Éditeur(s) : HAL CCSD Taylor & Francis
Résumé : International audience
INTRODUCTION: The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor historically known for regulating expression of several important drug-detoxifying proteins. Besides drug metabolism pathways, cytokines have been recently recognized as targeted by the AhR signaling cascade, which may contribute to toxicity and changes in xenobiotic detoxification caused by AhR agonists. AREAS COVERED: This article summarizes the nature of the main cytokines regulated by AhR ligands and reviews their involvement in toxic effects of AhR ligands, especially in relation with inflammation. The article also discusses the potential implications for drug detoxification pathways. EXPERT OPINION: Even if various cytokines, including inflammatory ones, have already been demonstrated to constitute robust targets for AhR, the exact role played by AhR with respect to inflammation remains to be determined. Further studies are also required to better characterize the molecular mechanisms implicated in regulation of cytokines by AhR ligands and to determine the role that may play AhR-targeted cytokines in alteration of xenobiotic detoxification. Finally, changes in cytokine receptor expression triggered by AhR ligands have additionally to be taken into account to better and more extensively comprehend the role played by AhR in the cytokine/inflammation area.
ISSN: 1742-5255

inserm-00831662
http://www.hal.inserm.fr/inserm-00831662
DOI : 10.1517/17425255.2013.738194
PUBMED : 23230817

Éditeur(s) : HAL CCSD American Academy of Neurology
Résumé : International audience
OBJECTIVE: We examined if the CNS Penetration-Effectiveness (CPE) score of antiretroviral drugs was associated with survival after a diagnosis of HIV-related encephalopathy, progressive multifocal leukoencephalopathy (PML), cerebral toxoplasmosis, or cryptococcal meningitis. METHODS: Using data from the FHDH-ANRS CO4, we compared the survival of 9,932 HIV-infected patients diagnosed with a first neurologic AIDS-defining event in the pre-combination antiretroviral therapy (cART) (1992-1995), early cART (1996-1998), or late cART (1999-2004) periods. Follow-up was subdivided (CPE < 1.5 and CPE ≥ 1.5), and relative rates (RR) of death were estimated using multivariable Poisson regression models. RESULTS: In the pre-cART and early cART periods, regimens with CPE ≥ 1.5 were associated with lower mortality after HIV-related encephalopathy (RR 0.64; 95% confidence interval [CI] 0.47-0.86 and RR 0.45; 95% CI 0.35-0.58) and after PML (RR 0.79; 95% CI 0.55-1.12 and RR 0.45; 95% CI 0.31-0.65), compared to regimens with CPE < 1.5, while in the late cART period there was no association between the CPE score and the mortality. A higher CPE score was also associated with a lower mortality in all periods after cerebral toxoplasmosis (RR 0.68, 95% CI 0.56-0.84) or cryptococcal meningitis (RR 0.50, 95% CI 0.34-0.74). Whatever the neurologic event, these associations were not maintained after adjustment on updated plasma HIV-RNA (missing, <500, ≥500 copies/mL) with RR ranging from 0.82 (95% CI 0.36-1.91) to 1.02 (0.69-1.52). CONCLUSION: At the beginning of the cART era, the CPE score was of importance for survival after severe neurologic event, while in the late cART period, the additional effect of CPE score vanished with more powerful antiretroviral regimens associated with plasma viral load control.
ISSN: 0028-3878

hal-00875434
https://hal.archives-ouvertes.fr/hal-00875434
DOI : 10.1212/WNL.0b013e31820c3089
PUBMED : 21248274

Éditeur(s) : HAL CCSD Lippincott, Williams & Wilkins
Résumé : International audience
Among 103 patients with multidrug-resistant HIV who initiated raltegravir, etravirine, and darunavir/ritonavir-containing regimen in the ANRS 139 TRIO trial, 100 participated in extended follow-up and continued study treatment until week 96. Among them, 87 (87%) received an optimized background therapy including either nucleoside reverse transcriptase inhibitors or enfuvirtide, they were 78 (78%) at week 96. At week 96, 88% achieved durable virologic response (<50 copies/mL). CD4 response was maintained (median change of +150 cells/mm(3)). No major toxicity was reported. This triple drug combination showed sustained efficacy and thus should be strongly considered for patients with multiclass-resistant virus.
ISSN: 1525-4135

hal-00875207
https://hal.archives-ouvertes.fr/hal-00875207
DOI : 10.1097/QAI.0b013e31824bb720
PUBMED : 22293546

Éditeur(s) : HAL CCSD Springer Verlag
Résumé : International audience
The purpose of this investigation was to characterize the management and prognosis of severe Pneumocystis jirovecii pneumonia (PJP) in human immunodeficiency virus (HIV)-negative patients. An observational cohort study of HIV-negative adults with PJP documented by bronchoalveolar lavage (BAL) through Gomori-Grocott staining or immunofluorescence, admitted to one intensive care unit (ICU) for acute respiratory failure, was undertaken. From 1990 to 2010, 70 patients (24 females, 46 males) were included, with a mean age of 58.6 ± 18.3 years. The mean Simplified Acute Physiology Score (SAPS)-II was 36.9 ± 20.4. Underlying conditions included hematologic malignancies (n = 21), vasculitis (n = 13), and solid tumors (n = 13). Most patients were receiving systemic corticosteroids (n = 63) and cytotoxic drugs (n = 51). Not a single patient received trimethoprim-sulfamethoxazole as PJP prophylaxis. Endotracheal intubation (ETI) was required in 42 patients (60.0 %), including 38 with acute respiratory distress syndrome (ARDS). In-ICU mortality was 52.9 % overall, reaching 80.9 % and 86.8 %, respectively, for patients who required ETI and for patients with ARDS. In the univariate analysis, in-ICU mortality was associated with SAPS-II (p = 0.0131), ARDS (p < 0.0001), shock (p < 0.0001), and herpes simplex virus (HSV) or cytomegalovirus (CMV) on BAL (p = 0.0031). In the multivariate analysis, only ARDS was associated with in-ICU mortality (odds ratio [OR] 23.4 [4.5-121.9], p < 0.0001). PJP in non-HIV patients remains a serious disease with high in-hospital mortality. Pulmonary co-infection with HSV or CMV may contribute to fatal outcome.
ISSN: 0934-9723

inserm-00872789
http://www.hal.inserm.fr/inserm-00872789
DOI : 10.1007/s10096-012-1730-7
PUBMED : 22930407

Éditeur(s) : HAL CCSD Cancer Research UK
Résumé : International audience
BACKGROUND: Cancer cell killing might be achieved by the combined use of available drugs. Statins are major anti-hypercholesterolemia drugs, which also trigger apoptosis of many cancer cell types, while docetaxel is a potent microtubule-stabilising agent. METHODS: Here, we looked at the combined effects of lovastatin and docetaxel in cancer cells. RESULTS: Whole transcriptome microarrays in HGT-1 gastric cancer cells demonstrated that lovastatin strongly suppressed expression of genes involved in cell division, while docetaxel had very little transcriptional effects. Both drugs triggered apoptosis, and their combination was more than additive. A marked rise in the cell-cycle inhibitor p21, together with reduction of aurora kinases A and B, cyclins B1 and D1 proteins was induced by lovastatin alone or in combination with docetaxel. The drug treatments induced the proteolytic cleavage of procaspase-3, a drop of the anti-apoptotic Mcl-1 protein, Poly-ADP-Ribose Polymerase and Bax. Strikingly, docetaxel-resistant HGT-1 cell derivatives overexpressing the MDR-1 gene were much more sensitive to lovastatin than docetaxel-sensitive cells. CONCLUSION: These results suggest that the association of lovastatin and docetaxel, or lovastatin alone, shows promise as plausible anticancer strategies, either as a direct therapeutic approach or following acquired P-glycoprotein-dependent resistance.
ISSN: 0007-0920

hal-00684528
https://hal.archives-ouvertes.fr/hal-00684528
DOI : 10.1038/bjc.2012.6
PUBMED : 22294184

Éditeur(s) : HAL CCSD Wiley-Blackwell Wiley
Résumé : International audience
Rhodamine 123 is a fluorescent cationic dye commonly used as a mitochondrial probe and known or suspected to be transported by certain drug membrane transporters. The present study was designed to characterize the putative interactions of rhodamine 123 with human organic cation transporter (OCT) 1 and OCT2. Intracellular uptake of the dye was demonstrated to be enhanced in both hOCT1- and hOCT2-overexpressing HEK293 cells when compared with control HEK293 cells. This increase of rhodamine 123 influxes was found to be a saturable carrier-mediated process, with low K(m) values (K(m) = 0.54 μm and K(m ) = 0.61 μm for transport of the dye in hOCT1- and hOCT2-positive HEK293 cells, respectively). Known inhibitors of hOCT1 and hOCT2 activities such as verapamil, amitriptyline, prazosin, and quinine were next demonstrated to decrease rhodamine 123 accumulation in hOCT1- and hOCT2-overexpressing HEK293 cells. In addition, the dye was found to inhibit hOCT1- and hOCT2-mediated uptake of tetraethylammonium (TEA), a model substrate for both hOCT1 and hOCT2; rhodamine 123 appeared nevertheless to be a more potent inhibitor of hOCT1-mediated TEA transport (IC(50) = 0.37 μm) than of that mediated by hOCT2 (IC(50 ) = 61.5 μm). Taken together, these data demonstrate that rhodamine 123 is a high-affinity substrate for both hOCT1 and hOCT2. This dye may be therefore useful for fluorimetrically investigating cellular hOCT1 or hOCT2 activity, knowing, however, that other factors potentially contributing to cellular accumulation of rhodamine 123, including mitochondrial membrane potential or expression of the efflux transporter P-glycoprotein, have also to be considered.
ISSN: 0767-3981

inserm-00872840
http://www.hal.inserm.fr/inserm-00872840
DOI : 10.1111/j.1472-8206.2012.01071.x
PUBMED : 22913740

Éditeur(s) : HAL CCSD
Résumé : International audience
OBJECTIVE: A better understanding of the perception of the rehabilitative and medical care's by persons with cerebral palsy (CP) and their families may help in providing better adherence to these cares. The main objective of this study was to assess overall satisfaction, self-perception of effectiveness and tolerance of the rehabilitative and medical cares in individuals with CP. MATERIAL AND METHODS: This was a cross-sectional questionnaire-based study. A total of 950 questionnaires were sent to French Britain children and adults with CP. Perceived effectiveness and tolerance were evaluated for each types of care using a Likert scale from 1 to 7 and overall satisfaction by a visual analog scale. Comparison of means and uni-and-multivariate analyzes for correlation analysis were carried out. RESULTS: A total of 512 (53.9%) questionnaires were analyzed; 230 (44.9%) were children and 54% were walkers (GMFCS I, II or III). The overall satisfaction was 6.83/10 (SD 2.21). Orthoptic, orthosis and physical therapy were reported to be the most effective cares (5.34/5.30/5.29) while botulinum toxins, intrathecal baclofen, and speech therapy the least effective (4.42/4.52/5.02). Intrathecal baclofen, orthosis and botulinum toxin were the less well-tolerated therapies (4.75/5.11/5.28). Antiepileptic drugs were reported to be the most effective and best-tolerated drug contrary to analgesics. Overall, satisfaction was inversely correlated to the GMFCS in the multivariate analysis (P=0.013). The perceived effectiveness of occupational therapy, botulinum toxin injections and physiotherapy are inversely related to GMFCS in the univariate analyzes. The tolerance and effectiveness of the orthosis have a positive correlation with the GMFCS in the uni-and-multivariate analyzes. DISCUSSION/CONCLUSION: This study shows a good overall satisfaction on medical and paramedical care but highlights a large discrepancy between user self-perception and evidence base medicine. More communication about the therapies between professionals and individuals with cerebral palsy is needed and comparing opinions of patients and their families to literature can give us the keys to improve communication around these therapies.
Annals of Physical and Rehabilitation Medicine

hal-01477212
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01477212
DOI : 10.1016/j.rehab.2016.07.014
PUBMED : 27676935

Éditeur(s) : HAL CCSD Public Library of Science
Résumé : International audience
IntroductionLeishmania RNA virus type 1 (LRV1) is an endosymbiont of some Leishmania (Vianna) species in South America. Presence of LRV1 in parasites exacerbates disease severity in animal models and humans, related to a disproportioned innate immune response, and is correlated with drug treatment failures in humans. Although the virus was identified decades ago, its genomic diversity has been overlooked until now.Methodology/Principles findingsWe subjected LRV1 strains from 19 L. (V.) guyanensis and one L. (V.) braziliensis isolates obtained from cutaneous leishmaniasis samples identified throughout French Guiana with next-generation sequencing and de novo sequence assembly. We generated and analyzed 24 unique LRV1 sequences over their full-length coding regions. Multiple alignment of these new sequences revealed variability (0.5%±23.5%) across the entire sequence except for highly conserved motifs within the 5' untranslated region. Phylogenetic analyses showed that viral genomes of L. (V.) guyanensis grouped into five distinct clusters. They further showed a species-dependent clustering between viral genomes of L. (V.) guyanensis and L. (V.) braziliensis, confirming a long-term co-evolutionary history. Noteworthy, we identified cases of multiple LRV1 infections in three of the 20 Leishmania isolates.Conclusions/SignificanceHere, we present the first-ever estimate of LRV1 genomic diversity that exists in Leishmania (V.) guyanensis parasites. Genetic characterization and phylogenetic analyses of these viruses has shed light on their evolutionary relationships. To our knowledge, this study is also the first to report cases of multiple LRV1 infections in some parasites. Finally, this work has made it possible to develop molecular tools for adequate identification and genotyping of LRV1 strains for diagnostic purposes. Given the suspected worsening role of LRV1 infection in the pathogenesis of human leishmaniasis, these data have a major impact from a clinical viewpoint and for the management of Leishmania-infected patients.
ISSN: 1935-2727

pasteur-01583523
https://hal-riip.archives-ouvertes.fr/pasteur-01583523
DOI : 10.1371/journal.pntd.0005764
PUBMED : 28715422

Éditeur(s) : Université des Antilles Études caribéennes
Résumé : Cet article examine l’activisme contre la toxicomanie et le SIDA qui a pris naissance aux Etats-Unis dans les années 1980, en particulier celui qui se développa dans la ville de New York. Dans le cadre de la théorie des mouvements sociaux, la perspective de « l’opportunité politique » semble appropriée pour analyser un tel mouvement. Cependant, contrairement à ce que suggère cette perspective, la thèse de cet article défend l’idée que « les opportunités scientifiques et légales », plutôt que « politiques » expliquent le succès relatif de ce mouvement entre les années 1980 et 1990.
This article examines the drug and AIDS movement in the United States of the mid-1980s, particularly the one that developed in New York City. Within social movement theory, the “political opportunity” perspective seems appropriate to analyze such a movement; however, unlike what this model suggests, it is contended that “scientific and legal opportunities” rather than “political opportunities” account for the movement’s relative success between the mid-1980s and the mid-1990s.
États-Unis
New York

Droits : info:eu-repo/semantics/openAccess
urn:doi:10.4000/etudescaribeennes.7171
http://journals.openedition.org/etudescaribeennes/7171

Éditeur(s) : HAL CCSD Wiley
Résumé : International audience
Organochlorine (OC) pesticides constitute a major class of persistent and toxic organic pollutants, known to modulate drug-detoxifying enzymes. In the present study, OCs were demonstrated to also alter the activity and expression of human hepatic drug transporters. Activity of the sinusoidal influx transporter OCT1 (organic cation transporter 1) was thus inhibited by endosulfan, chlordane, heptachlor, lindane, and dieldrine, but not by dichlorodiphenyltrichloroethane isomers, whereas those of the canalicular efflux pumps MRP2 (multidrug resistance-associated protein 2) and BCRP (breast cancer resistance protein) were blocked by endosulfan, chlordane, heptachlor, and chlordecone; this latter OC additionally inhibited the multidrug resistance gene 1 (MDR1)/P-glycoprotein (P-gp) activity. OCs, except endosulfan, were next found to induce MDR1/P-gp and MRP2 mRNA expressions in hepatoma HepaRG cells; some of them also upregulated BCRP. By contrast, expression of sinusoidal transporters was not impaired (organic anion-transporting polypeptide (OATP) 1B1 and OATP2B1) or was downregulated (sodium taurocholate co-transporting polypeptide (NTCP) and OCT1). Such regulations of drug transporter activity and expression, depending on the respective nature of OCs and transporters, may contribute to the toxicity of OC pesticides.
ISSN: 1095-6670

hal-01063656
https://hal.archives-ouvertes.fr/hal-01063656
DOI : 10.1002/jbt.21543
PUBMED : 24464585

Éditeur(s) : HAL CCSD IWA Publishing
Résumé : International audience
Anti-cancer drugs are an important class of pharmaceutical products. Methotrexate (MTX) is a folic acid antagonist used in high doses as antimetabolite in anti-cancer treatment as well as in low doses for the treatment of rheumatoid arthritis and adults' psoriasis. In the past, several anti-cancer drugs, including methotrexate, have been found in the environment. Their presence in water, especially if used for the production of drinking water, is even in low concentrations of particular interest, due to the risk to retrieve them in the consumed water and their high activity and grave effects. But prior to usage as drinking water, raw waters are treated and chlorination is a common practice in several countries. As such a treatment can lead to the formation of organochlorine in water, the study of the fate of MTX during chlorination in a batch trial was carried out. The reaction was monitored by dissolved organic carbon (DOC) and by fluorescence and UV spectroscopy. Investigation of by-products formed was done with liquid chromatography/mass spectrometry (LC/MS). Under the given experimental conditions, Methotrexate was eliminated rapidly (t1/2 around 21 min). However, DOC elimination was incomplete. Monitoring with LC-MS showed the formation of a monochlorinated transformation product of MTX. In silico analysis of the proposed transformation products for different carcinogenic, mutagenic and genotoxic endpoints with different software platforms provided no clear evidence that the possible transformation products after chlorination might be more toxic than the parent compound. However, since a number of alerts is altered after chlorination, it cannot be excluded that the toxicity of these transformation products might be modulated compared with the parent compound.
ISSN: 0043-1354

hal-01016617
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01016617
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01016617/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01016617/file/Monitoringsur methotrexate_final.pdf
DOI : 10.1016/j.watres.2014.03.008

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Fungi are major contributors to the opportunistic infections that affect patients with HIV/AIDS. Systemic infections are mainly with Pneumocystis jirovecii (pneumocystosis), Cryptococcus neoformans (cryptococcosis), Histoplasma capsulatum (histoplasmosis), and Talaromyces (Penicillium) marneffei (talaromycosis). The incidence of systemic fungal infections has decreased in people with HIV in high-income countries because of the widespread availability of antiretroviral drugs and early testing for HIV. However, in many areas with high HIV prevalence, patients present to care with advanced HIV infection and with a low CD4 cell count or represent with persistent low CD4 cell counts because of poor adherence, resistance to antiretroviral drugs, or both. Affordable, rapid point-of-care diagnostic tests (as have been developed for cryptococcosis) are urgently needed for pneumocystosis, talaromycosis, and histoplasmosis. Additionally, antifungal drugs, including amphotericin B, liposomal amphotericin B, and flucytosine, need to be much more widely available. Such measures, together with continued international efforts in education and training in the management of fungal disease, have the potential to improve patient outcomes substantially.
ISSN: 1473-3099

inserm-01574426
http://www.hal.inserm.fr/inserm-01574426
http://www.hal.inserm.fr/inserm-01574426/document
http://www.hal.inserm.fr/inserm-01574426/file/2017%2C%20Limper%20-%20Fungal%20infections%20in%20HIV%20AIDS.pdf
DOI : 10.1016/S1473-3099(17)30303-1

Éditeur(s) : HAL CCSD Oxford University Press (OUP)
Résumé : International audience
BACKGROUND: Surveillance of HIV-1 drug resistance in treated patients with plasma viral load (VL) >50 copies/mL. METHODS: The protease and reverse transcriptase (RT) genes were systematically sequenced in samples from 756 patients with VL >50 copies/mL in 2009. The genotyping results were interpreted for each antiretroviral drug (ARV) by using the ANRS algorithm v21. Weighted analyses were used to derive representative estimates of percentages of patients. Prevalence rates were compared with those obtained in 2004 among patients with VL >1000 copies/mL. RESULTS: Sequences were obtained for 506 patients. Sequencing was successful in 45%, 80% and 96% of samples with VL of 51-500, 501-1000 and >1000 copies/mL, respectively. Resistance or possible resistance to at least one ARV was observed in 59% of samples. Overall, 0.9% of samples contained viruses resistant to all drugs belonging to at least three drug classes. All resistance prevalence rates were significantly lower in 2009 than in 2004. CONCLUSION: In France, where 86% of patients were receiving combination antiretroviral therapy in 2009, only 15.0% of patients had a VL >50 copies/mL, suggesting that only 8.9% of treated patients could potentially transmit resistant viruses. Only 0.08% of patients harboured viruses fully resistant to at least three antiretroviral drug classes. Further studies are needed to determine whether resistance continues to decline over time.
ISSN: 0305-7453

hal-00875092
https://hal.archives-ouvertes.fr/hal-00875092
DOI : 10.1093/jac/dkt033
PUBMED : 23404192

Éditeur(s) : HAL CCSD
Résumé : International audience
Given the clinical success of commercial amphotericin B lipid products, investigators have begun making generic formulations of liposomal amphotericin B. Generic medicines are an attractive approach to help decrease the cost and accessibility to healthcare, provided that appropriate studies are performed to ensure bioequivalence with the parent product. This is of particular concern for liposomal drugs such as amphotericin B where liposomes are used as a carrier system to reduce the toxicity of the active agent. A favorable therapeutic profile for this form of the drug has to include the proper chemical composition along with strictly controlled manufacturing processes. Studies have shown that a comparison of liposomal amphotericin B products with different or the same chemical compositions, using different methods of production, will vary in size, and have significantly dissimilar in vitro and in vivo toxicities along with reduced efficacy. These results underscore the importance of establishing appropriate bioequivalence testing for liposome products to ensure uniformity of their therapeutic index
Medical Mycology

hal-01259233
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01259233
DOI : 10.1093/mmy/myv111
PUBMED : 26768369

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Whilst it used to affect mostly intravenous drug users and patients who underwent valvular surgery with suboptimal infection control procedures, fungal endocarditis is now mostly observed in patients with severe immunodeficiency (onco-haematology), in association with chronic central venous access and broad-spectrum antibiotic use. The incidence of fungal endocarditis has probably decreased in most developed countries with access to harm-reduction policies (i.e. needle exchange programmes) and with improved infection control procedures during cardiac surgery. Use of specific blood culture bottles for diagnosis of fungal endocarditis has decreased due to optimisation of media and automated culture systems. Meanwhile, the advent of rapid techniques, including fungal antigen detection (galactomannan, mannan/anti-mannan antibodies and β-1,3-d-glucans) and PCR (e.g. universal fungal PCR targeting 18S rRNA genes), shall improve sensitivity and reduce diagnostics delays, although limited data are available on their use for the diagnosis of fungal endocarditis. New antifungal agents available since the early 2000s may represent dramatic improvement for fungal endocarditis: (i) a new class, the echinocandins, has the potential to improve the management of Candida endocarditis owing to its fungicidal effect on yeasts as well as tolerability of increased dosages; and (ii) improved survival in patients with invasive aspergillosis with voriconazole compared with amphotericin B, and this may apply to Aspergillus sp. endocarditis as well, although its prognosis remains dismal. These achievements may allow selected patients to be cured with prolonged medical treatment alone when surgery is considered too risky.
ISSN: 0924-8579

hal-01118441
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01118441
DOI : 10.1016/j.ijantimicag.2014.07.003
PUBMED : 25178919

Éditeur(s) : HAL CCSD BioMed Central
Résumé : International audience
Background: HCV treatment uptake has drastically increased in HIV-HCV coinfected patients in France since direct-acting antiviral (DAA) treatment approval, resulting in HCV cure in 63% of all HIV-HCV patients by the end of 2015. We investigated the impact of scaling-up DAA on HCV prevalence in the whole HIV population and in various risk groups over the next 10 years in France using a transmission dynamic compartmental model.Methods: The model was based on epidemiological data from the French Dat’AIDS cohort. Eight risk groups wereconsidered, including high-risk (HR) and low-risk (LR) men who have sex with men (MSM) and male/female heterosexuals,intra-venous drug users, or patients from other risk groups. The model was calibrated on prevalence and incidence dataobserved in the cohort between 2012 and 2015.Results: On January 1, 2016, 156,811 patients were registered as infected with HIV in France (24,900 undiagnosedpatients) of whom 7938 (5.1%) had detectable HCV-RNA (722 undiagnosed patients). Assuming a treatmentcoverage (TC) rate of 30%/year (i.e., the observed rate in 2015), model projections showed that HCV prevalenceamong HIV patients is expected to drop to 0.81% in 2026. Sub-analyses showed a similar decrease of HIV-HCVprevalence in most risk groups, including LR MSM. Due to higher infection and reinfection rates, predicted prevalencein HR MSM remained stable from 6.96% in 2016 to 6.34% in 2026. Increasing annual TC rate in HR MSM to 50/70%would decrease HCV prevalence in this group to 2.35/1.25% in 2026. With a 30% TC rate, undiagnosed patients wouldaccount for 34% of HCV infections in 2026.Conclusions: Our model suggests that DAA could nearly eliminate coinfection in France within 10 years for most riskgroups, including LR MSM. Elimination in HR MSM will require increased TC.
ISSN: 1741-7015

Droits : info:eu-repo/semantics/OpenAccess
inserm-01685739
http://www.hal.inserm.fr/inserm-01685739
http://www.hal.inserm.fr/inserm-01685739/document
http://www.hal.inserm.fr/inserm-01685739/file/2017%2C%20Virlogeux%20-%20Modeling%20HIV-HCV%20coinfection.pdf
DOI : 10.1186/s12916-017-0979-1

Éditeur(s) : HAL CCSD Springer Verlag
Résumé : International audience
The prognosis of vertebral alveolar echinococcosis (AE) is poor. We report on the unique outcome of a patient with preexisting liver cirrhosis, in whom a diagnosis of vertebral AE was established on vertebral histopathology (D4 corporectomy in 2010 for paraplegia). Therapeutic drug monitoring of albendazole (ABZ) showed that a low dosage was appropriate. The patient recovered and ABZ withdrawal was decided in 2014, with no relapse 18 months later. In this patient, infection was purely or mainly localized in the dorsal spine, and this may have been favored by liver cirrhosis. A longer follow-up is, however, needed to confirm cure.
ISSN: 0300-8126

hal-01509561
https://hal.archives-ouvertes.fr/hal-01509561
PUBMED : 28004258

Éditeur(s) : HAL CCSD American Society for Microbiology
Résumé : International audience
A number of men receiving prolonged suppressive HAART still shed HIV in semen. To investigate whether this seminal shedding may be due to poor drug penetration and/or viral production by long-lived cells within male genital tissues, we analyzed semen and reproductive tissues from macaques chronically infected with SIVmac251 submitted to HAART for 4 months, intensified over the last seven weeks with an integrase inhibitor. We showed that a subset of treated animals continued shedding SIV in semen despite efficient HAART. This shedding was not associated with low antiretroviral drug concentrations in semen, or in testis, epididymis, seminal vesicles and prostate. HAART had no significant impact on SIV RNA in the urethra, whereas it drastically reduced SIV RNA levels in the prostate and vas deferens, and to a lesser extent in the epididymis and seminal vesicle. The only detectable SIV RNA positive cells within the male genital tract after HAART were urethral macrophages. SIV DNA levels in genital tissues were not decreased by HAART, suggesting the presence throughout the male genital tract of non-productively infected cells. In conclusion, our results demonstrate that 4 months of HAART induced variable and limited control of viral infection in the male reproductive organs, particularly the urethra, and suggest that infected long-lived cells in the male genital tract may be involved in persistent seminal shedding during HAART. These results pave the way for further investigations of male genital organs infection in long term treated infected individuals. A substantial subset of men receiving prolonged suppressive HAART in the blood still harbor HIV in semen, and cases of sexual transmission have been reported. To understand the origin of this persistence, we analyzed the semen and male reproductive tissues from SIV-infected macaques treated by HAART. We demonstrated that persistent seminal shedding was not linked to poor drug penetration in semen or semen-producing prostate, seminal vesicle, epididymis and testis. We revealed that HAART decreased SIV RNA to various extents in all male genital organs, with the exception of the urethra, in which SIV RNA+ macrophages were observed despite HAART. Importantly also, HAART did not impact SIV DNA levels in the male genital organs. These results suggest that infection of male genital organs, and particularly the urethra, could be involved in the release of virus in semen during HAART.
ISSN: 0022-538X

hal-01139816
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01139816
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01139816/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01139816/file/Detection%20of%20SIV%20in%20Semen%2C%20Urethra%2C%20and%20Male%20Reproductive%20Organs%20during%20Efficient%20Highly%20Active%20Antiretroviral%20Therapy.pdf
PUBMEDCENTRAL : PMC4442442

Éditeur(s) : HAL CCSD Lippincott, Williams & Wilkins
Résumé : International audience
We report the first transmitted drug resistance survey study in HIV-2-infected patients living in France. The prevalence of transmitted drug resistance was 5.0% (95% confidence interval, 0.1-9.9) with mutations detected only in protease, not in reverse transcriptase. In this series, 10% of patients displayed X4/dual-mixed viruses. These findings classified the rate of transmitted drug resistance in the HIV-2 French Cohort as low prevalence.
ISSN: 0269-9370

hal-00875077
https://hal.archives-ouvertes.fr/hal-00875077
PUBMED : 23595155
DOI : 10.1097/QAD.0b013e32836207f3

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
ISSN: 0887-2333

hal-00866007
https://hal-univ-rennes1.archives-ouvertes.fr/hal-00866007
DOI : 10.1016/j.tiv.2013.07.003
PUBMED : 23850984