Academic literature on the topic 'Virus de l' hépatite B [HBV]'

Background and aims: The hepatitis B virus (HBV), hepatitis C virus (HCV) and human immunodeficiency virus (HIV) are associated with major public health concerns. The aim of the study was to determine the seroprevalence of HBV, HCV and HIV in the western region of Nepal.Methods: This was a cross-sectional observational study, in which 15,791 patients, attending to Manipal Teaching Hospital, Pokhara, Nepal, were investigated for HBV, HCV and HIV from June 2013 to March 2016; demographic and biochemical profile were studied among the patients with positive test results.Results: Among 15,791 patients [male 6614 (41.9%) and female 9177 (58.1%)], HBV was found in 180 (1.1%), HCV in 52 (0.3%) and HIV in 77 (0.5%). The HBV was found in 63.9% of males and 36.1% of females, HCV in 67.3% of males and 32.7% of females, and HIV in 61% of males and 39% of females which showed that males had more positivity of HBV (P<0.001), HCV (P<0.001) and HIV (P 0.001) than that of female. The HBV was found more in 20-29 years age group (27.2%), HCV in 30-39 years (32.7%), and HIV in 40-49 years (28.6%), with all having p<0.001. Among the patients of HBV, HCV and HIV, the mean values of total bilirubin were 1.4 mg/dl, 0.8 mg/dl and 2.6 mg/dl, Aspartate Transaminase 75.9 U/L, 54.3 U/L and 92.7 U/L, Alanine Transaminase 54.6 U/L, 55.5 U/L and 56.1 U/L, and Alkaline Phosphatase 124.2 U/L, 109.2 U/L and 107.2 U/L, respectively. The majority of patients with HCV had a history of intravenous drug abuse and HIV had concomitant alcoholic liver disease.Conclusion: The HBV was more prevalent followed by HIV and HCV in the western region of Nepal with more prevalence seen in males than in females. Regular screening of HBV, HCV and HIV among the selected patients can help detecting many new cases in Nepal.Journal of Advances in Internal Medicine 2016;05(01):6-10

ABSTRACT A unique series of simple “unnatural” nucleosides has been discovered to inhibit hepatitis B virus (HBV) replication. Through structure-activity analysis it was found that the 3′-OH group of the β-l-2′-deoxyribose of the β-l-2′-deoxynucleoside confers specific antihepadnavirus activity. The unsubstituted nucleosides β-l-2′-deoxycytidine, β-l-thymidine, and β-l-2′-deoxyadenosine had the most potent, selective, and specific antiviral activity against HBV replication. Human DNA polymerases (α, β, and γ) and mitochondrial function were not affected. In the woodchuck model of chronic HBV infection, viral load was reduced by as much as 108 genome equivalents/ml of serum and there was no drug-related toxicity. In addition, the decline in woodchuck hepatitis virus surface antigen paralleled the decrease in viral load. These investigational drugs, used alone or in combination, are expected to offer new therapeutic options for patients with chronic HBV infection.

ABSTRACTA hepatitis B virus (HBV) vaccine has been developed using a new adjuvant and HBV surface antigens produced from a CHO cell line. The purified HBV surface antigens are composed of L protein, M protein, and S protein in a mixture of 20- and 40-nm-diameter particles and filamentous forms. This HBV surface antigen, formulated with L-pampo, a proprietary adjuvant, induced 10 times more antibody than the same antigen with alum and was capable of inducing strong immune responses in three different HBV transgenic mice. In spite of the presence of a large amount of HBV antigen in the blood, no antibody against HBV surface antigen was normally detected in these transgenic mice. After immunization, the HBV antigen was also cleared from the blood.

Abstract We developed a nonisotopic technique, Hepagene, for measuring hepatitis B virus (HBV) DNA in human serum by using a sulfonated probe that is detected by a sandwich immunoenzymatic reaction. The detection limit, determined by serum dilution tests, was 2.5 ng/L. The precision of the Hepagene test was demonstrated by the accurate reproducibility observed for low (3 ng/L) and medium (38 ng/L) concentrations of HBV DNA assayed in 24 different series. Specificity was established by assaying HBV DNA in sera from 98 patients by the Hepagene technique or by a solution hybridization assay with an 125I-labeled probe. Results by both techniques agreed for 94 sera (96%), with 68 being concordant for HBV DNA negativity and 26 for positivity. HBV DNA titers assayed by both methods also agreed. Hepagene represents the first nonisotopic HBV DNA assay involving a sulfonated probe and with performance characteristics equivalent to those of classical radioactive hybridization techniques.

ABSTRACT It has been difficult to propagate and titrate hepatitis B virus (HBV) in tissue culture. We examined whether vesicular stomatitis virus (VSV) pseudotypes bearing HBV surface (HBs) proteins infectious for human cell lines could be prepared. For this, expression plasmids for three surface proteins, L, M, and S, of HBV were made. 293T cells were then transfected with these plasmids either individually or in different combinations. 293T cells expressing HBs proteins were infected with VSVΔG*-G, a recombinant VSV expressing green fluorescent protein (GFP), to make VSV pseudotypes. Culture supernatants together with cells were harvested and sonicated for a short time. The infectivities of freshly harvested supernatants were determined by quantifying the number of cells expressing GFP after neutralization with anti-VSV serum and mouse monoclonal antibodies (MAbs) against HBs protein. Among 14 cell lines tested for susceptibility to HBV pseudotype samples, HepG2, JHH-7, and 293T cells were judged to be the most susceptible. Namely, the infectious units (IU) of the culture supernatant samples neutralized with anti-VSV in the absence and presence of anti-HBs S MAbs and titrated on HepG2 cells ranged from 1,000 to 4,000 IU/ml and 200 to 400 IU/ml, respectively, suggesting the presence of VSVΔG*(HBV) pseudotypes. This infectivity was inhibited by treatment with lactoferrin or dextran sulfate. Pretreatment of the cells with trypsin or tunicamycin inhibited plating of the pseudotype samples. The HBV pseudotypes can be used to analyze early steps of HBV infection, including the entry mechanism of HBV.

ABSTRACT We previously showed that the intrahepatic induction of cytokines such as alpha/beta interferon (IFN-α/β) and gamma interferon (IFN-γ) inhibits hepatitis B virus (HBV) replication noncytopathically in the livers of transgenic mice. The intracellular pathway(s) responsible for this effect is still poorly understood. To identify interferon (IFN)-inducible intracellular genes that could play a role in our system, we crossed HBV transgenic mice with mice deficient in IFN regulatory factor 1 (IRF-1), the double-stranded RNA-activated protein kinase (PKR), or RNase L (RNase L) (IRF-1−/−, PKR−/−, or RNase L−/− mice, respectively), three well-characterized IFN-inducible genes that mediate antiviral activity. We showed that unmanipulated IRF-1−/− or PKR−/− transgenic mice replicate HBV in the liver at slightly higher levels than the respective controls, suggesting that both IRF-1 and PKR individually appear to mediate signals that modulate HBV replication under basal conditions. These same animals were responsive to the antiviral effects of the IFN-α/β inducer poly(I-C) or recombinant murine IFN-γ, suggesting that under these conditions, either the IRF-1 or the PKR genes can mediate the antiviral activity of the IFNs or other IFN-inducible genes mediate the antiviral effects. Finally, RNase L−/− transgenic mice were undistinguishable from controls under basal conditions and after poly(I-C) or IFN-γ administration, suggesting that RNase L does not modulate HBV replication in this model.

A novel anti-hepatitis B virus (anti-HBV) agent, 2'-fluoro-5-methyl-beta-L-arabinofuranosyluracil (L-FMAU), was synthesized and found to be a potent anti-HBV and anti-Epstein-Barr virus agent. Its in vitro potency was evaluated in 2.2.15 and H1 cells for anti-HBV and anti-Epstein-Barr virus activities, respectively. In vitro cytotoxicity in MT2, CEM, 2.2.15, and H1 cells was also assessed, and the results indicated high antiviral selectivities of L-FMAU in these cells.

2'-Fluoro-5-methyl-beta-L-arabinofuranosyl uracil (L-FMAU) was discovered to have potent antiviral activity against hepatitis B virus (HBV). L-FMAU was more potent than its D-enantiomer and produced dose-dependent inhibition of the viral DNA replication in 2.2.15 cells (human HepG2 cells with the HBV genome), with a 50% inhibitory concentration of 0.1 microM. There was no inhibitory effect on HBV transcription or protein synthesis. In the 2.2.15 cell system, L-FMAU did not show any toxicity up to 200 microM, whereas the D-enantiomer was toxic, with a 50% inhibitory concentration of 50 microM. Repeated treatments of HepG2 cells with L-FMAU at a 1 microM concentration for 9 days did not result in any decrease in the total mitochondrial DNA content, suggesting that a mode of toxicity similar to that produced by 2',3'-dideoxycytidine is unlikely. Also at concentrations as high as 200 microM, L-FMAU did not adversely affect mitochondrial function as determined by lactic acid production by L-FMAU-treated hepatoma cells. L-FMAU was metabolized in the cells to its mono-, di-, and triphosphates, A dose-dependent inhibition of HBV DNA synthesis by L-FMAU triphosphate was observed in the DNA polymerase assays with isolated HBV particles, suggesting that the mode of action of this compound could involve viral polymerase. However, L-FMAU was not incorporated into the cellular DNA. Considering the potent inhibition of the viral DNA synthesis and the nontoxicity of L-FMAU towards the host DNA synthetic machinery, this compound should be further explored for development as asn anti-HBV drug.

ABSTRACT Hepatitis B virus (HBV) is unusual in that its surface proteins (small [S], medium, and large [L]) are not only incorporated into the virion envelope but they also bud into empty subviral particles in great excess over virions. The morphogenesis of these subviral envelope particles remains unclear, but the S protein is essential and sufficient for budding. We show here that, in contrast to the presumed model, the HBV subviral particle formed by the S protein self-assembles into branched filaments in the lumen of the endoplasmic reticulum (ER). These long filaments are then folded and bridged for packing into crystal-like structures, which are then transported by ER-derived vesicles to the ER-Golgi intermediate compartment (ERGIC). Within the ERGIC, they are unpacked and relaxed, and their size and shape probably limits further progression through the secretory pathway. Such progression requires their conversion into spherical particles, which occurred spontaneously during the purification of these filaments by affinity chromatography. Small branched filaments are also formed by the L protein in the ER lumen, but these filaments are not packed into transport vesicles. They are transported less efficiently to the ERGIC, potentially accounting for the retention of the L protein within cells. These findings shed light on an important step in the HBV infectious cycle, as the intracellular accumulation of HBV subviral filaments may be directly linked to viral pathogenesis.

ABSTRACT l-Nucleoside analogs are new therapeutic agents for treatment of chronic hepatitis B. However, their clinical application was limited by the emergence of viral resistance. It is important to develop a new system to evaluate drug cross-resistance and to test new agents that may overcome resistant virus. In this report, three cell lines HepG2-WT10, HepG2-SM1, and HepG2-DM2 are presented; these cell lines were established by transfection of HepG2 cells with unique fully functional 1.1× hepatitis B virus (HBV) genomes: wild-type HBV-adr and its L526M and L526MM550V variants, respectively. We have demonstrated that these genomes have different susceptibilities to lamivudine [l(−)SddC] and penciclovir (PCV). By examining HBV RNA transcription, antigen expression, progeny DNA replication, and viral susceptibilities to l(−)SddC, PCV, and other nucleoside analogs, it is concluded that the cell lines are able to stably producel(−)SddC- and PCV-sensitive and -resistant HBV virions. In addition, the relative susceptibilities of the wild-type and mutant HBV produced from the stably transfected cell lines to several anti-HBV nucleoside analogs were also examined and found to be about the same as those found by using a transient infection system. PMEA [9-(2-phosphonylmethoxytehyl)-adenine] and QYL685 are able to suppress l(−)SddC- and PCV-resistant HBV. In conclusion, this cell culture system is a novel and useful tool for evaluating anti-HBV compounds and biologics.

Le virus de l’hépatite delta (HDV) est un satellite du virus de l’hépatite B (HBV) dont il utilise la protéine S-AgHBs pour la formation de ses virions. Nous avons étudié les mécanismes moléculaires entre celle-ci et la protéine L-AgHD de l’HDV nécessaire à l’assemblage des virions. Nous avons prouvé que les résidus W196, W199 et W201 de la protéine S-AgHBs et les résidus P201, P205 et P208 de la protéine L-AgHD étaient essentiels à la maturation HDV, sans révéler d’interaction directe entre ces deux protéines. D’autres résultats ont révélé que les protéines S-AgHBs des génotypes A à E, contrairement aux protéines de génotype F et G, étaient capables d’incorporer la protéine L-AgHD de génotype 1. Enfin, nous avons estimé qu’il y a quatre fois plus de protéines S-AgHBs que de protéines L-AgHD dans les particules formées de ces deux protéines. Une connaissance approfondie de ces interactions permettrait le développement d’approches thérapeutiques spécifiques de l’HDV.

Il existe 10 génotypes du virus de l'hépatite B (HBV) dans le monde. Les protéines d'enveloppe HBV et du virus de l'hépatite delta (HDV) possèdent en position 146 de leur domaine commun un site de N-Glycosylation. Seules 50% de ces protéines sont toujours glycosylées quel que soit le génotype. La première partie de mon projet a consisté à étudier l'influence de la variabilité génétique HBV sur l'activité des protéines d'enveloppe à différentes étapes du cycle viral et sur l'efficacité de neutralisation par des anticorps anti-AGHBS. Les résultats montrent que les variations de séquence des protéines HBV ont peu de conséquences sur l'efficacité d'assemblage/sécrétion des particules sous virales (PSV) et virions HDV, et sur le caractère infectieux. En revanche, les variations de séquences des épitopes du déterminant-A de la boucle antigénique (BAG) affectent l'activité neutralisante des anticorps. La seconde partie de mon projet a pour but de déterminer la (ou les) fonction(s) associée(s) au phénomène de glycosylation N146 des protéines d'enveloppe. Nos résultats montrent que la glycosylation N146 n'est pas essentielle à la production des PSV HBV et des virions HDV, mais elle est importante pour l'assemblage/sécrétion des virions HBV. Cette glycosylation n'est pas nécessaire au caractère infectieux, et une hyperglycosylation des protéines d'enveloppe -par ajout de plusieurs sites de N-glycosylation- est compatible avec la production de PSV, et avec la préservation du caractère infectieux si la BAG porte moins de 4 glycanes. Nous montrons aussi qu'une hyperglycosylation bloque l'accès d'anticorps monoclonaux anti-AGHBS à certains épitopes du déterminant-A
There are 10 genotypes of hepatitis B virus (HBV) in the world. The HBV and hepatitis delta virus (HDV) envelope proteins have, in the position 146 of the common's domain, a N-Glycosylation site. Only 50% of these proteins are always glycosylated, whatever the genotype. The first part of my project consists in studying the influence of the HBV genetic variability with regard to the envelope protein's activities at different step of the viral circle and with regard to the neutralization's efficiency of anti-HBSAG antibodies. The results show that variations in the aminoacid sequence of the HBV proteins have minor consequences on the assembly/secretion of subviral particles (SVP), HDV virions and the infectivity. However, sequence variations in the epitope of the A-determinant of the antigenic loop (AGL) affect the neutralizing activity of the anti-HBSAG antibodies. The second part of my project consists on determining the function(s) associated with the N146 glycosylation of the envelope proteins. Our results show that N146 glycosylation isn't essential for the HBV SVP and HDV virions production, but important for the assembly/secretion of the HBV virions. This glycosylation is not required for infectivity and hyperglycosylated envelope proteins - by adding several glycosylation sites in the AGL - is compatible with the SVP production and the conservation of the infectivity, in the AGL presents less than 4 glycans. We also show that hyperglycosylation prevents access of the anti-HBSAG Monoconal antibodies to epitope of the A-determinant

Dans les régions de fortes endémicités, 70-80% des carcinomes hépatocellulaires sont induits par le VHB. Bien qu’un vaccin prophylactique très efficace existe, il n’est d’aucune utilité pour les 250 millions de personnes chroniquement infectées. Les traitements actuels pour contrôler l'infection chronique par le VHB montrent des limites et le besoin de nouvelles thérapies se fait ressentir. La Polo-like kinase-1 (PLK1), qui joue un rôle essentiel dans la mitose et est surexprimée dans de nombreux cancers, représente une cible prometteuse. Outre son rôle lors de la division cellulaire, PLK1 est impliquée dans la régulation de l'expression des gènes en interphase. Il a été montré que la protéine X du VHB (HBx) active PLK1 dans des modèles de cellules murines. Cependant, il restait à déterminer si PLK1 jouait un rôle au niveau de la réplication du VHB dans des hépatocytes quiescents. Des études récentes ont mis en évidence un lien positif entre l'activation de PLK1 et la réplication du VHB. Le but de ce projet de thèse a été d'étudier le(s) mécanisme(s) par le(s)quel(s) PLK1 jouait un rôle positif sur la réplication virale, avec pour objectif futur d'explorer l’inhibition de PLK1 comme cible antivirale. L'interaction entre PLK1 et la réplication du VHB a d'abord été décrite à l'aide du modèle HepAD38. Dans ce contexte, l'ADN viral est intégré dans le génome hôte, sous le contrôle d'un système d'expression Tet-off. La transcription de l'ARN prégénomique (pgRNA), à la base de la réplication virale, est initiée par la suppression de tétracycline. Dans ce contexte, l'augmentation de l'expression de PLK1 est corrélée avec la régulation négative de deux protéines; SUZ12 et ZNF198, faisant partie de complexes de remodelage de la chromatine. L'inhibition de PLK1 bloque la réplication du VHB, en agissant au niveau de la transcription virale. D'autre part, dans les modèles de réplication du VHB qui miment au mieux une infection, comprenant les hépatocytes primaires humains (PHH) et les cellules non transformées/différenciées HepaRG (dHepaRG), où le VHB se réplique dans des cellules quiescentes, nous avons mis en évidence que: 1) L'inhibition pharmacologique de PLK1 bloque la réplication virale, semblablement en perturbant l’encapsidation du pgRNA via une interaction avec la protéine core du VHB (HBc). 2) Un knocking-down de PLK1 en utilisant des ARN interférents délivrés par nanoparticules lipidiques résulte en une forte baisse de la production de pgRNA et dans la sécrétion des antigènes HBeAg/HBsAg, sans impact sur la viabilité cellulaire. Ce projet a donc permis la preuve de concept que PLK1 pouvait être une cible thérapeutique afin de controler la réplication du VHB. De plus, grâce à la technologie de délivrance par nanoparticules lipidiques d’ARN interférents, nous avons pu cibler spécifiquement les hépatocytes, augmentant de ce fait la spécificité et l’efficacité de nos traitements. Un travail sur la compréhension précise des méchanismes cellulaires impliqués permettra de mieux cerner cette interaction hôte/virus afin de poursuivre le développement de stratégies antivirales innovantes portant sur l’inhibition de PLK1. De manière significative, l'inhibition de PLK1 est non toxique pour les cellules quiescentes par rapport à des cellules cancéreuses à fort taux réplicatif, ce qui fait de PLK1 une cible thérapeutique attrayante. Des inhibiteurs spécifiques sont déjà en essais cliniques pour certains cancers (e.g., Volasertib pour le traitement de la leucémie myéloïde aiguë) et pourraient servir de thérapie bimodale dans le cadre de patients infectés par le VHB, en inhibant la réplication virale, ainsi qu’en prévenant l'émergence de cellules néoplasiques. L'inhibition de la PLK1 est une approche antivirale innovante, qui, en combinaison avec les thérapies actuelles de type IFN-α ou analogues nucléotidiques offre de grandes promesses pour endiguer l'infection chronique par le VHB mais également prévenir les événements carcinogéniques
In highly HBV endemic regions, 70-80% of hepatocellular carcinoma cases are attributable to this virus. Despite the existence of an HBV vaccine, the World Health Organization estimates 240 million individuals are chronically infected with HBV worldwide. Current antiviral treatments to control chronic HBV infections, and consequently reduce the incidence of liver cancer, are ineffective. New and effective therapies are needed not only for fighting the virus but also to prevent HCC emergence or progression. The polo-like-kinase 1 (PLK1), which plays pivotal roles in mitosis and is over-expressed in many human cancers, represents a promising druggable target in oncology. Beside its role during cell division, PLK1 is also thought to be involved in gene expression regulation during interphase. It was shown that the X protein (HBx) could activate PLK1 in murine cell transformation models. Yet it remained to be determined whether PLK1 could also play a role for HBV replication in non-dividing hepatocytes. Our, and collaborators, recent studies have identified a positive link between PLK1 activation and HBV replication. The goal of this thesis project was to investigate the mechanism(s) by which PLK1 exerts a positive effect on HBV replication, with the future goal of exploring PLK1 as an antiviral target. The interplay between PLK1 and HBV replication was firstly described using the HepAD38 cellular model of HBV replication. In this context, the HBV DNA is stably integrated into the host genome, under control of a Tet-off expression system. Transcription of HBV pregenomic RNA (pgRNA), the template of viral replication, is initiated by tetracycline removal. It has been shown that in HBV-replicating HepAD38 cells, increased PLK1 expression correlates with down-regulation of two proteins that are components of chromatin modifying complexes; SUZ12 protein of the PRC2 complex, and ZNF198 of the LSD1-CoREST-HDAC1 complex. PLK1 inhibition was described to inhibit HBV replication by reducing viral transcription. How PLK1 regulates HBV transcription remains unknown. On the other hand, in HBV replication models that resemble physiologic HBV infection, comprised of Primary Human Hepatocytes (PHH) and non-transformed/differentiated HepaRG cells (dHepaRG), where HBV replicates in non-transformed and non-dividing cells, thus enabling the study of the inter-phasic role of PLK1, irrespective of its well-established cell division implication, we have demonstrated that: 1) A pharmacological inhibition of PLK1 suppressed HBV replication by a different mechanism, likely targeting the packaging of pgRNA by the HBV core antigen (HBc). 2) Knocking-down PLK1 using siRNA delivered by lipid nanoparticles (LNP siPLK1) results in a strong drop of HBV DNAs, RNAs and HBe/HBsAg secretion without affecting the cell viability. This thesis project brought the proof of concept that PLK1 could be a drug target in HBV infection. Furthermore, the use of LNP allowed us to improve the delivery of siPLK1 to hepatocytes. Significantly, PLK1 inhibition is not toxic to quiescent cells in comparison to fast growing cancer cells, rendering PLK1 an attractive therapy target. High level of viremia in chronic HBV patients is a risk factor for progression to liver cancer. PLK1 specific inhibitors are already in clinical trials for other types of cancer (e.g., acute myeloid leukaemia) and could serve as bimodal therapy in HBV infected patients, by inhibiting virus replication as well as preventing emergence and spreading of neoplastic cells. This project was part of a full-working group of experts and thus, has beneficiated of a strong support. The proximity of the oncology-specialized hospital, the Centre Léon Bérard provided us with fresh hepatic biopsy [etc...]

En France et en Italie, le sida et l’hépatite b touchent de façon massive les migrants qui proviennent d’Afrique Subsaharienne, majoritairement ceux vivant des situations de précarité politique, sociale et économique. Depuis 2010 on assiste dans ces deux pays à un intérêt croissant des politiques publiques autour de l’hépatite b, celle-ci étant de plus en plus associée au VIH dans les stratégies de lutte mises en place au sein des populations migrantes. En dépit de ce constat les difficultés concernant l’accès aux soins et aux droits se sont accrues pour les migrants vivant avec ces deux infections dans les deux pays. En croisant les trajectoires politiques des deux infections et leur utilisation dans le domaine des politiques migratoires, cette thèse présente et analyse les modalités de prise en charge du sida et de l’hépatite b au sein des migrants « primo-arrivants » originaires d’Afrique Subsaharienne. Ce travail entend démontrer que ces pratiques de prise en charge, telle qu’elle se pratique aujourd’hui en France et en Italie, sont partie prenante de la construction de nouvelles formes d’inégalité. L'analyse est comparative et associe une étude microsociale et ethnographique des pratiques quotidiennes de prise en charge des patients migrants atteints du sida et de l’hépatite b – des pratiques observées dans deux structures qui s'occupent des migrants « primo-arrivants » à Paris et à Rome (Comede à Paris, Samifo à Rome) – et une étude macrosociale portant sur la traduction des évolutions politiques de la santé des migrants et de la lutte contre le VIH et l’hépatite b, et ce du niveau international à celui des deux pays concernés, la France et l’Italie
In France and in Italy, AIDS and hepatitis B profoundly affect migrants from sub-Saharan Africa, particularly those living under precarious political, social, and economic conditions. Since 2010, when the AIDS epidemic had normalized in Western countries, in France and Italy there has been increasing interest in public policies regarding hepatitis B, which is associated more and more with HIV, and disease control strategies for migrant populations. Despite this, following a recent tightening of migration policies, difficulties with accessing healthcare and with asserting one’s rights have increased for migrants living with these two infections in France or in Italy. Building on the intersection of the policy trajectories for these two infections and their use in the area of migration policies, this thesis presents an analysis of the way the treatment of AIDS and hepatitis B currently in effect in France and in Italy for newly arrived migrants from sub-Saharan Africa contributes to the development of new forms of inequality. The analysis is comparative and associated with a microsocial and ethnographic study of the everyday treatments for migrant patients afflicted with AIDS and hepatitis B that are provided by two entities that take care of newly arrived migrants in Paris and in Rome (Comede in Paris, Samifo in Rome), and a macrosocial study of the translation of policy developments in regard to the health of migrants and the fight against AIDS and hepatitis B at the international level and at the national level in France and Italy

Les tests de laboratoire basés sur des techniques de biologie moléculaire sont des outils inestimables pour le suivi des patients, en particulier dans le cadre de l’infectiologie. Dans ce contexte clinique, ils peuvent permettre d’établir un diagnostic, un pronostic ainsi que de déterminer la stratégie thérapeutique antivirale la plus adaptée. Les virus hautement variables tel que le virus de l’immunodéficience humaine (VIH), de l’hépatite B (VHB) et de l’hépatite C (VHC) sont présents sous forme de quasi-espèces au sein de leur environnement réplicatif. Lorsque des pressions de sélection s’exercent telle que l’administration d’un antiviral, une redistribution des variants majoritaires est fréquemment observée en variants mutés pour mieux s’adapter à cet environnement. Nos travaux ont permis, dans ce contexte, de valider l’impact clinique des mutations majoritaires mais aussi minoritaires grâce à la mise en œuvre de plusieurs techniques de séquençage (pyroséquençage, séquençage à haut débit et PCR en allèle spécifique). Nous avons également validé l’utilisation d’un logiciel simple, fiable et utilisable en routine par le clinicien pour l’interprétation clinique de la masse de données générées par le séquençage à haut débit. Enfin dans le contexte du test diagnostique, nous avons cliniquement validé sur une cohorte de patients infectés par le VHB, l’utilisation du papier buvard (Dried Blood Spot) comme support de prélèvement alternatif non invasif de diagnostic, en particulier pour les populations n’ayant pas accès aux structures classiques de soins et pour les pays en voie de développement
Molecular biology based assays are invaluable tools for the patients follow-up. They can help to establish the prognosis, guide for the treatment decisions and assess the virological response to therapy. Highly variable viruses like Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV) and Hepatitis C virus (HCV) which have a quasispecies distribution. Selection pressure on viral replicative environment such as an antiviral drug treatment, generally lead to a redistribution of the viral quasispecies with an increasing of the best adapted viral mutant. Our work allowed in this context to validate the clinical impact of majority but also minority mutations through the implementation of several sequencing techniques (pyrosequencing, high-throughput sequencing and allele-specific PCR). We also validated the use of a simple, reliable and routinely software solution by clinician for clinical interpretation of the mass of data generated by high-throughput sequencing. Finally, in the context of the diagnostic testing, we clinically validated in a cohort of patients infected with HBV, use the Dried Blood Spot technique as a supporting noninvasive diagnostic alternative sampling, especially for populations that have no access to conventional health structures and developing countries

Les immigrés originaires d’Afrique subsaharienne (ASS) sont souvent exposés à des périodes de précarité et sont également une des populations les plus touchées par les infections par le VIH et le VHB. L’objectif de cette thèse était d’étudier leur accès aux soins en fonction de leur statut vis-à-vis du VIH ou le VHB. L’enquête ANRS-Parcours a été réalisée auprès de 2468 immigrés d’ASS vivant en Ile-de-France. Elle a utilisé une grille biographique analysée à l’aide de modèles de régression logistique à temps discret. L’enquête Baromètre santé 2010 a interrogé 27 653 personnes vivant en France dont 9% d’immigrés. Les immigrés subsahariens accèdent à une couverture maladie l’année de leur arrivée en France, mais un sur dix n’en disposait toujours pas trois ans après l’arrivée (plus souvent en l'absence de droit au séjour). Ils renoncent plus souvent aux soins pour raisons financières que la population majoritaire. Ce constat est aggravé par des refus de prise en charge des bénéficiaires de la CMU-C ou l’AME et des participants vivant avec le VIH. L’entrée en soins a lieu la même année que celle du diagnostic. La probabilité d’avoir fait une demande de titre de séjour pour raison de santé était plus élevée parmi les participants vivant avec le VIH. Les difficultés que peuvent rencontrer les immigrés dans la prise en charge de leurs maladies dépendent de leur situation sociale qui peut varier selon les étapes de la vie. Dans des vies marquées par une migration, ces situations sociales diffèrent selon les raisons et les conditions d’arrivée en France, selon le statut du séjour en France (avoir ou pas un titre de séjour, le droit de travailler…) et la façon dont celui-ci évolue
Immigrants from sub-Saharan Africa (SSA) are often exposed to periods of precariousness after arriving in France and are also one of the most affected populations by HIV and HBV infections. The aim of this thesis was to study the access to care of SSA immigrants according to their HIV or HBV status. The ANRS-Parcours survey was conducted among 2,468 SSA immigrants living in Paris area and the Baromètre santé 2010 among 27,653 people living in France. The Parcours survey used a biographical grid to collect indicators year after year analysed with a discrete-time logistic regression method. Sub-Saharan immigrants have access to health insurance coverage the year they arrived in France, but one in ten still did not have one three years after their arrival (more often in the absence of a permit of residence). They are more exposed to unmet health care needs than the rest of the population in France. This finding is aggravated by refusals to provide healthcare for participants covered by the specific health insurance for precarious or undocumented migrants and people living with HIV. The linkage to care takes place the year of the diagnosis. The likelihood of applying for a medical residence permit was higher among participants living with HIV. Social situations, which can change over time, affect the ability of immigrants to access health care. In the context of immigration, these social situations differ according to the reasons and conditions of arrival in France, depending on the status of the stay in France (having or not a residence permit, the right to work ...) and the way in which it evolves