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1. In vitro phenotypic susceptibility of HIV-1 non-group M to CCR5 inhibitor (maraviroc): TROPI-CO study

Author

Ségolène Gracias, Ikrame El Yaalaoui, Benoît Visseaux, Charlotte Charpentier, Diane Descamps, Charlène Martin, Fanny Lermechain, Jean-Christophe Plantier, and Elodie Alessandri-Gradt

Subjects
human immunodeficiency virus, genetic diversity, phenotypic susceptibility, maraviroc, Microbiology, QR1-502
Abstract

ABSTRACT The susceptibility of genetically divergent HIV-1 strains (HIV-1 non-M) from groups O, N, and P to the CCR5 co-receptor antagonist, maraviroc (MVC), was investigated among a large panel of 45 clinical strains, representative of the viral genetic diversity. The results were compared to the reference strains of HIV-1 group M (HIV-1/M) with known tropism. Among the non-M strains, a wide range of phenotypic susceptibilities to MVC were observed. The large majority of HIV-1/O strains (40/42) displayed a high susceptibility to MVC, with median and mean IC50 values of 1.23 and 1.33 nM, respectively, similar to the HIV-1/M R5 strain (1.89 nM). However, the two remaining HIV-1/O strains exhibited a lower susceptibility (IC50 at 482 and 496 nM), in accordance with their dual/mixed (DM) tropism. Interestingly, the two HIV-1/N strains demonstrated varying susceptibility patterns, despite always having relatively low IC50 values (2.87 and 47.5 nM). This emphasized the complexity of determining susceptibility solely based on IC50 values. Our study examined the susceptibility of all HIV-1 non-M groups to MVC and correlated these findings with virus tropism (X4, R5, or DM). The results confirm the critical significance of tropism determination before initiating MVC treatment in patients infected with HIV-1 non-M. Furthermore, we advocate for the consideration of additional parameters, such as the slope of inhibition curves, to provide a more thorough characterization of phenotypic susceptibility profiles.IMPORTANCEUnlike HIV-1 group M, the scarcity of studies on HIV-1 non-M groups (O, N, and P) presents challenges in understanding their susceptibility to antiretroviral treatments, particularly due to their natural resistance to non-nucleoside reverse transcriptase inhibitors. The TROPI-CO study logically complements our prior investigations into integrase inhibitors and anti-gp120 efficacy. The largest panel of 45 non-M strains existing so far yielded valuable results on maraviroc (MVC) susceptibility. The significant variations in MVC IC50 reveal a spectrum of susceptibilities, with most strains displaying R5 tropism. Notably, the absence of MVC-resistant strains suggests a potential therapeutic avenue. The study also employs a robust novel cell-based phenotropism assay and identifies distinct groups of susceptibilities based on inhibition curve slopes. Our findings emphasize the importance of determining tropism before initiating MVC and provide crucial insights for selecting effective therapeutic strategies in the delicate context of HIV-1 non-M infections.

Published
2024
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2. In vitro replicative potential of an HIV-1/MO intergroup recombinant virus compared to HIV-1/M and HIV-1/O parental viruses

Author

Alice Moisan, Fabienne Tombette, Manon Vautrin, Elodie Alessandri-Gradt, Thomas Mourez, and Jean-Christophe Plantier

Subjects
Medicine, Science
Abstract

Abstract Genetic recombination is one of the major evolution processes of HIV-1. Despite their great genetic divergence, HIV-1 groups M and O can generate HIV-1/MO intergroup recombinants. The current description of 20 HIV-1/MO unique recombinant forms suggests a possible benefit of the recombination. The aim of this work was to study in vitro the replicative potential of HIV-1/MO recombinant forms. This analysis was based on a simple recombination pattern, [Ogag/pol-Menv], harboring a breakpoint in Vpr. A chimeric infectious molecular clone, pOM-TB-2016 was synthesized from HIV-1/M subtype B and HIV-1/O subgroup T and recombinant viruses were obtained by transfection/co-culture. To compare the replicative potential of these viruses, two markers were monitored in culture supernatants: Reverse Transcriptase (RT) activity and P24 antigen concentration. The results showed a superiority of the group M parental virus compared to group O for both markers. In contrast, for the recombinant virus, RT activity data did not overlap with the concentration of P24 antigen, suggesting a hybrid behavior of the recombinant, in terms of enzyme activity and P24 production. These results highlighted many hypotheses about the impact of recombination on replicative potential and demonstrated again the significant plasticity of HIV genomes and their infinite possibility of evolution.

Published
2024
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3. Performance evaluation of the Access HBsAg and Access HBsAg confirmatory assays on the DxI 9000 Access Immunoassay Analyzer

Author

Benoit Visseaux, Jérémie Gautier, Françoise Le Boulaire, Catherine Coignard, Claire Vincent, Sandrine Gréaume, Isabelle Voisin, Veronique Lemée, Jean-Christophe Plantier, Yves-Edouard Herpe, Etienne Brochot, Stephanie Bord, Marc Turini, Vanessa Roulet, and Juliane Hey

Subjects
Hepatitis B infection, HBsAg, Chemiluminescence immunoassay, Analytical performances, Clinical performances, Medicine (General), R5-920, Chemistry, QD1-999
Abstract

Introduction: This study evaluated the clinical and analytical performances of the Access HBsAg and the Access HBsAg Confirmatory assays on the DxI 9000 Access Immunoassay Analyzer (Beckman Coulter, Inc.). Materials and methods: Diagnostic specificity and sensitivity of the Access HBsAg and Access HBsAg Confirmatory assays were evaluated by comparing the Access assays to the final HBsAg sample status determined using the Architect, PRISM, or Elecsys HBsAg assays, along with Architect or PRISM HBsAg Confirmatory assays. Imprecision, sensitivity on seroconversion panels, analytical sensitivity on WHO, and recognition of HBV variants were also evaluated. Results: A total of 7534 samples were included in the analysis (6047 blood donors, 1032 hospitalized patients, 455 positive patients’ samples). Access HBsAg assay sensitivity and specificity were at 100.00% (99.19–100.0) and 99.92% (99.82–99.97), respectively. Sensitivity of Access HBsAg Confirmatory assay was 100.00% (99.21–100.0) on the 464 HBsAg positive samples. The use of a high positive algorithm for the Access HBsAg assay, wherein samples with S/CO ≥ 100.00 were considered positive without requiring repeat or confirmatory testing, was successfully evaluated with all 450 specimens with S/CO greater than 100.00 (sensitivity 100.00%; 99.19–100.0). Access HBsAg assay demonstrated good analytical performance, equivalent recognition of seroconversion panels compared to Architect assay, and an analytical sensitivity between 0.022 and 0.025 IU/mL. All HBV genotypes, subtypes and mutants were well detected without analytical sensitivity loss. Conclusion: Access HBsAg and Access HBsAg Confirmatory assays demonstrated robust performances. They provide low samples volume requirements and a simplified process, no systematic retesting for high positive samples.

Published
2024
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4. Molecular confirmation of HIV-1 and HIV-2 coinfections among initially serologically dually-reactive samples from patients living in West Africa.

Author

Boris K Tchounga, Mélanie Bertine, Florence Damond, Valentine Marie Ferré, André Inwoley, Simon P Boni, Alice Moisan, Jean-Christophe Plantier, Diane Descamps, Didier K Ekouevi, and Charlotte Charpentier

Subjects
Medicine, Science
Abstract

ObjectivesThis study aimed to confirm the co-infection with HIV-1 and HIV-2, among West African patients using in-house HIV type/group enzyme-immuno assays and molecular diagnosis.DesignA cross-sectional survey was conducted from April 2016 to October 2017 in the biggest HIV clinics of Côte d'Ivoire and Burkina Faso.MethodA first serological confirmation was done in the referral laboratory using an in-house, indirect immuno-enzymatic essay allowing the qualitative detection of both HIV-1 and HIV-2 antibodies. In order to separately detect anti-HIV-1 and anti-HIV-2 antibodies, a type/group specific enzyme-immuno assay (HIV-GSEIA) was used. To confirm the co-infections, HIV-1 and HIV-2 DNA-qualitative PCR assays were performed.ResultsA total of 91 patients were enrolled in the study and provided blood sample for HIV type confirmatory testing including 13 (14.3%) HIV-2 mono-reactive and 78 (85.7%) HIV-1/HIV-2 dually-reactive based on the HIV testing National Algorithms. The first serological ELISA confirmatory test performed showed that 80 (78.9%) of the 91 participants were dually-reactive. The HIV-GSEIA performed on these 80 serum samples retrieve one 61 HIV-1/HIV-2 dually-reactive samples. HIV-1 and HIV-2 DNA PCR were performed on 54 of the 61 HIV-1/HIV-2 dually-reactive samples and 46 out of 61 (75.4%) samples were found HIV-1/HIV-2 coinfected.ConclusionThe contribution of type/group specific enzyme-immuno assay to accurately identify HIV-1/HIV-2 coinfections remain suboptimal, emphasizing the need for molecular diagnosis platforms in West Africa, to avail HIV DNA PCR test for the confirmation of HIV-1/HIV-2 co-infections.

Published
2023
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6. Evaluation of Analytical and Clinical Performance and Usefulness in a Real-Life Hospital Setting of Two in-House Real-Time RT-PCR Assays to Track SARS-CoV-2 Variants of Concern

Author

Alice Moisan, Anaïs Soares, Fabienne De Oliveira, Elodie Alessandri-Gradt, François Lecoquierre, Steeve Fourneaux, Jean-Christophe Plantier, and Marie Gueudin

Subjects
variants of concern, SARS-CoV-2 diversity, in-house RT-PCR, next-generation sequencing, mutations of interest, Microbiology, QR1-502
Abstract

Since the end of 2020, multiple severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) have emerged and spread worldwide. Tracking their evolution has been a challenge due to the huge number of positive samples and limited capacities of whole-genome sequencing. Two in-house variant-screening RT-PCR assays were successively designed in our laboratory in order to detect specific known mutations in the spike region and to rapidly detect successively emerging VOCs. The first one (RT-PCR#1) targeted the 69–70 deletion and the N501Y substitution simultaneously, whereas the second one (RT-PCR#2) targeted the E484K, E484Q, and L452R substitutions simultaneously. To evaluate the analytical performance of these two RT-PCRs, 90 negative and 30 positive thawed nasopharyngeal swabs were retrospectively analyzed, and no discordant results were observed. Concerning the sensitivity, for RT-PCR#1, serial dilutions of the WHO international standard SARS-CoV-2 RNA, corresponding to the genome of an Alpha variant, were all detected up to 500 IU/mL. For RT-PCR#2, dilutions of a sample harboring the E484K substitution and of a sample harboring the L452R and E484Q substitutions were all detected up to 1000 IU/mL and 2000 IU/mL, respectively. To evaluate the performance in a real-life hospital setting, 1308 and 915 profiles of mutations, obtained with RT-PCR#1 and RT-PCR#2, respectively, were prospectively compared to next-generation sequencing (NGS) data. The two RT-PCR assays showed an excellent concordance with the NGS data, with 99.8% for RT-PCR#1 and 99.2% for RT-PCR#2. Finally, for each mutation targeted, the clinical sensitivity, the clinical specificity and the positive and negative predictive values showed excellent clinical performance. Since the beginning of the SARS-CoV-2 pandemic, the emergence of variants—impacting the disease’s severity and the efficacy of vaccines and therapies—has forced medical analysis laboratories to constantly adapt to the strong demand for screening them. Our data showed that in-house RT-PCRs are useful and adaptable tools for monitoring such rapid evolution and spread of SARS-CoV-2 VOCs.

Published
2023
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7. HIV-1 Non-Group M Strains and ART

Author

Elodie Alessandri-Gradt, Alice Moisan, and Jean-Christophe Plantier

Subjects
HIV-1, genetic variants, ART, elimination, Microbiology, QR1-502
Abstract

To eliminate HIV infection, there are several elements to take into account to limit transmission and break viral replication, such as epidemiological, preventive or therapeutic management. The UNAIDS goals of screening, treatment and efficacy should allow for this elimination if properly followed. For some infections, the difficulty is linked to the strong genetic divergence of the viruses, which can impact the virological and therapeutic management of patients. To completely eliminate HIV by 2030, we must therefore also be able to act on these atypical variants (HIV-1 non-group M) which are distinct from the group M pandemic viruses. While this diversity has had an impact on the efficacy of antiretroviral treatment in the past, recent data show that there is real hope of eliminating these forms, while maintaining vigilance and constant surveillance, so as not to allow more divergent and resistant forms to emerge. The aim of this work is therefore to share an update on the current knowledge on epidemiology, diagnosis and antiretroviral agent efficacy of HIV-1 non-M variants.

Published
2023
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8. Dissociated humoral and cellular immune responses after a three-dose schema of BNT162b2 vaccine in patients receiving anti-CD20 monoclonal antibody maintenance treatment for B-cell lymphomas

Author

Sophie Candon, Veronique Lemee, Emilie Leveque, Pascaline Etancelin, Cedric Paquin, Marion Carette, Nathalie Contentin, Victor Bobee, Mustafa Alani, Nathalie Cardinael, Stephane Lepretre, Vincent Camus, Florian Bouclet, Edwige Boulet, Anne-Lise Menard, Helene Lanic, Aspasia Stamatoullas, Emilie Lemasle, Louis-Ferdinand Pepin, Doriane Richard, Sydney Dubois, Herve Tilly, Alain Dalleac, Jean-Christophe Plantier, Manuel Etienne, and Fabrice Jardin

Subjects
Diseases of the blood and blood-forming organs, RC633-647.5
Published
2021
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9. Convergent Evolution of HLA-C Downmodulation in HIV-1 and HIV-2

Author

Kristina Hopfensperger, Jonathan Richard, Christina M. Stürzel, Frederic Bibollet-Ruche, Richard Apps, Marie Leoz, Jean-Christophe Plantier, Beatrice H. Hahn, Andrés Finzi, Frank Kirchhoff, and Daniel Sauter

Subjects
HIV-1, HIV-2, SIV, HLA-C, Vpu, Vif, Microbiology, QR1-502
Abstract

ABSTRACT HLA-C-mediated antigen presentation induces the killing of human immunodeficiency virus (HIV)-infected CD4+ T cells by cytotoxic T lymphocytes (CTLs). To evade killing, many HIV-1 group M strains decrease HLA-C surface levels using their accessory protein Vpu. However, some HIV-1 group M isolates lack this activity, possibly to prevent the activation of natural killer (NK) cells. Analyzing diverse primate lentiviruses, we found that Vpu-mediated HLA-C downregulation is not limited to pandemic group M but is also found in HIV-1 groups O and P as well as several simian immunodeficiency viruses (SIVs). We show that Vpu targets HLA-C primarily at the protein level, independently of its ability to suppress NF-κB-driven gene expression, and that in some viral lineages, HLA-C downregulation may come at the cost of efficient counteraction of the restriction factor tetherin. Remarkably, HIV-2, which does not carry a vpu gene, uses its accessory protein Vif to decrease HLA-C surface expression. This Vif activity requires intact binding sites for the Cullin5/Elongin ubiquitin ligase complex but is separable from its ability to counteract APOBEC3G. Similar to HIV-1 Vpu, the degree of HIV-2 Vif-mediated HLA-C downregulation varies considerably among different virus isolates. In agreement with opposing selection pressures in vivo, we show that the reduction of HLA-C surface levels by HIV-2 Vif is accompanied by increased NK cell-mediated killing. In summary, our results highlight the complex role of HLA-C in lentiviral infections and demonstrate that HIV-1 and HIV-2 have evolved at least two independent mechanisms to decrease HLA-C levels on infected cells. IMPORTANCE Genome-wide association studies suggest that HLA-C expression is a major determinant of viral load set points and CD4+ T cell counts in HIV-infected individuals. On the one hand, efficient HLA-C expression enables the killing of infected cells by cytotoxic T lymphocytes (CTLs). On the other hand, HLA-C sends inhibitory signals to natural killer (NK) cells and enhances the infectivity of newly produced HIV particles. HIV-1 group M viruses modulate HLA-C expression using the accessory protein Vpu, possibly to balance CTL- and NK cell-mediated immune responses. Here, we show that the second human immunodeficiency virus, HIV-2, can use its accessory protein Vif to evade HLA-C-mediated restriction. Furthermore, our mutational analyses provide insights into the underlying molecular mechanisms. In summary, our results reveal how the two human AIDS viruses modulate HLA-C, a key component of the antiviral immune response.

Published
2020
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10. Dried Blood Spot Tests for the Diagnosis and Therapeutic Monitoring of HIV and Viral Hepatitis B and C

Author

Edouard Tuaillon, Dramane Kania, Amandine Pisoni, Karine Bollore, Fabien Taieb, Esther Nina Ontsira Ngoyi, Roxane Schaub, Jean-Christophe Plantier, Alain Makinson, and Philippe Van de Perre

Subjects
dried blood spot, hepatitis B, hepatitis C, HIV, diagnosis, hard-to-reach population, Microbiology, QR1-502
Abstract

Blood collected and dried on a paper card – dried blood spot (DBS) – knows a growing interest as a sampling method that can be performed outside care facilities by capillary puncture, and transported in a simple and safe manner by mail. The benefits of this method for blood collection and transport has recently led the World Health Organization to recommend DBS for HIV and hepatitis B and C diagnosis. The clinical utility of DBS sampling to improve diagnostics and care of HIV and hepatitis B and C infection in hard to reach populations, key populations and people living in low-income settings was highlighted. Literature about usefulness of DBS specimens in the therapeutic cascade of care – screening, confirmation, quantification of nucleic acids, and resistance genotyping -, was reviewed. DBS samples are suitable for testing antibodies, antigens, or nucleic acids using most laboratory methods. Good sensibility and specificity have been reported for infant HIV diagnosis and diagnosis of hepatitis B and C. The performance of HIV RNA testing on DBS to identified virological failure on antiretroviral therapy is also high but not optimal because of the dilution of dried blood in the elution buffer, reducing the analytical sensitivity, and because of the contamination by intracellular HIV DNA. Standardized protocols are needed for inter-laboratory comparisons, and manufacturers should pursue regulatory approval for in vitro diagnostics using DBS specimens. Despite these limitations, DBS sampling is a clinically relevant tool to improve access to infectious disease diagnosis worldwide.

Published
2020
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11. Confirmation of HCV viremia using HCV RNA and core antigen testing on dried blood spot in HIV infected peoples who inject drugs in Vietnam

Author

Truong Tam Nguyen, Véronique Lemee, Karine Bollore, Hai Vinh Vu, Karine Lacombe, Xuan Lien Truong Thi, Que Anh Luong, Charline Dubos, Jean-Christophe Plantier, Huong Duong Thi, Didier Laureillard, Maud Lemoine, and Edouard Tuaillon

Subjects
Hepatitis C virus (HCV), Human immunodeficiency virus (HIV), HCV core antigen, HCV RNA, Vietnam, Infectious and parasitic diseases, RC109-216
Abstract

Abstract Background Nucleic acid tests performed on blood samples collected on Dried Blood Spot (DBS) and detection of HCV core antigen (HCVcAg) are two approaches that may facilitate access to HCV diagnosis in low and middle incomes countries. In this study we evaluate HCV RNA and HCV antigen testing on DBS in HIV/HCV co-infected peoples who inject drugs in Vietnam. Method One hundred and four HIV/HCV seropositive patients managed in outpatient care at the Haiphong Viet Tiep hospital were included in this study from February to March, 2014 (ANRS 12262 study). Results Eighty-six subjects were tested positive for HCV RNA in serum, median (IQR): 6.9 log10 IU/ml (5.6–7.4 log10 IU/ml). Genotypes consisted of 57 G1 (69%), 3 G3 (4%), and 22 G6 (27%). HCV RNA was detected on DBS specimens in 79 out 86 subjects with chronic hepatitis C (sensitivity 92.5%; 95% CI: 85.1–96.9%). HCV RNA level on DBS and serum was moderately correlated (r = 0.24; p = 0.05) suggesting a degradation of HCV RNA due to transportation and storage conditions. HCVcAg was detected in 75/86 dB specimens (sensitivity: 87.2%; 95% CI: 78.3–93.4%), with a strong positive relationship between DBS HCVcAg and serum HCV RNA levels (r = 0.80; P

Published
2018
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12. HIV rapid screening tests and self-tests: Be aware of differences in performance and cautious of vendorsResearch in context

Author

Thomas Mourez, Véronique Lemée, Valérie Delbos, Constance Delaugerre, Elodie Alessandri-Gradt, Manuel Etienne, François Simon, Marie-Laure Chaix, and Jean-Christophe Plantier

Subjects
Medicine, Medicine (General), R5-920
Abstract

Background: Rapid tests for HIV testing are essential tools to achieve the 90-90-90 target of the World Health Organization. Many tests are available, some directly from websites. Evaluation of the performance of rapid tests, under close to real-life usage, is therefore needed to ensure accurate diagnosis in the context of the recommendation for their more widespread use. Method: Nine third- (3G) or fourth-generation (4G) rapid screening tests or self-tests (two bought on websites), were evaluated on an extensive panel of 200 HIV-negative and 312 HIV-positive samples, representative of a wide variety of clinical situations and HIV genetic diversity. A whole blood reconstitution protocol was designed to simulate real-life usage of these tests in community-based and private settings. Findings: The specificity was high (98.5–100%) and sensitivity excellent (100%) for samples from patients chronically infected with the pandemic strains. The performance for infrequent situations with a major epidemiological and clinical impact, such as infection with divergent viruses or primary infection, was highly variable, depending on the test. One of the two 4G tests allowed detection of additional positive samples from early stages of infection, whereas the second (sold as a 4G test on a website) corresponded in reality to a 3G test. Interpretation: Our study showed that not all tests are equal for the detection of major HIV variants or early stages of HIV infection; adding the detection of specific p24Ag improved the latter point. This study also showed, for the first time, that buying through web-based vendors can be risky, due to the varying performance of the tests and questionable sales practices. Our results are of particular importance in the context of the increasing use of rapid tests in an “outside laboratory” settings. Fund: Santé Publique France, COREVIH – Normandie, and Rouen University Hospital.

Published
2018
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13. Performance evaluation of three rapid screening assays for detection of antibodies to hepatitis C virus in Cameroon

Author

Clavel Landry Kouam Fondjo, Paul Alain Tagnouokam Ngoupo, Laure Ngono, Jean-Christophe Plantier, and Richard Njouom

Subjects
Cameroon, HCV, Rapid diagnostic test, Performance, Plasma, Medicine, Biology (General), QH301-705.5, Science (General), Q1-390
Abstract

Abstract Objective This study was aimed at evaluating the performance of three CE-marked rapid diagnostic tests (RDTs): Multisure-HCV, First Response® and Toyo®; for screening anti- HCV antibody using plasma samples. Results Overall, 200 plasma samples were used. Sensibility and specificity of these RDTs range from 71 to 99 and 78 to 100% respectively. Multisure scored a sensitivity at 99% (95% CI 97–100%) and First Response reached a specificity at 90% (95% CI 85–94.9%). Further studies should be conducted to establish an algorithm using these RTDs for the detection of HCV infection in Cameroon.

Published
2018
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14. Prevalence of respiratory pathogens in COVID patients

Author

Johnny MICHEL, Maria-Alexandra STOICA, Myriam AOUITI-TRABELSI, Fabienne DE OLIVEIRA, Eva HONG, Luc-Marie JOLY, Ala-Eddine DEGHMANE, Jean-Christophe PLANTIER, and Muhamed-Kheir TAHA

Abstract

Background: Management of a novel respiratory virus causing severe pneumonitis included the use of antibiotics to prevent bacterial co-infections and secondary infections. However, the impact of this antibiotic use on the selection of resistant bacterial isolates needs to be evaluated. Methods: We conducted a single-center retrospective study from November 14, 2020 to December 31, 2021 to assess the prevalence of several members of the nasopharyngeal microbiota from PCR-positive SARS-CoV-2 subjects. The study population corresponded to 1030 nasopharyngeal swabs positive for SARS-CoV-2 at the university hospital of Rouen site in symptomatic patients aged 16 years and older. Real-time PCR was used to detect the presence of Haemophilus influenzae, Streptococcus pneumonia, Neisseria meningitidis and influenza A virus. An analysis of the ftsI gene was further used to analyze beta-lactam resistance in H. influenzae. Results: The results reveled less than expected carriage rate with 5% for H. influenzae, 1.2% for N. meningitidisand 3.7% for S. pneumoniae and an absence of influenza A. On the other hand, there was a significant difference (pftsI gene reveals 26% of predicted resistance to amoxicillin without resistance to third generation cephalosporins. Conclusions: COVID-19 pandemic has disrupted bacterial and viral epidemiology, leading to lower circulation of several respiratory pathogens.

Published
2023
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15. Antibody and T-cell response to a third dose of SARS-CoV-2 mRNA BNT162b2 vaccine in kidney transplant recipients

Author

Sophie Candon, Dominique Guerrot, Charlotte Laurent, Olivier Boyer, Véronique Lemée, Dorian Nezam, Isabelle Etienne, Jean-Christophe Plantier, Julie Lamulle, M. Hanoy, Mathilde Lemoine, Mouad Hamzaoui, Frank Le Roy, Ludivine Lebourg, Dominique Bertrand, and Fabienne Farce

Subjects
2019-20 coronavirus outbreak, COVID-19 Vaccines, Coronavirus disease 2019 (COVID-19), T-Lymphocytes, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), T cell response, Kidney transplant, medicine, Humans, RNA, Messenger, Letter to the Editor, BNT162 Vaccine, Kidney transplantation, Messenger RNA, biology, SARS-CoV-2, business.industry, COVID-19, medicine.disease, Kidney Transplantation, Virology, Transplant Recipients, Nephrology, biology.protein, Antibody, business
Published
2021
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16. Differential Regulation of NF-κB-Mediated Proviral and Antiviral Host Gene Expression by Primate Lentiviral Nef and Vpu Proteins

Author

Daniel Sauter, Dominik Hotter, Benoît Van Driessche, Christina M. Stürzel, Silvia F. Kluge, Steffen Wildum, Hangxing Yu, Bernd Baumann, Thomas Wirth, Jean-Christophe Plantier, Marie Leoz, Beatrice H. Hahn, Carine Van Lint, and Frank Kirchhoff

Subjects
Biology (General), QH301-705.5
Abstract

NF-κB is essential for effective transcription of primate lentiviral genomes and also activates antiviral host genes. Here, we show that the early protein Nef of most primate lentiviruses enhances NF-κB activation. In contrast, the late protein Vpu of HIV-1 and its simian precursors inhibits activation of NF-κB, even in the presence of Nef. Although this effect of Vpu did not correlate with its ability to interact with β-TrCP, it involved the stabilization of IκB and reduced nuclear translocation of p65. Interestingly, however, Vpu did not affect casein kinase II-mediated phosphorylation of p65. Lack of Vpu was associated with increased NF-κB activation and induction of interferon and interferon-stimulated genes (ISGs) in HIV-1-infected T cells. Thus, HIV-1 and its simian precursors employ Nef to boost NF-κB activation early during the viral life cycle to initiate proviral transcription, while Vpu is used to downmodulate NF-κB-dependent expression of ISGs at later stages.

Published
2015
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17. Waning antibody response and cellular immunity 6 months after third dose SARS-Cov-2 mRNA BNT162b2 vaccine in kidney transplant recipients

Author

Dominique Bertrand, Veronique Lemée, Charlotte Laurent, Mathilde Lemoine, Mélanie Hanoy, Frank Le Roy, Dorian Nezam, Diana Pruteanu, Ludivine Lebourg, Steven Grange, Jean-Christophe Plantier, Olivier Boyer, Dominique Guerrot, and Sophie Candon

Subjects
Immunity, Cellular, Transplantation, SARS-CoV-2, Antibody Formation, Immunization, Secondary, COVID-19, Humans, Immunology and Allergy, Pharmacology (medical), Antibodies, Viral, Kidney Transplantation, BNT162 Vaccine, Transplant Recipients
Published
2022
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18. In vitroreplicative potential of an HIV-1/MO intergroup recombinant virus compared to HIV-1/M and HIV-1/O parental viruses

Author

Alice Moisan, Fabienne De Oliveira, Manon Mabillotte, Elodie Alessandri-Gradt, Thomas Mourez, and Jean-Christophe Plantier

Abstract

HIV-1 is characterized by high genetic diversity and genetic recombination is one of the major evolution processes. Despite their great genetic divergence, HIV-1 group M, pandemic, and group O, endemic in Cameroon, can generate HIV-1/MO intergroup recombinants. The current description of 19 HIV-1/MO recombinant forms (URF_MO) raises the question of a possible benefit of the recombination and the modalities of their emergence.Therefore, the objectives of this work were to studyin vitrothe replicative potential of HIV-1/MO recombinant forms.The replicative potential was analyzed, based on a simple recombination pattern, [Ogag/pol-Menv], harboring a breakpoint in Vpr, due to a recombination hotspot in this region. For this, a chimeric infectious molecular clone (IMC) was synthesized from HIV-1/M subtype B and HIV-1/O subgroup T and recombinant viruses were obtained by transfection and co-culture. To compare the replicative potential of recombinant viruses with HIV-1/M and HIV-1/O parental viruses, two markers were monitored in culture supernatants: Reverse Transcriptase (RT) activity and P24 antigen concentration. The results showed a superiority of the group M parental virus compared to group O for both markers. In contrast, for the HIV-1/OM recombinant virus, RT activity data did not overlap with the concentration of P24 antigen, suggesting a hybrid behavior of the recombinant, in terms of enzyme activity and P24 production.These results highlighted many hypotheses about the impact of recombination on replicative potential and demonstrated once again the significant plasticity of HIV genomes and their infinite possibility of evolution.ImportanceHIV-1/M and HIV-1/O can generate HIV-1/MO intergroup recombinants. The current description of 19 URF_MO raises the question of a possible benefit of recombination in terms of emergence. The objectives of this work were to studyin vitrothe replicative potential of HIV-1/MO recombinant viruses. For this, a chimeric infectious molecular clone (IMC) generated from HIV-1/M subtype B and HIV-1/O subgroup T and recombinant viruses were obtained by transfection and co-culture. To compare the replicative potential of recombinant viruses with HIV-1/M and HIV-1/O parental viruses, RT activity and P24 antigen concentration were monitored in culture supernatants. A superiority of the group M parental virus compared to group O was observed for both markers whereas a hybrid behavior in terms of enzyme activity and P24 production was found for the recombinant virus. These results demonstrated once again the significant plasticity of HIV genomes and their infinite possibility of evolution.

Published
2022
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19. [Human Immunodeficiency Virus type 1 variants of groups N, 0 and P]

Author

Aurélia, Vessière, François, Simon, and Jean-Christophe, Plantier

Abstract

The HIV pandemic is caused by viruses of type 1 group M (HIV-M). Beside the majority of these viruses, there are many divergent variants, leading to the definition of HIV-2 and group N, O and P in HIV-1. HIV-1 groups are the result of independent cross-species of viruses from chim- panzees and gorillas living in Western Central Africa. These simian origins and the necessary adaptation to the human species are the sources of genomic characteristics, phylogenetic and viral properties, specific to each group. The natural history of the infections associated to these variants nevertheless seems similar to that of HIV-M, with a high viral replication in vivo associated with immunosuppression. These non-M variants all have been described for the first time in patients of Cameroonian origin. The Western Central Africa is the epicenter of the epidemics of non-M variants, and the diffusion outside this area is anecdotal, except in France. In Cameroon, the origin of all groups cur- rently described, HIV-O infections account for 1% of HIV infections, while only 15 cases of HIV-N infections and two HIV-P infections have been repor- ted to date. If the important genetic diversity of these variants requires the use of specific tools for serological identification and molecular characterization, diagnosis and virological monitoring of these infections now appear possible with current commercial kits; however, very little data are available on the response to antiretroviral therapy and no recommendations are defined in case of failure. Despite improved knowledge on these rare variants, many fascinating questions persist about their origin, genetic evolution and reasons for their low epidemiological spread. Their discovery, and the description of many simian viruses, demonstrates a dynamic transmission to humans, making it likely that other variants may exist; we should therefore pursue a careful surveillance, especially when faced to discrepancy between screening and therapeutic management of HIV infections.

Published
2022

20. HIV-1 non-group M phenotypic susceptibility in vitro to bictegravir and cabotegravir

Author

Quentin Le Hingrat, Charlotte Charpentier, Diane Descamps, Charlène Martin, Jean-Christophe Plantier, Elodie Alessandri-Gradt, and Ségolène Gracias

Subjects
Microbiology (medical), Pyridones, Population, HIV Infections, HIV Integrase, Piperazines, chemistry.chemical_compound, Cabotegravir, Polymorphism (computer science), Drug Resistance, Viral, Humans, Pharmacology (medical), HIV Integrase Inhibitors, education, IC50, Pharmacology, education.field_of_study, biology, Bictegravir, Amides, Phenotype, Virology, In vitro, Integrase, Infectious Diseases, chemistry, HIV-1, biology.protein, Heterocyclic Compounds, 3-Ring
Abstract

Objectives HIV-1 group O (HIV-1/O) is one of the four HIV-1 groups and is endemic in Cameroon, representing 1% of HIV-1 infections in the population. Around 50% of the strains of this group naturally show a mutation (Y181C) providing them with resistance to NNRTIs and making therapeutic management more difficult. Today, the WHO recommends the use of integrase strand transfer inhibitors (INSTIs) as first-line treatment. Bictegravir and cabotegravir are the two most recent INSTIs. Because of the genetic polymorphism of HIV-1/O, studies are required to evaluate their phenotypic susceptibility to these two drugs. Patients and methods We performed a phenotypic study on a large panel including 41 HIV-1/O clinical isolates and other rare non-group M HIV-1 (2 HIV-1/N and 1 HIV-1/P) to evaluate in vitro susceptibility to bictegravir and cabotegravir. Results The results showed an overall susceptibility of non-group M strains to the two drugs compared with HIV-1 group M. There was no difference between the mean (min–max) IC50 of HIV-1/M [1.86 (0.93–4.12) and 5.24 (1.76–12.41) nM for bictegravir and cabotegravir, respectively] and HIV-1/non-M [2.17 (0.03–9.47) and 4.88 (0.02–15.64) nM for bictegravir and cabotegravir, respectively]. However, we found a significant difference between IC50 values for bictegravir and cabotegravir in the whole panel (P value Conclusions This study has shown encouraging results regarding the clinical use of these drugs in HIV-1/non-M-infected patients, which will need to be confirmed with clinical data.

Published
2021
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22. Assessment of Multiplex Digital Droplet RT-PCR as a Diagnostic Tool for SARS-CoV-2 Detection in Nasopharyngeal Swabs and Saliva Samples

Author

Thierry Frebourg, Kévin Cassinari, Ségolène Gracias, Kevin Alexandre, Jean-Christophe Plantier, Ludivine Beaussire, Manuel Etienne, François Caron, Elodie Alessandri-Gradt, Nasrin Sarafan-Vasseur, Pascal Chambon, Françoise Charbonnier, and Claude Houdayer

Subjects
0301 basic medicine, 2019-20 coronavirus outbreak, Saliva, Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Clinical Biochemistry, Article, Specimen Handling, 03 medical and health sciences, 0302 clinical medicine, stomatognathic system, Limit of Detection, Nasopharynx, Humans, Medicine, Sampling (medicine), Multiplex, 030212 general & internal medicine, Biochemistry, medical, saliva, SARS-CoV-2, Reverse Transcriptase Polymerase Chain Reaction, business.industry, Biochemistry (medical), COVID-19, Reproducibility of Results, RT-ddPCR, sensitivity, nasopharyngeal swab, Virology, 030104 developmental biology, Real-time polymerase chain reaction, COVID-19 Nucleic Acid Testing, RNA, Viral, business
Abstract

Background Reverse transcription-quantitative PCR on nasopharyngeal swabs is currently the reference COVID-19 diagnosis method but exhibits imperfect sensitivity. Methods We developed a multiplex reverse transcription-digital droplet PCR (RT-ddPCR) assay, targeting 6 SARS-CoV-2 genomic regions, and evaluated it on nasopharyngeal swabs and saliva samples collected from 130 COVID-19 positive or negative ambulatory individuals, who presented symptoms suggestive of mild or moderate SARS-CoV2 infection. Results For the nasopharyngeal swab samples, the results obtained using the 6-plex RT-ddPCR and RT-qPCR assays were all concordant. The 6-plex RT-ddPCR assay was more sensitive than RT-qPCR (85% versus 62%) on saliva samples from patients with positive nasopharyngeal swabs. Conclusion Multiplex RT-ddPCR represents an alternative and complementary tool for the diagnosis of COVID-19, in particular to control RT-qPCR ambiguous results. It can also be applied to saliva for repetitive sampling and testing individuals for whom nasopharyngeal swabbing is not possible.

Published
2021
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23. Differential utilization of CD4+ by transmitted/founder and chronic envelope glycoproteins in a MSM HIV-1 subtype B transmission cluster

Author

Olivia Blake, Denys Brand, Nicolas Bellini, Emmanuelle Roch, Fabrizio Mammano, Alain Moreau, Martine Braibant, Julie Migraine, Jean-Christophe Plantier, Mélanie Bouvin-Pley, Marie Leoz, Morphogénèse et antigénicité du VIH et du virus des Hépatites (MAVIVH - U1259 Inserm - CHRU Tours ), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Groupe de Recherche sur les Antimicrobiens et les Micro-Organismes (GRAM 1.0), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU), CHU Rouen, Normandie Université (NU), Université de Montréal (UdeM), Institut de Recherches Cliniques de Montréal (IRCM), Génétique et Ecologie des Virus, Génétique des Virus et Pathogénèse des Maladies Virales, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Mammano, Fabrizio, Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7)

Subjects
CD4-Positive T-Lymphocytes, Male, 0301 basic medicine, [SDV]Life Sciences [q-bio], Immunology, MESH: Glycoproteins, HIV Infections, Context (language use), Viral quasispecies, CCR5 receptor antagonist, Biology, HIV transmission cluster, MESH: HIV-1, MESH: Homosexuality, Male, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Viral Envelope Proteins, Interferon, Genotype, medicine, Humans, Immunology and Allergy, 030212 general & internal medicine, Homosexuality, Male, Glycoproteins, Maraviroc, Infectivity, MESH: Humans, Transmission (medicine), envelope glycoproteins, MESH: CD4-Positive T-Lymphocytes, MESH: HIV Infections, Virology, MESH: Male, 3. Good health, [SDV] Life Sciences [q-bio], 030104 developmental biology, Infectious Diseases, chemistry, MESH: Viral Envelope Proteins, HIV-1, CD4 þ binding, genetic bottleneck, medicine.drug
Abstract

International audience; Objective: HIV-1 transmission leads to a genetic bottleneck, with one or a few variants of the donor quasispecies establishing an infection in the new host. We aimed to characterize this bottleneck in more detail, by comparing the properties of HIV envelope glycoproteins from acute and chronic infections within the particular context of a male-to-male transmission cluster. Design: We compared the genotypic and phenotypic properties of envelope glycoproteins from viral variants derived from five study participants from the same transmission cluster. Methods: We used single-genome amplification to generate a collection of full-length env sequences. We then constructed pseudotyped viruses expressing selected Env variants from the quasispecies infecting each study participant and compared their infectivities and sensitivities to various entry inhibitors. Results: The genotypic analyses confirmed the genetic bottleneck expected after HIV transmission, with a limited number of variants identified in four study participants during acute infection. However, the transmitted sequences harbored no evident common signature and belonged to various genetic lineages. The phenotypic analyses revealed no difference in infectivity, susceptibility to the CCR5 antagonist maraviroc, the fusion inhibitor enfurvitide or type-I interferon between viruses from participants with acute and chronic infections. The key property distinguishing transmitted viruses was a higher resistance to soluble CD4 þ , correlated with greater sensitivity to occupation of the CD4 þ receptor by the anti-CD4 þ antibodies LM52 and SK3. Conclusion: These results suggest that envelope glycoproteins from transmitted/ founder viruses bind CD4 þ less efficiently than those of viruses from chronic infections.

Published
2020
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24. Evidence of Transmission and Circulation of Deltacron XD Recombinant Severe Acute Respiratory Syndrome Coronavirus 2 in Northwest France

Author

Alice Moisan, Brice Mastrovito, Fabienne De Oliveira, Mélanie Martel, Hugues Hedin, Marie Leoz, Nicolas Nesi, Justine Schaeffer, Meriadeg Ar Gouilh, and Jean-Christophe Plantier

Subjects
Microbiology (medical), Infectious Diseases, SARS-CoV-2, Humans, COVID-19, France
Abstract

In February 2022, samples collected in northwest France showed discordant molecular results. After virological and epidemiological investigations, 17 cases of Deltacron XD recombinant severe acute respiratory syndrome coronavirus 2 were confirmed by sequencing or suspected due to epidemiological links, showing evidence of an extended transmission event and circulation of this form, with low clinical severity.

Published
2022

25. Investigation of outbreak cases infected with the SARS-CoV-2 B.1.640 variant in a fully vaccinated elderly population, Normandy, France, November to December 2021

Author

Brice Mastrovito, Chloé Naimi, Leslie Kouam, Xavier Naudot, Lucie Fournier, Guillaume Spaccaferri, Jean-Christophe Plantier, Anaïs Soares, Fabienne De Oliveira, Marie Gueudin, Véronique Jacomo, Céline Leroy, Alice Moisan, Mélanie Martel, Santé publique France - French National Public Health Agency [Saint-Maurice, France], Eurofins Biomnis, Dynamique Microbienne associée aux Infections Urinaires et Respiratoires (DYNAMICURE), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de virologie [Rouen], Hôpital Charles Nicolle [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Normandie Université (NU)-Département de microbiologie : Bactério, Virologie, Parasito, Hygiène, Agence Régionale de Santé de Normandie [Caen] (ARS Normandie), and Mzembaba, Sandy

Subjects
[SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Epidemiology, SARS-CoV-2, Public Health, Environmental and Occupational Health, COVID-19, [SDV.MP.PRO] Life Sciences [q-bio]/Microbiology and Parasitology/Protistology, [SDV.MP.PRO]Life Sciences [q-bio]/Microbiology and Parasitology/Protistology, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, [SDV.MP.MYC] Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, Disease Outbreaks, Virology, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Humans, France, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, [SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, Aged
Abstract

International audience; Three confirmed infections with the SARS-CoV-2 B.1.640 variant under monitoring were reported in Normandy, north-western France in late November 2021. Investigations led to the identification of two events linked to the same cluster. A total of 75 confirmed and probable B.1.640 cases were reported. All had completed the primary vaccination series. Sixty-two cases were older than 65 years. Fifty-six cases had symptoms and four were hospitalised. This investigation provides preliminary results concerning a variant with limited information currently available.

Published
2022
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26. The Two-Phase Emergence of Non Pandemic HIV-1 Group O in Cameroon.

Author

Marie Leoz, Felix Feyertag, Anfumbom Kfutwah, Philippe Mauclère, Guillaume Lachenal, Florence Damond, Fabienne De Oliveira, Véronique Lemée, François Simon, David L Robertson, and Jean-Christophe Plantier

Subjects
Immunologic diseases. Allergy, RC581-607, Biology (General), QH301-705.5
Abstract

Unlike the pandemic form of HIV-1 (group M), group O viruses are endemic in west central Africa, especially in Cameroon. However, little is known about group O's genetic evolution, and why this highly divergent lineage has not become pandemic. Using a unique and large set of group O sequences from samples collected from 1987 to 2012, we find that this lineage has evolved in successive slow and fast phases of diversification, with a most recent common ancestor estimated to have existed around 1930 (1914-1944). The most rapid periods of diversification occurred in the 1950s and in the 1980s, and could be linked to favourable epidemiological contexts in Cameroon. Group O genetic diversity reflects this two-phase evolution, with two distinct populations potentially having different viral properties. The currently predominant viral population emerged in the 1980s, from an ancient population which had first developed in the 1950s, and is characterized by higher growth and evolutionary rates, and the natural presence of the Y181C resistance mutation, thought to confer a phenotypic advantage. Our findings show that although this evolutionary pattern is specific to HIV-1 group O, it paralleled the early spread of HIV-1 group M in the Democratic Republic of Congo. Both viral lineages are likely to have benefited from similar epidemiological contexts. The relative role of virological and social factors in the distinct epidemic histories of HIV-1 group O and M needs to be reassessed.

Published
2015
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27. Dissociated humoral and cellular immune responses after a three-dose schema of BNT162b2 vaccine in patients receiving anti-CD20 monoclonal antibody maintenance treatment for B-cell lymphomas

Author

Sydney Dubois, Doriane Richard, Louis-Ferdinand Pepin, Marion Carette, Sophie Candon, Nathalie Contentin, Stéphane Leprêtre, Emilie Leveque, Aspasia Stamatoullas, Florian Bouclet, Jean-Christophe Plantier, Alain Dalleac, Edwige Boulet, Veronique Lemee, Pascaline Etancelin, Anne-Lise Menard, Cedric Paquin, Hélène Lanic, Manuel Etienne, Hervé Tilly, Victor Bobée, Fabrice Jardin, Vincent Camus, Nathalie Cardinael, Mustafa Alani, and Emilie Lemasle

Subjects
Immunity, Cellular, Vaccines, Lymphoma, B-Cell, medicine.drug_class, business.industry, Antibodies, Monoclonal, Hematology, Monoclonal antibody, Antibodies, Viral, Schema (genetic algorithms), medicine.anatomical_structure, Immune system, Immunology, medicine, Humans, In patient, Anti cd20, business, B cell, BNT162 Vaccine
Published
2021

28. Plasma HIV-2 RNA According to CD4 Count Strata among HIV-2-Infected Adults in the IeDEA West Africa Collaboration.

Author

Didier K Ekouévi, Véronique Avettand-Fènoël, Boris K Tchounga, Patrick A Coffie, Adrien Sawadogo, Daouda Minta, Albert Minga, Serge P Eholie, Jean-Christophe Plantier, Florence Damond, François Dabis, Christine Rouzioux, and IeDEA West Africa collaboration

Subjects
Medicine, Science
Abstract

Plasma HIV-1 RNA monitoring is one of the standard tests for the management of HIV-1 infection. While HIV-1 RNA can be quantified using several commercial tests, no test has been commercialized for HIV-2 RNA quantification. We studied the relationship between plasma HIV-2 viral load (VL) and CD4 count in West African patients who were either receiving antiretroviral therapy (ART) or treatment-naïve.A cross sectional survey was conducted among HIV-2-infected individuals followed in three countries in West Africa from March to December 2012. All HIV-2 infected-patients who attended one of the participating clinics were proposed a plasma HIV-2 viral load measurement. HIV-2 RNA was quantified using the new ultrasensitive in-house real-time PCR assay with a detection threshold of 10 copies/ mL (cps/mL).A total of 351 HIV-2-infected individuals participated in this study, of whom 131 (37.3%) were treatment naïve and 220 (62.7%) had initiated ART. Among treatment-naïve patients, 60 (46.5%) had undetectable plasma HIV-2 viral load (1000 cps/mL in 6.0% of the patients. Most of the treatment-naïve patients (70.2%) had CD4-T cell count ≥500 cells/mm3 and 43 (46.7%) of these patients had a detectable VL (≥10 cps/mL). Among the 220 patients receiving ART, the median CD4-T cell count rose from 231 to 393 cells/mm3 (IQR [259-561]) after a median follow-up duration of 38 months and 145 (66.0%) patients had CD4-T cell count ≤ 500 cells/mm3 with a median viral load of 10 cps/mL (IQR [10-33]). Seventy five (34.0%) patients had CD4-T cell count ≥ 500 cells/mm3, among them 14 (18.7%) had a VL between 10-100 cps/mL and 2 (2.6%) had VL >100 cps/mL.This study suggests that the combination of CD4-T cell count and ultrasensitive HIV-2 viral load quantification with a threshold of 10 cps/mL, could improve ART initiation among treatment naïve HIV-2-infected patients and the monitoring of ART response among patients receiving treatment.

Published
2015
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29. False-negative Results of Human Immunodeficiency Virus (HIV) Rapid Testing in HIV Controllers

Author

Mehdi Hage-Sleiman, Olivier Lambotte, Christine Rouzioux, Elise Gardiennet, Véronique Avettand-Fenoel, Alice-Andrée Mariaggi, Marine Fillion, Faroudy Boufassa, Pauline Trémeaux, Jean-Christophe Plantier, Adeline Melard, CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Virologie [CHU Cochin], Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris-Sud - Paris 11 (UP11), Université Paris-Saclay, Groupe de Recherche sur l'Adaptation Microbienne (GRAM 2.0), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Université de Caen Normandie (UNICAEN), Normandie Université (NU), Laboratoire de virologie [Rouen], Hôpital Charles Nicolle [Rouen]-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Département de microbiologie : Bactério, Virologie, Parasito, Hygiène, Laboratoire de Virologie [CHU Necker], Université Paris Descartes - Paris 5 (UPD5), Immunologie des Maladies Virales et Autoimmunes (IMVA - U1184), 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), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Codex ANRS cohort study group, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Université de Caen Normandie (UNICAEN), Hôpital Charles Nicolle [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Cochin [AP-HP], Epidemiology and Population Health, Epidemiology of HIV and STI Team (U1018 Inserm ), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Normandie Université (NU)-Normandie Université (NU)-Département de microbiologie : Bactério, Virologie, Parasito, Hygiène-Hôpital Charles Nicolle [Rouen]-CHU Rouen, and Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP]

Subjects
0301 basic medicine, Microbiology (medical), HIV rapid screening test, Blotting, Western, HIV diagnosis, Human immunodeficiency virus (HIV), Enzyme-Linked Immunosorbent Assay, HIV Infections, HIV Antibodies, medicine.disease_cause, [SDV.MP.PRO]Life Sciences [q-bio]/Microbiology and Parasitology/Protistology, Serology, Immunoenzyme Techniques, 03 medical and health sciences, Rapid screening test, 0302 clinical medicine, Western blot, medicine, Humans, 030212 general & internal medicine, [SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, Rapid testing, medicine.diagnostic_test, business.industry, HIV, HIV controllers, MESH: ELISA, HIV-1 Western blot, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, 030112 virology, Virology, 3. Good health, Infectious Diseases, Immunoassay, HIV-2, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, ELISA, business, Negative Results
Abstract

Serological assays were performed on 85 human immunodeficiency virus-controller samples . 6% presented a negative rapid screening test 7% presented an indeterminate Western blot. The enzyme immunoassay ratio decreased in controllers who had continual negative ultrasensitive HIV RNA results since inclusion.

Published
2019
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30. Virological response to integrase strand transfer inhibitor-based antiretroviral combinations in HIV-1 group O-infected patients

Author

Jean-Christophe Plantier, Elodie Alessandri-Gradt, Marie Leoz, Guillemette Unal, Groupe de Recherche sur l'Adaptation Microbienne (GRAM 2.0), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Université de Caen Normandie (UNICAEN), Normandie Université (NU), Laboratoire de virologie [Rouen], Hôpital Charles Nicolle [Rouen]-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), and Normandie Université (NU)-Département de microbiologie : Bactério, Virologie, Parasito, Hygiène

Subjects
Adult, Male, 0301 basic medicine, Cart, Adolescent, Genotype, Immunology, Human immunodeficiency virus (HIV), HIV Infections, Context (language use), HIV Integrase, medicine.disease_cause, [SDV.MP.PRO]Life Sciences [q-bio]/Microbiology and Parasitology/Protistology, Virological response, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Acquired immunodeficiency syndrome (AIDS), Antiretroviral Therapy, Highly Active, Drug Resistance, Viral, medicine, Humans, Immunology and Allergy, HIV Integrase Inhibitors, 030212 general & internal medicine, [SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, Aged, biology, business.industry, virus diseases, Middle Aged, Viral Load, medicine.disease, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Virology, 3. Good health, Integrase, Integrase strand transfer inhibitor, Treatment Outcome, 030104 developmental biology, Infectious Diseases, Anti-Retroviral Agents, Mutation, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, HIV-1, biology.protein, Female, Viral hepatitis, business
Abstract

International audience; Although integrase strand transfer inhibitors (INSTIs) are widely used in HIV-1 group M (HIV-1/M) infections, little is known about their efficacy against genetically divergent HIV-1 group O (HIV-1/O) strains. Previous phenotypic works have demonstrated the variable susceptibility of HIV-1/O strains, depending on INSTI drugs. Clinical data are very limited and obtained from a few patients.OBJECTIVES:To investigate the virological success rate of an INSTI-based combination of antiretroviral therapy (cART) in a large population of HIV-1/O-infected patients, and to describe resistance-associated mutations (RAM) at virological failure.METHODS:The virological response of 39 patients receiving INSTI-based cART during their follow-up was analysed i) at the last point of the first INSTI initiation and ii) at their most recent visit. RAM analysis was performed at virological failures. Resistance interpretation was based on the French National Agency of Research on AIDS and viral hepatitis (ANRS) rules.RESULTS:Virological success at both time points of analysis was high, with more than 87% of the patients with undetectable plasma viral load. Among the six patients with virological failure, three selected RAM described for HIV-1/M resistance, and two had already RAM, before INSTI initiation.CONCLUSION:Our results show that HIV-1/O infected patients receiving INSTI-based cART presented a high rate of virological success whatever their previous lines; we have also shown that resistance rules for HIV-1/M could be considered when failure occurs. These data are of importance especially in the context of WHO recommendations for a wider use of this class.

Published
2019
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31. Antibody response to SARS-CoV-2 messenger RNA BNT162b2 vaccine in kidney transplant recipients and in-centre and satellite centre haemodialysis patients

Author

Dorian Nezam, Frank Le Roy, Dominique Bertrand, Stéphane Edet, Charlotte Laurent, Isabelle Etienne, Sophie Candon, Mathilde Lemoine, Lebourg Ludivine, Mouad Hamzaoui, Dominique Guerrot, M. Hanoy, Véronique Lemée, and Jean-Christophe Plantier

Subjects
Transplantation, Messenger RNA, 2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), biology, business.industry, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), biology.organism_classification, Virology, Kidney transplant, Antibody response, Nephrology, Medicine, Satellite (biology), business, AcademicSubjects/MED00340, Letter to the Editor
Published
2021

32. Viral etiology of respiratory tract infections in children at the pediatric hospital in Ouagadougou (Burkina Faso).

Author

Solange Ouédraogo, Blaise Traoré, Zah Ange Brice Nene Bi, Firmin Tiandama Yonli, Donatien Kima, Pierre Bonané, Lassané Congo, Rasmata Ouédraogo Traoré, Diarra Yé, Christophe Marguet, Jean-Christophe Plantier, Astrid Vabret, and Marie Gueudin

Subjects
Medicine, Science
Abstract

BACKGROUND: Acute respiratory infections (ARIs) are a major cause of morbidity and mortality in children in Africa. The circulation of viruses classically implicated in ARIs is poorly known in Burkina Faso. The aim of this study was to identify the respiratory viruses present in children admitted to or consulting at the pediatric hospital in Ouagadougou. METHODS: From July 2010 to July 2011, we tested nasal aspirates of 209 children with upper or lower respiratory infection for main respiratory viruses (respiratory syncytial virus (RSV), metapneumovirus, adenovirus, parainfluenza viruses 1, 2 and 3, influenza A, B and C, rhinovirus/enterovirus), by immunofluorescence locally in Ouagadougou, and by PCR in France. Bacteria have also been investigated in 97 samples. RESULTS: 153 children (73.2%) carried at least one virus and 175 viruses were detected. Rhinoviruses/enteroviruses were most frequently detected (rhinovirus n = 88; enterovirus n = 38) and were found to circulate throughout the year. An epidemic of RSV infections (n = 25) was identified in September/October, followed by an epidemic of influenza virus (n = 13), mostly H1N1pdm09. This epidemic occurred during the period of the year in which nighttime temperatures and humidity were at their lowest. Other viruses tested were detected only sporadically. Twenty-two viral co-infections were observed. Bacteria were detected in 29/97 samples with 22 viral/bacterial co-infections. CONCLUSIONS: This study, the first of its type in Burkina Faso, warrants further investigation to confirm the seasonality of RSV infection and to improve local diagnosis of influenza. The long-term objective is to optimize therapeutic management of infected children.

Published
2014
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33. Early phylodynamics analysis of the COVID-19 epidemic in France

Author

Jean-Christophe Plantier, Antonin Bal, Gonché Danesh, Anne-Geneviève Marcelin, Laurence Josset, Sonia Burrel, Sylvie Behillil, Sylvie van der Werf, Etienne Simon-Loriere, Samuel Alizon, Grégory Destras, Yannis Michalakis, Vincent Enouf, Vincent Thibault, Bruno Lina, Baptiste Elie, David Boutolleau, Mircea T. Sofonea, Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), Institut des Agents Infectieux [Lyon] (IAI), Hospices Civils de Lyon (HCL), Hôpital de la Croix-Rousse [CHU - HCL], Virology and human respiratory Pathologies - Virology and human respiratory Pathologies (VirPath), Centre International de Recherche en Infectiologie - UMR (CIRI), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Génétique Moléculaire des Virus à ARN - Molecular Genetics of RNA Viruses (GMV-ARN (UMR_3569 / U-Pasteur_2)), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Centre National de Référence des Virus des Infections Respiratoires (dont la Grippe) [Lyon] (CNR), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Sorbonne Université (SU)-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), Hôpital Charles Nicolle [Rouen], CHU Pontchaillou [Rennes], Génomique évolutive des virus à ARN - Evolutionary genomics of RNA viruses, Institut Pasteur [Paris], Pasteur International Bioresources network (PIBNet), Evolution Théorique et Expérimentale (MIVEGEC-ETE), Perturbations, Evolution, Virulence (PEV), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), ANR-20-COVI-0098,PHYEPI,Intégration de données de séquences et d'incidence pour analyser et contrôler les épidémies virales(2020), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Centre National de Référence des virus des infections respiratoires (dont la grippe) - National Reference Center Virus Influenzae [Paris] (CNR - laboratoire coordonnateur), Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Centre National de Référence des Virus des Infections Respiratoires (dont la Grippe) [Lyon] (CNR - laboratoire associé), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), CHU Rouen, Normandie Université (NU)-Normandie Université (NU), Centre interdisciplinaire de recherche en biologie (CIRB), Labex MemoLife, École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Collège de France (CdF (institution))-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris]-Université de Paris (UP), Génétique et évolution des maladies infectieuses (GEMI), Centre National de Référence des virus des infections respiratoires (dont la grippe) - National Reference Center Virus Influenzae [Paris] (CNR), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Génétique et évolution des maladies infectieuses (GEMI), Alizon, Samuel, and Intégration de données de séquences et d'incidence pour analyser et contrôler les épidémies virales - - PHYEPI2020 - ANR-20-COVI-0098 - COVID-19 - VALID

Subjects
0106 biological sciences, Coronavirus disease 2019 (COVID-19), Genomic data, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Context (language use), [SDV.BID.SPT]Life Sciences [q-bio]/Biodiversity/Systematics, Phylogenetics and taxonomy, 010603 evolutionary biology, 01 natural sciences, 03 medical and health sciences, [SDV.EE.ECO]Life Sciences [q-bio]/Ecology, environment/Ecosystems, Incidence data, Pandemic, [SDV.BID.SPT] Life Sciences [q-bio]/Biodiversity/Systematics, Phylogenetics and taxonomy, [SDV.BID.EVO] Life Sciences [q-bio]/Biodiversity/Populations and Evolution [q-bio.PE], [SDV.EE.ECO] Life Sciences [q-bio]/Ecology, environment/Ecosystems, [SDV.EE.SANT] Life Sciences [q-bio]/Ecology, environment/Health, 030304 developmental biology, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.EE.SANT]Life Sciences [q-bio]/Ecology, environment/Health, 0303 health sciences, [SDV.BIBS] Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], [SDV.GEN.GPO]Life Sciences [q-bio]/Genetics/Populations and Evolution [q-bio.PE], [SDV.BID.EVO]Life Sciences [q-bio]/Biodiversity/Populations and Evolution [q-bio.PE], [SDV.EE.IEO] Life Sciences [q-bio]/Ecology, environment/Symbiosis, [INFO.INFO-MO]Computer Science [cs]/Modeling and Simulation, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], 3. Good health, [SDE.BE] Environmental Sciences/Biodiversity and Ecology, Geography, Viral phylodynamics, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.GEN.GPO] Life Sciences [q-bio]/Genetics/Populations and Evolution [q-bio.PE], [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, [INFO.INFO-MO] Computer Science [cs]/Modeling and Simulation, [SDE.BE]Environmental Sciences/Biodiversity and Ecology, Contact tracing, Demography, [SDV.EE.IEO]Life Sciences [q-bio]/Ecology, environment/Symbiosis
Abstract

France was one of the first countries to be reached by the COVID-19 pandemic. Here, we analyse 196 SARS-Cov-2 genomes collected between Jan 24 and Mar 24 2020, and perform a phylodynamics analysis. In particular, we analyse the doubling time, reproduction number (ℛt) and infection duration associated with the epidemic wave that was detected in incidence data starting from Feb 27. Different models suggest a slowing down of the epidemic in Mar, which would be consistent with the implementation of the national lock-down on Mar 17. The inferred distributions for the effective infection duration andℛtare in line with those estimated from contact tracing data. Finally, based on the available sequence data, we estimate that the French epidemic wave originated between mid-Jan and early Feb. Overall, this analysis shows the potential to use sequence genomic data to inform public health decisions in an epidemic crisis context and calls for further analyses with denser sampling.

Published
2021
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34. Performance Analysis of Three Commercial Kits Designed for RNA Quantification of HIV-1 Group O Variants

Author

Marie Gueudin, Guillemette Unal, Adeline Baron, Marie Leoz, Elodie Alessandri-Gradt, and Jean-Christophe Plantier

Subjects
Chromatography, Cobas taqman, Human immunodeficiency virus (HIV), RNA, Reproducibility of Results, HIV Infections, Viral Load, medicine.disease_cause, Real-Time Polymerase Chain Reaction, Spearman's rank correlation coefficient, Sensitivity and Specificity, Infectious Diseases, Rna quantification, HIV Seropositivity, medicine, HIV-1, Humans, RNA, Viral, Pharmacology (medical), Reagent Kits, Diagnostic, Quantitative analysis (chemistry), Viral load, Mathematics
Abstract

BACKGROUND The genetic divergence of HIV-1 group O is high relative to pandemic group M, which could impact detection and quantification of plasma RNA. Recent commercial kits for RNA quantification seem to show good performances in HIV-1/O, but discrepancies are still observed. Here, we compare the performances of 3 commercial assays for the RNA quantification of HIV-1/O. METHODS We studied the RNA quantification of 117 clinical samples using Abbott RealTime HIV-1, Cepheid Xpert HIV-1 Viral Load, or Roche Cobas TaqMan HIV-1 v2. First, we conducted a qualitative description, and second, we focused on a quantitative analysis of the results above 40 cp/mL. The degree of agreement between methods and the strength of the correlation of viral load determination were estimated using Bland-Altman plot and Passing-Bablok regression with the Spearman coefficient, respectively. RESULTS Our 2-by-2 analysis showed that the Abbott and Cepheid assays were very close in terms of correlation and dispersion of points, whereas Roche presented higher values in the highest range of quantification (>5 log10). The Cepheid assay combined better correlation with the consensus value and a lower dispersion of values, leading to an overall better performance of quantification. The quantification was still impacted by intragroup genetic diversity with, here, 1 strain (YBF26). CONCLUSIONS Using a new approach to compare the performances of RNA quantification between more than 2 techniques, we demonstrated that Cepheid could be the most suitable assay for HIV-1/O quantification, although the results from all assays remained strain dependent.

Published
2020

35. Convergent Evolution of HLA-C Downmodulation in HIV-1 and HIV-2

Author

Richard Apps, Kristina Hopfensperger, Daniel Sauter, Andrés Finzi, Frederic Bibollet-Ruche, Beatrice H. Hahn, Jonathan Richard, Marie Leoz, Frank Kirchhoff, Christina M. Stürzel, and Jean-Christophe Plantier

Subjects
CD4-Positive T-Lymphocytes, HLA-C, viruses, T cell, Human Immunodeficiency Virus Proteins, Antigen presentation, HIV Infections, HLA-C Antigens, Biology, Microbiology, Virus, Host-Microbe Biology, Evolution, Molecular, 03 medical and health sciences, 0302 clinical medicine, Immune system, Virology, Vpu, vif Gene Products, Human Immunodeficiency Virus, medicine, Humans, Cytotoxic T cell, Viral Regulatory and Accessory Proteins, APOBEC3G, 030304 developmental biology, 0303 health sciences, virus diseases, QR1-502, Vif, Killer Cells, Natural, HEK293 Cells, medicine.anatomical_structure, SIV, Ubiquitin ligase complex, HIV-2, Host-Pathogen Interactions, HIV-1, Tetherin, T-Lymphocytes, Cytotoxic, Research Article, 030215 immunology
Abstract

Genome-wide association studies suggest that HLA-C expression is a major determinant of viral load set points and CD4+ T cell counts in HIV-infected individuals. On the one hand, efficient HLA-C expression enables the killing of infected cells by cytotoxic T lymphocytes (CTLs). On the other hand, HLA-C sends inhibitory signals to natural killer (NK) cells and enhances the infectivity of newly produced HIV particles. HIV-1 group M viruses modulate HLA-C expression using the accessory protein Vpu, possibly to balance CTL- and NK cell-mediated immune responses. Here, we show that the second human immunodeficiency virus, HIV-2, can use its accessory protein Vif to evade HLA-C-mediated restriction. Furthermore, our mutational analyses provide insights into the underlying molecular mechanisms. In summary, our results reveal how the two human AIDS viruses modulate HLA-C, a key component of the antiviral immune response., HLA-C-mediated antigen presentation induces the killing of human immunodeficiency virus (HIV)-infected CD4+ T cells by cytotoxic T lymphocytes (CTLs). To evade killing, many HIV-1 group M strains decrease HLA-C surface levels using their accessory protein Vpu. However, some HIV-1 group M isolates lack this activity, possibly to prevent the activation of natural killer (NK) cells. Analyzing diverse primate lentiviruses, we found that Vpu-mediated HLA-C downregulation is not limited to pandemic group M but is also found in HIV-1 groups O and P as well as several simian immunodeficiency viruses (SIVs). We show that Vpu targets HLA-C primarily at the protein level, independently of its ability to suppress NF-κB-driven gene expression, and that in some viral lineages, HLA-C downregulation may come at the cost of efficient counteraction of the restriction factor tetherin. Remarkably, HIV-2, which does not carry a vpu gene, uses its accessory protein Vif to decrease HLA-C surface expression. This Vif activity requires intact binding sites for the Cullin5/Elongin ubiquitin ligase complex but is separable from its ability to counteract APOBEC3G. Similar to HIV-1 Vpu, the degree of HIV-2 Vif-mediated HLA-C downregulation varies considerably among different virus isolates. In agreement with opposing selection pressures in vivo, we show that the reduction of HLA-C surface levels by HIV-2 Vif is accompanied by increased NK cell-mediated killing. In summary, our results highlight the complex role of HLA-C in lentiviral infections and demonstrate that HIV-1 and HIV-2 have evolved at least two independent mechanisms to decrease HLA-C levels on infected cells.

Published
2020
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36. Assessment of multiplex digital droplet RT-PCR as an accurate diagnosis tool for SARS-CoV-2 detection in nasopharyngeal swabs and saliva samples

Author

Ségolène Gracias, Thierry Frebourg, Elodie Alessandri-Gradt, Ludivine Beaussire, Nasrin Sarafan-Vasseur, Kévin Cassinari, Manuel Etienne, Kevin Alexandre, Françoise Charbonnier, Claude Houdayer, Jean-Christophe Plantier, François Caron, and Pascal Chambon

Subjects
Saliva, Real-time polymerase chain reaction, Coronavirus disease 2019 (COVID-19), stomatognathic system, business.industry, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Immunology, Diagnosis tool, Medicine, Sampling (medicine), Multiplex, business
Abstract

RT-qPCR on nasopharyngeal swabs is currently the reference COVID-19 diagnosis method. We developed a multiplex RT-ddPCR assay, targeting six SARS-CoV-2 genomic regions, and evaluated it on nasopharyngeal swabs and saliva samples collected from 130 COVID-19 positive or negative ambulatory individuals, who presented symptoms suggestive of mild or moderate Sars-CoV2 infection. The 6-plex RT-ddPCR assay was shown to have 100% sensitivity on nasopharyngeal swabs and a higher sensibility than RT-qPCR on saliva (85% versus 62%). Saliva samples from 2 individuals with negative results on nasopharyngeal swabs were found to be positive. These results show that multiplex RT-ddPCR should represent an alternative and complementary tool for the diagnosis of COVID-19, in particular to control RT-qPCR ambiguous results, and its application to saliva an appropriate strategy for repetitive sampling and testing individuals for whom nasopharyngeal swabbing is not possible.

Published
2020
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37. Sensitivity of five rapid HIV tests on oral fluid or finger-stick whole blood: a real-time comparison in a healthcare setting.

Author

Juliette Pavie, Anne Rachline, Bénédicte Loze, Laurence Niedbalski, Constance Delaugerre, Eric Laforgerie, Jean-Christophe Plantier, Willy Rozenbaum, Sylvie Chevret, Jean-Michel Molina, and François Simon

Subjects
Medicine, Science
Abstract

BackgroundHealth authorities in several countries recently recommended the expansion of human immunodeficiency virus (HIV) antibody testing, including the use of rapid tests. Several HIV rapid tests are now licensed in Europe but their sensitivity on total blood and/or oral fluid in routine healthcare settings is not known.Methods and findings200 adults with documented HIV-1 (n=194) or HIV-2 infection (n=6) were prospectively screened with five HIV rapid tests using either oral fluid (OF) or finger-stick whole blood (FSB). The OraQuick Advance rapid HIV1/2 was first applied to OF and then to FSB, while the other tests were applied to FSB, in the following order: Vikia HIV 1/2, Determine HIV 1-2, Determine HIV-1/2 Ag/Ab Combo and INSTI HIV-1/HIV-2. Tests negative on FSB were repeated on paired serum samples. Twenty randomly selected HIV-seronegative subjects served as controls, and the results were read blindly. Most patients had HIV-1 subtype B infection (63.3%) and most were on antiretroviral therapy (68.5%). Sensitivity was 86.5%, 94.5%, 98.5%, 94.9%, 95.8% and 99% respectively, with OraQuick OF, OraQuick FSB, Vikia, Determine, Determine Ag/Ab Combo and INSTI (pConclusionWhen evaluated in a healthcare setting, rapid HIV tests were less sensitive on oral fluid than on finger-stick whole blood and less sensitive on finger-stick whole blood than on serum.

Published
2010
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38. HIV-1 non-group M phenotypic susceptibility to integrase strand transfer inhibitors

Author

Diane Descamps, Guillemette Unal, Mélanie Bertine, Charlotte Charpentier, Elodie Alessandri-Gradt, Gilles Collin, Marie Leoz, Jean-Christophe Plantier, A. Tourneroche, Groupe de Recherche sur l'Adaptation Microbienne (GRAM 2.0), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Université de Caen Normandie (UNICAEN), Normandie Université (NU), Laboratoire de virologie [Rouen], Hôpital Charles Nicolle [Rouen]-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Département de microbiologie : Bactério, Virologie, Parasito, Hygiène, 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], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)

Subjects
0301 basic medicine, HIV Infections, HIV Integrase, Drug resistance, Quinolones, Piperazines, polymorphism, chemistry.chemical_compound, Genotype, Pharmacology (medical), Transfer technique, [SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, Phylogeny, Genetics, Elvitegravir, Phenotype, dolutegravir, 3. Good health, Integrase, Infectious Diseases, transfer technique, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Dolutegravir, elvitegravir, raltegravir, Heterocyclic Compounds, 3-Ring, medicine.drug, Microbiology (medical), Pyridones, 030106 microbiology, Biology, [SDV.MP.PRO]Life Sciences [q-bio]/Microbiology and Parasitology/Protistology, Inhibitory Concentration 50, 03 medical and health sciences, Raltegravir Potassium, Drug Resistance, Viral, Oxazines, medicine, Humans, HIV Integrase Inhibitors, Pharmacology, Polymorphism, Genetic, Raltegravir, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, 030112 virology, Amino Acid Substitution, chemistry, Mutation, HIV-1, biology.protein, integrase
Abstract

International audience; ObjectivesTo determine natural phenotypic susceptibility of non-group M HIV-1 to integrase strand transfer inhibitors (INSTIs) in a large panel of 39 clinical strains from groups O, N and P and to identify genotypic polymorphisms according to susceptibility levels.MethodsSusceptibility to raltegravir, elvitegravir and dolutegravir was evaluated in 36 HIV-1/O, 2 HIV-1/N and 1 HIV-1/P strains plus an HIV-1/M reference strain. IC50 values were determined after 3 days, and fold changes (FCs) were calculated relative to the HIV-1/M strain. Genotypic polymorphism was determined by amplification of codons 19–263 of the integrase; the natural occurrence of resistance-associated mutations was analysed using the main resistance algorithms and the IAS-USA list. VESPA analysis of the strain sequences was used to determine a signature pattern associated with higher FC.ResultsSimilar IC50 results were observed for the three drugs. Based on the value for the HIV-1/M reference strain, the data showed FC values 10 for six strains (15%). Analysis of the non-M integrase sequences showed a high level of polymorphism without a major genotypic impact; it also revealed mutations that may be associated with the highest FC values obtained for elvitegravir.ConclusionsOur phenotypic data showed that non-M strains are globally susceptible to the three currently used INSTIs, but the impact of the high FC values observed for some strains with elvitegravir needs to be explored. Clinical data are now needed to confirm these phenotypic results.

Published
2017
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39. Origine, diffusion et évolution des VIH-1 de groupe O

Author

Marie, Leoz, Fabienne, De Oliveira, and Jean-Christophe, Plantier

Abstract

HIV-1 group O (HIV-1/O) are rare variants that are mainly found in Cameroon, where they represent several thousands of cases. The reasons for their limited diffusion remains poorly understood: their emergence is estimated as ancient as that of pandemic HIV-1/M, and ancient cases of exportation on diverse continents have been identified for both groups. In France, more than a hundred cases have been identified so far that are mostly linked with Cameroon. HIV-1/O have developed a great level of genetic diversity and an atypical phylogenetic structure whose description remained ambiguous, due to the existence of several nomenclatures, which have only recently been unified. Their great genetic diversity and divergence from HIV-1/M probably impacts diverse properties, such as counteraction of Tetherin. Further studying the epidemiologic, evolutionary and virologic characteristics of these variants will allow for a better understanding of their limited spread and the future of this epidemic. In this respect, the recent description of diverse M/O intergroup recombinant forms underlines an evolutionary potential.

Published
2020

40. Origin, diffusion and evolution of HIV-1 group O viruses

Author

Marie, Leoz, Fabienne, De Oliveira, and Jean-Christophe, Plantier

Abstract

HIV-1 group O (HIV-1/O) are rare variants that are mainly found in Cameroon, where they have caused several thousand cases. The reasons for their limited diffusion remain poorly understood: their emergence is estimated to have been as long ago as that of the HIV-1/M pandemic, and old cases of exportation to different continents have been identified for both groups. In France, more than a hundred cases have been identified thus far, mostly linked to Cameroon. HIV-1/O have developed a high level of genetic diversity and an atypical phylogenetic structure, for which the description has remained ambiguous due to the existence of several nomenclatures. These have only recently been unified by taking the evolutionary history of the viruses into account. Their high genetic diversity and divergence from HIV-1/M likely affects diverse properties of the strains, such as their ability to counteract the action of tetherin. Further studies of the epidemiological, evolutionary, and virological characteristics of these variants will allow a better understanding of the reasons for their limited spread and the future of the epidemic. In this respect, the recent description of diverse M/O intergroup recombinants highlights their evolutionary potential.

Published
2020

41. Dried Blood Spot Tests for the Diagnosis and Therapeutic Monitoring of HIV and Viral Hepatitis B and C

Author

Fabien Taieb, Amandine Pisoni, Roxane Schaub, Alain Makinson, Philippe Van de Perre, Jean-Christophe Plantier, Esther Nina Ontsira Ngoyi, Edouard Tuaillon, Karine Bollore, Dramane Kania, Pathogénèse et contrôle des infections chroniques (PCCI), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut de Recherche en Sciences de la Santé (IRSS) / Centre Muraz, Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques et émergentes (TransVIHMI), Institut de Recherche pour le Développement (IRD)-Université de Yaoundé I-Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Ecosystemes Amazoniens et Pathologie Tropicale (EPat), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Guyane (UG), 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), Boutin, Marion, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre Hospitalier Universitaire de Montpellier (CHU Montpellier ), Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques er émergentes (TransVIHMI), Normandie Université (NU)-Département de microbiologie : Bactério, Virologie, Parasito, Hygiène, Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Institut de Recherche pour le Développement (IRD)-Université de Yaoundé I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Université Montpellier 1 (UM1), and Hôpital Charles Nicolle [Rouen]-CHU Rouen

Subjects
Microbiology (medical), medicine.medical_specialty, diagnosis, Mini Review, Hepatitis C virus, [SDV]Life Sciences [q-bio], lcsh:QR1-502, Human immunodeficiency virus (HIV), medicine.disease_cause, Microbiology, lcsh:Microbiology, 03 medical and health sciences, medicine, Intensive care medicine, Genotyping, 030304 developmental biology, Hepatitis B virus, 0303 health sciences, 030306 microbiology, business.industry, HIV, Viral hepatitis b, Hepatitis C, Hepatitis B, medicine.disease, dried blood spot, 3. Good health, Dried blood spot, [SDV] Life Sciences [q-bio], hard-to-reach population, hepatitis B, hepatitis C, business
Abstract

International audience; Blood collected and dried on a paper card - dried blood spot (DBS) - knows a growing interest as a sampling method that can be performed outside care facilities by capillary puncture, and transported in a simple and safe manner by mail. The benefits of this method for blood collection and transport has recently led the World Health Organization to recommend DBS for HIV and hepatitis B and C diagnosis. The clinical utility of DBS sampling to improve diagnostics and care of HIV and hepatitis B and C infection in hard to reach populations, key populations and people living in low-income settings was highlighted. Literature about usefulness of DBS specimens in the therapeutic cascade of care - screening, confirmation, quantification of nucleic acids, and resistance genotyping -, was reviewed. DBS samples are suitable for testing antibodies, antigens, or nucleic acids using most laboratory methods. Good sensibility and specificity have been reported for infant HIV diagnosis and diagnosis of hepatitis B and C. The performance of HIV RNA testing on DBS to identified virological failure on antiretroviral therapy is also high but not optimal because of the dilution of dried blood in the elution buffer, reducing the analytical sensitivity, and because of the contamination by intracellular HIV DNA. Standardized protocols are needed for inter-laboratory comparisons, and manufacturers should pursue regulatory approval for in vitro diagnostics using DBS specimens. Despite these limitations, DBS sampling is a clinically relevant tool to improve access to infectious disease diagnosis worldwide.

Published
2019
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42. Severe underquantification of HIV-1 group O isolates by major commercial PCR-based assays

Author

Ina Ambiel, Mark Wasner, Robert Ehret, Lutz Gürtler, Jean-Christophe Plantier, Lena Stegmann, Albert Heim, Volker Daniel, Annemarie Berger, Josef Eberle, Christoph Sarrazin, Marhild Kortenbusch, Kai Hourfar, Annette Haberl, Martin Stürmer, Maximilian Muenchhoff, and Oliver T. Keppler

Subjects
0301 basic medicine, Microbiology (medical), Serial dilution, 030106 microbiology, Pcr assay, Human immunodeficiency virus (HIV), HIV Infections, Biology, medicine.disease_cause, 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, 030212 general & internal medicine, Genetic diversity, virus diseases, Reproducibility of Results, General Medicine, Viral Load, Virology, Therapeutic monitoring, Infectious Diseases, Nucleic acid, HIV-1, RNA, Viral, Viral load, Nucleic Acid Amplification Techniques, Nucleic acid detection
Abstract

HIV-1 diversity poses major challenges to viral load assays because genetic polymorphisms can impede nucleic acid detection. In addition to the on-going viral diversification within the HIV-1 group M pandemic, HIV-1 genetic diversity is further increased by non-group M infections, such as HIV-1 groups O (HIV-1-O), N and P. We here conducted a systematic evaluation of commercially available PCR assays to detect HIV-1-O isolates. We collected 25 primary HIV-1-O isolates covering all genetic clusters within HIV-1-O. Subsequently, this panel of isolates was tested on eight commercially available quantitative and five qualitative HIV-1 PCR-based assays in serial dilutions. Sequence analyses were performed for severe cases of underquantification or lack of detection. We observed differences between the assays in quantification that depended on the HIV-1-O isolate's subgroup. All three tested HIV-1-O subgroup IV isolates were underquantified by the Roche CAP/CTM >800-fold compared to the Abbott RealTime assay. In contrast, the latter assay underquantified several subgroup I isolates >200-fold. Notably, the Xpert HIV-1 Viral Load test from Cepheid failed to detect two of the HIV-1-O isolates, whereas the Roche Cobas 8800 assay readily detected all isolates. Comparative sequence analyses identified polymorphisms in the HIV-1-O long-terminal repeat and integrase genes that likely underlie inadequate nucleic acid amplification. Potential viral load underquantification should be considered in therapeutic monitoring of HIV-1-O-infected patients. Pre-clinical assessments of HIV-1 diagnostic assays could be harmonized by establishing improved and internationally standardized panels of HIV-1 isolates that cover the dynamic diversity of circulating HIV-1 strains.

Published
2019

43. New HIV-1 circulating recombinant form 94: from phylogenetic detection of a large transmission cluster to prevention in the age of geosocial-networking apps in France, 2013 to 2017

Author

Ali Si-Mohammed, Jean-Dominique Poveda, Theresa Rabenja, B Visseaux, Karl Stefic, Fabienne De Oliveira, Anne Signori-Schmuck, Audrey Mirand, Magali Bouvier-Alias, Stéphanie Raymond, Vincent Calvez, Pantxika Bellecave, Coralie Pallier, Anne-Geneviève Marcelin, Véronique Schneider, Sidonie Lambert-Niclot, Chakib Alloui, Marie-Laure Chaix, Jean-Christophe Plantier, Diane Descamps, Elisabeth André-Garnier, Brice Malve, Marc Wirden, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Service de Virologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), 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)-Département de microbiologie : Bactério, Virologie, Parasito, Hygiène, Groupe de Recherche sur les Antimicrobiens et les Micro-Organismes (GRAM 1.0), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU), CHU Henri Mondor, 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), Laboratoire de Virologie [CHU Saint-Louis], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Génomes, biologie cellulaire et thérapeutiques (GenCellDi (U944 / UMR7212)), Collège de France (CdF (institution))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), 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), Laboratoire de sérologie-virologie (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Service de bactériologie-Virologie-Hygiène [Avicenne], Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], Service de virologie [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Service de virologie et unité de surveillance biologique [Bordeaux], CHU Bordeaux [Bordeaux], Service de Virologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service de Virologie Médicale et Moléculaire [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand, Service de Virologie [Villejuif], Hôpital Paul Brousse, Laboratoire CERBA [Saint Ouen l'Aumône], Grand Hôpital de l'Est Francilien (GHEF), Service de virologie [Hôpital Tenon], CHU Tenon [AP-HP], Département de virologie [Grenoble], Centre Hospitalier Universitaire [Grenoble] (CHU), Service de bactériologie-virologie [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau, 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], Mzembaba, Sandy, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Charles Nicolle [Rouen]-CHU Rouen, Génomes, biologie cellulaire et thérapeutiques (GenCellDi (UMR_S_944)), Collège de France (CdF (institution))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPC), Laboratoire de Virologie [Toulouse], CHU Toulouse [Toulouse], Hôpital Bretonneau-Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Groupe de Recherche sur l'Adaptation Microbienne (GRAM 2.0), Normandie Université (NU)-Normandie Université (NU)-Université de Caen Normandie (UNICAEN), Normandie Université (NU), Hôpital Henri Mondor, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre National de Référence des virus entériques [CHU de Dijon] (CNR virus entériques), Laboratoire Microorganismes : Génome et Environnement (LMGE), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), Sorbonne Université (SU)-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 National de la Santé et de la Recherche Médicale (INSERM), Normandie Université (NU)-Normandie Université (NU)-Département de microbiologie : Bactério, Virologie, Parasito, Hygiène-Hôpital Charles Nicolle [Rouen]-CHU Rouen, Université de Caen Normandie (UNICAEN), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris 13 (UP13)-Hôpital Avicenne [AP-HP]

Subjects
Male, 0301 basic medicine, Epidemiology, HIV Infections, Disease Outbreaks, Men who have sex with men, MESH: HIV Infections / epidemiology, Sexual and Gender Minorities, 0302 clinical medicine, Pandemic, Cluster Analysis, 030212 general & internal medicine, MESH: Phylogeny, Phylogeny, [SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, MESH: HIV cluster, HIV CRF94, phylogenetic analysis, HIV Outbreak, HIV Prevention, Recombination, Genetic, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, education.field_of_study, MESH: France / epidemiology, Surveillance, Virulence, Reverse Transcriptase Polymerase Chain Reaction, Transmission (medicine), Viral Load, MESH: Drug Resistance, Viral / genetics, 3. Good health, MESH: HIV-1 / genetics, Phylogeography, MESH: Online Social Networking, Online Social Networking, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, France, MESH: Disease Outbreaks / prevention & control, Adult, medicine.medical_specialty, Population, MESH: HIV-1 / classification, MESH: HIV-1 / pathogenicity, [SDV.MP.PRO] Life Sciences [q-bio]/Microbiology and Parasitology/Protistology, Disease cluster, [SDV.MP.PRO]Life Sciences [q-bio]/Microbiology and Parasitology/Protistology, MESH: HIV Infections / transmission, 03 medical and health sciences, Virology, Environmental health, Drug Resistance, Viral, medicine, Humans, MESH: DNA, Viral / genetics, MESH: HIV Infections / virology, Viremia, MESH: HIV Infections / prevention & control, education, Genotyping, Whole Genome Sequencing, business.industry, Public Health, Environmental and Occupational Health, MESH: Adult, MESH: Cluster Analysis, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, [SDV.MP.MYC] Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, HIV cluster, 030104 developmental biology, DNA, Viral, HIV-1, Observational study, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, business, Sequence Alignment
Abstract

Background Ending the HIV pandemic must involve new tools to rapidly identify and control local outbreaks and prevent the emergence of recombinant strains with epidemiological advantages. Aim This observational study aimed to investigate in France a cluster of HIV-1 cases related to a new circulating recombinant form (CRF). The confirmation this CRF’s novelty as well as measures to control its spread are presented. Methods Phylogenetic analyses of HIV sequences routinely generated for drug resistance genotyping before 2018 in French laboratories were employed to detect the transmission chain. The CRF involved was characterised by almost full-length viral sequencing for six cases. Cases’ clinical data were reviewed. Where possible, epidemiological information was collected with a questionnaire. Results The transmission cluster comprised 49 cases, mostly diagnosed in 2016–2017 (n = 37). All were infected with a new CRF, CRF94_cpx. The molecular proximity of this CRF to X4 strains and the high median viraemia, exceeding 5.0 log10 copies/mL, at diagnosis, even in chronic infection, raise concerns of enhanced virulence. Overall, 41 cases were diagnosed in the Ile-de-France region and 45 were men who have sex with men. Among 24 cases with available information, 20 reported finding partners through a geosocial networking app. Prevention activities in the area and population affected were undertaken. Conclusion We advocate the systematic use of routinely generated HIV molecular data by a dedicated reactive network, to improve and accelerate targeted prevention interventions. Geosocial networking apps can play a role in the spread of outbreaks, but could also deliver local targeted preventive alerts.

Published
2019
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44. Evaluation of four commercial extraction-quantification systems to monitor EBV or CMV viral load in whole blood

Author

Adeline Baron, Albane Gicquel, Marie Gueudin, Jean-Christophe Plantier, Laboratoire de virologie [Rouen], Hôpital Charles Nicolle [Rouen]-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), and Normandie Université (NU)-Département de microbiologie : Bactério, Virologie, Parasito, Hygiène

Subjects
0301 basic medicine, Epstein-Barr Virus Infections, Herpesvirus 4, Human, Early introduction, Serial dilution, [SDV]Life Sciences [q-bio], 030106 microbiology, Cytomegalovirus, 03 medical and health sciences, 0302 clinical medicine, Limit of Detection, Virology, Humans, Medicine, 030212 general & internal medicine, Whole blood, business.industry, Reproducibility of Results, Viral Load, 3. Good health, Infectious Diseases, Cytomegalovirus Infections, DNA, Viral, Reagent Kits, Diagnostic, business, Viral load
Abstract

Background Measurement of cytomegalovirus (CMV) and Epstein-Barr virus (EBV) viral loads is commonly used to monitor posttransplant patients. Two new systems (eMAG/eSTREAM and Versant/kPCR) have been recently commercialized. Objectives To evaluate the performance of four systems to quantify CMV and EBV in whole blood. Study design Three extraction and real-time PCR amplification systems: m2000SP/RT (M2000), eMAG/eSTREAM (EMAG), and Versant/kPCR (KPCR) were compared with our routine system Qiasymphony/RGQ (QS/RGQ). The 4 systems were tested using 3 dilutions in triplicate according to the WHO international standard (WHO-IS) for intra-assay reproducibility; 56 whole blood samples (24 patients, 4 follow-ups) for CMV and 45 samples (27 patients, 3 follow-ups) for EBV. Results For CMV, the mean of the WHO-IS (expected value: 4.7 Log IU/ml) was: QS/RGQ=4.84, M2000=4.61, EMAG=4.33, and KPCR=4.79. One patient (10 samples) presented a major underquantification by QS/RGQ. Of the 46 remaining samples, 41 were quantified with QS/RGQ, 43 with M2000, 33 with EMAG and 24 with KPCR. For EBV, the mean of the WHO-IS was: QS/RGQ=4.70, M2000=4.61, EMAG=4.62, and KPCR=4.57. Among the 45 samples, 43 were quantified with QS/RGQ, 39 with M2000, 40 with EMAG and 32 with KPCR. Conclusion The results obtained with the WHO-IS were very good. The results of patients' samples were well correlated with the announced sensitivity of each system. The elevated threshold of the KPCR CMV assay may be problematic for the follow-up of highly immunocompromised patients who require early introduction of treatment.

Published
2019
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45. Performance of Cepheid Xpert HIV-1 viral load plasma assay to accurately detect treatment failure

Author

Lara Vojnov, Smita Kulkarni, Etienne Karita, Mauro Andreotti, Fausta Mosha, Lesley Scott, Orna Mor, Jilian A. Sacks, Youyi Fong, Nigel Garrett, Mercedes Pérez González, Zibusiso Ndlovu, Trevor Peter, Shanmugam Saravanan, Shrikala Baliga, Jeanne A. Jordan, Jean-Christophe Plantier, Meg Doherty, Clinton health Access Initiative Boston (CHAI), Fred Hutchinson Cancer Research Center [Seattle] (FHCRC), World Health Organisation (WHO), Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Istituto Superiore di Sanita [Rome], Kasturba Medical College, Manipal, University of KwaZulu-Natal (UKZN), Georgetown University [Washington] (GU), Université libre de Kigali, Indian Council of Medical Research [New Dehli] (ICMR), Central Virology Laboratory, Ministry of Health, Chaim Sheba Medical Center, National Health Laboratory Quality Assurance and Training Centre (NHLQATC), Médecins sans Frontières [Genève] (MSF), Groupe de Recherche sur l'Adaptation Microbienne (GRAM 2.0), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Université de Caen Normandie (UNICAEN), Normandie Université (NU), and University of the Witwatersrand [Johannesburg] (WITS)

Subjects
0301 basic medicine, Computer science, Immunology, Clinical performance, Human immunodeficiency virus (HIV), ComputerApplications_COMPUTERSINOTHERSYSTEMS, Computational biology, medicine.disease_cause, [SDV.MP.PRO]Life Sciences [q-bio]/Microbiology and Parasitology/Protistology, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Treatment failure, 3. Good health, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Infectious Diseases, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, medicine, Immunology and Allergy, Molecular diagnostic techniques, 030212 general & internal medicine, Throughput (business), Viral load, ComputingMilieux_MISCELLANEOUS, [SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology
Abstract

Background:Coverage of viral load testing remains low with only half of the patients in need having adequate access. Alternative technologies to high throughput centralized machines can be used to support viral load scale-up; however, clinical performance data are lacking. We conducted a meta-analys

Published
2019
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46. Comparative performance of the Biocentric Generic Viral Load, Roche CAP/CTM v1.5, Roche CAP/CTM v2.0 and m2000 Abbott assays for quantifying HIV-1 B and non-B strains: Underestimation of some CRF02 strains

Author

M Gousset, Adeline Mélard, Marie Gueudin, Marie-Laure Chaix, Laurence Meyer, N. Lerolle, Julia Dina, Jean-Paul Viard, Jean-Christophe Plantier, Véronique Avettand-Fenoel, Christine Rouzioux, Anne Maillard, Laboratoire de Virologie [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Groupe de Recherche sur l'Adaptation Microbienne (GRAM 2.0), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Laboratoire de virologie [Rouen], CHU Rouen, Laboratoire de Virologie CHU de Rennes, Service de Virologie [CHU Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Laboratoire de Virologie [CHU Saint-Louis], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Centre de recherche en épidémiologie et santé des populations (CESP), Hôpital Paul Brousse-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Infection à VIH, réservoirs, diversité génétique et résistance aux antirétroviraux (ARV) (EA 7327), Université Paris Descartes - Paris 5 (UPD5), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Université de Caen Normandie (UNICAEN), Laboratoire de Virologie [Rennes] = Virology [Rennes], CHU Pontchaillou [Rennes], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)

Subjects
0301 basic medicine, 030106 microbiology, Human immunodeficiency virus (HIV), HIV Infections, Biology, medicine.disease_cause, Sensitivity and Specificity, World health, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Genetic Evolution, Virology, HIV Seropositivity, medicine, Humans, Mass Screening, 030212 general & internal medicine, ComputingMilieux_MISCELLANEOUS, Plasma samples, Clinical Laboratory Techniques, Viral Load, Antiretroviral therapy, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, 3. Good health, Infectious Diseases, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Epidemiological surveillance, HIV-1, RNA, Viral, France, Viral load
Abstract

Background HIV-1 viral load testing is now recommended by the World Health Organization for every patient receiving antiretroviral therapy (ART). Objectives The objective of this study is to evaluate the performance of commercial assays for their ability to quantify HIV-1 strains currently circulating in France. Study design The performances of the Generic HIV-RNA assay from Biocentric were compared to those of the Roche CAP/CTM v1.5, Roche CAP/CTM v2.0 and Abbott m2000 RealTime HIV-1 assays. A total of 1885 HIV-1 plasma samples were tested, including 684 samples from patients included in the ANRS-Primo Cohort. Results We found a good concordance of quantification between the Roche v2.0 and the Biocentric assays, both of which were superior to the Roche v1.5 assay. We show moderate agreement between techniques; however, CRF02_AG strains and undetermined viruses were underestimated when quantified with the Roche CAP/CTM v2.0. In contrast, a comparison of the Biocentric and Abbott assay results showed strong agreement between assays, indicating that both are well suited for quantification of CRF02_AG strains. Moreover, a 2% underestimation of the B subtypes was observed with the Biocentric assay. Conclusions These results have implications for viral load monitoring in Western Africa, where CRF02_AG strains are highly prevalent. Closer epidemiological surveillance and evaluation of commercial assays are still necessary to better evaluate the impact of the genetic evolution of circulating viruses on HIV-RNA quantification in the regions most affected by the HIV-1 epidemic.

Published
2019
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47. Confirmation of HCV viremia using HCV RNA and core antigen testing on dried blood spot in HIV infected peoples who inject drugs in Vietnam

Author

Charline Dubos, Huong Duong Thi, Karine Lacombe, Karine Bollore, Jean-Christophe Plantier, Xuan Lien Truong Thi, Didier Laureillard, Véronique Lemée, Truong Tam Nguyen, Que Anh Luong, Hai Vinh Vu, Maud Lemoine, Edouard Tuaillon, University of Medicine Pham Ngoc Thach, Pathogénèse et contrôle des infections chroniques (PCCI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre Hospitalier Universitaire de Montpellier (CHU Montpellier ), CHU Rouen, Normandie Université (NU), 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), 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 Pasteur d'Ho Chi Minh Ville, Réseau International des Instituts Pasteur (RIIP), Dpt of Public Health [Hai Phong], University of Medicine and Pharmacy (VIETNAM), Imperial College London, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)

Subjects
Male, 0301 basic medicine, HIV Infections, Hepacivirus, Drug Users, 0302 clinical medicine, Medical microbiology, 1108 Medical Microbiology, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Genotype, Medicine, 030212 general & internal medicine, Substance Abuse, Intravenous, HCV core antigen, Antigen testing, Coinfection, Viral Core Proteins, virus diseases, Human immunodeficiency virus (HIV), Hepatitis C virus (HCV), Hepatitis C, 3. Good health, Dried blood spot, Infectious Diseases, Vietnam, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, RNA, Viral, Female, Life Sciences & Biomedicine, Research Article, 0605 Microbiology, Adult, medicine.medical_specialty, HCV RNA, 030106 microbiology, Viremia, Immunologic Tests, Sensitivity and Specificity, Microbiology, Injections, lcsh:Infectious and parasitic diseases, 03 medical and health sciences, Humans, lcsh:RC109-216, Science & Technology, Diagnostic Tests, Routine, business.industry, HIV, Reproducibility of Results, 1103 Clinical Sciences, medicine.disease, Virology, digestive system diseases, Cross-Sectional Studies, Parasitology, Viral replication, Nucleic acid, Dried Blood Spot Testing, business
Abstract

International audience; Background: Nucleic acid tests performed on blood samples collected on Dried Blood Spot (DBS) and detection of HCV core antigen (HCVcAg) are two approaches that may facilitate access to HCV diagnosis in low and middle incomes countries. In this study we evaluate HCV RNA and HCV antigen testing on DBS in HIV/HCV co-infected peoples who inject drugs in Vietnam.Method: One hundred and four HIV/HCV seropositive patients managed in outpatient care at the Haiphong Viet Tiep hospital were included in this study from February to March, 2014 (ANRS 12262 study).Results: Eighty-six subjects were tested positive for HCV RNA in serum, median (IQR): 6.9 log10 IU/ml (5.6–7.4 log10 IU/ml). Genotypes consisted of 57 G1 (69%), 3 G3 (4%), and 22 G6 (27%). HCV RNA was detected on DBS specimens in 79 out 86 subjects with chronic hepatitis C (sensitivity 92.5%; 95% CI: 85.1–96.9%). HCV RNA level on DBS and serum was moderately correlated (r = 0.24; p = 0.05) suggesting a degradation of HCV RNA due to transportation and storage conditions. HCVcAg was detected in 75/86 dB specimens (sensitivity: 87.2%; 95% CI: 78.3–93.4%), with a strong positive relationship between DBS HCVcAg and serum HCV RNA levels (r = 0.80; P

Published
2018
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48. Impact of natural polymorphisms of HIV-1 non-group M on genotypic susceptibility to the attachment inhibitor fostemsavir

Author

Jean-Christophe Plantier, Diane Descamps, Marie Leoz, Charlotte Charpentier, Elodie Alessandri-Gradt, Thomas Mourez, Groupe de Recherche sur l'Adaptation Microbienne (GRAM 2.0), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Université de Caen Normandie (UNICAEN), Normandie Université (NU), Laboratoire de virologie [Rouen], Hôpital Charles Nicolle [Rouen]-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Département de microbiologie : Bactério, Virologie, Parasito, Hygiène, 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), Université de Caen Normandie (UNICAEN), Hôpital Charles Nicolle [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, and Mzembaba, Sandy

Subjects
CD4-Positive T-Lymphocytes, 0301 basic medicine, Microbiology (medical), Anti-HIV Agents, phenotype, genotype, 030106 microbiology, Human immunodeficiency virus (HIV), Virus Attachment, HIV Infections, hiv, hiv-1, Drug resistance, Biology, [SDV.MP.PRO] Life Sciences [q-bio]/Microbiology and Parasitology/Protistology, medicine.disease_cause, [SDV.MP.PRO]Life Sciences [q-bio]/Microbiology and Parasitology/Protistology, Piperazines, polymorphism, 03 medical and health sciences, Phylogenetics, Drug Resistance, Viral, Genotype, medicine, Genetic predisposition, Humans, Pharmacology (medical), genetics, viruses, fostemsavir, Phylogeny, [SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, Pharmacology, Genetics, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Genetic diversity, Polymorphism, Genetic, hiv envelope protein gp120, Phenotype, [SDV.MP.MYC] Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, immunity, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Organophosphates, 3. Good health, 030104 developmental biology, Infectious Diseases, Fostemsavir, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology
Abstract

International audience; Background:Fostemsavir belongs to the new class of attachment inhibitors (AIs); it inhibits the entry of HIV into CD4+ T-lymphocytes by blocking conformational changes in gp120. This is a promising AI, but previous phenotypic data showed that genetically divergent HIV-1 group O could present natural resistance to this drug. These data were obtained from only two strains, which are not representative of the high intra-group genetic diversity. Moreover, no data are available concerning the other divergent HIV-1 groups (N and P).Objectives:To further investigate the natural genotypic susceptibility of HIV-1 groups O, N and P (HIV-1 non-M) to fostemsavir, using a large set of sequences.Methods:The frequency of eight substitutions associated with decreased susceptibility to fostemsavir (L116P, A204D, S375M/H, M426L, M434I, M475I and V506M), was investigated in 111 gp120 sequences from groups O (n = 100), N (n = 9) and P (n = 2).Results:All HIV-1 group N sequences harboured the three substitutions S375M, M426L and M434I, whereas only 1% and 10% of HIV-1 group O sequences harboured the S375H + M426L and S375H + M434I patterns, respectively. The main genetic profile of HIV-1 groups P and O combined S375H with two atypical substitutions (M426S and M434L). Five group O sequences did not display any of the eight substitutions, but had atypical residues with unknown impact.Conclusions:The genetic polymorphisms in the gp120 of HIV-1 non-M viruses support the hypothesis that these viruses could largely be resistant to inhibition by fostemsavir. Only 5% of group O strains could display full genetic susceptibility. Extensive phenotypic studies are now required.

Published
2018
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49. Stable prevalence of transmitted drug resistance mutations and increased circulation of non-B subtypes in antiretroviral-naive chronically HIV-infected patients in 2015/2016 in France

Author

Gilles Peytavin, Mary-Anne Trabaud, Anne Signori-Schmuck, Charlotte Charpentier, Marc Wirden, Cécile Henquell, Laurence Bocket, Catherine Delamare, Samira Fafi-Kremer, Jacques Izopet, Chakib Allaoui, Georges Dos Santos, A. Beby-Defaux, Benoit Visseaux, Virginie Ferré, Coralie Pallier, Diane Descamps, Stéphanie Marque-Juillet, Lambert Assoumou, Magali Bouvier-Alias, Sophie Vallet, Alexis de Rougemont, Hélène Le Guillou-Guillemette, Vincent Calvez, Stéphanie Raymond, Corinne Amiel, Honorine Fenaux, Anne De Monte, Francis Barin, Anne Krivine, Véronique Avettand-Fenoel, Annick Allardet-Servent, Jean-Christophe Plantier, Rachid Ait-Namane, Laurence Morand-Joubert, Marie-Laure Chaix, Camille Tumiotto, Maxime Grude, Anne Maillard, Laurence Courdavault, Brigitte Montes, 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), CIC CHU ( Lille)/inserm, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé, Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), 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 Bordelais de Recherche en Informatique (LaBRI), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)-École Nationale Supérieure d'Électronique, Informatique et Radiocommunications de Bordeaux (ENSEIRB), 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), Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL), Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques (HIFIH), Université d'Angers (UA), Hôpital Avicenne [AP-HP], CHU Clermont-Ferrand, Service de Virologie [CHU Cochin], Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU de la Martinique [Fort de France], Centre hospitalier régional Metz-Thionville (CHR Metz-Thionville), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre hospitalier universitaire de Nantes (CHU Nantes), CHU Nice [Cimiez], Hôpital Cimiez [Nice] (CHU), Institut de biologie structurale (IBS - UMR 5075 ), Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Virologie [Rennes] = Virology [Rennes], CHU Pontchaillou [Rennes], 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), CHU Bordeaux [Bordeaux], Interaction virus-hôte et maladies du foie, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre Hospitalier de Versailles André Mignot (CHV), Centre Hospitalier Victor Dupouy, Laboratoire Universitaire de Biodiversité et Ecologie Microbienne (LUBEM), Université de Brest (UBO), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Procédés Alimentaires et Microbiologiques [Dijon] (PAM), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Service de Virologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Université Sorbonne Paris Cité (USPC), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Groupe de Recherche sur l'Adaptation Microbienne (GRAM 2.0), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Université de Caen Normandie (UNICAEN), Normandie Université (NU), Laboratoire de virologie [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Laboratoire de Virologie [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Université de Caen Normandie (UNICAEN), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Mzembaba, Sandy, Epidémiologie, Systèmes d'Information, Modélisation, Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-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)-Sorbonne Université (SU), Service de Virologie [Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Hôpital Paul Brousse, Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Service de Virologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Service de Virologie Médicale et Moléculaire [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Estaing [Clermont-Ferrand], Laboratoire de Virologie-Immunologie [Fort de France, Martinique] (EA 4537), Centre Hospitalier Universitaire de Martinique [Fort-de-France, Martinique], CHU Henri Mondor, Centre Hospitalier Universitaire [Grenoble] (CHU), Laboratoire de Virologie [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Sorbonne Université (SU), Service de virologie et unité de surveillance biologique [Bordeaux], CHU Strasbourg, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre hospitalier Argenteuil (CH Argenteuil), CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Université Paris Descartes, Sorbonne Paris Cité, Groupe de Recherche sur les Antimicrobiens et les Micro-Organismes (GRAM 1.0), Normandie Université (NU)-Normandie Université (NU), Pathologie cellulaire : aspects moléculaires et viraux / Pathologie et Virologie Moléculaire, Institut Universitaire d'Hématologie (IUH), Université Paris Diderot - Paris 7 (UPD7)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS), and ANRS – France REcherche Nord&Sud Sida-hiv Hépatites

Subjects
0301 basic medicine, Male, MESH: CD4 Lymphocyte Count, [SDV]Life Sciences [q-bio], Integrase inhibitor, hiv, HIV Infections, Drug resistance, MESH: HIV-1 / genetics, MESH: Genotype, MESH: HIV Infections / epidemiology, 0302 clinical medicine, Genotype, Blood plasma, HIV Seropositivity, rna-directed dna polymerase, Prevalence, rna, Pharmacology (medical), 030212 general & internal medicine, MESH: Chronic Disease / epidemiology, ComputingMilieux_MISCELLANEOUS, cd4 count determination procedure, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, anti-retroviral agents, MESH: France / epidemiology, Antiinfective agent, MESH: Middle Aged, Incidence (epidemiology), Middle Aged, MESH: Drug Resistance, Viral / genetics, 3. Good health, endopeptidases, [SDV] Life Sciences [q-bio], integrase inhibitors, Infectious Diseases, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, RNA, Viral, MESH: RNA, Viral / blood, Female, France, MESH: HIV Seropositivity / epidemiology, Microbiology (medical), Adult, medicine.medical_specialty, peptide hydrolases, MESH: Mutation, Anti-HIV Agents, 030106 microbiology, MESH: HIV Infections / drug therapy, MESH: HIV-1 / classification, MESH: HIV-1 / drug effects, Virus, MESH: HIV Infections / transmission, 03 medical and health sciences, Pharmacotherapy, Internal medicine, Drug Resistance, Viral, medicine, Humans, viruses, [SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology, plasma, safe sex, MESH: Prevalence, Pharmacology, drug resistance, MESH: Humans, business.industry, MESH: Adult, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, MESH: Male, CD4 Lymphocyte Count, MESH: Anti-HIV Agents / therapeutic use, Chronic Disease, Mutation, HIV-1, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, business, MESH: Female
Abstract

International audience; Objectives: We estimated the prevalence of transmitted-drug-resistance-associated mutations (TDRAMs) in antiretroviral-naive chronically HIV-1-infected patients.Patients and methods: TDRAMs were sought in samples from 660 diagnosed HIV-1-infected individuals in 2015/2016 in 33 HIV clinical centres. Weighted analyses, considering the number of patients followed in each centre, were used to derive representative estimates of the percentage of individuals with TDRAMs. Results were compared with those of the 2010/2011 survey (n = 661) using the same methodology.Results: At inclusion, median CD4 cell counts and plasma HIV-1 RNA were 394 and 350/mm3 (P = 0.056) and 4.6 and 4.6 log10 copies/mL (P = 0.360) in the 2010/2011 survey and the 2015/2016 survey, respectively. The frequency of non-B subtypes increased from 42.9% in 2010/2011 to 54.8% in 2015/2016 (P < 0.001), including 23.4% and 30.6% of CRF02_AG (P = 0.004). The prevalence of virus with protease or reverse-transcriptase TDRAMs was 9.0% (95% CI = 6.8-11.2) in 2010/2011 and 10.8% (95% CI = 8.4-13.2) in 2015/2016 (P = 0.269). No significant increase was observed in integrase inhibitor TDRAMs (6.7% versus 9.2%, P = 0.146). Multivariable analysis showed that men infected with the B subtype were the group with the highest risk of being infected with a resistant virus compared with others (adjusted OR = 2.2, 95% CI = 1.3-3.9).Conclusions: In France in 2015/2016, the overall prevalence of TDRAMs was 10.8% and stable compared with 9.0% in the 2010/2011 survey. Non-B subtypes dramatically increased after 2010. Men infected with B subtype were the group with the highest risk of being infected with a resistant virus, highlighting the need to re-emphasize safe sex messages.

Published
2018
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50. Short Communication: Characterization of a New HIV-1 Group N Isolate Originating from a Cameroonian Patient

Author

Elodie Téclaire Ngo-Malabo, Jean-Christophe Plantier, Anfumbom Kfutwah, Laure Ngono, Paul Alain Ngoupo, Fabienne De Oliveira, Serge Alain Sadeuh-Mba, Richard Njouom, Centre Pasteur du Cameroun, Réseau International des Instituts Pasteur (RIIP), Groupe de Recherche sur l'Adaptation Microbienne (GRAM 2.0), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Université de Caen Normandie (UNICAEN), Normandie Université (NU), Laboratoire de virologie [Rouen], Hôpital Charles Nicolle [Rouen]-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), and Normandie Université (NU)-Département de microbiologie : Bactério, Virologie, Parasito, Hygiène

Subjects
Adult, Genotype, HIV-1 group N, Immunology, Human immunodeficiency virus (HIV), HIV Infections, Biology, medicine.disease_cause, Genome, [SDV.MP.PRO]Life Sciences [q-bio]/Microbiology and Parasitology/Protistology, 03 medical and health sciences, 0302 clinical medicine, Virus strain, Virology, medicine, Humans, 030212 general & internal medicine, Cameroon, [SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, 030304 developmental biology, chemistry.chemical_classification, 0303 health sciences, Whole Genome Sequencing, virus diseases, HIV screening, tetherin, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, 3. Good health, Amino acid, Infectious Diseases, chemistry, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Tetherin, HIV-1, Female, Vpu protein, epidemiology, Antagonism
Abstract

International audience; HIV-1 group N (HIV-1/N) remains rare and mainly restricted to Cameroon. In this study, we report a new HIV-1/N infected case identified during routine HIV screening activities in Yaounde. The genetic characterization of the near full-length genome of this virus strain revealed that it is genetically distinct to all HIV-1/N described to date. However, the Vpu protein responsible for tetherin antagonism displayed the same amino acid substitutions (E15A, V19A, I25L, and V26L) as other HIV-1/N from Cameroon.

Published
2018
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