haematological malignancies

Author

Lemaitre, Florian, Le Guillou, Adrien, Pugliese, Pascal, Raffi, François, Cuzin, Lise, Katlama, Christine, Allavena, Clotilde, Dramé, Moustapha, Cotte, Laurent, Bani-Sadr, Firouzé, Orticoni, M, Soavi, M, Luquet- Besson, I, Ressiot, E, Carta- Padovani, M, Ducassou, M, Bertone, H, Galie, S, Galinier, A., Monclar, M, Ritleng, A, Ivanova, A., Blanco-Betancourt, C, Lions, C., Poizot-Martin, I., Dhiver, C, Saadia Mokhtari, M, Menard, A., Tissot Dupont, H, Toméi, C, Meddeb, L., Belkhir, A., Ravaux, I., Alvarez, M., Biezunski, N, Debard, A., Delpierre, C, Lansalot, P, Lelievre, L., Martin-Blondel, G., Piffaut, M, Porte, L., Saune, K, Delobel, P., Breaud, S., Ceppi, C, Chirio, D, Cua, E, Dellamonica, P., Demonchy, E, De Monte, A, Durant, J., Etienne, C, Ferrando, S, Garraffo, R, Michelangeli, C, Mondain, V., Bernaud, C, Billaud, E., Biron, C, Bonnet, B, Bouchez, S, Boutoille, D., Brunet-Cartier, C, Deschanvres, C, Gaborit, B., Hall, N, Le Turnier, P., Morineau, P, Reliquet, V., Sécher, S, Cavellec, M, Soria, A., Ferre, V., André-Garnier, E., Rodallec, A., Lefebvre, M, Grossi, O, Aubry, O., Amazzough, K., Benabdelmoumen, G, Bossi, P, Cessot, G, Charlier, C., Consigny, P, Danion, F., Dureault, A, Duvivier, C., Goesch, J, Guery, R., Henry, B., Jidar, K, Lanternier, F., Loubet, P., Lortholary, O., Louisin, C, Lourenco, J, Parize, P., Pilmis, B., Touam, F, Valantin, M, Tubiana, R., Agher, R, Seang, S, Schneider, L, PaLich, R, Blanc, C, Cabié, André, Abel, S., Pierre-François, S, Pasquier, J., Guitteaud, K, Turmel, J, Illiaquer, M, Fischer, P., Partisani, M., Cheneau, C., Priester, M, Batard, M, Bernard-Henry, C, de Mautort, E, Fafi-Kremer, S., Rey, D., Chirouze, C., Gardiennet, Q, Berger, J, N’Guyen, Y, Lambert, D., Hentzien, M., Lebrun, D., Brunet, A, Kmiec, I, Brodard, V, Chidiac, C., Ferry, T., Ader, F., Biron, F., Boibieux, A., Miailhes, P., Perpoint, T., Schlienger, I, Lippmann, J, Braun, E, Koffi, J, Longuet, C., Guéripel, V, Augustin-Normand, C, Brochier, C, Degroodt, S, Atoui, N, Le Moing, V., Makinson, A., Meftah, N., de Boever, C Merle, Montes, B, Montoya Ferrer, A, Reynes, J., Andre, M., Boyer, L, Bouillon, M, Delestan, M, May, T, Hocqueloux, L, Prazuck, T., Gubavu, C, Sève, A, Maka, A, Boulard, C., Thomas, G, Cheret, A, Goujard, C, Quertainmont, Y, Teicher, E., Lerolle, N., Deradji, O, Barrail-Tran, A, Landman, R, Joly, V, Rioux, C., Lariven, S, gervais, a, Lescure, F., Matheron, S., Louni, F, Godard, C, Julia, Z, Chansombat, M, Rahli, D, Mackoumbou-Nkouka, C, Charpentier, c, Descamps, D., Peytavin, G., Yazdanpanah, Y., Tattevin, P., Revest, M., Souala, F., Baldeyrou, M., Patrat-Delon, S, Chapplain, J, Bénézit, F., Dupont, M., Poinot, M., MAILLARD, A, Pronier, C., Guennoun, C, Poisson-Vanier, M, Jovelin, T., Sinteff, J, Arvieux, C, Botelho-Nevers, E., Gagneux-Brunon, A., Frésard, A., Lucht, F., Ajana, F, Aïssi, E, Alcaraz, I, Baclet, V, Bocket, L, Boucher, A, Choisy, P, Huleux, T., Lafon-Desmurs, B., Meybeck, A, Pradier, M, Robineau, O, Viget, N, Valette, M., Hoen, B., Lamaury, I, Fabre, I, Curlier, E, Ouissa, R, Schepers, K, Herrmann-Storck, C, Dournon, N, Merrien, D, Perré, P., Guimard, T, Bollangier, O, Leautez, S, Morrier, M, Boglione-Kerrien, C., Picard, S., Tron, C., Nimubona, S., Gangneux, J.-P., Lalanne, S., Lemaître, F., Bellissant, E., Verdier, M.-C., Petitcollin, A., Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre Hospitalier Universitaire de Nice (CHU Nice), Service des maladies infectieuses et tropicales [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Epidémiologie et analyses en santé publique : risques, maladies chroniques et handicaps (LEASP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Immunité et Infection, Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR113-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de maladies infectieuses et tropicales [Nantes], Université de Nantes (UN)-Hôtel-Dieu-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Hospitalier Universitaire de Reims (CHU Reims), Service de Maladies Infectieuses et Tropicales [Hôpital de la Croix-Rousse - HCL], Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Institut de biologie et chimie des protéines [Lyon] (IBCP), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Hôpital Sainte-Marguerite [CHU - APHM] (Hôpitaux Sud ), DDSIS 76, Institut national de recherche et de sécurité (Vandoeuvre lès Nancy) (INRS ( Vandoeuvre lès Nancy)), Service des Maladies Infectieuses et Tropicales [Hôpital de la Conception] (SMIT), Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital de la Conception [CHU - APHM] (LA CONCEPTION ), Laboratoire de Physique et Chimie Quantique, Université Mouloud Mamerri, Pôle des Maladies Infectieuses et Tropicales Clinique et Biologique, Fédération de Bactériologie-Hygiène-Virologie, Assistance Publique - Hôpitaux de Marseille (APHM), Département de Physique Nucléaire (ex SPhN) (DPHN), Institut de Recherches sur les lois Fondamentales de l'Univers (IRFU), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Génomique métabolique (UMR 8030), Genoscope - Centre national de séquençage [Evry] (GENOSCOPE), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Université d'Évry-Val-d'Essonne (UEVE)-Centre National de la Recherche Scientifique (CNRS), Hospices Civils de Lyon (HCL), Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Institut des Matériaux, de Microélectronique et des Nanosciences de Provence (IM2NP), Aix Marseille Université (AMU)-Université de Toulon (UTLN)-Centre National de la Recherche Scientifique (CNRS), Département Etude des Réacteurs (DER), CEA-Direction de l'Energie Nucléaire (CEA-DEN), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Hopital l'Archet, Centre d'Information et de Soins de I'Immunodéficience Humaine (CISIH). Hôpital l'Archet 1, Hôpital l'Archet, CHU Nice [Cimiez], Hôpital Cimiez [Nice] (CHU), Centre de résonance magnétique biologique et médicale (CRMBM), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française], Centre d'Immunologie et de Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Hôtel-Dieu de Nantes, Service de virologie [CHU Nantes], Centre d'infectiologie Necker-Pasteur [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Science et Technologie du Lait et de l'Oeuf (STLO), AGROCAMPUS OUEST-Institut National de la Recherche Agronomique (INRA), Institut des Sciences du Mouvement Etienne Jules Marey (ISM), Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Université Paris Descartes - Paris 5 (UPD5), Institut de Physique du Globe de Paris (IPGP), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut national des sciences de l'Univers (INSU - CNRS)-IPG PARIS-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Centre National de la Recherche Scientifique (CNRS), Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service des maladies infectieuses [CHU Pitié-Salêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Centre d'Investigation Clinique Antilles-Guyane (CIC - Antilles Guyane), Université des Antilles et de la Guyane (UAG)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -CHU de Fort de France-Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française], Système membranaires, photobiologie, stress et détoxication (SMPSD), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Weill Cornell Medicine [Qatar], Institut Rayonnement Matière de Saclay (IRAMIS), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Institut de pharmacologie moléculaire et cellulaire (IPMC), Université Nice Sophia Antipolis (UNS), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Laboratoire de Virologie [Strasbourg], GEOMA, Université de Vigo, Universidate de Vigo, Laboratoire Chrono-environnement - UFC (UMR 6249) (LCE), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Laboratoire d'aérologie (LA), Centre National de la Recherche Scientifique (CNRS)-Observatoire Midi-Pyrénées (OMP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées, Service des Maladies Infectieuses, Groupement Hospitalier Nord, Hospices Civils de Lyon, Lyon, France, parent, Pathogénie des Staphylocoques – Staphylococcal Pathogenesis, Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hosp Civils Lyon, Serv Malad Infect, Lyon, France, Equipe 15, Centre de Recherche en Cancérologie de Lyon (CRCL), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Recherches Translationnelles sur le VIH et les maladies infectieuses (TransVIHMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Recherche pour le Développement (IRD)-Université Montpellier 1 (UM1)-Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Universtié Yaoundé 1 [Cameroun]-Université de Montpellier (UM), Faculté des Mathématiques et des Sciences de la Matière, Université Kasdi Merbah Ouargla, Laboratoire de Géochimie Isotopique Environnementale (GIS) / Université de Nîmes (GIS), Université de Nîmes (UNIMES)-Centre National de la Recherche Scientifique (CNRS), CHU UCL Namur, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Bicêtre, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Bicêtre, Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Service des maladies infectieuses et tropicales, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris]-Université Paris Diderot - Paris 7 (UPD7), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Centre d'Etudes Lasers Intenses et Applications (CELIA), Université de Bordeaux (UB)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Pharmacie de l'Hôpital Bichat, UMR CNRS 8179, Université de Lille, Sciences et Technologies-Centre National de la Recherche Scientifique (CNRS), Service des maladies infectieuses et réanimation médicale, Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou, Les Hôpitaux Universitaires de Strasbourg (HUS), Service de pneumologie, Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Unité des Rickettsies et pathogènes émergents (URPE), Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes (URMITE), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR48, INSB-INSB-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR48, INSB-INSB-Centre National de la Recherche Scientifique (CNRS), CHU Saint-Etienne, University Hospital and University Jean Monnet, Centre Hospitalier Tourcoing, CHU de Fort de France, Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon)-Hôpital Saint-Jacques, Laboratoire de Génie des Procédés et Matériaux - EA 4038 (LGPM), CentraleSupélec, Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), and Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )

Subjects
0301 basic medicine, Male, Cancer Research, Posaconazole, Antifungal Agents, [SDV]Life Sciences [q-bio], Administration, Oral, Dat’AIDS cohort, Pharmacology, 030226 pharmacology & pharmacy, Gastroenterology, 0302 clinical medicine, MESH: Drug Monitoring, Medicine, Prospective Studies, Haematological malignancies, media_common, MESH: Aged, Hematology, MESH: Middle Aged, medicine.diagnostic_test, General Medicine, Middle Aged, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, 90-90-90 target, 3. Good health, Posaconazole oral tablet, Oncology, Quartile, MESH: Young Adult, Hematologic Neoplasms, MESH: Administration, Oral, Female, Drug Monitoring, Antifungal prophylaxis, Safety, medicine.drug, Tablets, Drug, Adult, medicine.medical_specialty, media_common.quotation_subject, 030106 microbiology, Therapeutic drug monitoring, 03 medical and health sciences, Young Adult, Pharmacokinetics, Invasive fungal infections, Internal medicine, Pharmacovigilance, primary HIV infection, cascade of care, Humans, Aged, MESH: Humans, business.industry, MESH: Adult, TasP, Triazoles, MESH: Antifungal Agents, MESH: Prospective Studies, MESH: Male, MESH: Triazoles, MESH: Tablets, business, Liver function tests, MESH: Female, MESH: Hematologic Neoplasms
Abstract

International audience; PurposePosaconazole is a triazole antifungal widely used for prophylaxis of invasive fungal disease (IFI). Posaconazole tablets allow reaching higher plasma levels than the oral suspension, but safety data with this formulation in real life are scarce. This study aimed at evaluating the safety profile, the pharmacokinetic variability, and the concentration–toxicity relationship of posaconazole tablets in patients with haematological malignancies.MethodsSixty neutropenic patients treated with posaconazole tablets for prophylaxis of IFI were prospectively included in the study. Adverse drug reactions (ADR) were recorded and analyzed by the Regional Pharmacovigilance Centre to assess posaconazole implication. Blood samples were drawn once a week and plasma trough concentrations (C min) were assayed by LC–MS/MS. The rates of ADR by quartile of C min were compared.ResultsEighteen patients (30%) experienced at least one ADR attributed to posaconazole. Liver function test (LFT) abnormalities were encountered in 20% of patients and resulted in four (6.7%) treatment discontinuations. Posaconazole median (range) C min was 1.36 (< 0.1–3.44) µg/mL (inter-patient CV = 43.9%). During follow-up, 28.6% of patients had at least one concentration < 0.7 µg/mL, and 35.7% had at least one concentration > 2 µg/mL. Rates of ADR by quartile of C min were not different.ConclusionsPosaconazole was well tolerated; however, LFT abnormalities were frequent. ADR occurrence was not linked to posaconazole exposure. Because posaconazole concentrations were highly variable, TDM can be helpful to avoid underexposure to the drug and increase its efficacy in preventing IFI. Conversely, a large proportion of patients was overexposed and might have benefited of a dose reduction.

Published
2018

5. Population pharmacokinetics of Rilpivirine in HIV-1-infected patients treated with the single-tablet regimen rilpivirine/tenofovir/emtricitabine

Author

Nadège Néant, Bruno Lacarelle, Catherine Dhiver, Florence Gattacceca, Caroline Solas, Diane Descamps, Saadia Mokhtari, Minh Patrick Lê, Sylvie Bregigeon, Yazdan Yazdanpanah, Catherine Tamalet, and Gilles Peytavin

Subjects
0301 basic medicine, Male, Human immunodeficiency virus (HIV), Administration, Oral, HIV Infections, medicine.disease_cause, 030226 pharmacology & pharmacy, chemistry.chemical_compound, 0302 clinical medicine, Tandem Mass Spectrometry, Pharmacology (medical), Drug Dosage Calculations, Aged, 80 and over, education.field_of_study, medicine.diagnostic_test, General Medicine, Middle Aged, Rilpivirine, Area Under Curve, Female, France, Drug Monitoring, medicine.drug, Half-Life, Tablets, Adult, medicine.medical_specialty, Anti-HIV Agents, Metabolic Clearance Rate, 030106 microbiology, Population, Emtricitabine, Models, Biological, 03 medical and health sciences, Young Adult, Pharmacokinetics, Internal medicine, medicine, Humans, Computer Simulation, education, Aged, Retrospective Studies, Pharmacology, business.industry, NONMEM, Regimen, chemistry, Nonlinear Dynamics, Therapeutic drug monitoring, HIV-1, Emtricitabine, Rilpivirine, Tenofovir Drug Combination, business, Software, Chromatography, Liquid
Abstract

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. 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. 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%. 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.

Published
2017

6. Emergence of uncommon HIV-1 non-B subtypes and circulating recombinant forms and trends in transmission of antiretroviral drug resistance in patients with primary infection during the 2013-2015 period in Marseille, Southeastern France

Author

Anne Motte, Philippe Colson, Saadia Mokhtari, Isabelle Ravaux, Christian Tourres, Catherine Tamalet, Hélène Laroche, Catherine Dhiver, Sarah Aherfi, Hervé Tissot-Dupont, Isabelle Poizot-Martin, Hervé Chaudet, Sylvie Bregigeon, Andreas Stein, Olivia Zaegel-Faucher, Philippe Brouqui, Thérèse Dieng, Amélie Menard, Christelle Tomei, Microbes évolution phylogénie et infections (MEPHI), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Service d'Immuno-hématologie clinique [Hôpital Sainte Marguerite - APHM], Hôpital Sainte-Marguerite [CHU - APHM] (Hôpitaux Sud )-Assistance Publique - Hôpitaux de Marseille (APHM), Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U1252 INSERM - Aix Marseille Univ - UMR 259 IRD), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), This study was supported by a grant from the French State managed by the National Research Agency under the 'Investissements d’’avenir (Investments for the Future)' program with the referenceANR‐10‐IAHU‐03 (Méditerranée Infection)., ANR-10-IAHU-0003,Méditerranée Infection,I.H.U. Méditerranée Infection(2010), COMBE, Isabelle, Instituts Hospitalo-Universitaires - I.H.U. Méditerranée Infection - - Méditerranée Infection2010 - ANR-10-IAHU-0003 - IAHU - VALID, and Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital Sainte-Marguerite [CHU - APHM] (Hôpitaux Sud )

Subjects
0301 basic medicine, Adult, Male, resistance-associated mutations, recombinant subtypes, Genotype, Anti-HIV Agents, Period (gene), men having sex with men, Etravirine, HIV Infections, non-B subtypes, law.invention, Men who have sex with men, 03 medical and health sciences, Acquired immunodeficiency syndrome (AIDS), [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, law, Virology, Drug Resistance, Viral, medicine, Prevalence, Humans, In patient, Recombination, Genetic, Transmission (medicine), business.industry, Sequence Analysis, DNA, primary HIV Infection, Middle Aged, medicine.disease, Reverse transcriptase, 3. Good health, 030104 developmental biology, Infectious Diseases, Mutation, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Recombinant DNA, HIV-1, Female, France, primary antiretroviral resistance, business, medicine.drug
Abstract

International audience; Primary HIV-1 infections (PHI) with non-B subtypes are increasing in developed countries while transmission of HIV-1 harboring antiretroviral resistance-associated mutations (RAMs) remains a concern. This study assessed non-B HIV-1 subtypes and RAMs prevalence among patients with PHI in university hospitals of Marseille, Southeastern France, in 2005-2015 (11 years). HIV-1 sequences were obtained by inhouse protocols from 115 patients with PHI, including 38 for the 2013-2015 period. On the basis of the phylogenetic analysis of the reverse transcriptase region, non-B subtypes were identified in 31% of these patients. They included 3 different subtypes (3A, 1C, 4F), 23 circulating recombinant forms (CRFs) (CRF02_AG, best BLAST hits being CRF 36\ₓpx and CRF30 in 7 and 1 cases, respectively), and 5 unclassified sequences (U). Non-B subtypes proportion increased significantly, particularly in 2011-2013 vs in 2005-2010 (P = .03). CRF02_AG viruses largely predominated in 2005-2013 whereas atypical strains more difficult to classify and undetermined recombinants emerged recently (2014-2015). The prevalence of protease, nucleos(t) ide reverse transcriptase, and first-generation nonnucleoside reverse transcriptase inhibitors-associated RAMs were 1.7% (World Health Organization [WHO] list, 2009/2.6% International AIDS Society [IAS] list, 2017), 5.2%/4.3%, and 5.2%/5.2%, respectively. Etravirine/rilpivirine-associated RAM (IAS) prevalence was 4.3%. Men who have sex with men (MSM) were more frequently infected with drug-resistant viruses than other patients (26% vs 7%; P = .011). The recent increase of these rare HIV-1 strains and the spread of drug-resistant HIV-1 among MSM in Southeastern France might be considered when implementing prevention strategies and starting therapies.

Published
2017

7. Dolutegravir and weight gain: an unexpected bothering side effect?

Author

Catherine Dhiver, Amélie Menard, Philippe Brouqui, Philippe Colson, Hervé Tissot-Dupont, Christelle Tomei, Saadia Mokhtari, Andreas Stein, Isabelle Ravaux, Line Meddeb, Service de Maladies Infectieuses, Hôpital de la Conception [CHU - APHM] (LA CONCEPTION)-Centre de Référence des Infections Ostéo-articulaires Sud-Méditerranée (CRIOA), Assistance Publique - Hôpitaux de Marseille (APHM)-Institut Hospitalier Universitaire Méditerranée Infection (IHU Marseille)-Hôpital de la Conception [CHU - APHM] (LA CONCEPTION)-Assistance Publique - Hôpitaux de Marseille (APHM)-Institut Hospitalier Universitaire Méditerranée Infection (IHU Marseille), Service des Maladies Infectieuses et Tropicales [Hôpital de la Conception] (SMIT), Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Unité de Recherche sur les Maladies Infectieuses Tropicales Emergentes (URMITE), Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes (URMITE), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR48, Institut des sciences biologiques (INSB-CNRS)-Institut des sciences biologiques (INSB-CNRS)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR48, Institut des sciences biologiques (INSB-CNRS)-Institut des sciences biologiques (INSB-CNRS)-Centre National de la Recherche Scientifique (CNRS), Aix-Marseille Université - Faculté de pharmacie (AMU PHARM), Aix Marseille Université (AMU), Service des Maladies Infectieuses, Service des Maladies Infectieuses et Tropicales [CHU Hôpital Nord - Marseille] (M.I.T), Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital Nord [CHU - APHM], Hôpital Nord [CHU - APHM], Hôpital de la Conception [CHU - APHM] (LA CONCEPTION)-Assistance Publique - Hôpitaux de Marseille (APHM)-Institut Hospitalier Universitaire Méditerranée Infection (IHU Marseille)-Assistance Publique - Hôpitaux de Marseille (APHM)-Institut Hospitalier Universitaire Méditerranée Infection (IHU Marseille), INSB-INSB-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR48, and INSB-INSB-Centre National de la Recherche Scientifique (CNRS)

Subjects
Male, 0301 basic medicine, Cart, medicine.medical_specialty, Side effect, Pyridones, 030106 microbiology, Immunology, Weight Gain, Piperazines, Cohort Studies, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Internal medicine, Oxazines, medicine, Humans, Immunology and Allergy, HIV Integrase Inhibitors, 030212 general & internal medicine, Adverse effect, ComputingMilieux_MISCELLANEOUS, business.industry, virus diseases, Middle Aged, 3. Good health, Discontinuation, Infectious Diseases, chemistry, Cohort, Dolutegravir, Female, medicine.symptom, business, Heterocyclic Compounds, 3-Ring, Weight gain, Cohort study
Abstract

We recently analyzed, in our real-life cohort of 2260 HIV-infected patients, the reasons for discontinuation of dolutegravir-based combined antiretroviral therapies (cARTs) [1]. Of 517 patients, 55 (10.6%) discontinued this cART due to adverse effects. Unexpectedly, four (7%) of these adverse effect

Published
2017

8. Population Pharmacokinetics of Atazanavir in Human Immunodeficiency Virus-Infected Patients

Author

Nicolas Simon, Caroline Solas, Alain Lafeuillade, Bruno Lacarelle, Marie-Claude Gagnieu, Saadia Mokhtari, Isabelle Ravaux, and Marie-Pierre Drogoul

Subjects
Adult, Male, medicine.medical_specialty, Anti-HIV Agents, Pyridines, Atazanavir Sulfate, Population, HIV Infections, Context (language use), Pharmacology, Gastroenterology, Pharmacokinetics, Internal medicine, medicine, Humans, Pharmacology (medical), education, Aged, Retrospective Studies, Volume of distribution, education.field_of_study, business.industry, virus diseases, Middle Aged, Confidence interval, Atazanavir, NONMEM, Female, business, Oligopeptides, medicine.drug
Abstract

The aim of this study was to determine the population pharmacokinetic (PK) parameters of atazanavir in adult human immunodeficiency virus-infected patients to build up a Bayesian strategy for dosage regimen individualization. This was an observational study of patients treated with the once-daily regimen atazanavir associated with 100 mg of ritonavir. Blood samples were drawn at steady state at various times ranging from 1 to 26 hours postdose. Atazanavir plasma concentrations were determined by a validated reverse-phase high-performance liquid chromatography method. PK analysis of the atazanavir population was performed using a nonlinear mixed-effects model (NONMEM version 6). One hundred eighty-seven patients were included in the study. The atazanavir doses prescribed were 300 mg (n = 169), 400 mg (n = 12), 200 mg (n = 1), and 150 mg (n = 5). The atazanavir population PK was described using a 1-compartment model with first-order absorption. Mean PK parameter estimations (95% confidence interval, coefficients of variation %) were as follows: oral clearance (CL) = 7.6 L/h (6.9-8.3; 34%), volume of distribution (V) = 80.8 L (67.4-94; 37%), and absorption constant rate (Ka) = 1.05 hours (0.01-2.09; 156%). The mean estimated half-life (T-half) was 7.5 hours (95% confidence interval: 7.2 -7.8 hours). The estimated T-half of atazanavir was in agreement with that previously reported of 8.6 and 8.8 hours. We observed a wide interpatient variability for the PK parameters, especially for Ka. This population approach allowed us to determine atazanavir PK parameters in human immunodeficiency virus-infected patients in a real-life context and to perform Bayesian analysis to predict Ctrough from samples collected at any moment during the dosing interval. This could therefore improve therapeutic drug monitoring interpretations and provide an interesting tool for correlation with virologic data.

Published
2008

9. Diversity of 1,213 hepatitis C virus NS3 protease sequences from a clinical virology laboratory database in Marseille university hospitals, southeastern France

Author

Hind, Hajji, Sarah, Aherfi, Anne, Motte, Isabelle, Ravaux, Saadia, Mokhtari, Jean-Marie, Ruiz, Isabelle, Poizot-Martin, Christian, Tourres, Natacha, Tivoli, René, Gérolami, Catherine, Tamalet, and Philippe, Colson

Subjects
Male, Genotype, Genotyping Techniques, Molecular Sequence Data, Mutation, Missense, Genetic Variation, Sequence Homology, Hepacivirus, Sequence Analysis, DNA, Middle Aged, Viral Nonstructural Proteins, Hepatitis C, Hospitals, University, Drug Resistance, Viral, Cluster Analysis, Humans, Female, France, Phylogeny
Abstract

Infection with hepatitis C virus (HCV) represents a major public health concern worldwide. Recent therapeutic advances have been considerable, HCV genotype continuing to guide therapeutic management. Since 2008, HCV genotyping in our clinical microbiology laboratory at university hospitals of Marseille, Southeastern France, has been based on NS3 protease gene population sequencing, to allow concurrent HCV genotype and protease inhibitor (PI) genotypic resistance determinations. We aimed, first, to analyze the genetic diversity of HCV NS3 protease obtained from blood samples collected between 2003 and 2013 from patients monitored at university hospitals of Marseille and detect possible atypical sequences; and, second, to identify NS3 protease amino acid patterns associated with decreased susceptibility to HCV PIs. A total of 1,213 HCV NS3 protease sequences were available in our laboratory sequence database. We implemented a strategy based on bioinformatic tools to determine whether HCV sequences are representative of our local HCV genetic diversity, or divergent. In our 2003-2012 HCV NS3 protease sequence database, we delineated 32 clusters representative of the majority HCV genetic diversity, and 61 divergent sequences. Five of these divergent sequences showed less than 85% nucleotide identity with their top GenBank hit. In addition, among the 294 sequences obtained in 2013, three were divergent relative to these 32 previously delineated clusters. Finally, we detected both natural and on-treatment genotypic resistance to HCV NS3 PIs, including a substantial prevalence of Q80K substitutions associated with decreased susceptibility to simeprevir, a second generation PI.

Published
2015

10. First-line Highly Active Antiretroviral Regimens in 2001–2002 in the French Hospital Database on HIV: Combination Prescribed and Biological Outcomes

Author

Valérie Potard, Christian Pradier, Françoise Brun-Vézinet, Willy Rozenbaum, Véronique Frixon-Marin, Dominique Costagliola, David Rey, and Saadia Mokhtari

Subjects
Adult, Male, medicine.medical_specialty, Adolescent, Databases, Factual, First line, Human immunodeficiency virus (HIV), HIV Infections, medicine.disease_cause, Cohort Studies, Acquired immunodeficiency syndrome (AIDS), Antiretroviral Therapy, Highly Active, Internal medicine, medicine, Humans, Pharmacology (medical), Sida, Aged, Pharmacology, biology, business.industry, HIV, Middle Aged, Viral Load, biology.organism_classification, medicine.disease, Antiretroviral therapy, Hospitals, CD4 Lymphocyte Count, Infectious Diseases, Anti-Retroviral Agents, Lentivirus, Immunology, RNA, Viral, Regression Analysis, Female, France, Viral disease, business, Viral load
Abstract

Introduction We compared biological outcomes in anti-retroviral-naive patients with viral load (VL) >5,000 copies/ml starting combivir-based, three-drug highly active antiretroviral therapy regimens in 2001–2002 according to the third component, namely abacavir (ABC), nelfinavir (NFV), indinavir/ritonavir (IDV/r), lopinavir/ritonavir (LPV/r), nevirapine (NVP) or efavirenz (EFV). Methods We evaluated virological response (HIV RNA + T-cells/u, l) separately in patients with baseline VL Results Median follow up was 19 months. EFV had better virological efficacy than NFV and IDV/r among patients with baseline VL Conclusions For first-line therapy, in this observational setting, EFV, LPV/r and NVP, when added to the combivir backbone, were more likely to drive viral load

Published
2006

11. Hepatitis C virus NS3 protease genotyping and drug concentration determination during triple therapy with telaprevir or boceprevir for chronic infection with genotype 1 viruses, southeastern France

Author

Sarah, Aherfi, Caroline, Solas, Anne, Motte, Jacques, Moreau, Patrick, Borentain, Saadia, Mokhtari, Danielle, Botta-Fridlund, Catherine, Dhiver, Isabelle, Portal, Jean-Marie, Ruiz, Isabelle, Ravaux, Sylvie, Bregigeon, Isabelle, Poizot-Martin, Andreas, Stein, René, Gérolami, Philippe, Brouqui, Catherine, Tamalet, and Philippe, Colson

Subjects
Adult, Male, Genotype, Proline, Mutation, Missense, Interferon-alpha, Hepacivirus, Hepatitis C, Chronic, Middle Aged, Viral Load, Viral Nonstructural Proteins, Antiviral Agents, Hospitals, University, Plasma, Young Adult, Amino Acid Substitution, Drug Resistance, Viral, Ribavirin, Humans, Drug Therapy, Combination, Female, France, Treatment Failure, Oligopeptides
Abstract

Telaprevir and boceprevir, the two first hepatitis C virus (HCV) NS3 protease inhibitors (PIs), considerably increase rates of sustained virologic response in association with pegylated interferon and ribavirin in chronic HCV genotype 1 infections. The 30 first patients treated by telaprevir or boceprevir including anti-HCV therapies since 2011 in Marseille University hospitals, France, were monitored. HCV loads and plasmatic concentrations of telaprevir and boceprevir were determined on sequential blood samples. HCV NS3 protease gene population sequencing was performed at baseline of treatment and in case of treatment failure. Fifteen patients (including 7 co-infected with HIV) received telaprevir and the other 15 patients (including 4 co-infected with HIV) received boceprevir. At baseline, HCV NS3 protease from six patients harbored amino acid substitutions associated with PI-resistance. Treatment failure occurred at week 12 for 7 patients. Amino acid substitutions associated with PI-resistance were observed in six of these cases. HCV NS3 R155K and T54A/S mutants, all of genotype 1a, were found from four patients. Median (interquartile range) plasma concentrations were 3,092 ng/ml (2,320-3,525) for telaprevir and 486 ng/ml (265-619) for boceprevir. For HIV-HCV co-infected patients, median concentrations were 3,162 ng/ml (2,270-4,232) for telaprevir and 374 ng/ml (229-519) for boceprevir. Plasma drug concentration monitoring revealed undetectable concentrations for two patients at week 4, and probable non-adherence to therapy for another patient. These findings indicate that routine HCV NS3 protease sequencing and plasma PI concentration monitoring might be helpful to characterize cases of therapy failure, at a cost dramatically low compared to that of anti-HCV therapy.

Published
2014

12. Lopinavir/r no longer recommended as first line regimen: a comparative effectiveness analysis

Author

David Rey, Valérie Potard, Christian Pradier, Willy Rozenbaum, Françoise Brun-Vézinet, Dominique Costagliola, Isabelle Poizot-Martin, Saadia Mokhtari, Département Inserm Transfert, Institut Curie [Paris], Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Strasbourg, Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U912 INSERM - Aix Marseille Univ - IRD), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service des Maladies Infectieuses et Tropicales [CHU Hôpital Nord - Marseille] (M.I.T), Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital Nord [CHU - APHM], Service de santé publique [CHU Nice], Centre Hospitalier Universitaire de Nice (CHU Nice), Hôpital Saint-Louis, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Université Pierre et Marie Curie - Paris 6 (UPMC), Université Paris Diderot - Paris 7 (UPD7), Service de Virologie [CHU Bichat], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut de Recherche pour le Développement (IRD)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU), Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and HAL UPMC, Gestionnaire

Subjects
Male, HIV Infections, 030312 virology, Deoxycytidine, Lopinavir, Cohort Studies, chemistry.chemical_compound, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Antiretroviral Therapy, Highly Active, Emtricitabine, Prospective Studies, Treatment Failure, 030212 general & internal medicine, 0303 health sciences, Hazard ratio, Middle Aged, Viral Load, 3. Good health, Infectious Diseases, [SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Female, France, Viral load, Research Article, medicine.drug, Adult, medicine.medical_specialty, Efavirenz, Anti-HIV Agents, antiretroviral therapy, Organophosphonates, effectiveness, 03 medical and health sciences, Internal medicine, first-line therapy, medicine, Humans, Tenofovir, propensity score, Proportional hazards model, business.industry, Adenine, Public Health, Environmental and Occupational Health, HIV infection, Confidence interval, CD4 Lymphocyte Count, Atazanavir, Surgery, chemistry, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, business
Abstract

on behalf of the FHDH ANRS CO4 (French Hospital Database on HIV, Agence Nationale de Recherches sur le Sida, cohort 4); International audience; Introduction: We compared the effectiveness of tenofovir/emtricitabine (TDF/FTC) combined with either lopinavir/r (LPV/r) or another recommended third drug in the 2010 French guidelines in antiretroviral-naıve patients starting combination antiretroviral therapy in 2004Á2008 in the French Hospital Database on HIV.Methods: The outcomes were stop or switch of the third component, viral load (VL) B500 copies/ml, an increase of at least 100 CD4 cells/mm 3 , AIDS-defining event and non-AIDS-defining hospitalization or death. Propensity scores were estimated by logistic regression based on the clinical centre and other confounders. In each clinical centre, each patient initiating LPV/r was matched with a patient initiating another third drug (efavirenz or atazanavir/r) and having a close propensity score. Cox's proportional hazards models were then used, with treatment as covariate. Time was right-censored at four years.Results: 1269 patients started LPV/r plus TDF/FTC, and 890 could be matched to 890 patients receiving another third drug. Baseline characteristics were well balanced between these two groups. LPV/r was associated with a higher risk of third drug stop (hazard ratio (HR): 1.69; 95% confidence interval (CI), 1.42Á2.00) and with less rapid viral suppression (HR: 0.83; 95% CI, 0.72Á 0.95). There was no difference in the time required for a CD4 cell increment of at least 100/mm 3 , or to the occurrence of an AIDS-defining event. Non-AIDS-defining hospitalizations or deaths were more frequent with LPV/r (HR: 1.79; 95% CI, 1.33Á2.39).Conclusions: For first-line therapy, in this observational setting, TDF/FTC plus LPV/r were less durable than TDF/FTC plus another recommended third drug, led to a less rapid viral suppression and were associated with a higher risk of non-AIDS morbidity.

Published
2014

13. Post-exposure prophylaxis completion and condom use in the context of potential sexual exposure to HIV

Author

Claudine Duvivier, André Cabié, Sylvie Bregigeon, Alain Makinson, David Rey, C Allavena, Jacques Reynes, Laurent Cotte, Isabelle Ravaux, Pierre Gantner, Les Hôptaux universitaires de Strasbourg (HUS), CHU Strasbourg, Immuno-Rhumatologie Moléculaire, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôtel-Dieu de Nantes, Centre d'infectiologie Necker-Pasteur [CHU Necker], Institut Pasteur [Paris] (IP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Médical de l'Institut Pasteur (CMIP), Institut Pasteur [Paris] (IP), Infection à VIH, réservoirs, diversité génétique et résistance aux antirétroviraux (ARV) (EA 7327), Université Paris Descartes - Paris 5 (UPD5), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Centre d'Investigation Clinique Antilles-Guyane (CIC - Antilles Guyane), Université des Antilles et de la Guyane (UAG)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -CHU de Fort de France-Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française], Maladies infectieuses et tropicales dans la Caraïbe (MAITC EA 4537), CHU Pointe-à-Pitre/Abymes [Guadeloupe] -CHU de la Martinique [Fort de France]-Université des Antilles (UA), Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques et émergentes (TransVIHMI), Institut de Recherche pour le Développement (IRD)-Université de Yaoundé I-Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Institut Hospitalier Universitaire Méditerranée Infection (IHU Marseille), Hôpital Sainte-Marguerite [CHU - APHM] (Hôpitaux Sud ), Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL), Dat'AIDS Study Group: Besançon: C. Drobacheff-Thiébaut, A. Foltzer, K. Bouiller, L. Hustache-Mathieu, C. Chirouze, F. Bozon, O. Babre, P. Muret, Clermont-Ferrand: H. Laurichesse, O. Lesens, M. Vidal, N. Mrozek, C. Aumeran, O. Baud, V. Corbin, P. Letertre, S. Casanova, C. Jacomet, Guadeloupe: B. Hoen, I. Lamaury, I. Fabre, E. Curlier, R. Ouissa, K. Schepers, C. Herrmann-Storck, N. Dournon, La Roche sur Yon: D. Merrien, P. Perré, T. Guimard, O. Bollangier, S. Leautez, M. Morrier, Lyon: F. Ader, F. Biron, A. Boibieux, L. Cotte, T. Ferry, P. Miailhes, T. Perpoint, S. Roux, S. Degroodt, C. Brochier, F. Valour, C. Chidiac, Marseille (IHU): C. Dhiver, M. Saadia Mokhtari, A. Ménard, H. Tissot Dupont, C. Toméi, L. Meddeb, A.Y. Belkhir, I. Ravaux, Marseille (Ste Marguerite): S. Brégigeon, O. Zaegel-Faucher, V. Obry-Roguet, H. Laroche, M. Orticoni, M.J. Soavi, P. Geneau de Lamarlière, E. Ressiot, M.J. Ducassou, I. Jaquet, S. Galie, A. Galinier, P. Martinet, M. Landon, A.S. Ritleng, A. Ivanova, C. Debreux, C. Lions, I. Poizot-Martin, Martinique: S. Abel, R. Césaire, L. Cuzin, G. Dos Santos, L. Fagour, M. Illiaquer, F. Najioullah, D. Nguyen, M. Ouka, S. Pierre-François, J. Pasquier, M. Pircher, B. Rozé, A. Cabié, Montpellier: N. Atoui, V. Le Moing, A. Makinson, N. Meftah, C. Merle de Boever, B. Montes, A. Montoya Ferrer, J. Reynes, Nancy: M. André, L. Boyer, M.P. Bouillon, M. Delestan, T. May, Nantes: C. Allavena, C. Bernaud, E. Billaud, C. Biron, B. Bonnet, S. Bouchez, D. Boutoille, C. Brunet-Cartier, C. Deschanvres, N. Hall, T. Jovelin, P. Morineau, V. Reliquet, H. Hue, S. Sécher, M. Cavellec, A. Soria, V. Ferré, E. André-Garnier, A. Rodallec, M. Lefebvre, O. Grossi, O. Aubry, F. Raffi, Nice: P. Pugliese, S. Breaud, C. Ceppi, J. Courjon, E. Cua, J. Cottalorda, P. Dellamonica, E. Demonchy, A. De Monte, J. Durant, C. Etienne, S. Ferrando, J.G. Fuzibet, R. Garraffo, A. Joulie, K. Risso, V. Mondain, A. Naqvi, N. Oran, I. Perbost, S. Pillet, B. Prouvost-Keller, C. Pradier, S. Wehrlen-Pugliese, V. Rio, E. Rosenthal, S. Sausse, G. Zouzou, Orléans: L. Hocqueloux, T. Prazuck, C. Gubavu, A. Sève, M. Niang, C. Boulard, Paris (Bicêtre): A. Cheret, C. Goujard, Y. Quertainmont, E. Teicher, N. Lerolle, D. Vittecoq, O. Deradji, F. Fourreau, C. Pallier, A. Barrail-Tran, Paris (Bichat): R. Landman, V. Joly, C. Rioux, S. Lariven, A. Gervais, F.X. Lescure, S. Matheron, F. Louni, C. Godard, Z. Julia, M. Chansombat, D. Rahli, C. Mackoumbou-Nkouka, C. Charpentier, D. Descamps, G. Peytavin, Y. Yazdanpanah, Paris (Pasteur-Necker): P.H. Consigny, G. Cessot, P. Bossi, J. Goesch, J. Benabdelmoumen, F. Lanternier, C. Charlier, K. Amazzough, B. Henry, B. Pilmis, C. Rouzaud, M. Morgand, F. Touam, C. Louisin, C. Duvivier, O. Lortholary, R. Guery, F. Danion, J. Lourenco, P. Parize, M. Launay, V. Avettand-Fenoel, Paris (Pitié): M.A. Valantin, F. Caby, R. Tubiana, R. Agher, S. Seang, L. Schneider, R. Palich, C. Blanc, C. Katlama, Reims: J.L. Berger, Y. N'Guyen, D. Lambert, D. Lebrun, I. Kmiec, M. Hentzien, V. Brodard, F. Bani-Sadr, Saint-Etienne: E. Botelho-Nevers, A. Gagneux-Brunon, A. Frésard, F. Lucht, Strasbourg: P. Fischer, M. Partisani, C. Cheneau, M. Priester, M.L. Batard, C. Bernard-Henry, E. de Mautort, P. Gantner, D. Rey, Toulouse: M. Alvarez, N. Biezunski, A. Debard, C. Delpierre, P. Lansalot, L. Lelièvre, G. Martin-Blondel, M. Piffaut, L. Porte, K. Saune, P. Delobel, and Tourcoing: F. Ajana, I. Alcaraz, V. Baclet, A. Boucher, P. Choisy, T. Huleux, B. Lafon-Desmurs, H. Melliez, A. Meybeck, A. Pasquet, M. Pradier, O. Robineau, N. Viget, M. Valette.

Subjects
0301 basic medicine, Male, HIV Infections, law.invention, Men who have sex with men, Condoms, 0302 clinical medicine, MESH: Tenofovir, law, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, MESH: Emtricitabine, MESH: Sexual Partners, Emtricitabine, Pharmacology (medical), 030212 general & internal medicine, Condom use, Health Policy, MESH: HIV Infections, Infectious Diseases, Sexual Partners, Cohort, cardiovascular system, Female, France, Post-Exposure Prophylaxis, circulatory and respiratory physiology, medicine.drug, Adult, medicine.medical_specialty, Unprotected Sexual Intercourse, MESH: Unsafe Sex, Treatment discontinuation, education, Context (language use), MESH: Multivariate Analysis, Medication Adherence, MESH: Homosexuality, Male, 03 medical and health sciences, MESH: Condoms, Condom, Internal medicine, medicine, Humans, Homosexuality, Male, Tenofovir, Retrospective Studies, MESH: Humans, Unsafe Sex, business.industry, HIV, MESH: Adult, MESH: Retrospective Studies, Odds ratio, MESH: Medication Adherence, 030112 virology, MESH: Male, Discontinuation, Sexual exposure, MESH: France, Multivariate Analysis, business, MESH: Female, MESH: Post-Exposure Prophylaxis
Abstract

International audience; ObjectivesPost-exposure prophylaxis (PEP) care remains a challenge for individuals with potential sexual exposure to HIV in terms of PEP completion and ongoing risk behaviours.MethodsA retrospective analysis was carried out on data from the French Dat’AIDS prevention cohort (NCT03795376) for individuals evaluated for PEP between 2004 and 2017. A multivariable analysis was performed of predictors of both PEP completion and condom use [odds ratios (ORs)] and their associated probabilities (P, with P > 95% being clinically relevant).ResultsOverall, 29 060 sexual exposures to HIV were evaluated for PEP [36% in men who have sex with men (MSM) and 64% in heterosexuals]. Overall, 12 different PEP regimens were offered in 19 240 cases (46%). Tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC) was the preferred backbone (n = 14 304; 74%). We observed a shift from boosted protease inhibitor-based regimens to nonnucleoside reverse transcriptase inhibitor- or integrase inhibitor-based regimens in recent years. Overall, 20% of PEP prescriptions were prematurely discontinued. Older age, MSM, intercourse with a sex worker, rape and intercourse with a known HIV-infected source patient were factors associated with increased rates of PEP completion (OR > 1; P > 98%). None of the 12 PEP regimens was associated with premature discontinuation. We also found 12 774 cases of unprotected sexual intercourse (48%). Condom use decreased (OR < 1; P > 99%) with the year of exposure, and was lower in MSM and rape victims. Condom use increased (OR > 1, P > 99%) with age, and was higher in those who had intercourse with a sex worker or with a female partner and in those with knowledge of the partner’s HIV status.ConclusionsWe provide new insights into how rates of condom use and PEP completion might be improved in those receiving PEP by targeting certain groups of individuals for interventions. In particular, youth and MSM at risk should be linked in a prevention-to-care continuum.

Published
2020

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