Publications by authors named "Guillaume Martin-Blondel"

69 Publications

Maraviroc exposure is influenced by exogenous thyrotoxicosis.

AIDS 2021 Mar;35(4):701-703

Department of Infectious Diseases, University Hospital of Toulouse.

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http://dx.doi.org/10.1097/QAD.0000000000002754DOI Listing
March 2021

Neglecting plasma protein binding in COVID-19 patients leads to a wrong interpretation of lopinavir overexposure.

Clin Pharmacol Ther 2021 Feb 5. Epub 2021 Feb 5.

INTHERES, Université de Toulouse, INRA, ENVT, 23 Chemin des Capelles, BP 87614, 31 076, Toulouse Cedex 3, France.

Boffito et al. recalled the critical importance to correctly interpret protein binding. Changes of lopinavir pharmacokinetics in COVID-19 are a perfect illustration. Indeed, several studies described that total lopinavir plasma concentrations were considerably higher in severe COVID-19 patients than those reported in HIV patients. These findings have led to a reduction of the dose of lopinavir in some patients, hypothetizing an inhibitory effect of inflammation on lopinavir metabolism. Unfortunately, changes in plasma protein binding were never investigated. We performed a retrospective cohort study. Data were collected from the medical records of patients hospitalized for COVID-19 treated with lopinavir/ritonavir in intensive care units or infectious disease departments of Toulouse university hospital (France). Total and unbound concentrations of lopinavir, C reactive protein, albumin and alpha-1-acid glycoprotein (AAG) levels were measured during routine care on the same samples. In COVID-19 patients, increased total lopinavir concentration is the result of an increased AAG-bound lopinavir concentration whereas the unbound concentration remains constant, and insufficient to reduce the SARS-CoV-2 viral load. Although international guidelines have recently recommended against using lopinavir/ritonavir to treat severe COVID-19, the description of lopinavir pharmacokinetics changes in COVID-19 is a textbook case of the high risk of misinterpretation of a total drug exposure when changes in protein binding are not taken into consideration.
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http://dx.doi.org/10.1002/cpt.2196DOI Listing
February 2021

Protection of healthcare workers against SARS-CoV-2 reinfection.

Clin Infect Dis 2021 Jan 27. Epub 2021 Jan 27.

CHU Toulouse, Hôpital Purpan, Virology Laboratory, Toulouse, France.

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http://dx.doi.org/10.1093/cid/ciab069DOI Listing
January 2021

Tularemia: A Case Series of Patients Diagnosed at the National Reference Center for Rickettsioses From 2008 to 2017.

Open Forum Infect Dis 2020 Nov 19;7(11):ofaa440. Epub 2020 Sep 19.

Centre National de Référence des Rickettsia, Coxiella et Bartonella, IHU-Méditerranée Infection, Marseille, France.

Background: We describe the epidemiological, clinical, and prognostic aspects of 177 tularemia cases diagnosed at the National Reference Center for rickettsioses, coxiellosis, and bartonelloses between 2008 and 2017.

Methods: All patients with a microbiological diagnosis of tularemia made in the laboratory were included. Clinical and epidemiological data were collected retrospectively from clinicians in charge of patients using a standardized questionnaire. Diagnostic methods used were indirect immunofluorescence serology, real-time polymerase chain reaction (PCR), and universal PCR targeting the 16S ribosomal ribonucleic acid gene.

Results: The series included 54 females and 123 males (sex ratio, 2.28; mean age, 47.38 years). Eighty-nine (50.2%) were confirmed as having tularemia on the basis of a positive PCR or seroconversion, and 88 (49.8%) were considered as probable due to a single positive serum. The regions of France that were most affected included Pays de la Loire (22% of cases), Nouvelle Aquitaine (18.6% of cases), and Grand Est (12.4% of cases). Patients became infected mainly through contact with rodents or game (38 cases, 21.4%), through tick-bites (23 cases, 12.9%), or during outdoor leisure activities (37 cases, 20.9%). Glandular and ulceroglandular forms were the most frequent (109 cases, 61.5%). Two aortitis, an infectious endocarditis, a myocarditis, an osteoarticular infection, and a splenic hematoma were also diagnosed. Tularemia was discovered incidentally in 54.8% of cases. Seventy-eight patients were hospitalized, and no deaths were reported.

Conclusions: Our data suggest that in an endemic area and/or in certain epidemiological contexts, tularemia should be sought to allow an optimized antibiotic therapy and a faster recovery.
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http://dx.doi.org/10.1093/ofid/ofaa440DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7651688PMC
November 2020

Progressive multifocal leukoencephalopathy: MRI findings in HIV-infected patients are closer to rituximab- than natalizumab-associated PML.

Eur Radiol 2020 Nov 6. Epub 2020 Nov 6.

Hôpitaux Universitaires de Strasbourg, Service d'imagerie 2, Hôpital de Hautepierre, Strasbourg, France.

Objectives: To compare brain MRI findings in progressive multifocal leukoencephalopathy (PML) associated to rituximab and natalizumab treatments and HIV infection.

Materials And Methods: In this retrospective, multicentric study, we analyzed brain MRI exams from 72 patients diagnosed with definite PML: 32 after natalizumab treatment, 20 after rituximab treatment, and 20 HIV patients. We compared T2- or FLAIR-weighted images, diffusion-weighted images, T2*-weighted images, and contrast enhancement features, as well as lesion distribution, especially gray matter involvement.

Results: The three PML entities affect U-fibers associated with low signal intensities on T2*-weighted sequences. Natalizumab-associated PML showed a punctuate microcystic appearance in or in the vicinity of the main PML lesions, a potential involvement of the cortex, and contrast enhancement. HIV and rituximab-associated PML showed only mild contrast enhancement, punctuate appearance, and cortical involvement. The CD4/CD8 ratio showed a trend to be higher in the natalizumab group, possibly mirroring a more efficient immune response.

Conclusion: Imaging features of rituximab-associated PML are different from those of natalizumab-associated PML and are closer to those observed in HIV-associated PML.

Key Points: • Nowadays, PML is emerging as a complication of new effective therapies based on monoclonal antibodies. • Natalizumab-associated PML shows more inflammatory signs, a perivascular distribution "the milky way," and more cortex involvement than rituximab- and HIV-associated PML. • MRI differences are probably related to higher levels of immunosuppression in HIV patients and those under rituximab therapy.
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http://dx.doi.org/10.1007/s00330-020-07362-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7644389PMC
November 2020

Safety of Pyrazinamide for the Treatment of Tuberculosis in Older Patients Over 75 Years of Age: A Retrospective Monocentric Cohort Study.

Drugs Aging 2021 Jan 4;38(1):43-52. Epub 2020 Nov 4.

Department of Infectious and Tropical Diseases, Toulouse University Hospital, Place du Docteur Baylac, TSA 40031, 31059, Toulouse Cedex 9, France.

Objectives: Pyrazinamide (PZA) has a controversial safety profile in older patients. We aimed to assess the frequency and risk factors for adverse drug reactions (ADRs) in patients over 75 years of age treated for tuberculosis with or without PZA.

Methods: We conducted a retrospective monocentric study including patients aged over 75 years treated for active tuberculosis between 2008 and 2018. The frequency, type, seriousness, and causality assessment of ADRs to anti-tuberculosis treatment were compared between patients receiving PZA or not. Risk factors for ADRs were investigated using univariable and multivariable analyses by logistic regression.

Results: Among the 110 patients included, 54 (49.1%) received PZA (group 1) and 56 (50.9%) did not (group 2). ADRs to anti-tuberculosis drugs occurred in 31 patients (57.4%) in groups 1 and 15 (26.8%) in group 2 (p = 0.003). PZA-related ADRs occurred in 40.7% of exposed patients. Frequency of renal ADRs was higher in group 1 (9.3% vs 0%; p = 0.026). Rates of hepatic (18.5% vs 12.5%; p = 0.38), digestive (22.2% vs 8.9%; p = 0.054), and allergic (14.8% vs 5.4%; p = 0.12) ADRs were numerically higher in group 1 although the differences were not statistically significant. Serious ADRs occurred more frequently in group 1 (24.1% vs 8.9%; p = 0.03). The use of PZA was the only independent risk factor for ADRs to anti-tuberculosis drugs (odds ratio 3.75, 95% CI 1.5-9.6; p = 0.0056). No risk factors for PZA-related ADRs were identified.

Conclusion: In older French patients, the use of PZA was associated with more frequent ADRs to anti-tuberculosis drugs.
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http://dx.doi.org/10.1007/s40266-020-00811-9DOI Listing
January 2021

Outcome of patients hospitalized for COVID-19 and exposure to angiotensin-converting enzyme inhibitors and angiotensin-receptor blockers in France: results of the ACE-CoV study.

Fundam Clin Pharmacol 2021 Feb 28;35(1):194-203. Epub 2020 Oct 28.

Centre d'Investigation Clinique 1436, axe pharmacoépidémiologie, Centre Hospitalier Universitaire de Toulouse-Purpan, place du Dr Baylac, TSA40031, Toulouse Cedex 9, 31059, France.

Data are lacking on the impact of ACEI/ARB exposure on unfavorable outcome in the population of patients hospitalized for COVID-19 with hypertension/cardiovascular disease, particularly in Europe. The ACE-CoV study was designed to assess this question. The study was conducted in the Covid-Clinic-Toul cohort, which contains data about all patients hospitalized at Toulouse University hospital, France with a SARS-CoV-2 infection since March, 2020. We selected the patients with a history of cardiovascular disease (heart failure or coronary disease) and/or arterial hypertension. We conducted a subgroup analysis in patients with arterial hypertension. ACEI/ARB exposures at admission were assessed. The outcome was composite: admission to intensive care unit, need of mechanical ventilation or death during the 14 days after admission to hospital. We used logistic regression models with propensity scores (PS) weighted by overlap weighting (OW) and inverse probability of treatment weighting (IPTW). Between March 2020 and April 20, 2020, the Covid-Clinic-Toul included 263 patients. Among them, 111 were included in the ACE-CoV study population. In OW-PS-adjusted analyses, the association of exposure to ACEIs or ARBs with outcome occurrence was OR: 1.56 (95% CI: 0.73-3.33). It was 0.99 (95% CI: 0.68-1.45) for ACEIs and 1.64 (95% CI: 0.77-3.50) for ARBs. Analyses with weighting by the IPTW-PS method gave similar results. Results were similar when considering the subgroup of patients with arterial hypertension. The ACE-CoV study found no association between exposure to ACEIs or ARBs and unfavorable outcome in hospitalized patients for COVID-19 with a history of cardiovascular disease/arterial hypertension.
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http://dx.doi.org/10.1111/fcp.12613DOI Listing
February 2021

Sexual transmission of an extensively drug-resistant HIV-1 strain.

Lancet HIV 2020 08;7(8):e529-e530

Service des Maladies Infectieuses et Tropicales, Centre Hospitalier Universitaire de Toulouse, Toulouse 31320, France; INSERM UMR1043, Centre de Physiopathologie de Toulouse-Purpan, Toulouse, France; Université de Toulouse Paul Sabatier, Faculté de Médecine, Toulouse, France. Electronic address:

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http://dx.doi.org/10.1016/S2352-3018(20)30205-8DOI Listing
August 2020

Comparing ultrafiltration and equilibrium dialysis to measure unbound plasma dolutegravir concentrations based on a design of experiment approach.

Sci Rep 2020 07 23;10(1):12265. Epub 2020 Jul 23.

Department of Pharmacokinetics and Toxicology, Toulouse University Hospital, Toulouse, France.

Dolutegravir therapeutic drug monitoring (TDM) could be improved by measuring the unbound dolutegravir plasma concentration (Cu), particularly in patients experiencing virological failure or toxicity despite achieving appropriate DTG total plasma concentrations. Equilibrium dialysis (ED) is the gold standard to measure Cu, but ED is time consuming, precluding its use in clinical practice. In contrast, ultrafiltration is applicable to TDM, but is sensitive to numerous analytical conditions. In order to evaluate measurements of Cu by ultrafiltration, ultrafiltration conditions were validated by comparison with ED. DTG concentrations were measured by LC-MS/MS. Three ultrafiltration factors (temperature, duration and relative centrifugal force [RCF]) were evaluated and compared to ED (25/37 °C), using a design of experiment strategy. Temperature was found to influence Cu results by ED (p = 0.036) and UF (p = 0.002) when results were analysed with ANOVA. Relative centrifugal force (2000 g) and time (20 min) interacted to influence Cu (p = 0.006), while individually they did not influence Cu (p = 0.88 and p = 0.42 for RCF and time). Ultrafiltration conditions which yielded the most comparable results to ED were 37 °C, 1000 g for 20 min. Ultrafiltration results greatly depended on analytical conditions, confirming the need to validate the method by comparison with ED in order to correctly interpret DTG Cu.
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http://dx.doi.org/10.1038/s41598-020-69102-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7378073PMC
July 2020

Brain MRI Findings in Severe COVID-19: A Retrospective Observational Study.

Radiology 2020 11 16;297(2):E242-E251. Epub 2020 Jun 16.

From the Hôpitaux Universitaires de Strasbourg, Service d'Imagerie 2, Hôpital de Hautepierre, Strasbourg, France (S.K.).

Background Brain MRI parenchymal signal abnormalities have been associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Purpose To describe the neuroimaging findings (excluding ischemic infarcts) in patients with severe coronavirus disease 2019 (COVID-19) infection. Materials and Methods This was a retrospective study of patients evaluated from March 23, 2020, to April 27, 2020, at 16 hospitals. Inclusion criteria were () positive nasopharyngeal or lower respiratory tract reverse transcriptase polymerase chain reaction assays, () severe COVID-19 infection defined as a requirement for hospitalization and oxygen therapy, () neurologic manifestations, and () abnormal brain MRI findings. Exclusion criteria were patients with missing or noncontributory data regarding brain MRI or brain MRI showing ischemic infarcts, cerebral venous thrombosis, or chronic lesions unrelated to the current event. Categorical data were compared using the Fisher exact test. Quantitative data were compared using the Student test or Wilcoxon test. < .05 represented a significant difference. Results Thirty men (81%) and seven women (19%) met the inclusion criteria, with a mean age of 61 years ± 12 (standard deviation) (age range, 8-78 years). The most common neurologic manifestations were alteration of consciousness (27 of 37, 73%), abnormal wakefulness when sedation was stopped (15 of 37, 41%), confusion (12 of 37, 32%), and agitation (seven of 37, 19%). The most frequent MRI findings were signal abnormalities located in the medial temporal lobe in 16 of 37 patients (43%; 95% confidence interval [CI]: 27%, 59%), nonconfluent multifocal white matter hyperintense lesions seen with fluid-attenuated inversion recovery and diffusion-weighted sequences with variable enhancement, with associated hemorrhagic lesions in 11 of 37 patients (30%; 95% CI: 15%, 45%), and extensive and isolated white matter microhemorrhages in nine of 37 patients (24%; 95% CI: 10%, 38%). A majority of patients (20 of 37, 54%) had intracerebral hemorrhagic lesions with a more severe clinical presentation and a higher admission rate in intensive care units (20 of 20 patients [100%] vs 12 of 17 patients without hemorrhage [71%], = .01) and development of the acute respiratory distress syndrome (20 of 20 patients [100%] vs 11 of 17 patients [65%], = .005). Only one patient had SARS-CoV-2 RNA in the cerebrospinal fluid. Conclusion Patients with severe coronavirus disease 2019 and without ischemic infarcts had a wide range of neurologic manifestations that were associated with abnormal brain MRI scans. Eight distinctive neuroradiologic patterns were described. © RSNA, 2020.
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http://dx.doi.org/10.1148/radiol.2020202222DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7301613PMC
November 2020

Hydroxychloroquine in Coronavirus Disease 2019 Patients: What Still Needs to Be Known About the Kinetics.

Clin Infect Dis 2020 12;71(11):2962-2964

UMR INTHERES, INRA-ENVT, Toulouse, France.

Different dosage regimens of hydroxychloroquine are used to manage coronavirus disease 2019 (COVID-19) patients, without information on the pharmacokinetics in this population. Blood samples (n = 101) were collected from 57 COVID-19 patients for 7 days, and concentrations were compared with simulated kinetic profiles. Hydroxychloroquine exposure is low and cannot be predicted by other populations.
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http://dx.doi.org/10.1093/cid/ciaa558DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7239205PMC
December 2020

Th22 cells are efficiently recruited in the gut by CCL28 as an alternative to CCL20 but do not compensate for the loss of Th17 cells in treated HIV-1-infected individuals.

Mucosal Immunol 2021 01 28;14(1):219-228. Epub 2020 Apr 28.

INSERM, UMR1043, Toulouse, F-31300, France.

Gut CD4 T cells are incompletely restored in most HIV-1-infected individuals on antiretroviral therapy, notably Th17 cells, a key subset in mucosal homeostasis. By contrast, gut Th22 cells are usually restored at normal frequencies. Th22 cells display a CCR6CCR10 phenotype and could thus respond to CCL20- and CCL28-mediated chemotaxis, while Th17 cells, which express CCR6 but not CCR10, depend on CCL20. Herein, we found that CCL28 is normally expressed by duodenal enterocytes of treated HIV-1-infected individuals, while CCL20 expression is blunted. Ex vivo, we showed that Th22 cells contribute to the reduction of CCL20 production by enterocytes through an IL-22- and IL-18-dependent mechanism. Th22 cells preferentially migrate via CCL20- rather than CCL28-mediated chemotaxis when both chemokines are available in the microenvironment. However, when the CCL20/CCL28 ratio drops, as in treated HIV-1-infected individuals, Th22 cells can migrate via the CCR10-CCL28 axis, as an alternative to CCR6-CCL20. This could explain the better reconstitution of gut Th22 compared with Th17 cells on antiretroviral therapy. Lastly, we assessed the relationships between the frequencies of gut Th17 and Th22 cells and inflammatory markers related to microbial translocation, and showed that Th22 cells do not compensate for the loss of Th17 cells in treated HIV-1-infected individuals.
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http://dx.doi.org/10.1038/s41385-020-0286-6DOI Listing
January 2021

Two Cases of Late-Onset Anti-NMDAr Auto-Immune Encephalitis After Herpes Simplex Virus 1 Encephalitis.

Front Neurol 2020 18;11:38. Epub 2020 Feb 18.

Département de Neurologie, Hôpital Pierre Paul Riquet, CHU de Toulouse, Toulouse, France.

Encephalitis due to herpes simplex virus 1 (HSV-1) was described as a potential trigger for the development of anti-N-methyl-D-aspartate receptor (NMDAr) auto-immune encephalitis (AIE) within a few days to a few weeks after the infection. We assessed clinical, radiological, and biological diagnoses process, treatment response, and evolution. We report here cases of a 71-year-old man and a 57-year-old woman presenting anti-NMDAr AIE, respectively, 12 and 7 months after HSV-1 encephalitis. In both cases, the onset was brisk, and the symptoms were mainly neuropsychiatric (paranoid delirium, Capgras, and Cotard syndromes) and cognitive, with anterograde amnesia. Relapse of HSV encephalitis, epilepsy, and paraneoplastic neurologic syndromes were excluded. The clinical response to first-line treatments composed of intravenous immunoglobulins and high-dose corticosteroids was poor, whereas significant improvement was noticed after rituximab induction. Post-herpetic anti-NMDAr AIE could arise several months after infection. Clinicians must be aware of this possibility, particularly if cognitive and/or psychiatric symptoms occurred after a remitting period. In our two cases, only rituximab was associated with clinical improvement.
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http://dx.doi.org/10.3389/fneur.2020.00038DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7040193PMC
February 2020

CD8 T cell-mediated endotheliopathy is a targetable mechanism of neuro-inflammation in Susac syndrome.

Nat Commun 2019 12 18;10(1):5779. Epub 2019 Dec 18.

Centre de Physiopathologie Toulouse-Purpan (CPTP), Université de Toulouse, CNRS, Inserm, UPS, CHU Purpan - BP 3028 - 31024, Toulouse Cedex 3, Toulouse, France.

Neuroinflammation is often associated with blood-brain-barrier dysfunction, which contributes to neurological tissue damage. Here, we reveal the pathophysiology of Susac syndrome (SuS), an enigmatic neuroinflammatory disease with central nervous system (CNS) endotheliopathy. By investigating immune cells from the blood, cerebrospinal fluid, and CNS of SuS patients, we demonstrate oligoclonal expansion of terminally differentiated activated cytotoxic CD8 T cells (CTLs). Neuropathological data derived from both SuS patients and a newly-developed transgenic mouse model recapitulating the disease indicate that CTLs adhere to CNS microvessels in distinct areas and polarize granzyme B, which most likely results in the observed endothelial cell injury and microhemorrhages. Blocking T-cell adhesion by anti-α4 integrin-intervention ameliorates the disease in the preclinical model. Similarly, disease severity decreases in four SuS patients treated with natalizumab along with other therapy. Our study identifies CD8 T-cell-mediated endotheliopathy as a key disease mechanism in SuS and highlights therapeutic opportunities.
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http://dx.doi.org/10.1038/s41467-019-13593-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6920411PMC
December 2019

Performance evaluation of the Vela Dx Sentosa next-generation sequencing system for HIV-1 DNA genotypic resistance.

J Clin Virol 2020 01 26;122:104229. Epub 2019 Nov 26.

INSERM U1043, CNRS UMR 5282, Toulouse University Paul Sabatier, CPTP, Toulouse, F-31300 France; CHU de Toulouse, Hôpital Purpan, Laboratoire de Virologie, Toulouse, F-31300 France.

Background: Patients on antiretroviral therapy could benefit from HIV-1 DNA resistance genotyping for exploring virological failure with low viral load or to guide treatment simplification. Few new generation sequencing data are available.

Objective: To check that the automated deep sequencing Sentosa platform (Vela DX) detected minority resistant variants well enough for HIV DNA genotyping.

Study Design: We evaluated the Sentosa SQ HIV genotyping assay with automated extraction on 40 DNA longitudinal samples from treatment-experienced patients by comparison with Sanger sequencing. HIV drug resistance was interpreted using the ANRS algorithm (v29) at the threshold of 20 % and 3 %.

Results: The Sentosa SQ HIV genotyping assay was 100 % successful to amplify and sequence PR and RT and 86 % to amplify and sequence IN when the HIV DNA load was >2.5 log copies/million cells. The Sentosa and Sanger sequencing were concordant for predicting PR-RT resistance at the threshold of 20 % in 14/18 samples successfully sequenced. A higher level of resistance was predicted by Sentosa in three samples and by Sanger in one sample. The prevalence of resistance was 7 % to PI, 59 % to NRTI, 31 % to NNRTI and 20 % to integrase inhibitors using the Sentosa SQ genotyping assay at the threshold of 3 %. Seven additional mutations <20 % were detected using the Sentosa assay.

Conclusion: Automated DNA extraction and sequencing using the Sentosa SQ HIV genotyping assay accurately predicted HIV DNA drug resistance by comparison with Sanger. Prospective studies are needed to evaluate the clinical interest of HIV DNA genotyping.
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http://dx.doi.org/10.1016/j.jcv.2019.104229DOI Listing
January 2020

Ribavirin for Chronic Hepatitis E Virus Infection in Ibrutinib-Exposed Patients.

Open Forum Infect Dis 2019 Sep 28;6(9):ofz345. Epub 2019 Jul 28.

Hematology Department, Institut Universitaire du Cancer de Toulouse-Oncopole, Toulouse, France.

Ibrutinib is an oral first-in-class Bruton's tyrosine kinase inhibitor approved for the therapy of various B-cell lymphoid malignancies. Among ibrutinib-related infections, viral hepatitis are poorly described. We report our single-center experience with 4 cases of chronic hepatitis E virus infection and their management with ribavirin.
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http://dx.doi.org/10.1093/ofid/ofz345DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6798245PMC
September 2019

Sustained Response and Rationale of Programmed Cell Death-1-Targeting for Progressive Multifocal Leukoencephalopathy.

Open Forum Infect Dis 2019 Oct 30;6(10):ofz374. Epub 2019 Sep 30.

Department of Internal Medicine and Clinical Immunology, CHU de Caen, Caen, France.

In this study, we report a complete (clinical, radiological, and virological) sustained (1 year) response after nivolumab salvage therapy in a progressive multifocal leukoencephalopathy patient. Analyses of the cells infiltrate in a pretreatment brain biopsy suggest that parenchymal programmed cell death-L1 macrophages could be the T-cells partnership in immune exhaustion and virus escape.
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http://dx.doi.org/10.1093/ofid/ofz374DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6767972PMC
October 2019

Olecranon bursitis secondary to Mycobacterium europaeum infection in a patient receiving immunosuppressive drugs for rheumatoid arthritis.

Med Mal Infect 2019 Aug 14;49(5):358-359. Epub 2019 May 14.

Department of infectious and tropical diseases, Toulouse University Hospital, place du Docteur-Baylac TSA 40031, 31059 Toulouse cedex 9, France; Paul Sabatier Toulouse III University, 31330 Toulouse, France; Inserm U1043 - CNRS UMR 5282, Toulouse-Purpan pathophysiology center, 31173 Toulouse cedex, France. Electronic address:

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http://dx.doi.org/10.1016/j.medmal.2019.03.002DOI Listing
August 2019

Treatment of Progressive Multifocal Leukoencephalopathy with Nivolumab.

N Engl J Med 2019 04 10;380(17):1674-1676. Epub 2019 Apr 10.

Toulouse University Hospital, Toulouse, France

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http://dx.doi.org/10.1056/NEJMc1816198DOI Listing
April 2019

Peripheral Plasma and Semen Cytokine Response to Zika Virus in Humans.

Emerg Infect Dis 2019 04;25(4):823-825

We assessed Zika virus RNA and select cytokine levels in semen, blood, and plasma samples from an infected patient in South America. Viral RNA was detected in semen >2 months after viremia clearance; cytokine profiles differed in semen and plasma. After viremia, Zika virus appears to become compartmentalized in the male reproductive tract.
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http://dx.doi.org/10.3201/eid2504.171886DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6433016PMC
April 2019

Progressive Dementia Revealing an Atypical Encephalitis: Neuroimaging Aspects.

J Neuropsychiatry Clin Neurosci Summer 2019;31(3):268-271. Epub 2019 Mar 8.

The Department of Neurology and Neuropsychology, Pierre-Paul Riquet Hospital, Site Purpan, Place du Docteur Baylac, Toulouse, France (Makhtar Ba, Benaiteau, Rigal, Salleles, Pariente); INSERM UMR TONIC-Toulouse NeuroImaging Centre, Purpan University Hospital, Pavillon Baudot, Toulouse, France (Makhtar Ba, Guerrier, Rigal, Mirabel, Pariente); the Neurology Department, Albi Hospital, Albi, France (Perez); the Department of Infectious and Tropical Diseases, Purpan University Hospital, Toulouse, France (Martin-Blondel); and INSERM, Centre de Physiopathologie Toulouse-Purpan, Toulouse, France (Martin-Blondel).

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http://dx.doi.org/10.1176/appi.neuropsych.18050100DOI Listing
March 2020

Efficacy of teicoplanin monotherapy following initial standard therapy in Enterococcus faecalis infective endocarditis: a retrospective cohort study.

Infection 2019 Jun 27;47(3):463-469. Epub 2019 Feb 27.

Department of Infectious and Tropical Diseases, Toulouse University Hospital, Place du Docteur Baylac TSA 40031, 31059, Toulouse CEDEX 9, France.

Purpose: Teicoplanin is often used in Enterococcus faecalis infective endocarditis as a relay in case of penicillin side effects, or in outpatients. We assessed the efficacy of teicoplanin used as continuation therapy after initial standard treatment of E. faecalis endocarditis.

Methods: All adult patients consecutively diagnosed between 1997 and 2016 for E. faecalis endocarditis were retrospectively reviewed. Patients who received standard therapy (ST) were compared to those switched to teicoplanin to complete the treatment (teicoplanin therapy, TT).

Results: Seventy-one patients were enrolled: 34 in the ST group and 37 in the TT group. Amoxicillin was replaced by teicoplanin after a median duration of 18 days (IQ 12-21). Teicoplanin (5.8 ± 2.3 mg/kg) was administered for a median duration of 29 days (IQ 25-34). Gentamicin therapy was similar. Overall duration of antimicrobial therapy was 42 days (IQ 35-43) in the ST group, and 46 days (IQ 43-49) in the TT group (p = 0.001). Global and endocarditis-related mortality rates were 22/34 (65%) and 13/34 (38%) in the ST group, and 14/37 (38%) and 3/37 (8%) in the TT group (p ≤ 0.05). Relapses occurred in 2/26 patients who survived the treatment phase in the ST group (8%) and in 3/37 in the TT group (8%, p = 0.68). All relapses in the TT group occurred in patients presenting prosthetic valve endocarditis. Finally, 20 patients were cured in the ST group (59%), and 33 patients in the TT group (89%, p = 0.003).

Conclusions: In E. faecalis endocarditis, the switch to teicoplanin in selected patients following an initial phase of standard treatment represents an alternative, particularly for outpatient therapy. Caution should be exercised in cases of prosthetic valve endocarditis.
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http://dx.doi.org/10.1007/s15010-019-01290-wDOI Listing
June 2019

Caval replacement with parietal peritoneum tube graft for septic thrombophlebitis after hepatectomy: A case report.

World J Hepatol 2019 Jan;11(1):133-137

Digestive Surgery, Toulouse University Hospital, Toulouse 31400, France.

Background: Caval vein thrombosis after hepatectomy is rare, although it increases mortality and morbidity. The evolution of this thrombosis into a septic thrombophlebitis responsible for persistent septicaemia after a hepatectomy has not been reported to date in the literature. We here report the management of a 54-year-old woman operated for a peripheral cholangiocarcinoma who developed a suppurated thrombophlebitis of the vena cava following a hepatectomy.

Case Summary: This patient was operated by left lobectomy extended to segment V with bile duct resection and Roux-en-Y hepaticojejunostomy. After the surgery, she developed , and bacteraemias, as well as fungemia. A computed tomography scan revealed a bilioma which was percutaneously drained. Despite adequate antibiotic therapy, the patient's condition remained septic. A diagnosis of septic thrombophlebitis of the vena cava was made on post-operative day 25. The patient was then operated again for a surgical thrombectomy and complete caval reconstruction with a parietal peritoneum tube graft. Use of the peritoneum as a vascular graft is an inexpensive technique, it is readily and rapidly available, and it allows caval replacement in a septic area. Septic thrombophlebitis of the vena cava after hepatectomy has not been described previously and it warrants being added to the spectrum of potential complications of this procedure.

Conclusion: Septic thrombophlebitis of the vena cava was successfully treated with antibiotic and anticoagulation treatments, prompt surgical thrombectomy and caval reconstruction.
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http://dx.doi.org/10.4254/wjh.v11.i1.133DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6354118PMC
January 2019

HIV-1 escape in the central nervous system on elvitegravir-based antiretroviral therapy.

AIDS 2019 03;33(3):593-594

CHU de Toulouse, Service des Maladies Infectieuses et Tropicales.

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http://dx.doi.org/10.1097/QAD.0000000000002089DOI Listing
March 2019

Graft-versus-host disease, but not graft-versus-leukemia immunity, is mediated by GM-CSF-licensed myeloid cells.

Sci Transl Med 2018 11;10(469)

Institute of Experimental Immunology,University of Zurich, CH-8057 Zurich, Switzerland.

Allogeneic hematopoietic cell transplantation (allo-HCT) not only is an effective treatment for several hematologic malignancies but can also result in potentially life-threatening graft-versus-host disease (GvHD). GvHD is caused by T cells within the allograft attacking nonmalignant host tissues; however, these same T cells mediate the therapeutic graft-versus-leukemia (GvL) response. Thus, there is an urgent need to understand how to mechanistically uncouple GvL from GvHD. Using preclinical models of full and partial MHC-mismatched HCT, we here show that the granulocyte-macrophage colony-stimulating factor (GM-CSF) produced by allogeneic T cells distinguishes between the two processes. GM-CSF drives GvHD pathology by licensing donor-derived phagocytes to produce inflammatory mediators such as interleukin-1β and reactive oxygen species. In contrast, GM-CSF did not affect allogeneic T cells or their capacity to eliminate leukemic cells, retaining undiminished GvL responses. Last, tissue biopsies and peripheral blood mononuclear cells from patients with grade IV GvHD showed an elevation of GM-CSF-producing T cells, suggesting that GM-CSF neutralization has translational potential in allo-HCT.
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http://dx.doi.org/10.1126/scitranslmed.aat8410DOI Listing
November 2018

Detection of Zika, dengue and chikungunya viruses using single-reaction multiplex real-time RT-PCR.

Diagn Microbiol Infect Dis 2018 Dec 28;92(4):284-287. Epub 2018 Jun 28.

Department of Virology, CHU Purpan, Toulouse, France; INSERM, UMR1043, Toulouse, France; Université Paul Sabatier, Toulouse, France. Electronic address:

Zika (ZIKV), Dengue (DENV) and Chikungunya viruses (CHIKV) co-circulate in the same geographical areas during the same seasonal period through the same biting arthropods. Therefore a rapid sensitive and specific molecular assay for these viruses would be a considerable help in the disease management and the epidemiological survey. We developed a one-step multiplex real-time PCR for the simultaneous detection of these viruses. Intra and inter-reproducibilities varied from 0.41% to 3.29% and from 1.13% to 4.93% for each virus respectively. The specificity was 100%. Whole blood, plasma and urines were used for comparison with commercially available monoplex assays (RealStar® kits, Altona Diagnostics GmbH, Hamburg, Germany). The concordance was 96%, 92.9% and 95.7% for ZIKV, DENV and CHIKV respectively. No cross reaction and no PCR inhibition were observed for any of the clinical samples. This test can thus be used as a rapid molecular assay for ZIKV, DENV1-4 and CHIKV infections.
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http://dx.doi.org/10.1016/j.diagmicrobio.2018.06.019DOI Listing
December 2018

Risk of Progressive Multifocal Leukoencephalopathy in the Combination Antiretroviral Therapy Era in the French Hospital Database on Human Immunodeficiency Virus (ANRS-C4).

Clin Infect Dis 2018 07;67(2):275-282

Sorbonne Universités, UPMC Université Paris, INSERM, Institut Pierre Louis d'Épidémiologie et de Santé Publique.

Background: Risk factors for progressive multifocal leukoencephalopathy (PML) in individuals with human immunodeficiency virus (HIV) infection are poorly documented in the era of combination antiretroviral therapy (cART).

Methods: We studied HIV-1-infected individuals aged ≥15 years who had no history of PML and were prospectively followed up between 1997 and 2011 in the French Hospital Database on HIV (FHDH-ANRS CO4) cohort. Cox models were used to calculate adjusted hazard ratios (HRs), focusing on sub-Saharan origin, suggested to be protective, and recent cART initiation, potentially associated with an increased risk of PML.

Results: PML developed in 555 individuals, in 57 during the first 6 months of cART. From 1997-2000 to 2009-2011, the incidence fell from 1.15 (95% confidence interval [CI], .98-1.31) to 0.49 (.37-.61) per 1000 person-years. Sub-Saharan African origin had no clear influence (HR, 0.80; 95% CI, .58-1.11). Compared with men who have sex with men, injection drug users (IDUs) were at higher risk (HR, 1.80 [95% CI, 1.32-2.45] for male and 1.68 [1.13-2.48] for female IDUs). When IDUs were excluded, hepatitis C virus seropositivity was associated with an increased risk (HR, 1.40; 95% CI, 1.02-1.93). Compared with no cART initiation, initiation <6 months previously was associated with PML onset (HR, 4.91; 95% CI, 2.42-9.95).

Conclusions: Recent cART initiation is associated with an increased risk of PML, as are injection drug use and hepatitis C virus seropositivity. Sub-Saharan African origin had no protective effect.
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http://dx.doi.org/10.1093/cid/ciy074DOI Listing
July 2018

18F-Fluorodeoxyglucose positron emission tomography computed tomography detection threshold in follicular lymphoma: A case report.

Medicine (Baltimore) 2017 Nov;96(47):e8705

Departement de Pathologie, Institut Universitaire du Cancer Oncopole de Toulouse Institut National de la Sante et de la Recherche Médicale, U1037, Centre de Recherches en Cancérologie de Toulouse U1037 and Laboratoire d'Excellence (Labex Toucan) Université Paul Sabatier Departement des maladies Infectieuses et tropicales Service de médecine Nucléaire, Centre Hospitalier et universitaire de Toulouse Purpan, Place du Dr Baylac, Toulouse, France.

Rationale: Follicular Lymphoma in situ is generally identified as reactive follicular hyperplasia in which some of the hyperplastic germinal centers are colonized by few lymphoma cells. These cells can be detected through their strong 18F-Fluorodeoxyglucose avidity.

Patient Concerns: We report the case of a 70 year-old patient with arthralgia, weight loss and chronic fever over two months. A paraneoplastic polymyalgia rheumatica was initially suspected on abnormal 18F fluoro-deoxyglucose positron emission tomography (PET) pictures in two inguinal lymph nodes with a standardized uptake value at 8.6 and 5.8.

Diagnoses: The PET lymph nodes were removed and histological examination revealed subtle lymph nodes infiltration by follicular lymphoma in situ. The absolute number of the follicular lymphoma cells determined using virtual imaging and 3D reconstruction appeared very low with a total tumor cell volume estimated at around 0.026 mm for one lymph node and 0.041 mm for the other.

Interventions: The patient has been treated by corticotherapy alone.

Outcomes: A long-time follow-up should be highly suggested for this patient to avoid any risk of clinical progression to follicular lymphoma.

Lessons: Our findings show that low amounts of follicular lymphoma cells in reactive germinal center may reach a threshold of hypermetabolism detectable with positron emission tomography imaging, suggesting that tumor microenvironment also accounts for such as strong fluoro-deoxyglucose avidity. Thus, a systematic immunohistochemistry with anti-BCL2 antibodies should be performed on PET positive lymph node with apparent normal morphological features.
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http://dx.doi.org/10.1097/MD.0000000000008705DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5708955PMC
November 2017