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1. Long-term evolution of humoral immune response after SARS-CoV-2 infection

Author

Elisa, Teyssou, Karen, Zafilaza, Sophie, Sayon, Stéphane, Marot, Margot, Dropy, Cathia, Soulie, Basma, Abdi, Florence, Tubach, Pierre, Hausfater, Anne-Geneviève, Marcelin, David, Boutolleau, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Service de Virologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), BIOSFAST [CHU Pitié-Salpêtrière] (GRC 14), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases [IHU ICAN], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), and Centre National de Référence Herpèsvirus [CHU Pitié Salpêtrière]

Subjects
Microbiology (medical), COVID-19 Vaccines, SARS-CoV-2, COVID-19, General Medicine, Antibodies, Viral, Antibodies, Neutralizing, Immunity, Humoral, Immunoglobulin A, Infectious Diseases, Immunoglobulin G, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, ComputingMilieux_MISCELLANEOUS
Abstract

We aimed to characterize the evolution of humoral immune response up to 1 year after SARS-CoV-2 infection in healthcare workers (HCWs) during the first wave of COVID-19 in Paris.Serum samples from 92 HCWs were tested at month 0 (M0), M6, and M12 after SARS-CoV-2 infection for IgG targeting the nucleocapsid (N), IgG targeting the receptor-binding domain (RBD) of spike (S) protein, IgA targeting S, and anti-RBD neutralizing antibodies. After M6, 46 HCWs received a single dose of COVID-19 vaccine.We observed a significant decrease in all SARS-CoV-2 immunologic markers at M6 post-infection: median decreases were 0.26 log binding antibody units/mL (M0: 1.9 (interquartile range (IQR) 1.47-2.27); M6: 1.64 (IQR 1.22-1.92)) for anti-RBD IgG; 4.10 (index) (M0: 4.94 (IQR 2.72-6.82); M6: 0.84 (IQR 0.25-1.55)) for anti-N IgG; 0.64 (index) (M0: 2.50 (IQR 1.18-4.62); M6: 1.86 (IQR 0.85-3.54)) for anti-S IgA; and 24.4% (M0: 66.4 (IQR 39.7-82.5); M6: 42.0 (IQR 16.8-68.8)) inhibition activity for the RBD neutralizing antibodies. Between M6 and M12, anti-RBD IgG level, anti-S IgA index, and anti-RBD neutralizing activity significantly increased among COVID-19 vaccinated HCWs, whereas they remained stable among unvaccinated HCWs. Anti-N IgG index significantly decreased between M6 and M12 among both vaccinated (median: 0.73 (IQR 0.23-1.11) at M6 and 0.52 (IQR 0.20-0.73) at M12) and unvaccinated HCWs (median: 0.79 (IQR 0.21-4.67) at M6 and 0.34 (IQR 0.24-2.78) at M12).A steady decline in the anti-N IgG response was observed during the first year after SARS-CoV-2 infection among HCWs, whereas the anti-RBD IgG and the anti-S IgA responses remained stable and could be enhanced by COVID-19 vaccination.

Published
2022

2. Lack of a Clinically Significant Pharmacokinetic Interaction between Etravirine and Raltegravir Using an Original Approach Based on Drug Metabolism, Protein Binding, and Penetration in Seminal Fluid: A Pharmacokinetic Substudy of the ANRS-163 ETRAL Study

Author

Minh Patrick, Lê, Marc-Antoine, Valantin, Lambert, Assoumou, Cathia, Soulie, Soizic, Le Mestre, Laurence, Weiss, Yazdan, Yazdanpanah, Jean-Michel, Molina, Olivier, Bouchaud, François, Raffi, Jacques, Reynes, Vincent, Calvez, Anne-Geneviève, Marcelin, Dominique, Costagliola, Christine, Katlama, Gilles, Peytavin, Karima, Hamdoud, 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), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Service des maladies infectieuses et tropicales [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université (SU), Service de virologie [CHU Pitié-Salpêtrière], ANRS France Recherche Nord & sud Sida-hiv hépatites, Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Hopital Saint-Louis [AP-HP] (AP-HP), Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques er émergentes (TransVIHMI), Université Montpellier 1 (UM1)-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), Université de Montpellier (UM), CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques et émergentes (TransVIHMI), and 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)

Subjects
Male, Anti-HIV Agents, [SDV]Life Sciences [q-bio], antiretroviral, interaction, HIV Infections, dual therapy, Middle Aged, Pyridazines, Pyrimidines, Semen, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Raltegravir Potassium, Nitriles, HIV-1, Humans, Drug Interactions, Drug Therapy, Combination, Female, seminal fluid, etravirine, raltegravir, pharmacokinetics, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Protein Binding
Abstract

International audience; Study objective: The ANRS163-ETRAL study showed that etravirine 200 mg/raltegravir 400 mg twice-daily dual therapy was highly effective in the treatment of human immunodeficiency virus (HIV)-infected patients older than 45 years, with virologic and therapeutic success rates at week 48 of 99.4% and 94.5%, respectively. The objective of this study was to determine whether a clinically significant pharmacokinetic interaction between etravirine and raltegravir exists by assessing steady-state total and unbound etravirine, raltegravir, and inactive raltegravir-glucuronide concentrations 12 hours after last intake (C12h ) in blood plasma (BP) and seminal plasma (SP).Design: Pharmacokinetic analysis of data from the ANRS163-ETRAL study.Patients: One hundred forty-six HIV-1-infected patients (of the 165 patients included in the ANRS-163 ETRAL study) who were receiving etravirine 200 mg and raltegravir 400 mg twice daily.Measurements and main results: Blood was collected from all 146 patients at weeks 2-4, 12, 24, and 48, and semen was collected from 21 patients at week 48. The extent of BP and SP protein binding was determined by using ultrafiltration assay. Total and unbound etravirine, raltegravir, and raltegravir-glucuronide C12h were determined by ultra high performance liquid chromatography coupled with tandem mass spectrometry and interpreted by using the in vitro calculated protein-bound 95% inhibitory concentration (PBIC95 ) for wild-type (WT) HIV: etravirine (116 ng/ml) and raltegravir (15 ng/ml). Median (interquartile range [IQR]) total BP etravirine C12h (536 ng/ml [376-719]) and raltegravir (278 ng/ml [97-690]) were adequate in 99% and 96% of patients, respectively. Median (IQR) SP:BP C12h ratio and BP unbound fraction were etravirine 0.3 (0.2-0.5) and < 1%, respectively, raltegravir 1.8 (1.3-3.3) and 12%, respectively, and raltegravir-glucuronide 12.0 (6.5-17.7) and > 99%, respectively. The BP raltegravir metabolic ratio (raltegravir glucuronide:raltegravir ratio) was 1.7, suggesting only weak induction of raltegravir glucuronidation by etravirine. Only three patients had etravirine and raltegravir C12h < PBIC95 simultaneously.Conclusion: No clinically significant pharmacokinetic interaction between etravirine and raltegravir was detected. Total etravirine and raltegravir BP concentrations were adequate in most patients, favoring virologic efficacy and confirming good treatment adherence (> 95%), despite twice-daily administration. The long half-life of etravirine and higher unbound fraction SP of raltegravir (57%) ensured adequate concentrations of dual therapy in genital compartments. Our results indicate that etravirine and raltegravir have good, complementary pharmacokinetic profiles, suggesting that they could be used in a dual-treatment strategy.

Published
2019

3. Prevalence of pretreatment HIV drug resistance in West African and Southeast Asian countries

Author

Nicole, Ngo-Giang-Huong, Thu H K, Huynh, Anoumou Y, Dagnra, Thomas-d'Aquin, Toni, Almoustapha I, Maiga, Dramane, Kania, Sabrina, Eymard-Duvernay, Martine, Peeters, Cathia, Soulie, Gilles, Peytavin, Claire, Rekacewicz, Marie-Laure, Chaix, Avelin F, Aghokeng, Ton, Tran, Chiang Mai University (CMU), Institut Pasteur d'Ho Chi Minh Ville, Réseau International des Instituts Pasteur (RIIP), Université de Lomé [Togo], CENTRE INTÉGRÉ DE RECHERCHES BIOCLINIQUES D'ABIDJAN (CIRBA) (CIRBA), University of Bamako [Mali], Institut de Recherche en Sciences de la Santé (IRSS) / Centre Muraz, Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques er émergentes (TransVIHMI), Université Montpellier 1 (UM1)-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 Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), ANRS France Recherche Nord & sud Sida-hiv hépatites, Génétique et Ecologie des Virus, Génétique des Virus et Pathogénèse des Maladies Virales, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Virologie [CHU Saint-Louis], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), ANRS 1233 study group, 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 National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), and Mzembaba, Sandy

Subjects
0301 basic medicine, Microbiology (medical), Adult, Male, Anti-HIV Agents, 030106 microbiology, Developing country, HIV Infections, Drug resistance, [SDV.MP.PRO] Life Sciences [q-bio]/Microbiology and Parasitology/Protistology, Southeast asian, [SDV.MP.PRO]Life Sciences [q-bio]/Microbiology and Parasitology/Protistology, West africa, Southeast asia, 03 medical and health sciences, 0302 clinical medicine, Drug Resistance, Viral, parasitic diseases, Prevalence, Medicine, Humans, Pharmacology (medical), 030212 general & internal medicine, Asia, Southeastern, [SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, Original Research, Pharmacology, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, business.industry, virus diseases, Middle Aged, Viral Load, [SDV.MP.MYC] Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, 3. Good health, West african, Africa, Western, Infectious Diseases, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, HIV-1, Female, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, business, Viral load, HIV drug resistance, Demography
Abstract

International audience; Background:ART in the developing world has moved to a new era with the WHO recommendation to test and immediately treat HIV-positive individuals. A high frequency of pretreatment HIV drug resistance (PDR) can compromise ART efficacy. Our study presents updated estimates of PDR in seven countries from West Africa (Burkina Faso, Cameroon, Côte d'Ivoire, Mali and Togo) and Southeast Asia (Thailand and Vietnam).Methods:Eligible study participants were adult ART initiators, recruited from December 2015 to November 2016 in major ART clinics in each country. HIV drug resistance (HIVDR) tests were performed for all specimens and interpretation was done using the Stanford algorithm.Results:Overall, 1153 participants were recruited and 1020 nt sequences were generated. PDR frequency among all initiators was 15.9% (95% CI: 13.8%-18.3%) overall, ranging from 9.6% and 10.2% in Burkina Faso and Thailand, respectively, 14.7% in Vietnam, 15.4% in Mali, 16.5% in Côte d'Ivoire and 19.3% in Cameroon, to 24.6% in Togo. The prevalence of NNRTI resistance mutations was 12%; NRTI and PI PDR prevalences were 4% and 3%, respectively.Conclusions:Our study shows that in most countries PDR exceeded 10%, warranting the conduct of nationally representative surveys to confirm this trend. In the meantime, actions to prevent drug resistance, including transition from NNRTIs to more robust drug classes should be urgently implemented.

Published
2019

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