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1. Blunted response to combination antiretroviral therapy in HIV elite controllers: an international HIV controller collaboration.

Author

Faroudy Boufassa, Jérome Lechenadec, Laurence Meyer, Dominique Costagliola, Peter W Hunt, Florencia Pereyra, Steve Deeks, Gianfranco Pancino, Olivier Taulera, Mathias Lichterfeld, Pierre Delobel, Asier Saez-Cirion, Olivier Lambotte, ANRS CO18 HIV Controllers Cohort, Cascade Collaboration in Eurocoord, SCOPE Cohort, and International HIV Controllers Study

Subjects
Medicine, Science
Abstract

ObjectiveHIV "elite controllers" (ECs) spontaneously control viral load, but some eventually require combination antiretroviral treatment (cART), due to a loss of viral control or a decline in CD4 T-cell counts. Here we studied the CD4 T-cell count dynamics after cART initiation among 34 ECs followed in U.S. and European cohorts, by comparison with chronically viremic patients (VIRs).MethodsECs were defined as patients with at least ≥5 viral load (VL) measurements below 400 copies/mL during at least a 5-year period despite never receiving ART and were selected from the French ANRS CO18 cohort, the U.S. SCOPE cohort, the International HIV Controllers study and the European CASCADE collaboration. VIRs were selected from the ANRS COPANA cohort of recently-diagnosed (ResultsAfter cART initiation, CD4 T-cell counts showed a biphasic rise in VIRs with: an initial rapid increase during the first 3 months (+0.63√CD4/month), followed by +0.19√CD4/month. This first rapid phase was not observed in ECs, in whom the CD4Tc count increased steadily, at a rate similar to that of the second phase observed in VIRs. After cART initiation at a CD4 T-cell count of 300/mm(3), the estimated mean CD4 T-cell gain during the first 12 months was 139/mm(3) in VIRs and 80/mm(3) in ECs (p = 0.048).ConclusionscART increases CD4 T-cell counts in elite controllers, albeit less markedly than in other patients.

Published
2014
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2. Potential role for HIV-specific CD38-/HLA-DR+ CD8+ T cells in viral suppression and cytotoxicity in HIV controllers.

Author

Stéphane Hua, Camille Lécuroux, Asier Sáez-Cirión, Gianfranco Pancino, Isabelle Girault, Pierre Versmisse, Faroudy Boufassa, Olivier Taulera, Martine Sinet, Olivier Lambotte, and Alain Venet

Subjects
Medicine, Science
Abstract

BACKGROUND:HIV controllers (HIC) are rare HIV-1-infected patients who exhibit spontaneous viral control. HIC have high frequency of CD38-/HLA-DR+ HIV-specific CD8+ T cells. Here we examined the role of this subset in HIC status. MATERIALS AND METHODS:We compared CD38-/HLA-DR+ CD8+ T cells with the classical CD38+/HLA-DR+ activated phenotype in terms of 1) their activation status, reflected by CD69, CD25, CD71, CD40 and Ki67 expression, 2) functional parameters: Bcl-2 expression, proliferative capacity, and IFN-γ and IL-2 production, and 3) cytotoxic activity. We also investigated how this particular profile is generated. RESULTS:Compared to CD38+/HLA-DR+ cells, CD38-/HLA-DR+ cells exhibited lower expression of several activation markers, better survival capacity (Bcl-2 MFI, 367 [134-462] vs 638 [307-747], P = 0.001), higher frequency of polyfunctional cells (15% [7%-33%] vs 21% [16%-43%], P = 0.0003), greater proliferative capacity (0-fold [0-2] vs 3-fold [2]-[11], P = 0.007), and higher cytotoxicity in vitro (7% [3%-11%] vs 13% [6%-22%], P = 0.02). The CD38-/HLA-DR+ profile was preferentially generated in response to low viral antigen concentrations. CONCLUSIONS:These data highlight the role of CD38-/HLA-DR+ HIV-specific CD8+ T cell cytotoxicity in HIC status and provide insights into the mechanism by which they are generated. Induction of this protective CD8+ subset may be important for vaccine strategies.

Published
2014
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3. In-Depth Characterization of Full-Length Archived Viral Genomes after Nine Years of Posttreatment HIV Control

Author

Pauline Trémeaux, Frédéric Lemoine, Adeline Mélard, Marine Gousset, Faroudy Boufassa, Sylvie Orr, Valérie Monceaux, Olivier Gascuel, Olivier Lambotte, Laurent Hocqueloux, Asier Saez-Cirion, Christine Rouzioux, Véronique Avettand-Fenoel, Firouzé Bani-Sadr, Maxime Hentzien, Jean-Luc Berger, Isabelle Kmiec, Gilles Pichancourt, Safa Nasri, Gilles Hittinger, Véronique Lambry, Anne-Cécile Beaudrey, Gilles Pialoux, Julie Chas, Christia Palacios, Anne Adda, Jean Paul Viard, Marie-Josée Dulucq, Laurence Weiss, Marina Karmochkine, Mohamed Meghadecha, Dominique Salmon-Ceron, Marie-Pierre Piétri, Philippe Blanche, Jean-Michel Molina, Olivier Taulera, Diane Ponscarme, Jeannine Delgado Bertaut, Djamila Makhloufi, Matthieu Godinot, Valérie Artizzu, Patrick Miailhes, Laurent Cotte, Sophie Pailhes, Anne Conrad, Ludovic Karkowski, Stanislas Ogoudjobi, Yazdan Yazdanpanah, Sophie Matheron, Cindy Godard, Louis Bernard, Frédéric Bastides, Olivier Bourgault, Christine Jacomet, Emilie Goncalves, Pascal Chavanet, Lionel Piroth, Sandrine Gohier, Agnès Meybeck, Thomas Huleux, Pauline Cornavin, Yasmine Debab, David Théron, Thierry Prazuck, Barbara De Dieuleveult, Jean-Pierre Faller, Patricia Eglinger, Pascal Roblot, David Plainchamp, Hugues Aumaître, Martine Malet, Christine Rouger, Gérard Rémy, Melle Kmiec Isabelle, Jean-Luc Delassus, Alain Devidas, Eric Froguel, Sylvie Tassi, Philippe Genet, Juliette Gerbe, Olivier Patey, Richier Laurent, Marie-Christine Drobacheff, Aurélie Proust, Helder Gil, Laurence Gérard, Eric Oksenhendler, Caroline Lascoux, Sylvie Parlier, Frédéric Lucht, Véronique Ronat, Michel Dupon, Hervé Dutronc, Séverine Le Puil, Didier Neau, Patrick Mercié, Philippe Morlat, Sabrina Caldato, Jean-Luc Schmit, Nathalie Decaux, Jean-Pierre Bru, Gaëlle Clavere, Jean-François Delfraissy, Cécile Goujard, Katia Bourdic, Daniel Vittecoq, Claudine Bolliot, Thierry Lambert, Jean-François Bergmann, Maguy Parrinello, Yves Welker, Alain Lafeuillade, Gisèle Philip, Christophe Rapp, Melle Lerondel, Pierre de Truchis, Berthe Huguette, Vincent Jeantils, Fatouma Mchangama, Paul Henri Consigny, Fatima Touam, Sophie le Nagat, Olivier Bouchaud, Patricia Honoré, François Boué, Mariem Raho-Moussa, Jean-Paul Viard, Agnès Cros, Dominique Salmon-Céron, Marie-Pierre Pietri, Lio Collias, David Zucman, Olivier Blétry, Dominique Bornarel, Emmanuel Mortier, Zeng Feng, Jean-Daniel Lelièvre, Christine Katlama, Yasmine Dudoit, Anne Simon, Catherine Lupin, Pierre-Marie Girard, Michèle Pauchard, Sylvie Abel, André Cabié, Pascale Fialaire, Jean-Marie Chennebault, Sami Rehaiem, Luc de Saint Martin, •••• Perfezou, Jean-Charles Duthe, Pierre Weinbreck, Claire Genet, Florence Garnier, Isabelle Poizot-Martin, Olivia Fauche, Alena Ivanova, Patrick Philibert, Mame Penda Sow, Patrick Yeni, Cyndi Godard, François Raffi, Hervé Hüe, Philippe Perré, Pierre Marie Roger, Aline Joulie, Éric Rosenthal, Christian Michelet, Faouzi Souala, Maja Ratajczak, Marialuisa Partisani, Patricia Fischer, Pascale Nau, Pierre Delobel, Florence Balsarin, Marc De Lavaissiere, Renaud Verdon, Philippe Feret, Pascale Leclercq, •••• Gerberon, Agnés Meybeck, Raphaël Biekre, Thierry May, •••• Bouillon, François Caron, David Theron, Marc Gatfosse, Martin Martinot, Anne Pachart, Patrice Poubeau, Catherine Gaud, Agnès Uludag, Philippe Arsac, Lydia Bouaraba, Barbara de Dieulevault, Isabelle De Lacroix Szmania, Laurent Richier, Vincent Daneluzzi, Elisabeth Rouveix, Geneviève Beck-Wirth, Philippe Romand, Laurent Blum, Martine Deschaud, Christophe Michau, Christian Bernard, Florence Salaun, Philippe Muller, Yves Poinsignon, Annie Lepretre, Albert Sotto, •••• Doncesco, Pascale Perfezou, Jean Charles Duthe, Mathilde Aurore Niault, Virginie Mouton-Rioux, Jean-Philippe Talarmin, Jean Charles Duthé, Mathilde Dupont, Stéphane Natur, Hikombo Hitoto, and Ali Mahamadou Ibrahim

Subjects
Microbiology (medical), Infectious Diseases, General Immunology and Microbiology, Ecology, Physiology, Genetics, Cell Biology
Abstract

Most people living with HIV need antiretroviral therapy to control their infection and experience viral relapse in case of treatment interruption, because of viral reservoir (proviruses) persistence. Knowing that proviruses are very diverse and most of them are defective in treated individuals, we aimed to characterize the HIV blood reservoirs of posttreatment controllers (PTCs), rare models of drug-free remission, in comparison with spontaneous controllers and treated individuals.

Published
2023
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4. Nonorgan-specific autoantibodies in HIV-infected patients in the HAART era

Author

Djaouida Bengoufa, L. Iordache, Alfred Mahr, Agathe Rami, Nesrine Day, Caroline Lascoux-Combe, Pierre-Olivier Sellier, Maguy Parrinello, Olivier Taulera, and Jean-Michel Molina

Subjects
0301 basic medicine, Adult, Male, medicine.medical_specialty, HAART, Anti-nuclear antibody, autoantibodies, Observational Study, HIV Infections, antinuclear antibodies, Gastroenterology, Immunoglobulin G, 03 medical and health sciences, Antigen, Proteinase 3, immune system diseases, Internal medicine, Antiretroviral Therapy, Highly Active, medicine, Humans, Anti-neutrophil cytoplasmic antibody, biology, business.industry, Hypergammaglobulinemia, Autoantibody, HIV, General Medicine, Middle Aged, medicine.disease, 3. Good health, 030104 developmental biology, Cross-Sectional Studies, biology.protein, ANCAs, Female, Antibody, business, hypergammaglobulinemia, Research Article
Abstract

Nonorgan-specific autoantibodies (AAbs) are used for diagnosing autoimmune diseases but can also be detected in other conditions. We carried out a cross-sectional study with the aim to screen HIV1-infected patients in the era of highly active antiretroviral therapy (HAART) for AAbs and to analyze the association of their presence with hypergammaglobulinemia and immunovirological status. Blood samples from HIV1-infected patients without major concomitant illnesses followed in 2 hospitals in Paris, France were tested for immunovirological status, serum immunoglobulin G (IgG) level, antinuclear antibodies (ANAs), anti-double-stranded DNA (anti-dsDNA), anti-extractable nuclear antigens (anti-ENAs), anticardiolipin (aCL), anti-β2glycoprotein1 (anti-β2GP1), and antineutrophil cytoplasmic antibodies (ANCAs). Clinically relevant AAbs were defined as ANAs with titers ≥1:160, anti-dsDNA or anti-ENA antibodies; aCL or anti-β2GP1 antibodies with a level ≥40 U/ml; and ANCAs reacting with proteinase 3 or myeloperoxidase. We included 92 patients (mean age 47 years, men 55%, sub-Saharan African background 55%, HAART 85%, mean CD4 lymphocyte count 611/mm3, viral load

Published
2017

5. Infectious Zika virus in vaginal secretions from an HIV-infected woman, France, August 2016

Author

Jean Guilleminot, Emmanuel Gordien, Isabelle Leparc-Goffart, Pauline Penot, Caroline Lascoux-Combe, Jean-Michel Molina, Olivier Taulera, and Ségolène Brichler

Subjects
Conjunctival hyperaemia, Adult, Fever, Epidemiology, 030231 tropical medicine, vector-borne infections, Human immunodeficiency virus (HIV), HIV Infections, medicine.disease_cause, Zika virus, 03 medical and health sciences, 0302 clinical medicine, Virology, Hiv infected, Antiretroviral Therapy, Highly Active, medicine, Humans, Martinique, 030212 general & internal medicine, Symptom onset, Vaginal secretion, Pruritic rash, Guadeloupe, sexually transmitted infections, Travel, biology, business.industry, Zika Virus Infection, Public Health, Environmental and Occupational Health, imported viral disease, Myalgia, Zika Virus, biology.organism_classification, Body Fluids, Immunology, Vagina, RNA, Viral, Female, France, business, Viral load, Rapid Communication
Abstract

A woman with controlled HIV infection developed in late August 2016 a pruritic rash with fever and conjunctival hyperaemia after a trip to the French Caribbean islands. On day 3 after symptom onset, Zika virus RNA was detected in plasma, urine and vaginal samples with respective viral loads of 3.8, 6.1 and 5.3 log copies/mL. Notably, we demonstrated the presence of infectious Zika virus particles in the vaginal samples by isolation in cell culture.

Published
2016

6. Population analysis of the pregnancy-related modifications in lopinavir pharmacokinetics and their possible consequences for dose adjustment

Author

Jean-Marc Tréluyer, Stéphanie Chhun, Gérard Pons, Elie Azria, Marion Bouillon-Pichault, Odile Launay, Emmanuelle Pannier, Anne Krivine, Vincent Jullien, Olivier Taulera, Ghislaine Firtion, Laurent Finkielsztejn, and Alexandra Compagnucci

Subjects
Microbiology (medical), medicine.medical_specialty, Anti-HIV Agents, Metabolic Clearance Rate, Population, Urology, HIV Infections, Pyrimidinones, Pharmacology, Biology, Lopinavir, Plasma, Pharmacokinetics, Pregnancy, medicine, Humans, Tissue Distribution, Pharmacology (medical), Trough Concentration, education, Chromatography, High Pressure Liquid, Volume of distribution, education.field_of_study, medicine.diagnostic_test, Gestational age, medicine.disease, Infectious Diseases, Therapeutic drug monitoring, Female, Monte Carlo Method, medicine.drug
Abstract

Objectives To investigate the possible necessity of an increase in lopinavir dose during pregnancy in order to achieve the concentrations previously defined as predictive of virological efficacy. Patients and methods Lopinavir pharmacokinetics were investigated by a population approach performed on 145 HIV-infected women, including 74 pregnant women. The final model was used to determine the probability of achievement of the target trough concentrations by Monte Carlo simulations. Results The typical population estimates (inter-individual variability %) of apparent clearance (CL/F) and volume of distribution were 4.38 L/h (24%) and 58.4 L (59%), respectively. Pregnancy associated with a gestational age >15 weeks and delivery were found to increase lopinavir CL/F by 39% and 58%, respectively. With the standard 400 mg twice-a-day regimen, the probability of reaching the 1 mg/L target trough concentration for protease inhibitor (PI)-naive patients was 99% and 96% for non-pregnant and pregnant women, respectively. An important decrease in the probability of achieving the 5.7 mg/L target trough concentration for salvage therapy was observed for non-pregnant women (55%), this decrease being even greater for pregnant women (21%). Raising the lopinavir dose to 600 mg twice daily increased these probabilities to 87% and 53% for non-pregnant and pregnant women, respectively. Conclusions Modification of the lopinavir dose is unlikely to be required for PI-naive pregnant women; however, in pregnant women who have previously received a PI, therapeutic drug monitoring and/or empirical increasing of the dose should be considered.

Published
2009
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7. Pregnancy outcomes in women with HIV type-1 receiving a lopinavir/ritonavir-containing regimen

Author

Jean Patrick Le Meaux, Dominique Cabrol, Olivier Taulera, Thomas Schmitz, Odile Launay, Constance Moutafoff, Emmanuelle Pannier, Anne Krivine, Alexandra Compagnucci, Vassilis Tsatsaris, Ghislaine Firtion, Laurent Finkielsztejn, and Elie Azria

Subjects
Adult, medicine.medical_specialty, Lopinavir/ritonavir, HIV Infections, Pyrimidinones, Lopinavir, Cohort Studies, Obstetric Labor, Premature, Acquired immunodeficiency syndrome (AIDS), Pregnancy, Internal medicine, medicine, Humans, Pharmacology (medical), Pregnancy Complications, Infectious, Sida, Adverse effect, Pharmacology, Ritonavir, biology, business.industry, Pregnancy Outcome, HIV Protease Inhibitors, medicine.disease, biology.organism_classification, Regimen, Infectious Diseases, Immunology, HIV-1, Drug Therapy, Combination, Female, France, business, medicine.drug
Abstract

Background The pregnancy-related adverse effects of antiretroviral therapy (ART) have yielded discordant results, which could be explained in part by the heterogeneity of ART protocols. The objective of our study was to explore whether lopinavir/ritonavir (LPV/r) exposure during pregnancy is associated with adverse outcomes. Methods Data on 100 consecutive HIV type-1 (HIV-1)-infected women receiving LPV/r during pregnancy and who delivered after 15 weeks gestational age (GA) between January 2003 and June 2007 in a single centre were analysed. For each HIV-1-infected woman, two uninfected women matched by age, parity and geographical origin were selected among patients delivering during the same period. Preterm delivery (PTD), vasculoplacental complications, gestational glucose intolerance and post-partum complication rates were compared between cases and controls. Factors associated with PTD and post-partum complications were assessed in HIV-1-infected women by a logistic regression model. Results Rates of vasculoplacental complication and gestational glucose intolerance were not higher among HIV-1-infected women than in controls. PTD was higher in HIV-1-infected women (21%) than in controls (10%; PConclusions In this population of HIV-1-infected pregnant women receiving LPV/r, the risk of PTD was higher than in HIV-1-uninfected controls. As PTD risk was not associated with early exposure to LPV/r, these data support current guidelines to initiate ART earlier in pregnancy.

Published
2008
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8. Potential role for HIV-specific CD38-/HLA-DR+ CD8+ T cells in viral suppression and cytotoxicity in HIV controllers

Author

Olivier Taulera, Stephane Hua, Faroudy Boufassa, Gianfranco Pancino, Camille Lécuroux, Pierre Versmisse, Martine Sinet, Alain Venet, Olivier Lambotte, Isabelle Girault, Asier Sáez-Cirión, INSERM U1012, AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Régulation des Infections Rétrovirales, Institut Pasteur [Paris] (IP), Departement d'épidémiologie, Université Paris-Sud - Paris 11 (UP11), 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) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Saint-Louis, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Médecine interne [CHU Bicêtre], This work was supported in part by institutional grants from Institut National de la Santé et de la Recherche Médicale, Agence Nationale de Recherche sur le SIDA and Sidaction. SH received institutional grants from Ministère de l’Enseignement Supérieur et de la Recherche and Sidaction. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript, Institut Pasteur [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), and Guibert, Marie-Genevieve

Subjects
Male, Cytotoxic, T-Lymphocytes, lcsh:Medicine, HIV Infections, Clinical immunology, CD38, CD8-Positive T-Lymphocytes, Lymphocyte Activation, Immunophenotyping, Cytotoxic T cell, IL-2 receptor, lcsh:Science, Cells, Cultured, Multidisciplinary, Cultured, biology, Chemistry, Middle Aged, HIV immunopathogenesis, Flow Cytometry, 3. Good health, CD, Infectious diseases, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Viral load, Research Article, Adult, [SDV.IMM] Life Sciences [q-bio]/Immunology, Cells, Immunology, Viral diseases, Antigen, Antigens, CD, Humans, Antigens, Medicine and health sciences, CD40, Biology and life sciences, lcsh:R, HLA-DR Antigens, ADP-ribosyl Cyclase 1, Molecular biology, Case-Control Studies, biology.protein, HIV-1, lcsh:Q, CD8, T-Lymphocytes, Cytotoxic
Abstract

International audience; BACKGROUND: HIV controllers (HIC) are rare HIV-1-infected patients who exhibit spontaneous viral control. HIC have high frequency of CD38-/HLA-DR+ HIV-specific CD8+ T cells. Here we examined the role of this subset in HIC status. MATERIALS AND METHODS: We compared CD38-/HLA-DR+ CD8+ T cells with the classical CD38+/HLA-DR+ activated phenotype in terms of 1) their activation status, reflected by CD69, CD25, CD71, CD40 and Ki67 expression, 2) functional parameters: Bcl-2 expression, proliferative capacity, and IFN-γ and IL-2 production, and 3) cytotoxic activity. We also investigated how this particular profile is generated. RESULTS: Compared to CD38+/HLA-DR+ cells, CD38-/HLA-DR+ cells exhibited lower expression of several activation markers, better survival capacity (Bcl-2 MFI, 367 [134-462] vs 638 [307-747], P = 0.001), higher frequency of polyfunctional cells (15% [7%-33%] vs 21% [16%-43%], P = 0.0003), greater proliferative capacity (0-fold [0-2] vs 3-fold [2]-[11], P = 0.007), and higher cytotoxicity in vitro (7% [3%-11%] vs 13% [6%-22%], P = 0.02). The CD38-/HLA-DR+ profile was preferentially generated in response to low viral antigen concentrations. CONCLUSIONS: These data highlight the role of CD38-/HLA-DR+ HIV-specific CD8+ T cell cytotoxicity in HIC status and provide insights into the mechanism by which they are generated. Induction of this protective CD8+ subset may be important for vaccine strategies.

Published
2014
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9. Transient viral exposure drives functionally-coordinated humoral immune responses in HIV-1 post-treatment controllers

Author

Molinos-Albert, Luis, Lorin, Valerie, Monceaux, Valérie, Orr, Sylvie, Essat, Asma, Dufloo, Jérémy, Schwartz, Olivier, Rouzioux, Christine, Meyer, Laurence, Hocqueloux, Laurent, Sáez-Cirión, Asier, Mouquet, Hugo, Group, Anrs Visconti Study, Prazuck, Thierry, Dieuleveult, Barbara De, Bani-Sadr, Firouzé, Hentzien, Maxime, Berger, Jean-Luc, Kmiec, Isabelle, Pichancourt, Gilles, Nasri, Safa, Hittinger, Gilles, Lambry, Véronique, Beauey, Anne-Cécile, Pialoux, Gilles, Palacios, Christia, Siguier, Martin, Adda, Anne, Foucoin, Jane, Weiss, Laurence, Karmochkine, Marina, Meghadecha, Mohamed, Ptak, Magali, Salmon-Ceron, Dominique, Blanche, Philippe, Piétri, Marie-Pierre, Molina, Jean-Michel, Taulera, Olivier, Lascoux-Combe, Caroline, Ponscarme, Diane, Bertaut, Jeannine Delgado, Makhloufi, Djamila, Godinot, Matthieu, Artizzu, Valérie, Yazdanpanah, Yazdan, Matheron, Sophie, Godard, Cindy, Julia, Zélie, Bernard, Louis, Bastides, Frédéric, Bourgault, Olivier, Jacomet, Christine, Goncalves, Emilie, Meybeck, Agnès, Huleux, Thomas, Cornavin, Pauline, Debab, Yasmine, Théron, David, Miailhes, Patrick, Cotte, Laurent, Pailhes, Sophie, Ogoudjobi, Stanislas, Viard, Jean Paul, Dulucq, Marie-Josée, Bodard, Loïc, Churaqui, Francoise, Guimard, Thomas, Laine, Laetitia, Immunologie humorale - Humoral Immunology, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), HIV, Inflammation et persistance - HIV, Inflammation and Persistence, Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Virus et Immunité - Virus and immunity (CNRS-UMR3569), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Service de Microbiologie Clinique [Paris], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), La Source Hospital-CHR, Centre Hospitalier Universitaire de Reims (CHU Reims), Centre Hospitalier Henri Duffaut (Avignon), CHI de Toulon, CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), 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), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hopital Saint-Louis [AP-HP] (AP-HP), Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Hôpital Bretonneau, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand, Centre Hospitalier Gustave Dron [Tourcoing], Hôpital Charles Nicolle [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU), Hôpital de la Croix-Rousse [CHU - HCL], Hôpital Hôtel-Dieu [Paris], Institut mutualiste Monsouris (IMM), Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon (CHD Vendée), We thank the NIH AIDS Reagent Program (Division of AIDS, NIAID, NIH) for contributing to reagents and the Agence National de Recherche sur le SIDA et les hépatites virales (ANRS) for an equipment grant support (AO2013-2 #13553, H.M.). L.M. M-A. is the recipient of a postdoctoral fellowship from the Pasteur-Roux-Cantarini program (Institut Pasteur). H.M. received core grants from the Institut Pasteur, the INSERM and the Milieu Intérieur Program (ANR-10-LABX-69-01). This work was conducted in the context of the ANRS RHIVIERA consortium, and was supported by the ANRS and the NIH/NIAID (grant #: P01AI131365, H.M.)., ANRS VISCONTI Study Group Thierry Prazuck, Barbara De Dieuleveult, Firouzé Bani-Sadr, Maxime Hentzien, Jean-Luc Berger, Isabelle Kmiec, Gilles Pichancourt, Safa Nasri, Gilles Hittinger, Véronique Lambry, Anne-Cécile Beauey, Gilles Pialoux, Christia Palacios, Martin Siguier, Anne Adda, Jane Foucoin, Laurence Weiss, Marina Karmochkine, Mohamed Meghadecha, Magali Ptak, Dominique Salmon-Ceron, Philippe Blanche, Marie-Pierre Piétri, Jean-Michel Molina, Olivier Taulera, Caroline Lascoux-Combe, Diane Ponscarme, Jeannine Delgado Bertaut, Djamila Makhloufi, Matthieu Godinot, Valérie Artizzu, Yazdan Yazdanpanah, Sophie Matheron, Cindy Godard, Zélie Julia, Louis Bernard, Frédéric Bastides, Olivier Bourgault, Christine Jacomet, Emilie Goncalves, Agnès Meybeck, Thomas Huleux, Pauline Cornavin, Yasmine Debab, David Théron, Patrick Miailhes, Laurent Cotte, Sophie Pailhes, Stanislas Ogoudjobi, Jean Paul Viard, Marie-Josée Dulucq, Loïc Bodard, Francoise Churaqui, Thomas Guimard & Laetitia Laine, ANR-10-LABX-0069,MILIEU INTERIEUR,GENETIC & ENVIRONMENTAL CONTROL OF IMMUNE PHENOTYPE VARIANCE: ESTABLISHING A PATH TOWARDS PERSONALIZED MEDICINE(2010), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPC), Institut Pasteur [Paris]-Université Paris Cité (UPC), Virus et Immunité - Virus and immunity, and Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPC)

Subjects
Multidisciplinary, MESH: Humans, General Physics and Astronomy, HIV Infections, General Chemistry, MESH: HIV Infections, Antibodies, Neutralizing, General Biochemistry, Genetics and Molecular Biology, Immunity, Humoral, MESH: Antibodies, Neutralizing, MESH: HIV-1, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, HIV-1, Humans, Viremia, MESH: Immunity, Humoral, MESH: Viremia
Abstract

HIV-1 post-treatment controllers are rare individuals controlling HIV-1 infection for years after antiretroviral therapy interruption. Identification of immune correlates of control in post-treatment controllers could aid in designing effective HIV-1 vaccine and remission strategies. Here, we perform comprehensive immunoprofiling of the humoral response to HIV-1 in long-term post-treatment controllers. Global multivariate analyses combining clinico-virological and humoral immune data reveal distinct profiles in post-treatment controllers experiencing transient viremic episodes off therapy compared to those stably aviremic. Virally-exposed post-treatment controllers display stronger HIV-1 humoral responses, and develop more frequently Env-specific memory B cells and cross-neutralizing antibodies. Both are linked to short viremic exposures, which are also accompanied by an increase in blood atypical memory B cells and activated subsets of circulating follicular helper T cells. Still, most humoral immune variables only correlate with Th2-like circulating follicular helper T cells. Thus, post-treatment controllers form a heterogeneous group with two distinct viral behaviours and associated immune signatures. Post-treatment controllers stably aviremic present “silent” humoral profiles, while those virally-exposed develop functionally robust HIV-specific B-cell and antibody responses, which may participate in controlling infection.

Published
2022
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10. Antibodies attenuate the capacity of dendritic cells to stimulate HIV-specific cytotoxic T lymphocytes

Author

Sylvain Cardinaud, Wilfried Posch, Klaus Loacker, Cornelia Lass-Flörl, Manfred P. Dierich, Annelies Mühlbacher, Adam J. Fletcher, Asier Sáez-Cirión, Chiraz Hamimi, Doris Wilflingseder, Gianfranco Pancino, Paul Eichberger, Arnaud Moris, Innsbruck Medical University = Medizinische Universität Innsbruck (IMU), Immunité et Infection, Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR113-Institut National de la Santé et de la Recherche Médicale (INSERM), Régulation des Infections Rétrovirales, Institut Pasteur [Paris] (IP), University College of London [London] (UCL), This work was supported by the Austrian Science Fund [FWF, P22165 and P24598 to DW]and the Tyrolean Science Fund [TWF, project: D-155140-016-011 to WP]. The authors thankProf. Olivier Lambotte, Prof. Laurence Weiss, Dr. Caroline Lascoux, Dr. Olivier Taulera,Katia Bourdic, Jeannine Delgado, Maria Manea and all the other physicians and nurses whocared for the patients whose samples were included in the study. Additionally, we want tothank Polymun Scientific, Donaustrasse 99, Klosterneuburg, Austria who provided allreagents for p24 ELISA . The reagents ARP118 (HIV-BaL), ARP513 (HIVIg pool) andARP177.8 (HIV-92UG037) were obtained from the Centre for AIDS Reagents, NIBSCHPA UK, supported by the EC FP6/7 Europrise Network of Excellence, and NGIN consortiaand the Bill and Melinda Gates GHRC-CAVD Project and were donated by Dr.S.Gartner,Dr.M.Popovic, Dr.R.Gallo (Courtesy of the NIH AIDS Research and Reference ReagentProgram [BaL]), Dr B. Wahren, The Swedish Institute for Infectious Disease Control,Stockholm, Sweden [HIVIg pool] and the WHO UN AIDS Network for HIV-isolation andcharacterization [92UG037]., Innsbruck Medical University [Austria] (IMU), Institut Pasteur [Paris], and Guibert, Marie-Genevieve

Subjects
CD4-Positive T-Lymphocytes, [SDV.IMM] Life Sciences [q-bio]/Immunology, Cytotoxic, T-Lymphocytes, Immunology, Antigen presentation, Priming (immunology), HIV Infections, Biology, Antibodies, Viral, Lymphocyte Activation, Article, Antibodies, 03 medical and health sciences, Interferon-gamma, 0302 clinical medicine, Antigen, Immunology and Allergy, Cytotoxic T cell, Humans, Viral, Antigens, Antigens, Viral, 030304 developmental biology, Cell Proliferation, 0303 health sciences, Antigen Presentation, virus diseases, HIV, Dendritic cell, Complement System Proteins, Dendritic Cells, Molecular biology, 3. Good health, Clone Cells, Antibody opsonization, CTL, [SDV.IMM]Life Sciences [q-bio]/Immunology, CD8, T-Lymphocytes, Cytotoxic, 030215 immunology
Abstract

International audience; BACKGROUND: Control of HIV is suggested to depend on potent effector functions of the virus-specific CD8(+) T-cell response. Antigen opsonization can modulate the capture of antigen, its presentation, and the priming of specific CD8(+) T-cell responses. OBJECTIVE: We have previously shown that opsonization of retroviruses acts as an endogenous adjuvant for dendritic cell (DC)-mediated induction of specific cytotoxic T lymphocytes (CTLs). However, in some HIV-positive subjects, high levels of antibodies and low levels of complement fragments coat the HIV surface. METHODS: Therefore we analyzed the effect of IgG opsonization on the antigen-presenting capacity of DCs by using CD8(+) T-cell proliferation assays after repeated prime boosting, by measuring the antiviral activity against HIV-infected autologous CD4(+) T cells, and by determining IFN-γ secretion from HIV-specific CTL clones. RESULTS: We find that DCs exposed to IgG-opsonized HIV significantly decreased the HIV-specific CD8(+) T-cell response compared with the earlier described efficient CD8(+) T-cell activation induced by DCs loaded with complement-opsonized HIV. DCs exposed to HIV bearing high surface IgG levels after incubation in plasma from HIV-infected subjects acted as weak stimulators for HIV-specific CTL clones. In contrast, HIV opsonized with plasma from patients exhibiting high complement and low IgG deposition on the viral surface favored significantly higher activation of HIV-specific CD8(+) T-cell clones. CONCLUSION: Our ex vivo and in vitro observations provide the first evidence that IgG opsonization of HIV is associated with a decreased CTL-stimulatory capacity of DCs.

Published
2012
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