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1. Metabarcoding analysis of eukaryotic microbiota in the gut of HIV-infected patients.

Author

Ibrahim Hamad, Rita Abou Abdallah, Isabelle Ravaux, Saadia Mokhtari, Hervé Tissot-Dupont, Caroline Michelle, Andreas Stein, Jean-Christophe Lagier, Didier Raoult, and Fadi Bittar

Subjects
Medicine, Science
Abstract

Research on the relationship between changes in the gut microbiota and human disease, including AIDS, is a growing field. However, studies on the eukaryotic component of the intestinal microbiota have just begun and have not yet been conducted in HIV-infected patients. Moreover, eukaryotic community profiling is influenced by the use of different methodologies at each step of culture-independent techniques. Herein, initially, four DNA extraction protocols were compared to test the efficiency of each method in recovering eukaryotic DNA from fecal samples. Our results revealed that recovering eukaryotic components from fecal samples differs significantly among DNA extraction methods. Subsequently, the composition of the intestinal eukaryotic microbiota was evaluated in HIV-infected patients and healthy volunteers through clone sequencing, high-throughput sequencing of nuclear ribosomal internal transcribed spacers 1 (ITS1) and 2 (ITS2) amplicons and real-time PCRs. Our results revealed that not only richness (Chao-1 index) and alpha diversity (Shannon diversity) differ between HIV-infected patients and healthy volunteers, depending on the molecular strategy used, but also the global eukaryotic community composition, with little overlapping taxa found between techniques. Moreover, our results based on cloning libraries and ITS1/ITS2 metabarcoding sequencing showed significant differences in fungal composition between HIV-infected patients and healthy volunteers, but without distinct clusters separating the two groups. Malassezia restricta was significantly more prevalent in fecal samples of HIV-infected patients, according to cloning libraries, whereas operational taxonomic units (OTUs) belonging to Candida albicans and Candida tropicalis were significantly more abundant in fecal samples of HIV-infected patients compared to healthy subjects in both ITS subregions. Finally, real-time PCR showed the presence of Microsporidia, Giardia lamblia, Blastocystis and Hymenolepis diminuta in different proportions in fecal samples from HIV patients as compared to healthy individuals. Our work revealed that the use of different sequencing approaches can impact the perceived eukaryotic diversity results of the human gut. We also provide a more comprehensive view of the eukaryotic community in the gut of HIV-infected patients through the complementarity of the different molecular techniques used. Combining these various methodologies may provide a gold standard for a more complete characterization of the eukaryotic microbiome in future studies.

Published
2018
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2. Lopinavir/r no longer recommended as a first‐line regimen: a comparative effectiveness analysis

Author

Valérie Potard, David Rey, Isabelle Poizot‐Martin, Saadia Mokhtari, Christian Pradier, Willy Rozenbaum, Françoise Brun‐Vezinet, Dominique Costagliola, and on behalf of the FHDH ANRS CO4 (French Hospital Database on HIV, Agence Nationale de Recherches sur le Sida, cohort 4)

Subjects
first‐line therapy, HIV infection, antiretroviral therapy, effectiveness, propensity score, Immunologic diseases. Allergy, RC581-607
Abstract

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‐naïve patients starting combination antiretroviral therapy in 2004–2008 in the French Hospital Database on HIV. Methods The outcomes were stop or switch of the third component, viral load (VL)

Published
2014
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3. Reaching the Second and Third Joint United Nations Programme on Human Immunodeficiency Virus (HIV)/AIDS 90-90-90 Targets Is Accompanied by a Dramatic Reduction in Primary HIV Infection and in Recent HIV Infections in a Large French Nationwide HIV Cohort

Author

Claudine Duvivier, Clotilde Allavena, J Lippmann, P. Dellamonica, A Soria, Sandrine Pierre-François, B J Gaborit, Isabelle Poizot-Martin, Anne Frésard, Elodie Curlier, F. Biron, Eric Cua, M Saadia Mokhtari, I Luquet Besson, C Gubavu, Caroline Lions, Laurent Cotte, C. Tomei, Elina Teicher, Faouzi Souala, Karima Amazzough, C Merle de Boever, Romain Palich, C Brochier, Véronique Reliquet, Patrick Miailhes, M Priester, Samira Fafi-Kremer, Mathieu Dupont, M Piffaut, I. Schlienger, C Bernaud, A S Ritleng, F-Xavier Lescure, C Cheneau, L Lelièvre, C Biron, Adrien Le Guillou, Alexa Debard, Marc-Antoine Valantin, Gilles Peytavin, S Lariven, G Benabdelmoumen, Florence Ader, I Kmiec, I Fabre, Cyrille Delpierre, C. Longuet, François Raffi, A de Monte, M. Alvarez, David Rey, A Boucher, M. Valette, E de Mautort, Jean-Luc Berger, H Bertone, Bruno Hoen, M Poisson-Vanier, Pascal Pugliese, Virginie Ferré, M Pradier, Z Julia, Nathalie Dournon, M Baldeyrou, N Biezunski, Caroline Charlier, J Goesch, J Pasquier, M P Bouillon, Cécile Goujard, Sophie Matheron, V. Le Moing, Romain Guery, N. Viget, N Atoui, C Dhiver, A Meybeck, Fanny Lanternier, F Touam, Tristan Ferry, M Carta Padovani, G Thomas, C Ceppi, A Brunet, Alain Makinson, Isabelle Ravaux, Laurent Hocqueloux, A Maillard, Firouzé Bani-Sadr, P. Loubet, Laurent Boyer, O Deradji, I Alcaraz, T Prazuck, A Rodallec, F Lemaitre, B Lafon-Desmurs, J Turmel, A Sève, Benoit Pilmis, A Gervais, C. Augustin-Normand, D Chirio, Brigitte Montes, Cédric Arvieux, V Brodard, M Delestan, E Aïssi, C Louisin, Christian Chidiac, M Ducassou, S Leautez, Catherine Chirouze, M André, Dominique Merrien, Q Gardiennet, P Fischer, Sylvie Abel, Guillaume Martin-Blondel, Benoît Henry, H. Tissot Dupont, S Patrat-Delon, A Ménard, E. Billaud, Malikhone Chansombat, K Jidar, Karine Sauné, Colin Deschanvres, V. Gueripel, M Cavellec, K. Schepers, C Pronier, R Ouissa, P Choisy, A Cheret, A. Belkhir, P Parize, A Barrail-Tran, B. Bonnet, C Mackoumbou-Nkouka, A. Galinier, M Monclar, P Lansalot, S Bouchez, C Guennoun, N Meftah, C Brunet-Cartier, Pierre Tattevin, J. Durant, E Ressiot, T. Huleux, François Bénézit, C Boulard, M Poinot, Elisabeth André-Garnier, J Sinteff, André Cabié, Charlotte Charpentier, L Meddeb, Rodolphe Garraffo, M Batard, D. Lebrun, R Tubiana, M J Soavi, I Lamaury, Philippe Bossi, Y Quertainmont, S Galie, C Michelangeli, François Danion, N Lerolle, Y N’guyen, Amandine Gagneux-Brunon, Elisa Demonchy, Christine Katlama, C Bernard-Henry, V Mondain, S Seang, David Boutoille, P. Le Turnier, Faiza Ajana, André Boibieux, J Koffi, L. Porte, Laurence Bocket, O Bollangier, A Maka, S Sécher, Marine Morrier, T Guimard, Matthieu Revest, C Godard, C Rioux, C Etienne, M Illiaquer, O. Aubry, N Hall, Paul-Henri Consigny, C Blanc, P Morineau, K Guitteaud, T. Perpoint, G Cessot, V Baclet, Lise Cuzin, T May, E Braun, Marialuisa Partisani, Veronique Joly, Jacques Reynes, Olivier Lortholary, C Blanco-Betancourt, Philippe Van de Perre, D Lambert, Moustapha Dramé, S Ferrando, S Breaud, A Montoya Ferrer, Yazdan Yazdanpanah, M. Hentzien, Cécile Herrmann-Storck, A. Duréault, A. Ivanova, F. Lucht, Pierre Delobel, Thomas Jovelin, J. M. Chapplain, Olivier Robineau, Roland Landman, Olivier Grossi, F Louni, Elisabeth Botelho-Nevers, J Lourenco, M Lefebvre, Diane Descamps, Luminita Schneider, R Agher, M Orticoni, D Rahli, S Degroodt, CHU de la Martinique [Fort de France], Centre Hospitalier Universitaire de Nice (CHU Nice), Service de maladies infectieuses et tropicales [Nantes], Université de Nantes (UN)-Hôtel-Dieu-Centre hospitalier universitaire de Nantes (CHU Nantes), Department of Infectious Diseases [Nantes], Hôtel-Dieu de Nantes, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Infectious Diseases and Tropical Medicine Unit [Fort-de-France, Martinique], Centre Hospitalier Universitaire de Reims (CHU Reims), Laboratoire de Virologie Médicale et Moléculaire - EA 4684 (CardioVir), Université de Reims Champagne-Ardenne (URCA)-Centre Hospitalier Universitaire de Reims (CHU Reims)-SFR CAP Santé (Champagne-Ardenne Picardie Santé), Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV), Département de maladies infectieuses, and Hospices Civils de Lyon (HCL)

Subjects
0301 basic medicine, Microbiology (medical), Cart, medicine.medical_specialty, Longitudinal study, business.industry, Public health, Incidence (epidemiology), medicine.disease, 030112 virology, 3. Good health, 03 medical and health sciences, 0302 clinical medicine, Infectious Diseases, Acquired immunodeficiency syndrome (AIDS), Interquartile range, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Internal medicine, Epidemiology, Cohort, Medicine, 030212 general & internal medicine, business
Abstract

Background In late 2013, France was one of the first countries to recommend initiation of combination antiretroviral therapy (cART) irrespective of CD4 cell count. Methods To assess the impact of achieving the second and third Joint United Nations Programme on HIV/AIDS 90-90-90 targets (ie, 90% of diagnosed people on sustained cART, and, of those, 90% virologically controlled) on human immunodeficiency virus (HIV) incidence, we conducted a longitudinal study to describe the epidemiology of primary HIV infection (PHI) and/or recent HIV infection (patients with CD4 cell count ≥500/mm3 at HIV diagnosis; (PRHI) between 2007 and 2017 in a large French multicenter cohort. To identify changes in trends in PHI and PRHI, we used single breakpoint linear segmented regression analysis. Results During the study period, 61 822 patients were followed in the Dat’AIDS cohort; 2027 (10.0%) had PHI and 7314 (36.1%) had PRHI. The second and third targets were reached in 2014 and 2013, respectively. The median delay between HIV diagnosis and cART initiation decreased from 9.07 (interquartile range [IQR], 1.39–33.47) months in 2007 to 0.77 (IQR, 0.37–1.60) months in 2017. A decrease in PHI (−35.1%) and PRHI (−25.4%) was observed starting in 2013. The breakpoints for PHI and PRHI were 2012.6 (95% confidence interval [CI], 2010.8–2014.4) and 2013.1 (95% CI, 2011.3–2014.8), respectively. Conclusions Our findings show that the achievements of 2 public health targets in France and the early initiation of cART were accompanied by a reduction of about one-third in PHI and PRHI between 2013 and 2017. Clinical Trials Registration NCT02898987.

Published
2020

4. 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

5. 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

6. 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

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. Neuropsychiatric adverse effects on dolutegravir: an emerging concern in Europe

Author

Catherine Dhiver, Christelle Tomei, Clementine Montagnac, Philippe Colson, Amélie Menard, Saadia Mokhtari, Line Meddeb, Caroline Solas, Isabelle Ravaux, Andreas Stein, Hervé Tissot-Dupont, Service de Maladies Infectieuses, Hôpital de la Conception [CHU - APHM] (LA CONCEPTION)-Centre de Référence des Infections Ostéo-articulaires Sud-Méditerranée (CRIOA), 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), Service de Pharmacocinétique et de Toxicologie, Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Centre de Recherches en Oncologie biologique et Oncopharmacologie (CRO2), Institut National de la Santé et de la Recherche Médicale (INSERM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Aix Marseille Université (AMU), 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), Service des Maladies Infectieuses, Aix-Marseille Université - Faculté de pharmacie (AMU PHARM), Aix Marseille Université (AMU), 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, 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), Service des Maladies Infectieuses et Tropicales [CHU Hôpital Nord - Marseille] (M.I.T), Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital Nord [CHU - APHM], Aix Marseille Université (AMU)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), 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, and Institut des sciences biologiques (INSB-CNRS)-Institut des sciences biologiques (INSB-CNRS)-Centre National de la Recherche Scientifique (CNRS)

Subjects
0301 basic medicine, medicine.medical_specialty, business.industry, Immunology, MEDLINE, 030112 virology, 3. Good health, Toxicology, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Infectious Diseases, chemistry, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Dolutegravir, medicine, HIV Integrase Inhibitors, Immunology and Allergy, 030212 general & internal medicine, Intensive care medicine, business, Adverse effect, ComputingMilieux_MISCELLANEOUS
Abstract

International audience; no abstract

Published
2017

9. Psychiatric disorders after starting dolutegravir

Author

Saadia Mokhtari, Julie Allemand, Farid Kheloufi, and Anne Default

Subjects
Pediatrics, medicine.medical_specialty, business.industry, Immunology, MEDLINE, Antiretroviral therapy, chemistry.chemical_compound, Infectious Diseases, chemistry, Dolutegravir, Immunology and Allergy, Medicine, business, Viral load
Published
2015

10. Gut microbiota associated with HIV infection is significantly enriched in bacteria tolerant to oxygen

Author

Grégory, Dubourg, Jean-Christophe, Lagier, Sophie, Hüe, Mathieu, Surenaud, Dipankar, Bachar, Catherine, Robert, Caroline, Michelle, Isabelle, Ravaux, Saadia, Mokhtari, Matthieu, Million, Andreas, Stein, Philippe, Brouqui, Yves, Levy, and Didier, Raoult

Subjects
INFLAMMATION, INTESTINAL BACTERIA, HIV/AIDS, Intestinal Microflora, OXIDATIVE STRESS
Abstract

Objectives Gut microbiota modifications occurring during HIV infection have recently been associated with inflammation and microbial translocation. However, discrepancies between studies justified a comprehensive analysis performed on a large sample size. Design and methods In a case–control study, next-generation sequencing of the 16S rRNA gene was applied to the faecal microbiota of 31 HIV-infected patients, of whom 18 were treated with antiretroviral treatment (ART), compared with 27 healthy controls. 21 sera samples from HIV-infected patients and 7 sera samples from control participants were used to test the presence of 25 markers of inflammation and/or immune activation. Results Diversity was significantly reduced in HIV individuals when compared with controls and was not restored in the ART group. The relative abundance of several members of Ruminococcaceae such as Faecalibacterium prausnitzii was critically less abundant in the HIV-infected group and inversely correlated with inflammation/immune activation markers. Members of Enterobacteriaceae and Enterococcaceae were found to be enriched and positively correlated with these markers. There were significantly more aerotolerant species enriched in HIV samples (42/52 species, 80.8%) when compared with the control group (14/87 species, 16.1%; χ2 test, p

Published
2016

11. Expression of activating receptors on natural killer cells from AIDS-related lymphoma patients

Author

Karine Baumstarck, Régis Costello, Daniel Olive, Carole Sanchez, Delphine Mercier-Bataille, Thérèse Le Treut, Nicolas Mounier, Gérard Sébahoun, Saadia Mokhtari, Céline Baier, and Caroline Besson

Subjects
Antitumor immune response, Lymphoma, HIV Positivity, business.industry, Research, Lymphocyte, Chronic lymphocytic leukemia, Myeloid leukemia, medicine.disease, NKG2D, AIDS-related lymphoma, medicine.anatomical_structure, Natural cytotoxicity receptors, hemic and lymphatic diseases, Virology, Immunology, HIV-1, medicine, Natural killer cells, Molecular Medicine, Cytotoxic T cell, Pharmacology (medical), business
Abstract

Background: Abnormal NK phenotype and cytotoxic functions have been described in acute myeloid leukemia, chronic lymphocytic leukemia, myeloma and myelodysplastic syndromes. Defective NK cytotoxicity is due to decreased expression of the Natural Cytotoxicity Receptors (NCRs), 2B4/CD244/p38, or NKG2D. This prompted us to test the expression of these molecules on circulating NK cells from patients with AIDS-related lymphomas (RL) in comparison with HIV + patients without lymphoma, healthy subjects and HIV-negative patients with lymphoma. Methods: Blood samples were analyzed by flow cytometry for NCRs, 2B4/CD244/p38 and NKG2D expression on NK cells defined as CD3-/CD56+ lymphocytes. We also analyzed by quantitative PCR specific RNA for NKp30/NCR3 and NKp46/NCR1. Results: We could not detect any defect in NKp46/NCR1 expression between all groups. NKp44/NCR2, NKp30/NCR3 and NKG2D had lower expression in AIDS-RL in comparison with HIV + patients without lymphoma when compared to patients with similar (>0.3 G/L) CD4+ lymphocyte levels. Expression of 2B4/CD244/p38 was lower in AIDS-RL than in HIV-negative lymphoma. Comparison of specific NKp30/NCR3 and NKp46/NCR1 RNA showed increased steady state levels, despite decreased surface expression for NKp30/NCR3, suggesting abnormal post-transcriptional regulatory mechanisms. Conclusions: We show a more pronounced defect in NK activating molecule when HIV infection is associated with lymphoma than when only one condition (HIV positivity or lymphoma) is present. Defective NK phenotype, in addition to CD4+ depletion and dysfunction, may participate to the increased incidence of lymphoma in HIV patients.

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

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