154 results on '"G. Marcelin"'
Search Results
2. Comparison of HIV-Infected and Noninfected Patients Undergoing Bariatric Surgery: The ObeVIH Study
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V, Pourcher, J, Capeau, Y, Dudoit, F, Boccara, C, Soulié, A L, Ndoadoumgue, F, Charlotte, S, Fellahi, J P, Bastard, V, Béréziat, C, Lagathu, A G, Marcelin, G, Peytavin, M C, Boutron-Ruault, C, Tubbax, A, D'Avout D'Auerstaedt, M A, Valantin, L, Schneider, D, Costagliola, C, Katlama, L, Assoumou, and G, Pourcher
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Male ,Cross-Sectional Studies ,Infectious Diseases ,Bariatric Surgery ,Humans ,Female ,HIV Infections ,Pharmacology (medical) ,HIV Integrase Inhibitors ,Prospective Studies - Abstract
The aim of this study was to compare clinical characteristics and adipose/liver tissue histology analysis in HIV-infected and HIV-uninfected subjects undergoing bariatric surgery.This was a cross-sectional study of HIV-infected subjects undergoing single-port sleeve gastrectomy with prospective enrolment and frequency age (±5 years), sex, and body mass index (BMI, ± 5 kg/m2) matched on HIV-uninfected subjects.This study was conducted at a single clinical site at Pitié-Salpêtrière hospital-Paris-France comprising 19 HIV-uninfected and 21 HIV-infected subjects with plasma VL20 copies/mL, all with a BMI40 kg/m2 or35 kg/m2 with comorbidities. Histology of subcutaneous and visceral abdominal adipose tissue (SCAT/VAT) and liver biopsies was collected during single-port sleeve gastrectomy. Outcomes included anthropometric characteristics, comorbidities, cardiovascular parameters, adipose tissue, and liver histology.The age of HIV-infected participants was (median, interquartile range IQR) 48 y (42-51), with 76.2% females, a BMI of 41.4 kg/m2 (37.3-44.4), an antiretroviral duration of 16 y (8-21), current integrase strand transfer inhibitor (INSTI)-based regimen in 15 participants and non-INSTI regimen in 6 participants, and a CD4 count of 864/mm3 (560-1066). The age of controls was 43 y (37-51), with 78.9% females and a BMI of 39.2 kg/m2 (36.3-42.6). Anthropometric characteristics, comorbidities, and cardiovascular parameters did not differ according to HIV status and INSTI treatment. The number of macrophage crown-like structures in SCAT was lower in INSTI-treated participants than in HIV-uninfected participants (P = 0.02) and non-INSTI-treated HIV-infected subjects (P = 0.07). Hepatic steatosis and liver disease severity global score were lower in INSTI-treated participants than in non-INSTI-treated HIV-infected participants (P = 0.05 and P = 0.04, respectively).HIV-infected and HIV-uninfected subjects undergoing bariatric surgery presented a similar profile regarding anthropometric measures, cardiovascular parameters, and comorbidities. However, INSTI-treated participants presented milder SCAT and liver alterations than non-INSTI-treated participants.
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- 2022
3. [HHV8, Kaposi's disease and organ transplantation: should we screen ?]
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A-G, Marcelin
- Abstract
The incidence of Kaposi's sarcoma (KS) related to Kaposi's sarcoma associated herpesvirus (KSHV/HHV-8) after organ transplantation is 500-1 000 times greater than in the general population and its occurrence is associated with immunosuppressive therapy. The reported incidence of post-transplant KS ranges from 0.5 % to 5 %, depending on the patient's country of origin and the type of organ received, mainly following renal transplantation. Post-transplant KS is caused by two possible mechanisms: KSHV reactivation in patients who were infected before the graft and KSHV contamination from infected organs donor to the recipient. KSHV reactivation appears to play a greater role on the risk of KS than incident infections. However, some studies, with findings based not only on serological data but also on molecular tracing of the viral infection, have shown that organ-related transmission of KSHV could be more common than previously thought and associated in some cases with severe KSHV related disease. Precise estimates of KSHV seroprevalence in the organ donor and recipient populations in different countries are lacking. However, studies have reported seroprevalences among donors and recipients that are similar to those among the general population of the country considered. Many studies have suggested the potential interest of screening of KSHV antibodies among organ donors and recipients. However, to date the results of these studies have argued in favor of KSHV screening, even in low KSHV infection prevalence countries, not to exclude the graft but to have the KSHV status information in order to have the opportunity to monitor, clinically and biologically, patients at risk to KSHVrelated disease development. The detection of KSHV antibodies could be done the days after the transplantation and the results transmitted to the physicians retrospectively. In conclusion, the question of screening donors and recipients for KSHV, even in low KSHV infection prevalence countries, is still debated and prospective studies are needed to evaluate the benefit of pre and posttransplantation strategies.
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- 2022
4. Persistent low-level viraemia in antiretroviral treatment-experienced patients is not linked to viral resistance or inadequate drug concentrations
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B. Abdi, Marc-Antoine Valantin, Sophie Seang, Romain Palich, Gilles Peytavin, Vincent Calvez, Marc Wirden, Cathia Soulié, A G Marcelin, Olivier Paccoud, Minh Patrick Lê, Roland Tubiana, Christine Katlama, and Luminita Schneider
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Microbiology (medical) ,Drug ,medicine.medical_specialty ,Anti-HIV Agents ,media_common.quotation_subject ,Patient characteristics ,HIV Infections ,Viremia ,Drug resistance ,Viral resistance ,Antiretroviral Therapy, Highly Active ,Internal medicine ,Drug Resistance, Viral ,Antiretroviral treatment ,Humans ,Medicine ,Pharmacology (medical) ,In patient ,media_common ,Pharmacology ,business.industry ,Middle Aged ,Viral Load ,medicine.disease ,CD4 Lymphocyte Count ,Infectious Diseases ,Anti-Retroviral Agents ,Pharmaceutical Preparations ,HIV-1 ,business ,Viral load - Abstract
Objectives To assess genotypic sensitivity scores (GSSs), plasma antiretroviral concentrations (PACs) and immunovirological outcomes at Week 96 (W96) in patients with persistent low-level viraemia (LLV). Methods On 1 January 2017, we analysed data from patients on three-drug regimens with persistent LLV defined as at least two consecutive plasma viral loads (pVLs) between 21 and 200 copies/mL (including one pVL of ≥50 copies/mL), at the Pitié-Salpêtrière Hospital. Outcomes were: GSS, PACs and HIV-DNA load at study entry; and virological status and proportion of patients with resistance-associated mutations (RAMs) at W96. Results Fifty-seven patients were included, with median age of 52.6 years (IQR 45.2–57.9), last CD4 count of 658 cells/mm3 (IQR 462–909) and total ART duration of 10.2 years (IQR 5.7–15.2). LLV duration was 14.0 months (IQR 5.5–22.3). GSS was 3 in 46/57 (81%) patients and PACs were adequate in 53/57 (93%) patients. Median total HIV-DNA was 2.65 log10 copies/106 cells (IQR 2.44–2.86). During follow-up, 26/57 (46%) had experienced ART modifications. At W96, 38/57 (67%) patients remained with LLV, 15/60 (26%) had achieved confirmed pVL of Conclusions A substantial number of patients harbouring LLV had no resistance to ART and adequate PACs. Two-thirds of these patients remained with this LLV status.
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- 2020
5. Étude des acteurs cellulaires de la fibrose du tissu adipeux viscéral associés au contrôle de la glycémie au cours de l’obésité
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C. Rouault, K. Clément, and G. Marcelin
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Nutrition and Dietetics ,Endocrinology, Diabetes and Metabolism ,Internal Medicine - Published
- 2022
6. High seroconversion rate but low antibody titers after two injections of BNT162b2 (Pfizer-BioNTech) vaccine in patients treated by chemotherapy for solid cancers
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J. Barrière, Marianne Veyri, P. Maingon, Marc-Antoine Benderra, Romain Palich, J-P. Spano, Z. Adjoutah, Laurence Morand-Joubert, A G Marcelin, Stéphane Marot, Joseph Gligorov, Aurore Vozy, Service d'Oncologie médicale [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), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Universitaire de Cancérologie [Paris] (IUC), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service de virologie [CHU Pitié-Salpêtrière], Service d'Oncologie médicale [CHU Tenon], CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'Oncologie Radiothérapie [CHU Pitié Salpétrière], Laboratoire de Virologie [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Cerballiance, HAL-SU, Gestionnaire, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), and Service de Virologie [CHU Pitié-Salpêtrière]
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COVID-19 Vaccines ,medicine.medical_treatment ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,03 medical and health sciences ,0302 clinical medicine ,[SDV.IMM.VAC] Life Sciences [q-bio]/Immunology/Vaccinology ,[SDV.CAN] Life Sciences [q-bio]/Cancer ,[SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases ,Neoplasms ,medicine ,Humans ,In patient ,Seroconversion ,Letter to the Editor ,BNT162 Vaccine ,ComputingMilieux_MISCELLANEOUS ,030304 developmental biology ,Cancer ,[SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases ,0303 health sciences ,Chemotherapy ,Vaccines ,[SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases ,business.industry ,SARS-CoV-2 ,Vaccination ,Antibody titer ,COVID-19 ,Hematology ,3. Good health ,mRNA vaccine ,Serology ,Oncology ,030220 oncology & carcinogenesis ,Immunology ,[SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases ,[SDV.IMM.VAC]Life Sciences [q-bio]/Immunology/Vaccinology ,business - Abstract
International audience
- Published
- 2021
7. Second-line antiretroviral therapy failure and characterization of HIV-1 drug resistance patterns in children in Mali
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Robert L. Murphy, Seydou Doumbia, Oumar Dolo, Y.A. Coulibaly, Josue Togo, F. Traoré, Almoustapha Issiaka Maiga, A G Marcelin, D. B. Fofana, Souleymane Diallo, Vincent Calvez, Susan Orsega, F. Dicko-Traore, and MB Sylla
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Male ,medicine.medical_specialty ,Nevirapine ,Adolescent ,Anti-HIV Agents ,HIV Infections ,Drug resistance ,Mali ,Drug Administration Schedule ,03 medical and health sciences ,0302 clinical medicine ,Abacavir ,030225 pediatrics ,Internal medicine ,Drug Resistance, Viral ,medicine ,Humans ,Treatment Failure ,Child ,business.industry ,Stavudine ,virus diseases ,Lamivudine ,Lopinavir ,Viral Load ,Drug Combinations ,Cross-Sectional Studies ,Child, Preschool ,Mutation ,Pediatrics, Perinatology and Child Health ,HIV-1 ,Female ,Ritonavir ,business ,Viral load ,medicine.drug - Abstract
Introduction In recent years, children born to HIV-infected mothers have been receiving antiretroviral treatment (ART) with limited or no virologic monitoring, which increases the likelihood of development and accumulation of drug resistance mutations, which itself may limit the effectiveness of future ART. The objective of this study was to evaluate the prevalence of resistance mutations in children infected with HIV-1 experiencing virological failure to second-line ART in the Pediatric Department of Gabriel Toure Hospital in Mali. Methods Children aged from 5 to 18 infected with HIV-1 on second-line antiretroviral therapy and whose viral load was greater than 1000 copies/mL after observance reinforcement were enrolled. The protease and reverse transcriptase genes were sequenced with ViroSeq®. The results were interpreted according to the last version of the Stanford algorithm in 2018. The study was approved by the Ethics Committee of the Faculty of Medicine and Dentistry, University of Sciences, Techniques and Technologies of Bamako (Mali). Results Of 216 children, 33 (15.3%) who had a viral load (VL) > 1000 copies/mL in second line were recruited and included in the study. The median plasma viral load was 77,000 copies/mL [IQR (28,000–290,000)] and the median CD4 cell count was 310 cells/mm3 [IQR (152–412)]. The median age was 12 years; 48.5% of patients were treated with a combination of stavudine/lamivudine/nevirapine (Triomune®) for first-line treatment and 60.6% with abacavir/lamivudine/lopinavir/ritonavir for the second-line ART. The median treatment duration was 8.5 years [range, 3–13]. Of the 33 children whose treatment failed, the predominant HIV-1 subtype was CRF02_AG (66.7%). The prevalence of resistance to ART classes was 60.61% (20/33) to nucleoside reverse transcriptase inhibitors (NRTIs), 54.51% (18/33) to nonnucleoside reverse transcriptase inhibitors (NNRTIs), and 51.52% (17/33) to protease inhibitors (PIs). Of the patients studied, 90.9% were exposed to lopinavir/ritonavir (LPV/r) but only 15.2% (5/33) developed resistance to LPV/r. Conclusions This study demonstrated that LPV/r remains active in most patients after second-line ART failure. In children whose second-line ART fails, particular attention should be paid to their ART and adherence history when considering the next treatment option.
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- 2019
8. Weak immunogenicity after a single dose of SARS-CoV-2 mRNA vaccine in treated cancer patients
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S. Marot, Romain Palich, P. Maingon, A G Marcelin, Joseph Gligorov, Aurore Vozy, Marianne Veyri, J-P. Spano, HAL-SU, Gestionnaire, 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 d'Oncologie médicale [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), Institut Universitaire de Cancérologie [Paris] (IUC), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service de Virologie [CHU Pitié-Salpêtrière], Service d'Oncologie Radiothérapie [CHU Pitié Salpétrière], Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Service de virologie [CHU Pitié-Salpêtrière]
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2019-20 coronavirus outbreak ,COVID-19 Vaccines ,Coronavirus disease 2019 (COVID-19) ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,Serology ,03 medical and health sciences ,0302 clinical medicine ,[SDV.IMM.VAC] Life Sciences [q-bio]/Immunology/Vaccinology ,[SDV.CAN] Life Sciences [q-bio]/Cancer ,[SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases ,Neoplasms ,medicine ,Humans ,RNA, Messenger ,Letter to the Editor ,030304 developmental biology ,Cancer ,[SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases ,0303 health sciences ,Messenger RNA ,[SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases ,business.industry ,SARS-CoV-2 ,Immunogenicity ,Vaccination ,COVID-19 ,Hematology ,medicine.disease ,Virology ,3. Good health ,mRNA vaccine ,Oncology ,030220 oncology & carcinogenesis ,[SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases ,[SDV.IMM.VAC]Life Sciences [q-bio]/Immunology/Vaccinology ,business - Abstract
International audience; Active cancer and ongoing antineoplastic treatments are major factors for severe COVID-19 and death, reasons why the SARS-CoV-2 vaccination remains a priority in cancer patients (CPs). However, immunocompromised patients were excluded from major studies on mRNA vaccines, and could have a decreased response to vaccination, as recently demonstrated in solid organ transplant recipients. Herein, we aimed to assess the proportion of antibody response 4 weeks after the first injection of the BNT162b2 (Pfizer-BioNTech) vaccine in CPs and health care workers (HCWs) as the control population.
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- 2021
9. Tissu adipeux blanc
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C. Rose and G. Marcelin
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business.industry ,Medicine ,business - Published
- 2021
10. Étude du tissu adipeux en lien avec l’amélioration pondérale et la réponse métabolique après chirurgie bariatrique de conversion
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S. Guillerme, S. Adriouch, L. Genser, K. Clément, and G. Marcelin
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Nutrition and Dietetics ,Endocrinology, Diabetes and Metabolism ,Internal Medicine - Published
- 2022
11. Low immune response rate of HIV-infected patients to a single injection of hepatitis A vaccine
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Romain Palich, A G Marcelin, Marc-Antoine Valantin, L. Noël, Catherine Blanc, Christine Katlama, Eve Todesco, Roland Tubiana, A. Simon, and Vincent Calvez
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Adult ,medicine.medical_specialty ,Vaccination schedule ,Hepatitis A vaccine ,Population ,CD4-CD8 Ratio ,Context (language use) ,HIV Infections ,Hepatitis A Antibodies ,Serology ,Disease Outbreaks ,03 medical and health sciences ,Immune system ,Internal medicine ,medicine ,Humans ,education ,Immunization Schedule ,Retrospective Studies ,0303 health sciences ,education.field_of_study ,Hepatitis A Vaccines ,030306 microbiology ,business.industry ,Immunity ,virus diseases ,Hepatitis A ,Middle Aged ,Viral Load ,medicine.disease ,CD4 Lymphocyte Count ,Infectious Diseases ,business ,Viral load - Abstract
Objectives We aimed to evaluate the immune response of HIV-1 positive patients to a single injection of HAV vaccine in a context of vaccine shortage during the 2017 European outbreak. Methods We retrospectively enrolled all HIV-1 positive patients vaccinated by a single injection of HAV vaccine Vaqta 50®. HAV serology was performed before and > 30 days after the vaccine injection. Results Among the 73 patients, HIV-1 viral load was ≤ 50 copies/mL in 93.2% of the cases. Medians of CD4 and median ratio of T CD4/CD8 cells were 658/mm3 and 0.9, respectively. A low immune response rate (59.7%) was observed among the patients. Responders had a significantly higher CD4/CD8 cell ratio than non-responders. Conclusions A serologic control should be recommended in this population in the event of a single injection vaccination schedule. During routine follow-up, and prior to any untoward event, physicians should assess the vaccination coverage of HIV-infected patients.
- Published
- 2020
12. Evaluation of 31 Commercial SARS-CoV-2 Serology Assays
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Florence Damond, Fourati S, Charlotte Charpentier, Tiffany Guilleminot, Carol A, Alloui A, Samuel Le Pape, Baudier Mc, Jacques Fourgeaud, Héloïse Petit, Isabelle Podglajen, A G Marcelin, Marianne Leruez-Ville, Marot Ss, Stéphane Bonacorsi, Sepideh Akhavan, Laurent Dortet, Flore Rozenberg, Mackiewicz, Rona J, Elyanne Gault, Joël Gozlan, Thierry Naas, Gordien N, Fellous Cv, Guislaine Carcelain, François Moreau, Sarah Maylin, Ségolène Brichler, Constance Delaugerre, Laurence Morand-Joubert, Fenoel Va, Juliette Villemonteix, Boukli-Hacene N, Sonia Burrel, Elise Gardiennet, Afonso Ar, Pawlotsky Jm, Dubois C, Dominique Challine, Welti Mr, Jérôme Le Goff, Diane Descamps, Jean-François Meritet, and Houhou N
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medicine.medical_specialty ,biology ,business.industry ,Gold standard (test) ,medicine.disease ,Roche Diagnostics ,biology.organism_classification ,Abbott Diagnostics ,Rubella ,Serology ,Informed consent ,Internal medicine ,Pandemic ,Medicine ,business ,Sida - Abstract
Background: The virus responsible of severe acute respiratory syndrome named SARS-CoV-2 and causing the new coronavirus disease (COVID-19) has gone global within three months. The current gold standard technique used to detect SARS-CoV-2 is real-time reverse transcription-polymerase chain reaction (rRT-PCR) from naso-pharyngeal swabs but it may be negative in up to 30% of COVID-19 patients. Detection of specific antibodies against SARS-CoV-2 may therefore enhance sensitivity of the current biological diagnosis, as well as monitor the extent of the epidemics in global or specific population, such as health-care worker. Many serological assays are currently available, but their clinical performances are still to be evaluated. Material and Method: A total of 2,594 serum samples collected from patients with SARS-CoV-2 infection documented by a positive rRT-PCR were enrolled in this study. They were tested for IgM/IgG/IgA against SARS-CoV-2 using 31 commercial assays. Antibody response was assessed depending on the onset of symptoms. In addition, 1,996 pre-epidemic serum samples expected to be negative were tested to assess specificity. Results: Rapid tests for qualitative detection of anti-SARS-CoV-2 antibodies (RDTs) achieved 77.4-100%, and ELISA/CLIA (ELISA) assays 58.8-100% for SARS-CoV-2-specific total antibodies (TAb) specificity. From 15 days after onset of symptoms, 13/18 RDT and 8/13 ELISA reached sensitivity > 90%. However, only 4 RDT and 3 ELISA assays fitted both sensitivity (> 90%) and specificity (> 98%) criteria according to French recommendations. Conclusions: Serology may offer valuable information during the course of COVID-19 pandemic, at the condition that commercial assays give reliable results. Contrasted performances were observed among the 31 commercial assays we evaluated, which underlines the importance of independent evaluation before clinical implementation. Funding Statement: This study was funded by the Agence Nationale de Recherche sur le SIDA et les Hepatites Virales (ANRS, AC43)". Declaration of Interests: JM Pawlotsky has served as an advisor and/or a speaker for Abbvie, Gilead, GlaxoSmithKline, Merck, Regulus and Siemens Healthcare. C Vauloup-Fellous served as un expert (rubella and CMV serology) for Abbott Diagnostics, Roche Diagnostics, Siemens Healthcare and DiaSorin. No other authors have any competing interests to declare. Ethics Approval Statement: The study was carried out in accordance with the Declaration of Helsinki. This work was a retrospective non-interventional study with no addition to standard care procedures. Reclassification of biological remnants into research material after completion of the ordered virological tests was approved by the local interventional review board of hospital. According to the French Public Health Code (CSP Article L.1121-1.1) such protocols are exempted from individual informed consent.
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- 2020
13. Prevalence and clinical impact of minority resistant variants in patients failing an integrase inhibitor-based regimen by ultra-deep sequencing
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Eve Todesco, Maxime Grude, Sidonie Lambert-Niclot, A G Marcelin, Nathalie Désiré, Diane Descamps, Gilles Peytavin, Minh Patrick Lê, Christine Katlama, Philippe Flandre, Charlotte Charpentier, Thuy Van Nguyen, Marc Wirden, D. B. Fofana, Laurence Morand-Joubert, Vincent Calvez, Gestionnaire, Hal Sorbonne Université, 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), Service de Virologie [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), Laboratoire de Virologie [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), 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), Service de Virologie [CHU Bichat], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], and Service de Maladies Infectieuses et Tropicales [CHU Pitié-Salpêtrière]
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Adult ,Male ,0301 basic medicine ,Microbiology (medical) ,Paris ,medicine.medical_specialty ,Genotyping Techniques ,[SDV]Life Sciences [q-bio] ,030106 microbiology ,Integrase inhibitor ,HIV Infections ,Drug resistance ,03 medical and health sciences ,chemistry.chemical_compound ,symbols.namesake ,Antiretroviral Therapy, Highly Active ,Internal medicine ,Drug Resistance, Viral ,Prevalence ,medicine ,Humans ,Pharmacology (medical) ,HIV Integrase Inhibitors ,Treatment Failure ,Pharmacology ,Sanger sequencing ,Elvitegravir ,business.industry ,High-Throughput Nucleotide Sequencing ,Middle Aged ,Raltegravir ,Resistance mutation ,[SDV] Life Sciences [q-bio] ,Regimen ,Infectious Diseases ,chemistry ,Dolutegravir ,HIV-1 ,symbols ,Female ,business ,medicine.drug - Abstract
Background Integrase strand transfer inhibitors (INSTIs) are recommended by international guidelines as first-line therapy in antiretroviral-naive and -experienced HIV-1-infected patients. Objectives This study aimed at evaluating the prevalence at failure of INSTI-resistant variants and the impact of baseline minority resistant variants (MiRVs) on the virological response to an INSTI-based regimen. Methods Samples at failure of 134 patients failing a raltegravir-containing (n = 65), an elvitegravir-containing (n = 20) or a dolutegravir-containing (n = 49) regimen were sequenced by Sanger sequencing and ultra-deep sequencing (UDS). Baseline samples of patients with virological failure (VF) (n = 34) and of those with virological success (VS) (n = 31) under INSTI treatment were sequenced by UDS. Data were analysed using the SmartGene platform, and resistance was interpreted according to the ANRS algorithm version 27. Results At failure, the prevalence of at least one INSTI-resistant variant was 39.6% by Sanger sequencing and 57.5% by UDS, changing the interpretation of resistance in 17/134 (13%) patients. Among 53 patients harbouring at least one resistance mutation detected by both techniques, the most dominant INSTI resistance mutations were N155H (45%), Q148H/K/R (23%), T97A (19%) and Y143C (11%). There was no difference in prevalence of baseline MiRVs between patients with VF and those with VS. MiRVs found at baseline in patients with VF were not detected at failure either in majority or minority mutations. Conclusions UDS is more sensitive than Sanger sequencing at detecting INSTI MiRVs at treatment failure. The presence of MiRVs at failure could be important to the decision to switch to other INSTIs. However, there was no association between the presence of baseline MiRVs and the response to INSTI-based therapies in our study.
- Published
- 2018
14. Long-term follow-up of HIV-infected patients on dolutegravir monotherapy
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Lambert Assoumou, Luminita Schneider, Romain Palich, Catherine Blanc, R Agher, A G Marcelin, Marc-Antoine Valantin, Cathia Soulié, Sophie Seang, Roland Tubiana, Gianpiero Tebano, Gilles Peytavin, and Christine Katlama
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0301 basic medicine ,Microbiology (medical) ,medicine.medical_specialty ,Anti-HIV Agents ,Pyridones ,030106 microbiology ,Population ,Human immunodeficiency virus (HIV) ,Integrase inhibitor ,Viremia ,HIV Infections ,medicine.disease_cause ,Piperazines ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Internal medicine ,Oxazines ,medicine ,Humans ,Pharmacology (medical) ,030212 general & internal medicine ,Viral suppression ,HIV Integrase Inhibitors ,education ,Pharmacology ,education.field_of_study ,business.industry ,Retrospective cohort study ,Viral Load ,medicine.disease ,Regimen ,Infectious Diseases ,chemistry ,Dolutegravir ,business ,Heterocyclic Compounds, 3-Ring ,Follow-Up Studies - Abstract
Background In recent years, dolutegravir monotherapy has been explored as a drug-reduced regimen for HIV patients. Methods This was a retrospective observational study, including patients virologically suppressed for ≥6 months, without previous virological failure (VF) under integrase inhibitors (INIs), who had been switched to dolutegravir monotherapy (50 mg/day). The primary aim was to report the proportion of VF at week 48 (W48) and week 96 (W96) of dolutegravir monotherapy. The evolution from baseline to W48 of residual viraemia on ultra-deep sequencing and HIV DNA was also evaluated. Results Sixty-one patients were included. Prior to switching to dolutegravir monotherapy, they had a median (IQR) of 15.4 (6.5–19.9) years of antiretroviral exposure, 5.8 (3.2–10.3) years of viral suppression and 687 (461–848) CD4+ cells/mm3. They remained on dolutegravir monotherapy for a median (IQR) of 100 (29–148) weeks. Forty-two out of 61 patients (68.9%) reached W48 and 32 out of 61 patients (52.5%) reached W96. VF occurred in three patients, with the emergence of INI resistance. VF occurred before W24 and in patients pre-exposed to INIs. At W48, the probability of VF (Kaplan–Meier analysis) was 5.6% (95% CI = 1.8%–16.4%). The same result was obtained at W96. Detectable residual viraemia did not increase and median HIV DNA did not change significantly (2.4 log/106 cells at baseline and 2.3 log/106 cells at W48). Dolutegravir plasma concentration was above the IC90 in 41/41 samples, from 22 patients. Conclusions Long-term follow-up showed a low risk of VF under dolutegravir monotherapy, in a selected population of patients with previous long-term virological suppression and low HIV reservoir.
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- 2019
15. Description clinique et diagnostique sérologique des patients présentant des symptômes persistants après suspicion d’infection à SARS-COV-2
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R. Tubiana, A G Marcelin, B. Abdi, Valérie Pourcher, Christine Katlama, Eric Caumes, G. Monsel, N. Ktorza, Marc-Antoine Valantin, and Sophie Seang
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Gynecology ,2019-20 coronavirus outbreak ,medicine.medical_specialty ,Infectious Diseases ,Coronavirus disease 2019 (COVID-19) ,business.industry ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Medicine ,business ,Article - Abstract
Introduction La persistance d’une symptomatologie chez des patients suspects d’une infection à SARS-COV-2 est fréquente y compris chez des patients sans diagnostic virologique initial. L’organisation d’une consultation dite « post-COVID » initiée en mai 2020 et son évaluation constitue l’objectif de cette étude. Matériels et méthodes Étude rétrospective de cohorte des patients > 18 ans, présentant une histoire clinique compatible avec une infection à SARS-COV-2, une symptomatologie persistante ≥ 30 j du j0 et vus en consultation post-COVID entre mai–juin 2020. Le diagnostic d’infection à SARS-COV-2 a été définie par une RT-PCR SARS-COV-2 positive et/ou une sérologique positive en IgG (Architect, Abbott ; sensibilité 100 % [IC95 : 95,8–100 %] ; spécificité 99,6 % [IC95 : 99,0–99,9 %]). Les variables continues sont présentées en médiane et IQR. L’analyse présentée compare les caractéristiques des patients confirmés au SARS-COV-2 (COVID-19 positif) à ceux non confirmés (COVID-19 négatif). Résultats Un total de 83 patients (71 femmes [86 %], 46 ans [38–52]) ont consulté dans un délai 61 jours (j) (49–78) après le début des symptômes. Les manifestations cliniques persistantes après j30 les plus fréquentes étaient : asthénie/myalgies (n = 58, 70 %), toux (n = 34, 41 %), dyspnée (n = 45, 54 %) et douleur thoracique (n = 43, 52 %). Parmi eux, 32/83 (39 %) avaient eu une PCR SARS-COV-2 positive et 51/83 (61 %) n’avait pas de preuve virologique d’infection. Une sérologie réalisée chez 78 patients (27 avec PCR positive antérieure et 51 sans preuve virologique) montre la présence d’Ac anti-SARS-CoV chez 37/78 (47 %) : 26/27 (97 %) des patients avec PCR initiale positive et 11/51 (22 %) des patients sans preuve virologique initiale. Au total, 43/83 (52 %) patients de la consultation post-COVID ont eu un COVID-19 confirmé. Le groupe COVID-19 positif (n = 43, 33 femmes [77 %], 49 ans [44–59]) était significativement plus âgé (p = 0,005) avec un délai de consultation plus court par rapport au j0 (55 j [45–70] vs 73 j [53–82], p = 0,007) que les COVID-19 négatif (n = 40, 29 femmes [73 %], 42 ans [35–49]) avec à j0, significativement plus souvent de la toux (n = 36 [84 %] vs n = 25 [63 %], p = 0,028), une anosmie/dysgueusie (n = 29 [67 %] vs n = 8 [20 %], p
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- 2020
16. Resistance profile and treatment outcomes in HIV-infected children at virological failure in Benin, West Africa
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Laurence Morand-Joubert, D. B. Fofana, M d'Almeida, Gilles Peytavin, R K Keke, Sidonie Lambert-Niclot, A G Marcelin, B Lafia, L Zohoun-Guidigbi, Cathia Soulié, P M Girard, Gestionnaire, Hal Sorbonne Université, 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), Laboratoire de Virologie [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Université d’Abomey-Calavi = University of Abomey Calavi (UAC), Centre National Hospitalier Universitaire Hubert K. Maga de Cotonou (CNHU-HKM), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Services des Maladies Infectieuses et Tropicales [CHU Saint-Antoine], CHU Saint-Antoine [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), Programme Santé de Lutte contre le Sida (PSLS), Cotonou, Bénin, Service de Virologie [CHU Pitié-Salpêtrière], and CHU Pitié-Salpêtrière [AP-HP]
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0301 basic medicine ,Microbiology (medical) ,Male ,Pediatrics ,medicine.medical_specialty ,Adolescent ,Genotyping Techniques ,Anti-HIV Agents ,[SDV]Life Sciences [q-bio] ,030106 microbiology ,Population ,Integrase inhibitor ,HIV Infections ,Drug resistance ,Virus Replication ,03 medical and health sciences ,Acquired immunodeficiency syndrome (AIDS) ,Antiretroviral Therapy, Highly Active ,Drug Resistance, Viral ,medicine ,Benin ,Humans ,Pharmacology (medical) ,Treatment Failure ,education ,Child ,Genotyping ,Pharmacology ,education.field_of_study ,business.industry ,virus diseases ,Viral Load ,medicine.disease ,CD4 Lymphocyte Count ,[SDV] Life Sciences [q-bio] ,Regimen ,Africa, Western ,Infectious Diseases ,Treatment Outcome ,Child, Preschool ,HIV-1 ,Reverse Transcriptase Inhibitors ,Female ,Dried Blood Spot Testing ,business ,Viral load ,HIV drug resistance - Abstract
Background In Africa a high percentage of HIV-infected children continue to experience HIV treatment failure despite enormous progress. In Benin (West Africa), there are currently no data on HIV drug resistance at failure in paediatric populations. Objectives To assess the frequency and patterns of HIV drug resistance among children with virological ART failures. Methods Dried blood spots from 62 HIV-infected children with virological failure were collected at the paediatric clinic of the National Hospital Center in Cotonou for genotyping and plasma drug concentration determination. Results Characteristics of the population show a median age of 10 years (IQR 6-13) and a median duration on ART of 5 years (IQR 3-7). Viruses from 53 children were successfully amplified. Of these, 76% of patients were on an NNRTI-based regimen and 24% on a boosted PI-based regimen. NRTI, NNRTI and dual-class resistance was present in 71%, 84% and 65% of cases, respectively. Only 4% of the children had major resistance mutations to PIs and none had major resistance mutations to integrase inhibitors. Among the participants, 25% had undetectable antiretroviral concentrations. Conclusions Our results showed that the development of drug resistance could be one of the main consequences of high and continuous viral replication in HIV-infected children in Benin. Thus, inadequate attention to monitoring lifelong ART in children may prevent achievement of the goal of the United Nations Program on HIV and AIDS (UNAIDS) of 90% viral suppression among patients receiving ART.
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- 2018
17. Performance of genotypic algorithms for predicting tropism for HIV-1 CRF01_AE recombinant
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Samira Fafi-Kremer, Laurence Morand-Joubert, Audrey Mirand, Vincent Calvez, Cathia Soulié, Mary-Anne Trabaud, A G Marcelin, Jacqueline Cottalorda, Anne Signori-Schmuck, S. Berger, Julia Dina, Coralie Pallier, Véronique Avettand-Fenoel, Brigitte Montes, Pantxika Bellecave, Karen Zafilaza, Charlotte Charpentier, L. Le Guen, Sabine Yerly, Catherine Roussel, Corinne Amiel, Sophie Sayon, Service de Virologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], 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), Service de chirurgie pédiatrique [Hôpital Lapeyronie-Arnaud de Villeneuve], Hôpital Lapeyronie [Montpellier] (CHU), Microbiologie cellulaire et moléculaire et pathogénicité (MCMP), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Laboratoire de Virologie [Strasbourg], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Equipe de Recherche en Physico-Chimie et Biotechnologie (ERPCB), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), UR 0420 - Station de pathologie végétale, Laboratoire de pathologie forestière, Institut National de la Recherche Agronomique (INRA)-Institut National de la Recherche Agronomique (INRA), Neuroimagerie cognitive (LCogn), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de biologie structurale des interactions entre virus et cellule hôte, Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS), CHU Clermont-Ferrand, Laboratoire Microorganismes : Génome et Environnement - Clermont Auvergne (LMGE), Université Clermont Auvergne (UCA)-Centre National de la Recherche Scientifique (CNRS), Saint-Gobain Recherche (SGR), SAINT-GOBAIN, CHU Pitié-Salpêtrière [APHP], Service de virologie [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), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Biologie structurale des interactions entre virus et cellule hôte (UVHCI), European Molecular Biology Laboratory [Grenoble] (EMBL)-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF), Laboratoire Microorganismes : Génome et Environnement (LMGE), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Microbiologie Fondamentale et Pathogénicité (MFP), Université Joseph Fourier - Grenoble 1 (UJF)-European Molecular Biology Laboratory [Grenoble] (EMBL)-Centre National de la Recherche Scientifique (CNRS), Saint-Gobain, and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
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0301 basic medicine ,Genotype ,Genotyping Techniques ,viruses ,Concordance ,030106 microbiology ,Human immunodeficiency virus (HIV) ,HIV Infections ,ddc:616.07 ,HIV Envelope Protein gp120 ,Biology ,medicine.disease_cause ,[SDV.MP.PRO]Life Sciences [q-bio]/Microbiology and Parasitology/Protistology ,law.invention ,03 medical and health sciences ,0302 clinical medicine ,law ,Virology ,HIV tropism ,medicine ,Humans ,False Positive Reactions ,030212 general & internal medicine ,Tropism ,ComputingMilieux_MISCELLANEOUS ,virus diseases ,Viral Load ,[SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology ,CD4 Lymphocyte Count ,3. Good health ,Viral Tropism ,Infectious Diseases ,[SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology ,HIV-1 ,Recombinant DNA ,RNA, Viral ,France ,False positive rate ,Viral load ,Algorithm ,Algorithms ,Switzerland ,[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology - Abstract
Objectives There is no consensus about the performances of genotypic rules for predicting HIV-1 non-B subtype tropism. Three genotypic methods were compared for CRF01_AE HIV-1 tropism determination. Methods The V3 env region of 207 HIV-1 CRF01_AE and 178 B subtypes from 17 centers in France and 1 center in Switzerland was sequenced. Tropism was determined by Geno2Pheno algorithm with false positive rate (FPR) 5% or 10%, the 11/25 rule or the combined criteria of the 11/25, net charge rule and NXT/S mutations. Results Overall, 72.5%, 59.4%, 86.0%, 90.8% of the 207 HIV-1 CRF01_AE were R5-tropic viruses determined by Geno2pheno FPR5%, Geno2pheno FPR10%, the combined criteria and the 11/25 rule, respectively. A concordance of 82.6% was observed between Geno2pheno FPR5% and the combined criteria for CRF01_AE. The results were nearly similar for the comparison between Geno2pheno FPR5% and the 11/25 rule. More mismatches were observed when Geno2pheno was used with the FPR10%. Neither HIV viral load, nor current or nadir CD4 was associated with the discordance rate between the different algorithms. Conclusion Geno2pheno predicted more X4-tropic viruses for this set of CRF01_AE sequences than the combined criteria or the 11/25 rule alone. For a conservative approach, Geno2pheno FPR5% seems to be a good compromise to predict CRF01_AE tropism.
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- 2018
18. Dynamics of drug resistance-associated mutations in HIV-1 DNA reverse transcriptase sequence during effective ART
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Anne Simon, A G Marcelin, Sophie Sayon, Calvez, R Agher, Marc-Antoine Valantin, Cathia Soulié, Thuy Van Nguyen, A Nouchi, and Christine Katlama
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0301 basic medicine ,Microbiology (medical) ,Male ,Anti-HIV Agents ,030106 microbiology ,Etravirine ,Drug resistance ,Biology ,Emtricitabine ,Evolution, Molecular ,03 medical and health sciences ,chemistry.chemical_compound ,symbols.namesake ,Drug Resistance, Viral ,Nitriles ,medicine ,Humans ,Pharmacology (medical) ,Pharmacology ,Sanger sequencing ,Rilpivirine ,Lamivudine ,Middle Aged ,Virology ,Reverse transcriptase ,HIV Reverse Transcriptase ,Pyridazines ,Infectious Diseases ,Pyrimidines ,chemistry ,DNA, Viral ,Mutation ,symbols ,HIV-1 ,RNA, Viral ,Female ,DNA ,medicine.drug - Abstract
Objectives To investigate the dynamics of HIV-1 variants archived in cells harbouring drug resistance-associated mutations (DRAMs) to lamivudine/emtricitabine, etravirine and rilpivirine in patients under effective ART free from selective pressure on these DRAMs, in order to assess the possibility of recycling molecules with resistance history. Patients and methods We studied 25 patients with at least one DRAM to lamivudine/emtricitabine, etravirine and/or rilpivirine identified on an RNA sequence in their history and with virological control for at least 5 years under a regimen excluding all drugs from the resistant class. Longitudinal ultra-deep sequencing (UDS) and Sanger sequencing of the reverse transcriptase region were performed on cell-associated HIV-1 DNA samples taken over the 5 years of follow-up. Results Viral variants harbouring the analysed DRAMs were no longer detected by UDS over the 5 years in 72% of patients, with viruses susceptible to the molecules of interest found after 5 years in 80% of patients with UDS and in 88% of patients with Sanger. Residual viraemia with
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- 2017
19. Soluble biomarkers of immune activation and inflammation in HIV infection: impact of 2 years of effective first-line combination antiretroviral therapy
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Slim Fourati, Amélie Guihot, Fabienne Caby, Suhaib Hattab, Marguerite Guiguet, Guislaine Carcelain, Christine Katlama, A G Marcelin, Dominique Costagliola, and Brigitte Autran
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Cart ,medicine.medical_specialty ,business.industry ,Health Policy ,CD14 ,Monocyte ,Inflammation ,Odds ratio ,Logistic regression ,Gastroenterology ,Monokine ,Infectious Diseases ,medicine.anatomical_structure ,Internal medicine ,Immunology ,Medicine ,Biomarker (medicine) ,Pharmacology (medical) ,medicine.symptom ,business - Abstract
Objectives The aim of the study was to assess the impact of rapid and sustained viral control produced by combination antiretroviral therapy (cART) on HIV-associated immune activation and inflammation. Methods In this longitudinal observational study, we examined changes in interleukin-6 (IL-6), interferon-γ-inducible protein-10 (IP-10), monokine induced by interferon-γ (MIG) and soluble CD14 (sCD14) levels during 2 years of effective first-line cART. Biomarker levels before and after cART were compared with those observed in healthy subjects, using the Wilcoxon signed rank test. Elevated biomarker levels were defined with respect to values for healthy subject (mean + 2 standard deviations). Factors associated with persistently elevated biomarker levels after 2 years of cART were identified by logistic regression. Results We included in the study 139 patients with a median HIV-1 RNA level of 4.8 log10 HIV-1 RNA copies/mL and a median CD4 cell count of 294 cells/μL at cART initiation [day 0 (D0)]. At D0, all biomarker levels were higher than in healthy subjects (P 75% of patients. In contrast, sCD14 levels did not change significantly (0.18 × 106 pg/mL; P = 0.102) and remained elevated. Older age was associated with elevated levels of IP-10 [odds ratio (OR) 1.60 per 10 years older; P = 0.047] and MIG (OR 1.92 per 10 years older; P = 0.007) after 2 years of cART. Conclusions The rapid and sustained viral suppression produced by first-line cART reduced IL-6, IP-10 and MIG to normal levels, while sCD14, a marker of monocyte activation, remained elevated. High levels of IP-10 and MIG tended to persist in older patients.
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- 2015
20. Efficacy of etravirine combined with darunavir or other ritonavir-boosted protease inhibitors in HIV-1-infected patients: an observational study using pooled European cohort data
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Francesca Ceccherini-Silberstein, Vincent Calvez, Huldrych F. Günthard, A Cozzi-Lepri, Anders Sönnerborg, A G Marcelin, Mark T. Nelson, Rolf Kaiser, Steven Nijs, M Mercedes Santoro, Roger Paredes, Jens D Lundgren, Jesper Grarup, C-F Perno, Johan Vingerhoets, R Bateson, Lotke Tambuyzer, Philippe Flandre, A Hoogstoel, Ludo Lavreys, Magda Opsomer, Francesca Incardona, Bruno Ledergerber, and B Clotet
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medicine.medical_specialty ,business.industry ,Health Policy ,Etravirine ,Odds ratio ,Pharmacology ,Confidence interval ,Regimen ,Infectious Diseases ,Internal medicine ,Cohort ,medicine ,Pharmacology (medical) ,Ritonavir ,business ,Viral load ,Darunavir ,medicine.drug - Abstract
OBJECTIVES This observational study in antiretroviral treatment-experienced, HIV-1-infected adults explored the efficacy of etravirine plus darunavir/ritonavir (DRV group; n = 999) vs. etravirine plus an alternative boosted protease inhibitor (other PI group; n = 116) using pooled European cohort data. METHODS Two international (EuroSIDA; EUResist Network) and five national (France, Italy, Spain, Switzerland and UK) cohorts provided data (collected in 2007-2012). Stratum-adjusted (for confounding factors) Mantel-Haenszel differences in virological responses (viral load < 50 HIV-1 RNA copies/mL) and odds ratios (ORs) with 95% confidence intervals (CIs) were derived. RESULTS Baseline characteristics were balanced between groups except for previous use of antiretrovirals (≥ 10: 63% in the DRV group vs. 49% in the other PI group), including previous use of at least three PIs (64% vs. 53%, respectively) and mean number of PI resistance mutations (2.3 vs. 1.9, respectively). Week 24 responses were 73% vs. 75% (observed) and 49% vs. 43% (missing = failure), respectively. Week 48 responses were 75% vs. 73% and 32% vs. 30%, respectively. All 95% CIs around unadjusted and adjusted differences encompassed 0 (difference in responses) or 1 (ORs). While ORs by cohort indicated heterogeneity in response, for pooled data the difference between unadjusted and adjusted for cohort ORs was small. CONCLUSIONS These data do not indicate a difference in response between the DRV and other PI groups, although caution should be applied given the small size of the other PI group and the lack of randomization. This suggests that the efficacy and virology results from DUET can be extrapolated to a regimen of etravirine with a boosted PI other than darunavir/ritonavir.
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- 2015
21. Darunavir/ritonavir monotherapy at a low dose (600/100 mg/day) in HIV-1-infected individuals with suppressed HIV viraemia
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Ruxandra Calin, Fabienne Caby, Gilles Peytavin, Marc-Antoine Valantin, Lambert Assoumou, Luminita Schneider, Sophie Seang, Minh Patrick Lê, Thuy Van Nguyen, A G Marcelin, Cathia Soulié, Roland Tubiana, and Christine Katlama
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0301 basic medicine ,Microbiology (medical) ,Male ,medicine.medical_specialty ,Sustained Virologic Response ,Anti-HIV Agents ,030106 microbiology ,Human immunodeficiency virus (HIV) ,HIV Infections ,Drug resistance ,medicine.disease_cause ,Gastroenterology ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Drug Resistance, Viral ,medicine ,Humans ,Pharmacology (medical) ,030212 general & internal medicine ,Dose Reduced ,Darunavir ,Pharmacology ,Ritonavir ,business.industry ,virus diseases ,Lopinavir ,Middle Aged ,Viral Load ,Atazanavir ,Infectious Diseases ,Treatment Outcome ,HIV-1 ,Female ,business ,Viral load ,medicine.drug - Abstract
Background Darunavir/ritonavir is a potent PI with a high genetic barrier and pharmacological robustness favourably investigated as monotherapy. Whether darunavir could be dose reduced in the context of monotherapy deserves investigation. Methods Patients with HIV suppressed viraemia (plasma viral load
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- 2017
22. Disparities in HIV-1 transmitted drug resistance detected by ultradeep sequencing between men who have sex with men and heterosexual populations
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Sophie Sayon, M. Bertine, A G Marcelin, Marc Wirden, Eve Todesco, Christine Katlama, Alexandre Storto, Nathalie Désiré, Thuy Van Nguyen, Vincent Calvez, Maxime Grude, Diane Descamps, Y. Yazdanpanah, C. Charpentier, 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), Service de virologie [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), 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 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), Services de Maladies Infectieuses et Tropicales [CHU Bichat], AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service des maladies infectieuses et tropicales [CHU Pitié-Salpêtrière], Service de Virologie [CHU Pitié-Salpêtrière], Service de Maladies Infectieuses et Tropicales [CHU Pitié-Salpêtrière], HAL-UPMC, Gestionnaire, and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
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0301 basic medicine ,Adult ,Male ,Anti-HIV Agents ,030106 microbiology ,Human immunodeficiency virus (HIV) ,HIV Infections ,Drug resistance ,medicine.disease_cause ,Deep sequencing ,Men who have sex with men ,03 medical and health sciences ,symbols.namesake ,Risk groups ,[SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases ,Drug Resistance, Viral ,Medicine ,Humans ,Pharmacology (medical) ,Homosexuality, Male ,Heterosexuality ,Sanger sequencing ,Transmission (medicine) ,business.industry ,Sequence Analysis, RNA ,Health Policy ,High-Throughput Nucleotide Sequencing ,virus diseases ,Antiretroviral therapy ,Virology ,3. Good health ,030104 developmental biology ,Infectious Diseases ,[SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie ,Mutation ,symbols ,[SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases ,HIV-1 ,Reverse Transcriptase Inhibitors ,Female ,[SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie ,business - Abstract
International audience; Objectives: Transmitted drug resistance (TDR) can impair the response to first-line antiretroviral therapy. In treatment-naïve patients chronically infected with HIV type 1 (HIV-1), it was previously shown through Sanger sequencing that TDR was more common in men who have sex with men (MSM) than in other transmission risk groups. We aimed to compare two HIV-1 transmission groups in terms of the presence of TDR mutations.Methods: We investigated, through Sanger sequencing and ultradeep sequencing (UDS), the presence of resistance mutations, both in majority (> 20%) and in minority (1−20%) proportions, in 70 treatment-naïve MSM and 70 treatment-naïve heterosexual patients who recently screened positive for HIV-1.Results: The global prevalence of TDR was not significantly different between the two groups, either by Sanger or by UDS. Nevertheless, a higher frequency of nucleoside reverse transcriptase inhibitor TDR was observed among heterosexual patients (P = 0.04). There was also a trend for a higher frequency of TDR among MSM infected with HIV-1 subtype B compared with MSM infected with HIV-1 non-B subtypes (P = 0.06).Conclusions:Ultradeep sequencing UDS allowed sensitive monitoring of TDR, and highlighted some disparities between transmission groups.
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- 2017
23. Rapid plasma viral suppression in naive HIV-infected patients with high CD4 cells and low viraemia initiating a dual nucleoside reverse transcriptase inhibitor strategy: a proof-of-concept study
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Roland Tubiana, Luminita Schneider, Slim Fourati, A G Marcelin, Dominique Costagliola, Catherine Blanc, Y. Keita, Marc-Antoine Valantin, Sophie Seang, Ruxandra Calin, Fabienne Caby, Vincent Calvez, Christine Katlama, and Sidonie Lambert-Niclot
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Adult ,CD4-Positive T-Lymphocytes ,Male ,Microbiology (medical) ,Anti-HIV Agents ,HIV Infections ,Viremia ,Emtricitabine ,Peripheral blood mononuclear cell ,Virus ,Nucleoside Reverse Transcriptase Inhibitor ,Plasma ,Abacavir ,medicine ,Humans ,Pharmacology (medical) ,Pharmacology ,business.industry ,Lamivudine ,Nucleosides ,Middle Aged ,Viral Load ,medicine.disease ,Virology ,CD4 Lymphocyte Count ,Treatment Outcome ,Infectious Diseases ,Reverse Transcriptase Inhibitors ,Drug Therapy, Combination ,Female ,business ,Viral load ,medicine.drug - Abstract
OBJECTIVES To evaluate whether a dual nucleoside reverse transcriptase inhibitor (NRTI) strategy can control HIV replication in antiviral therapy (ART)-naive HIV-infected patients with a high CD4 cell count and a low viral load (VL). METHODS This observational study included all HIV-infected treatment-naive patients with a CD4 cell count >300 cells/mm(3), a plasma HIV RNA between 1000 copies/mL and 30,000 copies/mL and wild-type virus who initiated dual NRTI ART between January 2008 and December 2012. HIV RNA and CD4 cell count were assessed at Day 0, Week (W) 4, W12, W24 and W48. The primary endpoint was the proportion of patients with a plasma VL (pVL)
- Published
- 2014
24. NRTI-sparing regimens yield higher rates of drug resistance than NRTI-based regimens for HIV-1 treatment
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A. G. Marcelin, Charlotte Charpentier, Benoit Visseaux, Marc Wirden, Bernard Masquelier, Diane Descamps, Vincent Calvez, Cathia Soulié, and Laurence Morand-Joubert
- Subjects
Microbiology (medical) ,business.industry ,Immunology ,Human immunodeficiency virus (HIV) ,virus diseases ,Integrase inhibitor ,Drug resistance ,Raltegravir ,medicine.disease_cause ,Microbiology ,Virology ,immune system diseases ,Immunology and Allergy ,Medicine ,Initial treatment ,Protease inhibitor (pharmacology) ,In patient ,business ,Viral load ,medicine.drug - Abstract
To treat human immunodeficiency virus (HIV)-infected patients, international guidelines recommend the combination of two nucleos(t)ide reverse transcriptase inhibitors [N(t)RTIs] and a third agent [non-NRTI (NNRTI), boosted protease inhibitor (r/PI) or integrase inhibitor (INI)] for initial treatment. The objective of this study was to compare the selection of resistance to antiretrovirals (ARVs) for regimens containing or lacking N(t)RTIs in patients experiencing their first virological failure. Eligible patients had a first virological failure, defined as the occurrence of two consecutive HIV plasma viral loads ≥50copies/mL. Genotypic resistance testing was performed at the time of virological failure (on the second sample with detectable viral load ≥50copies/mL) in patients failing regimens of N(t)RTIs+r/PI or NNRTI or INI, r/PI+NNRTI or INI, and INI+NNRTI. Among 434 virological failures analysed, resistance testing results were available in 416 cases (95.9%). Higher rates of drug resistance were observed in patients receiving N(t)RTI-sparing regimens. When the combination of N(t)RTIs+r/PI was used, PIs protect themselves and the associated N(t)RTIs from the selection of resistance; however, this was not observed with the NNRTI+r/PI combination. The same phenomenon was observed for raltegravir: when used in combination with N(t)RTIs, INI resistance mutations were less frequently selected compared with its use in combination with PIs or NNRTIs. In conclusion, regimens of the ARV classes combined impact the frequency of resistance development. Lower resistance is observed for N(t)RTI-based regimens, with more therapeutic options for subsequent regimens after failure.
- Published
- 2014
25. High level of HIV-1 resistance in patients failing long-term first-line antiretroviral therapy in Mali
- Author
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Aliou Baldé, A G Marcelin, Sidonie Lambert-Niclot, Slim Fourati, B. Sangaré, Vincent Calvez, Fodié Diallo, Cathia Soulié, Mariam Sylla, O. Koita, Almoustapha Issiaka Maiga, Zaina Ait-Arkoub, Mamadou Cisse, Issouf Alassane Maiga, and D. B. Fofana
- Subjects
Adult ,Male ,Microbiology (medical) ,medicine.medical_specialty ,Adolescent ,Genotype ,Genotyping Techniques ,Anti-HIV Agents ,Mutation, Missense ,Etravirine ,HIV Infections ,Microbial Sensitivity Tests ,Drug resistance ,Mali ,Young Adult ,chemistry.chemical_compound ,Antiretroviral Therapy, Highly Active ,Internal medicine ,Drug Resistance, Viral ,medicine ,Humans ,Pharmacology (medical) ,Treatment Failure ,Pharmacology ,Hepatitis ,Reverse-transcriptase inhibitor ,business.industry ,Middle Aged ,medicine.disease ,Virology ,HIV Reverse Transcriptase ,Reverse transcriptase ,Regimen ,Infectious Diseases ,chemistry ,Rilpivirine ,HIV-1 ,RNA, Viral ,Female ,business ,Viral load ,medicine.drug - Abstract
OBJECTIVES In resource-limited settings, few data are available on virological failure after long-term first-line antiretroviral therapy. This study characterized the genotypic resistance patterns at the time of failure after at least 36 months of a first-line regimen in Mali, West Africa. METHODS Plasma samples from 84 patients who were receiving first-line antiretroviral treatment and with an HIV-1 RNA viral load (VL) >1000 copies/mL were analysed. Genotypic resistance testing was performed and HIV-1 drug resistance was interpreted according to the latest version of the National Agency for HIV and Hepatitis Research algorithm. RESULTS At the time of resistance testing, patients had been treated for a median of 60 months (IQR 36-132 months) and had a median CD4 cell count of 292 cells/mm(3) (IQR 6-1319 cells/mm(3)), a median HIV-1 RNA level of 28266 copies/mL (IQR 1000-2 93 495 copies/mL) and a median genotypic susceptibility score of 1 (IQR 1-4). The prevalence of nucleoside reverse transcriptase inhibitor (NRTI) and non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance mutations was 78% and 82%, respectively. Viruses were resistant to at least one drug in 92% of cases. Although etravirine and rilpivirine were not used in the first-line regimens, viruses were resistant to etravirine in 34% of cases and to rilpivirine in 49% of cases. The treatment duration, median number of NRTI and NNRTI mutations and some reverse transcriptase mutations (T215Y/F/N, L210W, L74I, M41L and H221Y) were associated with the VL at virological failure. CONCLUSIONS This study demonstrated a high level of resistance to NRTIs and NNRTIs, compromising second-generation NNRTIs, for patients who stayed on long-term first-line regimens. It is crucial to expand the accessibility of virological testing in resource-limited settings to limit the expansion of resistance and preserve second-line treatment efficacy.
- Published
- 2014
26. HIV, HBV and HCV screening practices in oncology: A cross-sectional interregional survey
- Author
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A G Marcelin, J-P. Spano, Caroline Solas, Alain Makinson, M. Taouqi, S. Bregigeon, Marianne Veyri, Isabelle Poizot-Martin, M. Pibarot, and Sylvain Choquet
- Subjects
medicine.medical_specialty ,business.industry ,Human immunodeficiency virus (HIV) ,virus diseases ,Cancer ,HIV screening ,Hematology ,Hiv testing ,medicine.disease ,medicine.disease_cause ,digestive system diseases ,Oncology ,Family medicine ,Health care ,medicine ,business - Abstract
Background HIV screening is recommended at time of cancer diagnosis. Moreover, HBV screening, is recommended during immunotherapy due to its risk of reactivation. Furthermore, HCV screening, before using immunotherapy is justified by the prevalence of dysimmune disorders during HCV infection. The main objective of this survey was to evaluate screening practices for HIV, HBV and HCV in cancer patients. Methods A cross-sectional study carried- out across 16 French regions between 25/10/2018 and 31/12/2018, evaluating performance of HIV, HBV and HCV systematic screening at time of cancer diagnosis and/or before immunotherapy. An electronic questionnaire was sent to participants in multidisciplinary concertation meetings. Results The responses of 290 participants (including 101 surgeons, 61 organ specialists, 50 oncologists, 30 radiotherapists, 21 hematologists and 13 general practitioners) were analyzed. Of the 16 regions targeted, 8 of them are represented by 160 participants (55%). A systematic screening for HIV, HBV and HCV at time of cancer diagnosis was reported by 59 (20%), 66 (23%) and 63 (22%) respondents, respectively. A screening on a case by case for HIV, HBV and HCV was reported by 113, 103 and 102 respondents, respectively while 117 respondents stated to never prescribe HIV testing (40%), 121, HBV testing (42%) and 125 HCV testing (43%). Before immunotherapy, 122 respondents stated that they were not concerned and 89 routinely screened for HIV (31%), 97 for HBV (33%) and 94 for HCV (32%). A screening on a case by case for HIV, HBV, and HCV was reported by 38, 36 and 34 respondents, respectively while 40 respondents stated to never prescribe HIV testing (14%), 34, HBV testing (12%) and 39, HCV testing (13%). Conclusions This survey highlights the insufficiency of HIV, HBV and HCV systematic screening at time of cancer diagnosis and/or before immunotherapy. There is a need to raise awareness about the importance of systematic screening in health care providers. Legal entity responsible for the study The authors. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest.
- Published
- 2019
27. Plasma concentrations of maraviroc and raltegravir after dual therapy in patients with long-term suppressed viraemia: ROCnRAL ANRS 157 study
- Author
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B. Hoen, P. Bourse, P. Leclercq, Lambert Assoumou, X. Rey-Coquais, J. P. Aboulker, P. Morlat, L. Chablais, J. M. Molina, C. Blanc, Claudine Duvivier, J. Reynes, V. Calvez, M. Shoai-Tehrani, F. Durand, P. Mercié, A. Makinson, F. Raffi, A. Canestri, C. Katlama, S. Gerberon, Gilles Peytavin, A. Cheret, A. Simon, S. Dominguez, C. Brochier, S. Scerra, J.-P. Bastard, Y. Dudoit, A.-S. Ritleng, I. Poizot Martin, S. Kolta, C. Soulié, S. Caldato, C. Lupin, Marc-Antoine Valantin, F. Touam, Y. Levy, N. Velazquez, O. Faucher, Minh Patrick Lê, S. Couffin Cadiergues, A G Marcelin, G. Pialoux, S. Bonne, V. Thoirain, J. Saillard, P. Geneau de la Marliere, Diane Ponscarme, Christine Katlama, C. Debreux, J. Capeau, M.-C. Marien, C. Crisol, K. Koffi, Vincent Calvez, H. Hue, H. Fisher, Cathia Soulié, L. Schneider, C. Lemarchand, L. Cotte, M.-J. Dulucq, C. Chesnel, D. Ponscarme, Anne-Geneviève Marcelin, L. Assoumou, Julie Chas, C. Haffner-Mauvais, C. Duvivier, L. Cuzin, Dominique Costagliola, J. Chas, and Marc Antoine Valantin
- Subjects
Pharmacology ,Microbiology (medical) ,medicine.medical_specialty ,business.industry ,Raltegravir ,Gastroenterology ,Term (time) ,chemistry.chemical_compound ,Infectious Diseases ,chemistry ,Internal medicine ,Plasma concentration ,medicine ,Pharmacology (medical) ,In patient ,Dual therapy ,business ,Maraviroc ,medicine.drug - Published
- 2015
28. Dual Therapy With Lamivudine + Protease Inhibitor During Pregnancy for Prevention of Mother-to-Child Transmission of HIV-1
- Author
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Smaranda S, Gliga, Cyril O, Clavel, Anne F, Alix, Marc, Dommergues, Marc A, Dommergues, Frederique, Quetin, Anne G, Marcelin, Luminita, Schneider, Hind, Stitou, Ruxandra, Calin, Fabienne, Caby, Marc A, Valantin, Christine, Katlama, and Roland, Tubiana
- Subjects
Adult ,Anti-HIV Agents ,Treatment outcome ,HIV Infections ,Plasma ,Pregnancy ,medicine ,Humans ,HIV Protease Inhibitor ,Pharmacology (medical) ,Protease inhibitor (pharmacology) ,Pregnancy Complications, Infectious ,Dual therapy ,business.industry ,Infant, Newborn ,Prevention of mother to child transmission ,Lamivudine ,HIV Protease Inhibitors ,Viral Load ,medicine.disease ,Virology ,Infectious Disease Transmission, Vertical ,Treatment Outcome ,Infectious Diseases ,HIV-1 ,Drug Therapy, Combination ,Female ,business ,Viral load ,medicine.drug - Published
- 2013
29. Expression pattern of the CXCL12/CXCR4-CXCR7 trio in Kaposi sarcoma skin lesions
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A Desnoyer, Valérie Pourcher, Claire Deback, Nicolas Dupin, A. Carlotti, Gilles Peytavin, F Boué, Françoise Gaudin, A G Marcelin, Lambert Assoumou, and Karl Balabanian
- Subjects
0301 basic medicine ,Adult ,Male ,Vascular Endothelial Growth Factor A ,Pathology ,medicine.medical_specialty ,Chemokine ,Receptors, CXCR4 ,Skin Neoplasms ,Angiogenesis Inhibitors ,Dermatology ,CXCR4 ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Antigen ,medicine ,Biomarkers, Tumor ,Humans ,Antigens, Viral ,Lenalidomide ,Sarcoma, Kaposi ,Receptors, CXCR ,biology ,business.industry ,Nuclear Proteins ,medicine.disease ,Pathophysiology ,Chemokine CXCL12 ,Thalidomide ,Vascular endothelial growth factor ,030104 developmental biology ,chemistry ,030220 oncology & carcinogenesis ,Case-Control Studies ,biology.protein ,Biomarker (medicine) ,Immunohistochemistry ,Female ,Sarcoma ,business - Abstract
Recent studies have independently implicated the chemokine CXCL12 and its receptors, CXCR4 and CXCR7, in the pathophysiology of Kaposi sarcoma (KS).We investigated whether the CXCL12/CXCR4-CXCR7 protein trio could constitute KS biomarkers.Endothelial and spindle cells positive for CXCL12/CXCR4-CXCR7, human herpesvirus-8 latency-associated nuclear antigen (LANA), Ki67 antigen (proliferation) and vascular endothelial growth factor (VEGF) were quantitated in skin lesions from patients with AIDS-associated KS, patients with classic KS and patients with angiomas, using immunohistochemistry and quantitative image analysis (16, 21 and 20 skin lesions, respectively). Plasma CXCL12 concentrations were measured by enzyme-linked immunosorbent assay from 20 patients with AIDS-KS, 12 HIV-infected patients without KS and 13 healthy donors' samples.Cells positive for CXCL12, CXCR4, CXCR7, LANA, Ki67 and VEGF were significantly enriched in patients with AIDS-associated KS and classic KS vs. angiomas (P0·001), and in nodular vs. macular/papular KS lesions (P0·05). CXCL12, CXCR4 and CXCR7 detection correlated with LANA, Ki67 and VEGF detection (r0·4; P0·05). However, plasma CXCL12 concentrations did not differ between patients with AIDS-associated KS, HIV-infected patients without KS, and healthy donors.The CXCL12/CXCR4-CXCR7 trio is upregulated in KS and correlates with KS pathophysiological markers and the severity of skin lesions. Histological assessment of the CXCL12 axis could serve as a valuable biomarker for KS diagnosis and progression.
- Published
- 2016
30. Performance of genotypic algorithms for predicting tropism of HIV-1CRF02_AG subtype
- Author
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A G Marcelin, N. Boukli, Pierre-Marie Girard, Sidonie Lambert-Niclot, Sophie Sayon, Anne Simon, Vincent Calvez, Cathia Soulié, Marc Wirden, D. B. Fofana, Laurence Morand-Joubert, Christine Katlama, 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 Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de médecine interne [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service des maladies infectieuses et tropicales [CHU Pitié-Salpêtrière], and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
- Subjects
0301 basic medicine ,Genotype ,Concordance ,030106 microbiology ,Human immunodeficiency virus (HIV) ,HIV Infections ,HIV Envelope Protein gp120 ,Biology ,medicine.disease_cause ,03 medical and health sciences ,Receptors, HIV ,Genotypic prediction ,Virology ,HIV tropism ,medicine ,Humans ,Non B subtype ,Tropism ,Computational Biology ,virus diseases ,Viral Load ,Peptide Fragments ,CD4 Lymphocyte Count ,3. Good health ,Viral Tropism ,Phenotype ,Infectious Diseases ,[SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology ,HIV-1 ,Tissue tropism ,RNA, Viral ,False positive rate ,Algorithm ,Viral load ,Algorithms - Abstract
Background Several genotypic rules for predicting HIV-1 non-B subtypes tropism are commonly used, but there is no consensus about their performances. Objectives Three genotypic methods were compared for CRF02_AG HIV-1 tropism determination. Study design V3 env region of 178HIV-1 CRF02_AG from Pitie-Salpetriere and Saint-Antoine Hospitals was sequenced from plasma HIV-1 RNA. HIV-1 tropism was determined by Geno2Pheno algorithm, false positive rate (FPR) 5% or 10%, the 11/25 rule or the combined criteria of the 11/25 and net charge rule. Results A concordance of 91.6% was observed between Geno2pheno 5% and the combined criteria. The results were nearly similar for the comparison between Geno2pheno 5% and the 11/25 rule. More mismatches were observed when Geno2pheno was used with the FPR 10%. A lower nadir CD4 cell count was associated with a discordance of tropism prediction between Geno2pheno 5% and the combined criteria or the 11/25 rule ( p = 0.02 and p = 0.03, respectively). A lower HIV-1 viral load was associated with some discordance for the comparison of Geno2pheno 10% and the combined rule ( p = 0.02). Conclusion Geno2pheno FPR 5% or 10% predicted more X4-tropic viruses for this set of CRF02_AG sequences than the combined criteria or the 11/25 rule alone. Furthermore, Geno2pheno FPR 5% was more concordant with the 11/25 rule and the combined rule than Geno2pheno 10% to predict HIV-1 tropism. Overall, Geno2pheno 5% could be used to predict CRF02_AG tropism as well as other genotypic rules.
- Published
- 2016
31. Dolutegravir as monotherapy in HIV-1-infected individuals with suppressed HIV viraemia
- Author
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Catherine Blanc, A G Marcelin, E. Valdenassi, Myriam Kirstetter, Roland Tubiana, Christine Katlama, A. Denis, Thuy Van Nguyen, Vincent Calvez, Gilles Peytavin, Cathia Soulié, Fabienne Caby, Marc-Antoine Valantin, Luminita Schneider, 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 Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), 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), Laboratoire de Toxicologie et Pharmacocinétique, Service de Pharmacie, AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service des maladies infectieuses et tropicales [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Service de virologie [CHU Pitié-Salpêtrière]
- Subjects
0301 basic medicine ,Microbiology (medical) ,Adult ,Male ,medicine.medical_specialty ,Sustained Virologic Response ,Pyridones ,030106 microbiology ,Human immunodeficiency virus (HIV) ,Integrase inhibitor ,HIV Infections ,medicine.disease_cause ,Piperazines ,Maintenance Chemotherapy ,03 medical and health sciences ,chemistry.chemical_compound ,[SDV.SP.MED]Life Sciences [q-bio]/Pharmaceutical sciences/Medication ,[SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases ,Internal medicine ,Oxazines ,medicine ,Potency ,Humans ,Pharmacology (medical) ,HIV Integrase Inhibitors ,Genotyping ,Pharmacology ,business.industry ,Elvitegravir ,Middle Aged ,Viral Load ,Virology ,3. Good health ,Regimen ,Infectious Diseases ,Treatment Outcome ,chemistry ,Dolutegravir ,HIV-1 ,Female ,business ,Viral load ,Heterocyclic Compounds, 3-Ring ,medicine.drug - Abstract
International audience; Background Reducing drug burden is a key challenge for achieving lifelong suppressive HIV therapy. Dolutegravir, with a high potency, long half-life and high genetic barrier, offers potential for monotherapy.Methods This observational single-centre study enrolled all patients with HIV RNA (viral load) 350 cells/mm3 and with no failure under integrase inhibitor therapy who had switched from suppressive ART to dolutegravir monotherapy (50 mg/day). Primary outcome was proportion of patients with viral load
- Published
- 2016
32. Factors associated with virological response to a switch regimen containing maraviroc for antiretroviral-experienced HIV-1-infected patients
- Author
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Minh Patrick Lê, Vincent Calvez, Cathia Soulié, Yazdan Yazdanpanah, Philippe Choisy, Enagnon Kazali Alidjinou, Diane Descamps, A G Marcelin, Charlotte Charpentier, Christine Katlama, Faiza Ajana, Laurence Bocket, Anne Simon, and Gilles Peytavin
- Subjects
0301 basic medicine ,Microbiology (medical) ,Adult ,Male ,medicine.medical_specialty ,030106 microbiology ,Human immunodeficiency virus (HIV) ,HIV Infections ,medicine.disease_cause ,Gastroenterology ,Virological response ,Maraviroc ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Cyclohexanes ,Internal medicine ,Antiretroviral Therapy, Highly Active ,medicine ,Humans ,Pharmacology (medical) ,030212 general & internal medicine ,Aged ,Pharmacology ,Univariate analysis ,business.industry ,Middle Aged ,Triazoles ,Viral Load ,Raltegravir ,Hiv subtype ,Virology ,Regimen ,Infectious Diseases ,Treatment Outcome ,chemistry ,Anti-Retroviral Agents ,CCR5 Receptor Antagonists ,HIV-1 ,Female ,business ,Viral load ,medicine.drug - Abstract
OBJECTIVES There are few data on clinical and virological factors associated with maraviroc virological response (VR) in clinical practice. This study aimed to identify factors associated with VR in 94 treatment-experienced, but CCR5 inhibitor-naive, HIV-1 patients switched to maraviroc-containing regimens. METHODS Patients with HIV-1 RNA viral load (VL)
- Published
- 2016
33. Usefulness of an HIV DNA resistance genotypic test in patients who are candidates for a switch to the rilpivirine/emtricitabine/tenofovir disoproxil fumarate combination
- Author
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Maxime Grude, Audrey Rodallec, A G Marcelin, François Raffi, Vincent Calvez, Marc Wirden, Sidonie Lambert-Niclot, Philippe Flandre, E. André, Clotilde Allavena, T. Jovelin, Christine Katlama, Sophie Sayon, 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), Service des maladies infectieuses et tropicales [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Service de virologie [CHU Nantes], Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and HAL-UPMC, Gestionnaire
- Subjects
0301 basic medicine ,Microbiology (medical) ,Genotype ,Genotyping Techniques ,Anti-HIV Agents ,[SDV]Life Sciences [q-bio] ,030106 microbiology ,Context (language use) ,HIV Infections ,Drug resistance ,Microbial Sensitivity Tests ,Emtricitabine ,rilpivirine ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Proviruses ,[SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases ,Drug Resistance, Viral ,Medicine ,Humans ,Pharmacology (medical) ,030212 general & internal medicine ,Tenofovir ,Genotyping ,[SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology ,Pharmacology ,business.industry ,Virology ,3. Good health ,DNA genotype ,Infectious Diseases ,chemistry ,Rilpivirine ,DNA, Viral ,Mutation ,[SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology ,[SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases ,Human Immunodeficiency Virus DNA ,RNA, Viral ,antiretroviral resistance ,business ,Viral load ,medicine.drug - Abstract
International audience; Objectives In the context of a rilpivirine/emtricitabine/tenofovir disoproxil fumarate switch in HIV-1-infected patients with at least 1 year of virological success, we determined whether proviral DNA is an alternative to plasma HIV RNA for resistance genotyping.Methods Resistance-associated mutations (RAMs) in DNA after at least 1 year of virological success [viral load (VL) 50 copies/mL). Kappa's coefficient was used to measure agreement between the DNA and RNA genotypes.Results In patients without VF (n = 130) and with VF (n = 114), RNA and DNA showed resistance to at least one drug of the rilpivirine/emtricitabine/tenofovir disoproxil fumarate combination in 8% and 9% and in 60% and 45%, respectively. For rilpivirine RAMs, correlation between RNA and DNA was higher in patients without VF than in patients with VF (kappa = 0.60 versus 0.19, P = 0.026). Overall, the prevalence of RAMs was lower in DNA than in RNA.Conclusions Incomplete information provided by the DNA genotypic test is more notable in patients with VF, suggesting that all resistance mutations associated with prior VF have not been archived in the proviral DNA or decreased to a level below the threshold of detection. In the case where no historical plasma genotypic test is available, DNA testing might be useful to rule out switching to rilpivirine/emtricitabine/tenofovir disoproxil fumarate.
- Published
- 2016
34. Switch From Etravirine Twice Daily to Once Daily in Non-Nucleoside Reverse Transcriptase Inhibitor (NNRTI)-Resistant HIV-Infected Patients With Suppressed Viremia: The Monetra Study
- Author
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A. G. Marcelin, E. Courbon, Vincent Calvez, Christine Katlama, Slim Fourati, Gilles Peytavin, Nadine Ktorza, F. Caby, Luminita Schneider, R. Agher, M. Tindel, C. Blanc, and Lambert Assoumou
- Subjects
Genotype ,Etravirine ,HIV Infections ,Pilot Projects ,Viremia ,Pharmacology ,Drug Administration Schedule ,Nucleoside Reverse Transcriptase Inhibitor ,Pharmacokinetics ,Drug Resistance, Viral ,Nitriles ,Clinical endpoint ,medicine ,Humans ,Pharmacology (medical) ,Dosing ,business.industry ,medicine.disease ,Pyridazines ,Regimen ,Pyrimidines ,Infectious Diseases ,Tolerability ,HIV-1 ,Reverse Transcriptase Inhibitors ,business ,medicine.drug - Abstract
Etravirine (ETR) is recommended as twice-daily dosing in pretreated patients. There are no data regarding the use of ETR once daily in HIV-experienced patients with prior resistance to first-generation non-nucleoside reverse transcripase inhibitors (NNRTIs).To evaluate the capacity of once-daily ETR to maintain suppressed viremia over 48 weeks after switching from ETR twice daily in NNRTI-experienced patients.In this pilot open-label study, patients with plasma viral load (pVL)50 copies/mL on a stable ETR 200 mg bid regimen were enrolled to switch to ETR 400 mg qd and followed up over 48 weeks. The primary endpoint was the proportion of patients with pVL50 copies/mL at week 24. Secondary endpoints included the rate of pVL50 copies/mL at week 48, ETR pharmacokinetic parameters, and tolerability and resistance profile.Twenty-four patients were included. They had extensive antiretroviral treatment for a median of 14 years (range, 1-19). All except for 2 had prior resistance to NNRTIs. Seven patients discontinued ETR once daily prior to week 48 for virological failure (3), protocol deviation (3), and side effects (1). At week 24, 95% of patients maintained pVL50 copies/mL (95% CI, 78.4-99.7) and 85% at week 48 (95%CI, 65.6-95.8). Two of the 3 patients with virological failure had ETR resistance mutations prior to initiation. The median ETR C(trough) level remained stable after switching from twice daily 515 ng/mL (340-758) to once daily 422 ng/mL (264-655).These results suggest that ETR is effective as a once-daily regimen in patients with prior NNRTI experience when HIV is sensitive to ETR. The stability of C(trough) concentrations on a once-daily regimen confirms the once-daily profile of the drug in experienced patients.
- Published
- 2012
35. Tolerance and efficacy of immune-checkpoint inhibitors for cancer in people living with HIV (PWHIV)
- Author
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V. Garrait, Marianne Veyri, S. Brosseau, C.-H. Poulet, Sophie Beaucaire-Danel, Ludovic Doucet, M. Kerjouan, Valérie Gounant, J-P. Spano, Christos Chouaid, N. Cloarec, Marie-Ange Massiani, Armelle Lavolé, A G Marcelin, Henri Montaudié, S. Bregigeon, M. Dewolf, A. Gobert, C. Helissey, and G. Le Garff
- Subjects
0301 basic medicine ,Cell cycle checkpoint ,business.industry ,Immune checkpoint inhibitors ,Human immunodeficiency virus (HIV) ,Cancer ,Hematology ,medicine.disease ,medicine.disease_cause ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Oncology ,030220 oncology & carcinogenesis ,Cancer research ,medicine ,business - Published
- 2018
36. Increasing prevalence of transmitted drug resistance mutations and non-B subtype circulation in antiretroviral-naive chronically HIV-infected patients from 2001 to 2006/2007 in France
- Author
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Jacques Izopet, Jacqueline Cottalorda, Vincent Calvez, Charlotte Charpentier, Henia Saoudin, Georges Dos Santos, Mary-Anne Trabaud, Francis Barin, V. Calvez, Cécile Henquell, Delphine Desbois, C. Delaugerre, Slim Fourati, D. Bettinger, Thomas Bourlet, Anne Krivine, Bernard Masquelier, S. Vallet, M. Bouvier-Alias, Catherine Tamalet, B. Masquelier, S. Rogez, Coralie Pallier, J. C. Plantier, C. Charpentier, F. Barin, J. Cottalorda, A. Maillard, Alexandre Storto, G. DosSantos, Chakib Alloui, B. Montes, Marie-Laure Chaix, A. G. Marcelin, Anne Signori-Schmuck, D. Desbois, Anne-Geneviève Marcelin, Marie Laure Chaix, C. Tamalet, F. Brun-Vézinet, Françoise Brun-Vézinet, J. Izopet, Philippe Flandre, G. Anies, Anne Maillard, Diane Descamps, Patrice Andre, Jean-Claude Tardy, Dominique Costagliola, Brigitte Montes, Laurence Morand-Joubert, Annick Ruffault, Jean-Christophe Plantier, Sophie Pakianather, L. Morand-Joubert, and Constance Delaugerre
- Subjects
Male ,Microbiology (medical) ,Anti-HIV Agents ,HIV Infections ,Drug resistance ,Nucleoside Reverse Transcriptase Inhibitor ,03 medical and health sciences ,0302 clinical medicine ,HIV Protease ,Drug Resistance, Viral ,HIV Seropositivity ,Prevalence ,medicine ,Humans ,Pharmacology (medical) ,030212 general & internal medicine ,Pharmacology ,0303 health sciences ,Reverse-transcriptase inhibitor ,biology ,030306 microbiology ,Proteolytic enzymes ,biology.organism_classification ,Virology ,HIV Reverse Transcriptase ,Reverse transcriptase ,3. Good health ,Infectious Diseases ,Chronic Disease ,Mutation ,Immunology ,Lentivirus ,HIV-1 ,Reverse Transcriptase Inhibitors ,Female ,France ,Viral disease ,Viral load ,medicine.drug - Abstract
Objectives: To estimate the prevalence of transmitted drug resistance mutations and non-B subtype circulation in antiretroviral-naive chronically HIV-1-infected patients in France. Methods: Resistance mutations were sought in samples from 530 newly diagnosed HIV-1-infected patients from October 2006 to March 2007. Protease and reverse transcriptase mutations were identified from the 2007 Stanford Resistance Surveillance list. Results: Reverse transcriptase and protease resistance mutations were determined in 466 patients with duration of seropositivity
- Published
- 2010
37. Efficacy of darunavir/ritonavir maintenance monotherapy in patients with HIV-1 viral suppression: a randomized open-label, noninferiority trial, MONOI-ANRS 136
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A. G. Marcelin, Sidonie Lambert-Niclot, Marc Antoine Valantin, Christine Katlama, Claudine Duvivier, Philippe Flandre, Pierre Marie Girard, Bruno Hoen, Jean Michel Molina, Michele Algarte-Genin, Gilles Peytavin, and Sophie Pakianather
- Subjects
Adult ,Male ,Oncology ,medicine.medical_specialty ,Immunology ,Population ,HIV Infections ,Pharmacology ,law.invention ,Drug Resistance, Multiple, Viral ,Maintenance therapy ,Randomized controlled trial ,law ,Internal medicine ,medicine ,Clinical endpoint ,Humans ,Immunology and Allergy ,Prospective Studies ,education ,Darunavir ,Sulfonamides ,education.field_of_study ,Ritonavir ,Nucleoside analogue ,business.industry ,HIV Protease Inhibitors ,Middle Aged ,Viral Load ,Treatment Outcome ,Infectious Diseases ,HIV-1 ,RNA, Viral ,Drug Therapy, Combination ,Female ,France ,business ,Viral load ,medicine.drug - Abstract
BACKGROUND Darunavir/ritonavir (darunavir/r) maintenance strategy, in patients with suppressed HIV RNA viremia, is a potential long-term strategy to avoid nucleoside analogue toxicities and to reduce costs. METHODS MONOtherapy Inhibitor protease is a prospective, open-label, noninferiority, 96-week safety and efficacy trial in virologically suppressed patients on triple therapy who were randomized to a darunavir/r triple drug regimen or darunavir/r monotherapy. The primary endpoint was the proportion of patients with HIV RNA less than 400 copies/ml at week 48; treatment failure was defined as two consecutive HIV RNA more than 400 copies/ml (time to loss of virologic response) or any change in treatment. The trial had 80% power to show noninferiority for the monotherapy arm (delta =-10%, 90% confidence interval). RESULTS A total of 242 patients were screened, 225 of whom were randomized. In the per protocol efficacy analysis, treatment success was 99% on darunavir/r triple drug versus 94% on darunavir/r monotherapy (delta = -4.9%, 90% confidence interval, from -9.1 to -0.8). Similar results were found in intent-to-treat population (92 versus 87.5%, delta = -4.5%, 90% confidence interval from -11.2 to 2.1). Three patients experienced virologic failure on darunavir/monotherapy and none on darunavir/r triple drug. No resistance to protease inhibitor emerged in patients with plasma viral load above 50 copies/ml. The two groups did not differ in the number of serious adverse events. CONCLUSION Darunavir/r monotherapy exhibited efficacy rate over 85% with concordant results in the magnitude of difference with darunavir/r triple drug regimen in both intent-to-treat and per protocol analyses, but discordant conclusions with respect to the noninferiority margin. Patients failing on darunavir/r monotherapy had no emergence of new darunavir resistance mutations preserving future treatment options.
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- 2010
38. Comparison of two genotypic algorithms to determine HIV-1 tropism*
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C Aimé, Christine Katlama, Cathia Soulié, Anne Derache, A G Marcelin, Vincent Calvez, Guislaine Carcelain, and Anne Simon
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Genetics ,viruses ,Health Policy ,Biology ,V3 loop ,Phenotype ,law.invention ,Infectious Diseases ,law ,Genotype ,Pharmacology (medical) ,Algorithm ,Viral load ,Gene ,Genotyping ,Polymerase chain reaction ,Tropism - Abstract
Objectives One or both of two co-receptors, CCR5 (R5) and CXCR4 (X4), are used by HIV-1 to enter into host cells. The glycoprotein 120 (gp120) V3 sequence is correlated with the R5 and X4 phenotype. CCR5 inhibitors are specifically active against R5 viruses, suggesting the need to determine tropism before the use of these antagonists. A comparison of the position-specific scoring matrices (PSSM) and Geno2pheno algorithms based on the V3 loop gp120 sequences and previously described to be correlated to the R5 or X4 phenotype was carried out. Methods V3 envelope (env) genes from 83 plasma samples were amplified and sequenced, and 69 sequences were analysed with the PSSM and Geno2pheno algorithms. Results These two algorithms were concordant in 86.5% of cases. The Geno2pheno algorithm gave a tropism result more frequently than the PSSM algorithm, but R5X4 or X4 viruses were less frequently detected by the Geno2pheno algorithm. R5X4 or X4 tropism was predicted in 29.9% of samples. There was more R5X4 co-receptor use in the antiretroviral-treated group than in the antiretroviral-naive group. Conclusions It is advisable to run a validated co-receptor use prediction tool before using co-receptor antagonists. If genotyping methods are considered, the PSSM and Geno2pheno algorithms are complementary and both are necessary. The association between predicted co-receptor use and virological response to co-receptor antagonists needs to be thoroughly evaluated.
- Published
- 2008
39. National survey of the prevalence and conditions of selection of HIV-1 reverse transcriptase K70E mutation
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C, Delaugerre, P, Flandre, A G, Marcelin, D, Descamps, C, Tamalet, J, Cottalorda, V, Schneider, S, Yerly, J, LeGoff, L, Morand-Joubert, M L, Chaix, D, Costagliola, and V, Calvez
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Combination therapy ,Anti-HIV Agents ,Mutation, Missense ,HIV Infections ,Drug resistance ,Virology ,Drug Resistance, Viral ,Humans ,Selection, Genetic ,Sida ,Retrospective Studies ,biology ,virus diseases ,biochemical phenomena, metabolism, and nutrition ,biology.organism_classification ,HIV Reverse Transcriptase ,Reverse transcriptase ,Regimen ,Infectious Diseases ,Amino Acid Substitution ,Concomitant ,Lentivirus ,Mutation (genetic algorithm) ,HIV-1 ,France - Abstract
Tenofovir disoproxil fumarate (TDF) has become an important component of HIV combination therapy because of its potency and once-daily dosing. Key mutation associated with resistance to TDF is a K65R in the reverse transcriptase (RT) gene. According to occurrence of K70E mutation after failure to TDF regimen, this mutation was recently reported as a mutation associated with TDF resistance in most resistance genotypic algorithms. The aim of this study was to analyze, retrospectively, the prevalence and conditions of selection of HIV-1 RT K70E mutation from a national clinical survey. Absence of selection of K70E in 850 HIV-1-infected naive patients suggests its role in NRTI drug resistance. Prevalence of K70E RT was low (99/41601, 0.24%) in patients treated between 1999 and 2005. Conversely with K65R mutation, thymidine analog mutations (TAMs) can be concomitantly observed with K70E mutation but its frequency decreased as the number of TAM increases. Concomitant association of K65R and K70E was possible but infrequent (11%). At the time of K70E selection, 60% of patients had received or received TDF-containing regimen and one-third received exclusive NRTI regimen. In conclusion, the K70E mutation could be an alternative pathway of TDF resistance, but as the K65R mutation, other NRTI as ABC, ddI, and 3TC could be also associated with the K70E selection.
- Published
- 2008
40. Alpha-D-Galactosidase does not Interfere with Trimebutine Oral Pharmacokinetics in Mexican Healthy Volunteers
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Becerra CA, Penaloza, primary, Escamilla E, Ortega, additional, Vasquez JE, Vasquez, additional, Jimenez G, Marcelin, additional, Moreno AC, P Angeles, additional, Gonzalez A, Garcia, additional, Leyte JS, Laguna, additional, SG, Koretzky, additional, Dieguez D, Batista, additional, and Sanchez P, Lopez, additional
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- 2017
- Full Text
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41. Efficacy of protease inhibitor monotherapy vs. triple therapy: meta-analysis of data from 2303 patients in 13 randomized trials
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D Elbirt, Andrew Hill, Maria Blanca Hadacek, A G Marcelin, Nicholas I. Paton, Alan Winston, P-M Girard, and Jose R. Arribas
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0301 basic medicine ,medicine.medical_specialty ,030106 microbiology ,Atazanavir Sulfate ,HIV Infections ,Drug resistance ,Pharmacology ,Gastroenterology ,Drug Administration Schedule ,Lopinavir ,law.invention ,03 medical and health sciences ,0302 clinical medicine ,Randomized controlled trial ,law ,Internal medicine ,medicine ,Humans ,Pharmacology (medical) ,030212 general & internal medicine ,Darunavir ,Cerebrospinal Fluid ,Randomized Controlled Trials as Topic ,Ritonavir ,business.industry ,Health Policy ,HIV Protease Inhibitors ,Confidence interval ,Atazanavir ,Infectious Diseases ,Treatment Outcome ,Meta-analysis ,HIV-1 ,RNA, Viral ,Drug Therapy, Combination ,business ,medicine.drug - Abstract
Objectives The aim of this analysis was to review the evidence and update a meta-analysis evaluating the efficacy and safety results from randomized controlled trials of ritonavir-boosted protease inhibitor (PI/r) monotherapy. Methods A PubMed/EMBASE search was conducted to find randomized trials of PI/r monotherapy vs. triple therapy in patients with HIV-1 RNA suppression at baseline (
- Published
- 2015
42. [European Antibiotic Awareness Day: What is new in France?]
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C, Pulcini, S, Alfandari, F, Ballereau, E, Bonnet, F, Bruneel, B, Castan, C, Chidiac, R, Cohen, D, Descamps, T, Doco-Lecompte, R, Gauzit, B, Guéry, V, Jarlier, P, Lesprit, A G, Marcelin, J M, Molina, C, Rabaud, A, Riché, D, Salmon-Céron, E, Senneville, J P, Stahl, P, Tattevin, E, Varon, and F, Roblot
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Anniversaries and Special Events ,Drug Resistance, Bacterial ,Humans ,France ,Health Education ,Anti-Bacterial Agents - Published
- 2015
43. Efficacy of etravirine combined with darunavir or other ritonavir-boosted protease inhibitors in HIV-1-infected patients: An observational study using pooled European cohort data
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J, Vingerhoets, V, Calvez, P, Flandre, A-G, Marcelin, F, Ceccherini-Silberstein, C-F, Perno, M, Mercedes Santoro, R, Bateson, M, Nelson, A, Cozzi-Lepri, J, Grarup, J, Lundgren, F, Incardona, R, Kaiser, A, Sonnerborg, B, Clotet, R, Paredes, H F, Günthard, B, Ledergerber, A, Hoogstoel, S, Nijs, L, Tambuyzer, L, Lavreys, and M, Opsomer
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Male ,efficacy ,HIV Infections ,protease inhibitor ,Meta-Analysis as Topic ,Nitriles ,Odds Ratio ,Humans ,darunavir/ritonavir ,etravirine ,Darunavir ,Sulfonamides ,Ritonavir ,HIV-1 ,HIV Protease Inhibitors ,Middle Aged ,Viral Load ,Settore MED/07 - Microbiologia e Microbiologia Clinica ,United Kingdom ,CD4 Lymphocyte Count ,Pyridazines ,Pyrimidines ,Italy ,Spain ,Drug Therapy, Combination ,Female ,France ,Switzerland - Abstract
This observational study in antiretroviral treatment-experienced, HIV-1-infected adults explored the efficacy of etravirine plus darunavir/ritonavir (DRV group; n = 999) vs. etravirine plus an alternative boosted protease inhibitor (other PI group; n = 116) using pooled European cohort data.Two international (EuroSIDA; EUResist Network) and five national (France, Italy, Spain, Switzerland and UK) cohorts provided data (collected in 2007-2012). Stratum-adjusted (for confounding factors) Mantel-Haenszel differences in virological responses (viral load50 HIV-1 RNA copies/mL) and odds ratios (ORs) with 95% confidence intervals (CIs) were derived.Baseline characteristics were balanced between groups except for previous use of antiretrovirals (≥ 10: 63% in the DRV group vs. 49% in the other PI group), including previous use of at least three PIs (64% vs. 53%, respectively) and mean number of PI resistance mutations (2.3 vs. 1.9, respectively). Week 24 responses were 73% vs. 75% (observed) and 49% vs. 43% (missing = failure), respectively. Week 48 responses were 75% vs. 73% and 32% vs. 30%, respectively. All 95% CIs around unadjusted and adjusted differences encompassed 0 (difference in responses) or 1 (ORs). While ORs by cohort indicated heterogeneity in response, for pooled data the difference between unadjusted and adjusted for cohort ORs was small.These data do not indicate a difference in response between the DRV and other PI groups, although caution should be applied given the small size of the other PI group and the lack of randomization. This suggests that the efficacy and virology results from DUET can be extrapolated to a regimen of etravirine with a boosted PI other than darunavir/ritonavir.
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- 2015
44. Soluble biomarkers of immune activation and inflammation in HIV infection: impact of 2 years of effective first-line combination antiretroviral therapy
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S, Hattab, M, Guiguet, G, Carcelain, S, Fourati, A, Guihot, B, Autran, F, Caby, A-G, Marcelin, D, Costagliola, and C, Katlama
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Adult ,Male ,Anti-HIV Agents ,Interleukin-6 ,Age Factors ,Lipopolysaccharide Receptors ,HIV Infections ,Middle Aged ,Chemokine CXCL9 ,Chemokine CXCL10 ,Treatment Outcome ,Antiretroviral Therapy, Highly Active ,Humans ,Female ,Longitudinal Studies ,Biomarkers - Abstract
The aim of the study was to assess the impact of rapid and sustained viral control produced by combination antiretroviral therapy (cART) on HIV-associated immune activation and inflammation.In this longitudinal observational study, we examined changes in interleukin-6 (IL-6), interferon-γ-inducible protein-10 (IP-10), monokine induced by interferon-γ (MIG) and soluble CD14 (sCD14) levels during 2 years of effective first-line cART. Biomarker levels before and after cART were compared with those observed in healthy subjects, using the Wilcoxon signed rank test. Elevated biomarker levels were defined with respect to values for healthy subject (mean + 2 standard deviations). Factors associated with persistently elevated biomarker levels after 2 years of cART were identified by logistic regression.We included in the study 139 patients with a median HIV-1 RNA level of 4.8 log10 HIV-1 RNA copies/mL and a median CD4 cell count of 294 cells/μL at cART initiation [day 0 (D0)]. At D0, all biomarker levels were higher than in healthy subjects (P 0.05). After 2 years of cART, IL-6, IP-10 and MIG levels fell significantly, by a median of 0.54, 420 and 1107 pg/mL, respectively (all P 0.001), and were no longer elevated in 75% of patients. In contrast, sCD14 levels did not change significantly (0.18 × 10(6) pg/mL; P = 0.102) and remained elevated. Older age was associated with elevated levels of IP-10 [odds ratio (OR) 1.60 per 10 years older; P = 0.047] and MIG (OR 1.92 per 10 years older; P = 0.007) after 2 years of cART.The rapid and sustained viral suppression produced by first-line cART reduced IL-6, IP-10 and MIG to normal levels, while sCD14, a marker of monocyte activation, remained elevated. High levels of IP-10 and MIG tended to persist in older patients.
- Published
- 2015
45. GENOPHAR: a randomized study of plasma drug measurements in association with genotypic resistance testing and expert advice to optimize therapy in patients failing antiretroviral therapy*
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Anne Simon, Manuela Bonmarchand, Vincent Calvez, L. Paris, Dominique Costagliola, C Lamotte, Hocine Ait-Mohand, Nadine Ktorza, Philippe Bossi, Constance Delaugerre, A-G Marcelin, D-J David, Gilles Peytavin, R Cacace, François Bricaire, and Christine Katlama
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Adult ,Male ,Drug ,medicine.medical_specialty ,Multivariate analysis ,Adolescent ,Genotype ,Anti-HIV Agents ,media_common.quotation_subject ,Statistics, Nonparametric ,law.invention ,Drug Resistance, Multiple, Viral ,Randomized controlled trial ,law ,Antiretroviral Therapy, Highly Active ,Internal medicine ,medicine ,Clinical endpoint ,Humans ,Pharmacology (medical) ,Prospective Studies ,Treatment Failure ,Aged ,media_common ,medicine.diagnostic_test ,business.industry ,Health Policy ,Middle Aged ,Viral Load ,Surgery ,Regimen ,Infectious Diseases ,Therapeutic drug monitoring ,Toxicity ,HIV-1 ,Female ,Drug Monitoring ,business ,Viral load - Abstract
Objectives To evaluate the benefits of therapeutic drug monitoring (TDM) in association with genotypic resistance testing and expert advice to optimize therapy in multiexperienced patients infected with HIV-1. Methods Patients with a viral load>1000 HIV-1 RNA copies/mL and an unchanged antiretroviral therapy regimen over the last 3 months were randomized into two groups: a genotypic group (G) and a geno-pharmacological group (GP). Treatment was selected by an expert committee according to genotypic resistance testing (the G and GP groups) and TDM (the GP group) at week 4. Treatment could be modified at each visit according to toxicity, poor virological response and TDM. Results of TDM were withheld from the G group until week 12. The primary endpoint of the study was the percentage of patients with viral load
- Published
- 2004
46. 377 Propionibacterium acnes CAMP factor 1 recognized Toll-Like Receptor-2
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Sophie Sayon, Nicolas Dupin, P. Morand, S. Corvec, Brigitte Dréno, Philippe Grange, A G Marcelin, C. Lheure, Nathalie Désiré, and Guillaume Ollagnier
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Toll-like receptor ,Propionibacterium acnes ,Cell Biology ,Dermatology ,Biology ,biology.organism_classification ,Molecular Biology ,Biochemistry ,CAMP test ,Microbiology - Published
- 2017
47. OUTCOME OF KIDNEY TRANSPLANT RECIPIENTS WITH PREVIOUS HUMAN HERPESVIRUS-8 INFECTION1
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Marc Olivier Bitker, Mouquet C, Stéphane Barete, Rachid Agher, Jean-Charles Piette, H. Benalia, D. Charron, A G Marcelin, Nicolas Dupin, Vincent Calvez, and Camille Francès
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Transplantation ,medicine.medical_specialty ,education.field_of_study ,business.industry ,viruses ,Incidence (epidemiology) ,Mortality rate ,Population ,virus diseases ,Odds ratio ,medicine.disease ,Gastroenterology ,Serology ,Internal medicine ,Immunology ,medicine ,business ,education ,Kidney transplantation ,Survival analysis - Abstract
Background. The consequences of a prior human herpesvirus-8 (HHV-8) infection in kidney-transplant recipients are still partially unknown. The aim of this monocentric study was to determine the prevalence of HHV-8-seropositive patients at the time of transplantation and to identify the main clinical events of these HHV-8 + recipients. Methods. From January 1,1990 to December 31, 1996, antibodies to HHV-8 latent nuclear antigen were detected by indirect immunofluorescent method in serum samples collected just before kidney transplantation from 400 consecutive patients. Conventional double or triple immunosuppressive treatment was prescribed. For the group of HHV-8 + recipients, data including death rate, graft survival, and occurrence of Kaposi's sarcoma (KS) were retrospectively collected until December 31, 1998. Cofactors associated with KS were studied in univariate and multivariate analyses using a Cox model. Results. Thirty-two patients (8%) had antibodies to HHV-8 in their sera at the time of transplantation. Among these 32, 3 years after transplantation, graft survival was 72%, and KS prevalence was 28% (KS incidence: 8.2/yr/100 HHV-8 + recipients). Multivariate analysis identified bacterial and/or Pneumocystis carinii infection (odds ratio: 8.6; P=0.019) and female gender (odds ratio: 5.34; P=0.047) as factors associated with KS. No KS was observed in patients without anti-HHV-8 antibodies at the time of transplantation. Conclusions. The low graft survival and the high prevalence of KS within the studied population of HHV-8 + transplant recipients are strong arguments for systematic screening of HHV-8 serologic features before transplantation, especially in patients of African origin. HHV-8 + transplant recipients should be closely monitored to severe infections.
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- 2000
48. The first reported case and management of multicentric Castleman's disease associated with Kaposi's sarcoma in an HIV-2-infected patient
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Damond F, Sophie Bouvresse, Nathalie Franck, Micheline Tulliez, Nicolas Dupin, A G Marcelin, and S. Regnier
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Pathology ,medicine.medical_specialty ,biology ,business.industry ,Multicentric Castleman's disease ,Castleman disease ,Immunology ,medicine.disease ,biology.organism_classification ,Dermatology ,Infectious Diseases ,Acquired immunodeficiency syndrome (AIDS) ,Infected patient ,Immunopathology ,Immunology and Allergy ,Medicine ,Viral disease ,business ,Sida ,Kaposi's sarcoma - Published
- 2007
49. HIV-1 integrase variability and relationship with drug resistance in antiretroviral-naive and -experienced patients with different HIV-1 subtypes
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S, Reigadas, A G, Marcelin, A, Houssaïni, S, Yerly, D, Descamps, J C, Plantier, A, Ruffault, C, Amiel, M A, Trabaud, Philippe, Flandre, H, Fleury, B, Masquelier, S, Marque-Juillet, Microbiologie Fondamentale et Pathogénicité (MFP), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Epidémiologie, stratégies thérapeutiques et virologie cliniques dans l'infection à VIH, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), Laboratoire de virologie [Rouen], Hôpital Charles Nicolle [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Unité de Rétrovirologie, Hôpital Pontchaillou, Infectious Diseases Department, Université Montpellier 1 (UM1), Virology Laboratory, Bordeaux University Hospital, Bordeaux, France, Service de virologie et d'immunologie biologique, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Microbiologie cellulaire et moléculaire et pathogénicité (MCMP), Service de virologie [CHU Pitié-Salpêtrière], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université de Bordeaux (UB), Université de Rouen Normandie (UNIROUEN), and Normandie Université (NU)-Normandie Université (NU)-Département de microbiologie : Bactério, Virologie, Parasito, Hygiène-Hôpital Charles Nicolle [Rouen]-CHU Rouen
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Microbiology (medical) ,Anti-HIV Agents ,HIV Integrase/genetics ,Molecular Sequence Data ,Human immunodeficiency virus (HIV) ,Mutation, Missense ,HIV Infections ,Drug resistance ,HIV Integrase ,Bioinformatics ,medicine.disease_cause ,03 medical and health sciences ,Anti-HIV Agents/pharmacology ,Drug Resistance, Viral ,medicine ,Antiretroviral naive ,Humans ,Pharmacology (medical) ,ComputingMilieux_MISCELLANEOUS ,030304 developmental biology ,ddc:616 ,HIV-1/drug effects/genetics/isolation & purification ,Pharmacology ,0303 health sciences ,biology ,Group study ,030306 microbiology ,Genetic Variation ,Sequence Analysis, DNA ,Hiv subtype ,Virology ,3. Good health ,Integrase ,Infectious Diseases ,[SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology ,Hiv 1 integrase ,biology.protein ,HIV-1 ,HIV Infections/virology - Abstract
H-932. American Society for Microbiology, Washington, DC, USA. 10 Nouhin J, Donchai T, Hoang KT et al. Natural polymorphisms of HIV-1 CRF01_AE integrase coding region in ARV-naive individuals in Cambodia, Thailand and Vietnam: an ANRS AC12 working group study. Infect Genet Evol 2011; 11: 38–43. 11 Wainberg MA, Brenner BG. Role of HIV subtype diversity in the development of resistance to antiviral drugs. Viruses 2010; 2: 2493–508. Research letter
- Published
- 2013
50. HIV-1 dynamics and coreceptor usage in Maraviroc-treated patients with ongoing replication
- Author
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P, Recordon-Pinson, S, Raymond, P, Bellecave, A G, Marcelin, C, Soulie, D, Descamps, V, Calvez, P R, Harrigan, H, Fleury, J, Izopet, B, Masquelier, Theresa, Mo, Microbiologie Fondamentale et Pathogénicité (MFP), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), Service de virologie et d'immunologie biologique, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Virologie [CHU Toulouse], Institut Fédératif de Biologie (IFB), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Epidémiologie, stratégies thérapeutiques et virologie cliniques dans l'infection à VIH, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), 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), Numerical Medicine (NUMED), Unité de Mathématiques Pures et Appliquées (UMPA-ENSL), École normale supérieure de Lyon (ENS de Lyon)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Centre National de la Recherche Scientifique (CNRS)-Inria Grenoble - Rhône-Alpes, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), British Columbia Centre for Excellence in HIV/AIDS [Vancouver], Laboratoire de Virologie, BC Centre for Excellence in HIV/AIDS, ANRS AC11 Resistance Study Group, Microbiologie cellulaire et moléculaire et pathogénicité (MCMP), Laboratoire de Virologie [Purpan], CHU Toulouse [Toulouse]-Institut Fédératif de Biologie (IFB) - Hôpital Purpan, Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Virologie [Toulouse], Service de virologie [CHU Pitié-Salpêtrière], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université de Bordeaux (UB), Inria Grenoble - Rhône-Alpes, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Unité de Mathématiques Pures et Appliquées (UMPA-ENSL), Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon), and Le Corre, Morgane
- Subjects
MESH: Selection, Genetic ,HIV Infections ,HIV Envelope Protein gp120 ,V3 loop ,MESH: Receptors, CCR5 ,Maraviroc ,MESH: Genotype ,MESH: HIV-1 ,chemistry.chemical_compound ,MESH: HIV Envelope Protein gp120 ,HIV Fusion Inhibitors ,Genotype ,MESH: Sequence Analysis, RNA ,Pharmacology (medical) ,MESH: Peptide Fragments ,MESH: High-Throughput Nucleotide Sequencing ,MESH: Evolution, Molecular ,[SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology ,Genetics ,0303 health sciences ,education.field_of_study ,MESH: Drug Resistance, Viral ,High-Throughput Nucleotide Sequencing ,virus diseases ,MESH: HIV Infections ,MESH: Cyclohexanes ,3. Good health ,Infectious Diseases ,[SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology ,Viral evolution ,CCR5 Receptor Antagonists ,[SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology ,Receptors, CXCR4 ,Receptors, CCR5 ,Population ,Viral quasispecies ,Biology ,Antiviral Agents ,MESH: Receptors, CXCR4 ,Evolution, Molecular ,03 medical and health sciences ,Cyclohexanes ,Drug Resistance, Viral ,Humans ,Selection, Genetic ,education ,MESH: HIV Fusion Inhibitors ,Tropism ,030304 developmental biology ,Pharmacology ,MESH: Humans ,Sequence Analysis, RNA ,030306 microbiology ,Triazoles ,Virology ,Peptide Fragments ,body regions ,Viral Tropism ,chemistry ,MESH: Triazoles ,HIV-1 ,Tissue tropism ,MESH: Viral Tropism ,human activities - Abstract
There is evidence that HIV-1 evolution under maraviroc (MVC) pressure can lead to the selection of either X4-tropic variants and/or R5-tropic, MVC-resistant isolates. However, the viral dynamics of HIV-1 variants in patients with virological failure (VF) on MVC-containing regimens remain poorly studied. Here, we investigated the V3 loop evolution of HIV-1 on MVC in relation to coreceptor usage and the nature of HIV-1 quasispecies before MVC therapy using bulk population sequences and ultradeep sequencing. The majority of patients had no detectable minority X4 variant at baseline. The evolution of tropism was followed up until VF and showed three possibilities for viral evolution in these patients: emergence of preexisting X4 variants, de novo selection of R5 variants presenting V3 loop mutations, or replication of R5 variants without selection of known mutations.
- Published
- 2013
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