Jean-Christophe Plantier

Hôpital Charles-Nicolle, Tunis-Ville, Tūnis, Tunisia

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Publications (76)403.72 Total impact

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    ABSTRACT: Background: Highly potent broadly neutralizing monoclonal antibodies (bNabs) have been obtained from individuals infected by HIV-1 group M variants. We analyzed the cross-group neutralization potency of these bNabs towards non-M primary isolates (PI). Material & methods: The sensitivity to neutralization was analyzed in a neutralization assay using TZM-bl cells. Twenty three bNabs were used, including reagents targeting the CD4 binding site (CD4bs), the N160 glycan-V1V2 site, the N332 glycan-V3 site, the membrane proximal external region of gp41, and complex epitopes spanning both Env subunits. Two bispecific antibodies that combine the inhibitory activity of an anti-CD4 with that of PG9 or PG16 (BibNabs) were included in the study (PG9-iMab and PG16-iMab). Results: Cross-group neutralization was observed only with the bNabs targeting the N160 glycan-V1V2 site. Four group O PIs, one group N PI and the group P PI were neutralized by PG9 and/or PG16 or PGT145 at low concentrations (0.04-9.39 µg/mL). None of the non-M PIs was neutralized by the bNabs targeting other regions at the highest concentration tested, except 10E8 that neutralized weakly two group N PIs and 35O22 that neutralized one group O PI. The BibNabs neutralized very efficiently all the non-M PIs with IC50 below 1 µg/mL, except two group O strains. Conclusion: The N160 glycan-V1V2 site is the most conserved neutralizing site within the four groups of HIV-1. This makes it an interesting target for the development of HIV vaccine immunogens. The corresponding bNabs may be useful for immunotherapeutic strategies in patients infected by non-M variants.
    JAIDS Journal of Acquired Immune Deficiency Syndromes 09/2015; DOI:10.1097/QAI.0000000000000854 · 4.56 Impact Factor
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    ABSTRACT: We recently published a paper in the Journal of Medical Virology titled "Performance of rapid tests for discrimination between HIV-1 and/or HIV-2 infections" [Gautheret-Dejean et al., 2015]. Hønge et al. followed up with a commentary on our findings, which we have read with great interest. We are grateful for this opportunity to respond to their comments and give some precisions/clarifications in this letter. This article is protected by copyright. All rights reserved.
    Journal of Medical Virology 09/2015; DOI:10.1002/jmv.24390 · 2.35 Impact Factor

  • AIDS 09/2015; DOI:10.1097/QAD.0000000000000880 · 5.55 Impact Factor
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    ABSTRACT: An improved version of the bioMérieux NucliSENS(®) EasyQ(®) HIV-1 v2.0 has been introduced to overcome the underquantification observed with previous versions, especially with non-B HIV-1 subtypes. Comparing bioMérieux NucliSENS(®) EasyQ(®) HIV-1 v2.0 versus Roche Cobas CA/CTM v2.0 and Abbott RealTime HIV-1 assays for HIV-1 group M and non-M (N, O, P) viral load measurement. The three assays were tested in parallel on 103HIV-1 group M plasma samples, and on non-group M HIV-1 culture supernatants. Values obtained for the 103HIV-1 group M plasma samples tested with bioMérieux assay showed good overall correlation compared to the 2 others. The Roche Cobas assay gave higher values than the bioMérieux assay, while Abbott and bioMérieux both displayed similar results. However, analysis showed a wider dispersion in results when comparing the bioMérieux NucliSENS(®) EasyQ(®) HIV-1 v2.0 and the other 2 techniques. All data taken into account, we observed frequent discrepancies in quantification, of the plasma samples and major differences above 1log in 10/72 (13.8%). The quantification of non-M HIV groups in culture supernatant has shown variable results, with better quantification of HIV-O and of HIV-N respectively with the Abbott assay and the bioMérieux assay. The bioMérieux NucliSENS(®) EasyQ(®) HIV-1 v2.0 showed improved sensitivity to non-B HIV-M subtypes compared to previous versions. Notwithstanding, we observed frequent discrepancies and a wide dispersion in results when comparing bioMérieux NucliSENS(®) EasyQ(®) HIV-1 v2.0 and the other 2 techniques. Copyright © 2015 Elsevier B.V. All rights reserved.
    Journal of clinical virology: the official publication of the Pan American Society for Clinical Virology 08/2015; 71:76-81. DOI:10.1016/j.jcv.2015.08.007 · 3.02 Impact Factor
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    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.
    PLoS Pathogens 08/2015; 11(8):e1005029. DOI:10.1371/journal.ppat.1005029 · 7.56 Impact Factor
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    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. © 2015 Ekouévi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
    PLoS ONE 06/2015; 10(6):e0129886. DOI:10.1371/journal.pone.0129886 · 3.23 Impact Factor

  • AIDS (London, England) 06/2015; 29(10):1271-1273. DOI:10.1097/QAD.0000000000000703 · 5.55 Impact Factor
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    ABSTRACT: Major differences exist between HIV-1 and HIV-2 in terms of epidemiology, pathogenicity, sensitivity to antiretrovirals. Determining the type of HIV infecting a patient is essential for management. The aim of this study was to evaluate the ability of simple/rapid tests to differentiate between HIV-1 and/or HIV-2 infections. We analyzed 116 samples from patients infected with HIV-1 (n = 61), HIV-2 (n = 47), or HIV-1+HIV-2 (n = 8) at the chronic stage of infection. Each sample was tested with SD Bioline HIV-1/2 3.0, ImmunoFlow HIV1-HIV2, ImmunoFlow HIV1-HIV2 (WB), Genie III HIV-1/HIV-2, ImmunoComb HIV1&2 BiSpot. HIV-1, or HIV-2 single infection was identified with a sensitivity ranging from 90% to 100%. The ability to detect dual infection was less sensitive (12.5-100%). SD Bioline HIV-1/2 3.0, ImmunoFlow HIV1-HIV2, and Genie III were unable to detect HIV-1 group O infection in one, one and two cases, respectively. The specificity of detection of HIV-1, HIV-2, or HIV-1+HIV-2 antibodies differed greatly (36-100%). ImmunoComb BiSpot had the highest sensitivity values (99-100% for HIV-1, 98% for HIV-2, and 75-87.5% for dual infection) and specificity values (94-100% for HIV-1, 100% for HIV-2, and 97-100% for dual infection). In conclusion, this study showed that no single rapid test had a perfect sensitivity/specificity ratio, particularly in the case of the double infections. J. Med. Virol. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.
    Journal of Medical Virology 06/2015; 16(12). DOI:10.1002/jmv.24282 · 2.35 Impact Factor
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    ABSTRACT: HIV-1 group O (HIV-O) is a rare variant that is characterized by a high number of natural polymorphisms in the integrase coding region that may impact on susceptibility to integrase strand transfer inhibitors (INSTIs) and on the emergence of resistance substitutions. We previously reported that HIV-O is more susceptible to RAL than HIV-1 group M (HIV-M). The aim of the present study was to assess pathways of resistance to INSTIs in group 0 variants. Accordingly, we selected for resistance to each of raltegravir (RAL), elvitegravir (EVG), and dolutegravir (DTG) in cord blood mononuclear cells using HIV group O subtypes A and B, a HIV-O divergent isolate, and HIV-1 group M (subtype B, which served as a reference). Site directed mutagenesis was performed on the pCOM2.5 HIV group 0 infectious clone to ascertain the impact of INSTI resistance substitutions at positions Q148R, N155H, and R263K within integrase on susceptibility to INSTIs and infectiousness. Cell culture selections of group O variants yielded similar patterns of resistance to RAL, EVG, and DTG as observed for subtype B. In the DTG selections, subtype B yielded S153Y whereas a natural S153A polymorphism sometimes led to A153V in group O. The pCMO2.5/Q148R and pCMO2.5/N155H variants displayed far higher levels of resistance to DTG (> 1000 FC) than was seen for group M viruses. HIV-O harboring Q148R and N155H show higher resistance to DTG compared to HIV-M subtype B.
    JAIDS Journal of Acquired Immune Deficiency Syndromes 05/2015; 70(1). DOI:10.1097/QAI.0000000000000698 · 4.56 Impact Factor
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    ABSTRACT: The pre-therapeutic presence of protease inhibitor (PI) resistance-associated variants (RAVs) has not been shown to be predictive of triple-therapy outcome in treatment-naïve patients. However, they may influence the outcome in patients with less effective Pegylated Interferon (IFN)-ribavirin (RBV) backbones. Using HCV population sequence analysis, we retrospectively investigated the prevalence of baseline NS3 RAVs in a multicenter cohort of poor IFN-RBV responders (i.e. prior null-responders or patients with a viral load decrease of <1 logUI/ml during the pegIFN/RBV lead-in phase). The impact of the presence of these RAVs on triple-therapy outcome was studied. Among 282 patients, the prevalence of baseline RAVs ranged from 5.7% [3.3%-9.0%] to 22.0% [17.3%-27.3%] according to the algorithm used. Among mutations conferring a >3-fold shift in IC50 for telaprevir or boceprevir, T54S was the most frequently detected mutation (3.9%), followed by A156T, R155K (0.7%), V36M and V55A (0.35%). Mutations were more frequently found in patients infected with genotype 1a (7.5-23.6%) than 1b (3.3-19.8%) (p=0.03). No other socio-demographic or viro-clinical characteristic was significantly associated with a higher prevalence of RAVs. No obvious effect of baseline RAVs was observed on viral load. In this cohort of poor responders to IFN-RBV, no link was found with the sustained virological response to triple-therapy, whatever the algorithm used for the detection of mutations. Based on cross-study comparison, baseline RAVs are not more frequent in poor IFN-RBV responders than in treatment-naïve patients and, even in these difficult-to-treat patients, this study demonstrates no impact on treatment outcome, arguing against resistance analysis prior to treatment. Copyright © 2015, American Society for Microbiology. All Rights Reserved.
    Journal of clinical microbiology 04/2015; 53(7). DOI:10.1128/JCM.03633-14 · 3.99 Impact Factor
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    ABSTRACT: Our study describes the prevalence of transmitted drug resistance (TDR) among 1318 French patients diagnosed at the time of primary HIV-1 infection (PHI) in 2007-12. HIV-1 resistance-associated mutations (RAMs) were characterized using both the 2009 WHO list of mutations and the French ANRS algorithm. A genotypic susceptibility score was estimated for each first-line recommended ART combination. Patients were mainly MSM (72.6%). Non-B variants were identified in 33.7% of patients. The proportion of TDR was estimated as 11.7% (95% CI 10.0-13.5). The prevalences of PI-, NRTI-, first-generation NNRTI and etravirine/rilpivirine-associated RAMs were 2.5%, 5.2%, 3.9% and 3.2%, respectively. Single, dual and triple class resistance was found in 9.6%, 1.0% and 1.1% of cases, respectively. Additionally, 5/331 strains isolated in 2010-12 had integrase inhibitor (II)-related RAMs (isolated E157Q mutation in all cases). TDR was more common among MSM than in other groups (12.9% versus 8.6%, P = 0.034), and in case of B versus non-B subtype infections (13.6% versus 7.9%, P = 0.002). The proportions of fully active combinations were ≥99.2%, ≥97.3% and ≥95.3% in cases of PI-, II- and NNRTI-based regimens, respectively. In 2010-12, the proportion of fully active efavirenz-based ART was lower in cases of subtype B versus non-B infection (P = 0.021). Compared with our previous studies, the proportion of NRTI- and first-generation NNRTI-related TDR has continued to decline in French seroconverters. However, subtype B-infected MSM could drive the spread of resistant HIV strains. Finally, we suggest preferring PI- or II- to NNRTI-based combinations to treat PHI patients. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail:
    Journal of Antimicrobial Chemotherapy 02/2015; 70(7). DOI:10.1093/jac/dkv049 · 5.31 Impact Factor
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    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. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.
    Cell Reports 01/2015; 10(4). DOI:10.1016/j.celrep.2014.12.047 · 8.36 Impact Factor
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    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.
    PLoS ONE 10/2014; 9(10):e110435. DOI:10.1371/journal.pone.0110435 · 3.23 Impact Factor
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    ABSTRACT: The presence of HIV-1 non-B subtypes in Western Europe is commonly attributed to migration of individuals from non-European countries, but the possible role of domestic infections with non-B subtypes is not well investigated. The French mandatory anonymous reporting system for HIV is linked to a virological surveillance using assays for recent infection (<6 months) and serotyping. During the first semester of years 2007 to 2010, any sample corresponding to a non-B recent infection was analyzed by sequencing a 415-bp env region, followed by phylogenetic analysis and search for transmission clusters. Two hundred thirty-three recent HIV-1 infections with non-B variants were identified. They involved 5 subtypes and 7 circulating recombinant forms (CRFs). Ninety-two cases (39.5%) were due to heterosexual transmissions, of which 39 occurred in patients born in France. Eighty-five cases (36.5%) were identified in men having sex with men (MSM). Forty-three recent non-B infections (18.5%) segregated into 14 clusters, MSM being involved in 11 of them. Clustered transmission events included 2 to 7 cases per cluster. The largest cluster involved MSM infected by a CRF02_AG variant. In conclusion, we found that the spread of non-B subtypes in France occurs in individuals of French origin and that MSM are particularly involved in this dynamic.
    Journal of Clinical Microbiology 09/2014; 58(11). DOI:10.1128/JCM.01141-14 · 3.99 Impact Factor
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    ABSTRACT: We report the case of a multi-experienced patient, infected with an HIV-1 strain, which selected multiple resistance mutations. We designed a novel well-tolerated and effective rescue treatment including dolutegravir, rilpivirine, and foscarnet, allowing a 60 week sustained virological response for the first time in 23 years of HIV infection.
    Journal of Clinical Virology 08/2014; 60(4). DOI:10.1016/j.jcv.2014.05.004 · 3.02 Impact Factor

  • Journal of Clinical Microbiology 07/2014; 52(7):2740-1. DOI:10.1128/JCM.00962-14 · 3.99 Impact Factor
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    ABSTRACT: The Agence Nationale de Recherche sur le Sida et les hépatites virales (ANRS) previously developed a widely used method for HIV-1 RNA quantification (Biocentric). Here, we report the development of a new specific and sensitive method for HIV-2 RNA quantification, based on an adaptation of the existing HIV-1 protocol. The new test is based on TaqMan one-step reverse transcription-quantitative PCR (qRT-PCR) targeting two conserved consensus regions of HIV-2 (long terminal repeat [LTR] and gag). Analytic performances were determined in three laboratories. Clinical performances were evaluated on 100 plasma samples from HIV-2-infected patients (groups A, B, and H) by comparison with the assay currently used for the ANRS HIV-2 cohort. The specificity was 100%. Sensitivity was 50 copies/ml (cp/ml) and was optimized to 10 cp/ml. The within-run coefficients of variation in the three laboratories varied from 0.54% to 1.61% at 4 log10 copies/ml and from 7.24% to 14.32% at 2 log10 cp/ml. The between-run coefficients of variation varied from 2.28% to 6.43%. Of the 39 clinical samples below 2 log10 in the current assay, the new test improved the detection or quantification of 17 samples, including eight group B samples. For quantifiable samples, similar loads were obtained with the two assays for group A samples. The median difference between the two assays for group B samples was +0.18 but with greater heterogeneity than for group A. The HIV-2 group H sample had similar results with the two assays. This new assay is highly sensitive and accurately quantifies the most prevalent HIV-2 groups. This test will be useful for monitoring low viral loads in HIV-2-infected patients.
    Journal of Clinical Microbiology 06/2014; 52(8). DOI:10.1128/JCM.00724-14 · 3.99 Impact Factor
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    ABSTRACT: To assess the virological response, genotypic resistance profiles, and antiretroviral plasma concentrations in HIV-2 antiretroviral-treated (antiretroviral therapy, ART) patients in Côte d'Ivoire. A cross-sectional survey was conducted among HIV-2 patients receiving ART. Plasma HIV-2 viral load was performed using the ANRS assay. Protease and reverse transcriptase sequencing was performed using in-house methods and antiretroviral plasma concentrations were assessed using ultra performance liquid chromatography combined with tandem mass spectrometry. One hundred forty five HIV-2-treated patients were enrolled with a median CD4 cell count of 360/μl (interquartile range, IQR = 215-528). Median duration of ART was 4 years (IQR = 2-7) and 74% of patients displayed viral load less than 50 copies/ml. Median plasma HIV-2 RNA among patients with viral load more than 50 copies/ml was 3016 copies/ml (IQR = 436-5156). Most patients (84%) received a lopinavir/ritonavir-based regimen. HIV-2 resistance mutations to nucleoside reverse transcriptase inhibitors and protease inhibitors were detected in 21 of 25 (84%) and 20 of 29 (69%) samples, respectively. The most prevalent nucleoside reverse transcriptase inhibitor resistance mutations were M184I/V (90%), Q151M (24%), and S215F/Y (24%). The most prevalent protease inhibitor resistance mutations were V47A (60%) and I54M (30%). Median CD4 cell counts were 434/μl (292-573) and 204/μl (122-281) in patients with viral load less than 50 copies/ml and those exhibiting virological failure (P < 0.0001), respectively. The proportions of patients with adequate antiretroviral plasma concentrations were 81 and 93% in patients displaying virological failure and in those with viral load less than 50 copies/ml, respectively (P = 0.046), suggesting good treatment adherence. We observed adequate drug plasma concentrations and virological suppression in a high proportion of HIV-2-infected patients. However, in cases of virological failure, the limited HIV-2 therapeutic arsenal and cross-resistance dramatically reduced treatment options.
    AIDS (London, England) 02/2014; 28(8). DOI:10.1097/QAD.0000000000000244 · 5.55 Impact Factor
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    ABSTRACT: Fourth generation assays for HIV diagnosis are progressively being introduced into routine services, due to their improvement of diagnosis. In spite of this, HIV diagnosis remains a challenge in sub-Saharan Africa, due to false positive reactivity. There is a continuous need for field evaluations and routine validations of fourth generation HIV tests in African populations. Evaluate the performances of the ARCHITECT HIV Ag/Ab kit (Abbott) in a population living in an African setting-Cameroon compared to a population living in a European setting-France. 645 HIV samples from both France and Cameroon were evaluated. The positive panel (378 samples) included a diverse series of HIV-1 variants (groups M, N, O, and P) as well as HIV-2 samples. Results were compared to original diagnosis done with other 4th generation assays (AxSYM HIV Ag/Ab (Abbott) and Vidas HIV DUO QUICK) (bioMérieux). Sensitivity of the ARCHITECT was 100% in both sites. It diagnosed all variants of the panel with different reactivity profiles following strain diversity. A wider range of reactivity was observed for group O. Specificity was slightly lower (97.6%) in Cameroon than in France (98.6%), probably due to a higher rate of false positive reactivity. ARCHITECT HIV Ag/Ab assay had high performances in clinical sensitivity and specificity and is adapted to the wide genetic diversity of viruses circulating in West Central Africa. Our results further highlight the need to evaluate HIV diagnostic tests before introduction into routine diagnostic services both in the North and in the South.
    Journal of clinical virology: the official publication of the Pan American Society for Clinical Virology 12/2013; 58 Suppl 1:e70-5. DOI:10.1016/j.jcv.2013.08.015 · 3.02 Impact Factor
  • M. Morgand · M. Braibant · M. Bouvin-Pley · E. Gong · J. Plantier · F. Simon · F. Barin ·

    Conference on AIDS Vaccine; 11/2013

Publication Stats

1k Citations
403.72 Total Impact Points


  • 2013-2015
    • Hôpital Charles-Nicolle
      Tunis-Ville, Tūnis, Tunisia
  • 2003-2015
    • Centre Hospitalier Universitaire Rouen
      Rouen, Haute-Normandie, France
  • 2014
    • Université de Caen Basse-Normandie
      Caen, Lower Normandy, France
  • 2008-2014
    • Université de Rouen
      Mont-Saint-Aignan, Haute-Normandie, France
  • 2009
    • Robert Koch Institut
      Berlín, Berlin, Germany
  • 2002
    • Cheikh Anta Diop University, Dakar
      Dakar, Dakar, Senegal