Place des microbicides vaginaux dans la prévention de l'infection par le virus de l'immunodéficience humaine

Les microbicides peuvent se définir comme des substances topiques susceptibles de réduire le risque d'infections sexuellement transmissibles. L'objet de cette revue est de présenter un état des lieux des connaissances relatives aux microbicides vaginaux susceptibles de protéger les femmes contre l'infection par le virus de l'immunodéficience humaine de type 1 (VIH-1). Les molécules microbicides à visée anti-VIH comprennent des composés non spécifiques comme les détergents, les polyanions ou les inhibiteurs d'entrée, et des molécules spécifiques de VIH-1 qui incluent principalement des inhibiteurs des étapes précoces de l'infection virale et des inhibiteurs de la réverse transcriptase. Bien que l'approche microbicide soit très séduisante sous l'angle conceptuel, aucun essai clinique contrôlé et randomisé, conduit avec des molécules de première génération n'a fait la preuve de l'efficacité préventive de ces composés contre l'infection par VIH-1. Des résultats encourageants ont été obtenus chez des primates non humains et plusieurs essais cliniques menés à travers le monde devraient livrer leur verdict assez vite. Cette revue discute ces différents aspects et encore l'évaluation préclinique de la balance bénéfices-risques des produits microbicides, les associations de composés microbicides anti-VIH-1 et la capacité de ces substances à sélectionner des mutants résistants. Une meilleure connaissance des modes de franchissement de la muqueuse cervico-vaginale par VIH-1 devrait permettre d'affiner les stratégies microbicides qui, en l'absence de vaccination préventive à moyen terme, constituent une alternative à évaluer pour protéger les femmes — et notamment les plus vulnérables d'entre elles — vis-à-vis de l'infection par VIH-1

Trouble with Bleeding: Risk Factors for Acute Hepatitis C among HIV-Positive Gay Men from Germany—A Case-Control Study

OBJECTIVES: To identify risk factors for hepatitis C among HIV-positive men who have sex with men (MSM), focusing on potential sexual, nosocomial, and other non-sexual determinants. BACKGROUND: Outbreaks of hepatitis C virus (HCV) infections among HIV-positive MSM have been reported by clinicians in post-industrialized countries since 2000. The sexual acquisition of HCV by gay men who are HIV positive is not, however, fully understood. METHODS: Between 2006 and 2008, a case-control study was embedded into a behavioural survey of MSM in Germany. Cases were HIV-positive and acutely HCV-co-infected, with no history of injection drug use. HIV-positive MSM without known HCV infection, matched for age group, served as controls. The HCV-serostatus of controls was assessed by serological testing of dried blood specimens. Univariable and multivariable regression analyses were used to identify factors independently associated with HCV-co-infection. RESULTS: 34 cases and 67 controls were included. Sex-associated rectal bleeding, receptive fisting and snorting cocaine/amphetamines, combined with group sex, were independently associated with case status. Among cases, surgical interventions overlapped with sex-associated rectal bleeding. CONCLUSIONS: Sexual practices leading to rectal bleeding, and snorting drugs in settings of increased HCV-prevalence are risk factors for acute hepatitis C. We suggest that sharing snorting equipment as well as sharing sexual partners might be modes of sexual transmission. Condoms and gloves may not provide adequate protection if they are contaminated with blood. Public health interventions for HIV-positive gay men should address the role of blood in sexual risk behaviour. Further research is needed into the interplay of proctosurgery and sex-associated rectal bleeding

Infection of Semen-Producing Organs by SIV during the Acute and Chronic Stages of the Disease

International audienceBACKGROUND: Although indirect evidence suggests the male genital tract as a possible source of persistent HIV shedding in semen during antiretroviral therapy, this phenomenon is poorly understood due to the difficulty of sampling semen-producing organs in HIV+ asymptomatic individuals. METHODOLOGY/PRINCIPAL FINDINGS: Using a range of molecular and cell biological techniques, this study investigates SIV infection within reproductive organs of macaques during the acute and chronic stages of the disease. We demonstrate for the first time the presence of SIV in the testes, epididymides, prostate and seminal vesicles as early as 14 days post-inoculation. This infection persists throughout the chronic stage and positively correlates with blood viremia. The prostate and seminal vesicles appear to be the most efficiently infected reproductive organs, followed by the epididymides and testes. Within the male genital tract, mostly T lymphocytes and a small number of germ cells harbour SIV antigens and RNA. In contrast to the other organs studied, the testis does not display an immune response to the infection. Testosteronemia is transiently increased during the early phase of the infection but spermatogenesis remains unaffected. CONCLUSIONS/SIGNIFICANCE: The present study reveals that SIV infection of the macaque male genital tract is an early event and that semen-producing organs display differential infection levels and immune responses. These results help elucidate the origin of HIV in semen and constitute an essential base to improving the design of antiretroviral therapies to eradicate virus from semen

Antiretroviral-naive and -treated HIV-1 patients can harbour more resistant viruses in CSF than in plasma

Objectives The neurological disorders in HIV-1-infected patients remain prevalent. The HIV-1 resistance in plasma and CSF was compared in patients with neurological disorders in a multicentre study. Methods Blood and CSF samples were collected at time of neurological disorders for 244 patients. The viral loads were >50 copies/mL in both compartments and bulk genotypic tests were realized. Results On 244 patients, 89 and 155 were antiretroviral (ARV) naive and ARV treated, respectively. In ARV-naive patients, detection of mutations in CSF and not in plasma were reported for the reverse transcriptase (RT) gene in 2/89 patients (2.2%) and for the protease gene in 1/89 patients (1.1%). In ARV-treated patients, 19/152 (12.5%) patients had HIV-1 mutations only in the CSF for the RT gene and 30/151 (19.8%) for the protease gene. Two mutations appeared statistically more prevalent in the CSF than in plasma: M41L (P = 0.0455) and T215Y (P = 0.0455). Conclusions In most cases, resistance mutations were present and similar in both studied compartments. However, in 3.4% of ARV-naive and 8.8% of ARV-treated patients, the virus was more resistant in CSF than in plasma. These results support the need for genotypic resistance testing when lumbar puncture is performe

Validation and utilization of an internally controlled multiplex Real-time RT-PCR assay for simultaneous detection of enteroviruses and enterovirus A71 associated with hand foot and mouth disease

BACKGROUND: Hand foot and mouth disease (HFMD) is a disease of public health importance across the Asia-Pacific region. The disease is caused by enteroviruses (EVs), in particular enterovirus A71 (EV-A71). In EV-A71-associated HFMD, the infection is sometimes associated with severe manifestations including neurological involvement and fatal outcome. The availability of a robust diagnostic assay to distinguish EV-A71 from other EVs is important for patient management and outbreak response. METHODS: We developed and validated an internally controlled one-step single-tube real-time RT-PCR in terms of sensitivity, linearity, precision, and specificity for simultaneous detection of EVs and EV-A71. Subsequently, the assay was then applied on throat and rectal swabs sampled from 434 HFMD patients. RESULTS: The assay was evaluated using both plasmid DNA and viral RNA and has shown to be reproducible with a maximum assay variation of 4.41 % and sensitive with a limit of detection less than 10 copies of target template per reaction, while cross-reactivity with other EV serotypes was not observed. When compared against a published VP1 nested RT-PCR using 112 diagnostic throat and rectal swabs from 112 children with a clinical diagnosis of HFMD during 2014, the multiplex assay had a higher sensitivity and 100 % concordance with sequencing results which showed EVs in 77/112 (68.8 %) and EV-A71 in 7/112 (6.3 %). When applied to clinical diagnostics for 322 children, the assay detected EVs in throat swabs of 257/322 (79.8 %) of which EV-A71 was detected in 36/322 (11.2 %) children. The detection rate increased to 93.5 % (301/322) and 13.4 % (43/322) for EVs and EV-A71, respectively, when rectal swabs from 65 throat-negative children were further analyzed. CONCLUSION: We have successfully developed and validated a sensitive internally controlled multiplex assay for rapid detection of EVs and EV-A71, which is useful for clinical management and outbreak control of HFMD. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12985-015-0316-2) contains supplementary material, which is available to authorized users

MODELO DE GESTIÓN DE LA DEMANDA ENERGÉTICA INTEGRAL

La gestión energética significa optimizar una de las más complejas e importantes técnicas crea ciones que conocemos: el sistema de energía. Existen una buena cantidad de métodos para la optimización de la generación de energía y su distribución. Por lo que el modelo de la demanda energética integral (DSM) es una estrategia para mejorar el sistema de energía en el lado del consumo. Se extiende desde la política energética, la economía experimental, la teoría de los agentes, la mejora de la eficiencia energética mediante software de soporte y aplicación, las tarifas de energía inteligente con incentivos para ciertos patrones de consumo, hasta los sofisticados sistemas de control en tiempo real de los recursos energéticos distribuidos. Este documento proporciona una visión general y una taxonomía para el desarrollo de un modelo sistemático integral de DSM, que analiza los distintos elementos de construcción, y ofrece un panorama sobre cómo emplear un modelo de análisis jerárquico de procesos y evaluación integral difusa para su implementación

Thermomechanical(physical) performances of SiC/SiC composites for nuclear applications

International audienceThe interest of SiC/SiC composites as structural materials for nuclear applications has grown over the past decade. Due to their high thermomechanical properties over a wide range of temperature as well as their stability under neutron irradiation, SiC/SiC were initially considered for both the fuel cladding element and the hexagonal sub-assembly body for the fast fission neutron reactors. In 2011, the major accident at Fukushima Daiichi highlighted the need to improve the safety of current facilities and future planned designs of light water reactors (LWRs). The use of a refractory and less reactive material under oxidizing conditions such as a SiC-based fuel cladding could be an alternative solution to the conventional zirconium alloys to improve the accident tolerance.The present work primarily focuses on the thermomechanical performances of SiC/SiC composites under severe environments including high temperature (> 1000DC) in neutral then steam atmospheres. A first objective is to specify the relevant and suitable working range for using the composites under normal operating conditions. The determination of temperature limits before occurring significant degradation, as well as the underlying causes of such a decrease were investigated on representative composite structures. A second objective addresses the thermal shock tolerance of SiC/SiC composites to demonstrate their ability to remain structurally sound after water quenching during the re-flooding phase in situation of accidents for LWRs. Preservation of the geometry which maintain core coolability up to very high temperature are very positive results. Close examinations of the oxidized surfaces evidence the efficiency of the passivation layer in protecting substrate. Finally, a correlation between the observations and the residual mechanical properties was developed to propose a mechanism

Thermomechanical performances of SiC/SiC composites for nuclear applications

International audienceThe interest of SiC/SiC composites as structural materials for nuclear applications has grown over the past decade. Due to their high thermomechanical properties over a wide range of temperature as well as their stability under neutron irradiation, SiC/SiC were initially considered for both the fuel cladding element and the hexagonal sub-assembly body for the fast fission neutron reactors. In 2011, the major accident at Fukushima Daiichi highlighted the need to improve the safety of current facilities and future planned designs of light water reactors (LWRs). The use of a refractory and less reactive material under oxidizing conditions such as a SiC-based fuel cladding could be an alternative solution to the conventional zirconium alloys to improve the accident tolerance.The present work primarily focuses on the thermomechanical performances of SiC/SiC composites under severe environments including high temperature (> 1000DC) in neutral then steam atmospheres. A first objective is to specify the relevant and suitable working range for using the composites under normal operating conditions. The determination of temperature limits before occurring significant degradation, as well as the underlying causes of such a decrease were investigated on representative composite structures. A second objective addresses the thermal shock tolerance of SiC/SiC composites to demonstrate their ability to remain structurally sound after water quenching during the re-flooding phase in situation of accidents for LWRs. Preservation of the geometry which maintain core coolability up to very high temperature are very positive results. Close examinations of the oxidized surfaces evidence the efficiency of the passivation layer in protecting substrate. Finally, a correlation between the observations and the residual mechanical properties was developed to propose a mechanism