Short- and Long-term Immunological and Virological Outcome in HIV-Infected Infants According to the Age at Antiretroviral Treatment Initiation

The clinical benefit of antiretroviral therapy in infants is established. In this cohort collaboration, we compare immunological and virological response to treatment started before or after 3 months of age. Early initiation provides a better short-term response, although evolution after 12 months of age is similar in both group

PLoS One

AIM: Metabolic risk factors are poorly documented for the first generation of young adults who have lived with HIV since childhood. We compared their metabolic profile with that of adults of same age from the general population. METHODS: We conducted a cross-sectional analysis of data from two populations: (1) COVERTE (ANRS-CO19), a French national cohort of 18 to 30-year-old patients HIV-infected since childhood, and (2) ENNS, a national cross-sectional population-based household survey on nutrition. Body mass index (BMI), blood pressure, waist circumference, fasting glucose, triglycerides, and HDL-, LDL- and total cholesterol were measured in both studies. Direct standardization on overweight and education level and logistic regression were used to compare the prevalence of metabolic abnormalities between the two populations. RESULTS: Data from 268 patients from COVERTE and 245 subjects from ENNS were analyzed. Tobacco use was similar in both groups. HIV-infected patients had increased mean waist-to-hip ratio and triglycerides to HDL-cholesterol ratio and decreased mean HDL-cholesterol as compared to their counterparts from the general population in both genders. In HIV-infected patients, metabolic syndrome was identified in 13.2% of men (95% confidence interval [CI]: 7.1-19.2) and 10.4% (95% CI: 5.4-15.3) of women versus 10.6% (95%CI: 1.5-19.7) and 1.7% (95%CI: 0-4.1) in subjects from the general population, respectively. CONCLUSION: Young adults infected with HIV since childhood had a higher prevalence of dyslipidemia and metabolically detrimental fat distribution than adults of same age of the general population, supporting close monitoring for cardiometabolic diseases

Complete exon sequencing of all known Usher syndrome genes greatly improves molecular diagnosis

<p>Abstract</p> <p>Background</p> <p>Usher syndrome (USH) combines sensorineural deafness with blindness. It is inherited in an autosomal recessive mode. Early diagnosis is critical for adapted educational and patient management choices, and for genetic counseling. To date, nine causative genes have been identified for the three clinical subtypes (USH1, USH2 and USH3). Current diagnostic strategies make use of a genotyping microarray that is based on the previously reported mutations. The purpose of this study was to design a more accurate molecular diagnosis tool.</p> <p>Methods</p> <p>We sequenced the 366 coding exons and flanking regions of the nine known USH genes, in 54 USH patients (27 USH1, 21 USH2 and 6 USH3).</p> <p>Results</p> <p>Biallelic mutations were detected in 39 patients (72%) and monoallelic mutations in an additional 10 patients (18.5%). In addition to biallelic mutations in one of the USH genes, presumably pathogenic mutations in another USH gene were detected in seven patients (13%), and another patient carried monoallelic mutations in three different USH genes. Notably, none of the USH3 patients carried detectable mutations in the only known USH3 gene, whereas they all carried mutations in USH2 genes. Most importantly, the currently used microarray would have detected only 30 of the 81 different mutations that we found, of which 39 (48%) were novel.</p> <p>Conclusions</p> <p>Based on these results, complete exon sequencing of the currently known USH genes stands as a definite improvement for molecular diagnosis of this disease, which is of utmost importance in the perspective of gene therapy.</p

Perinatal acquisition of drug-resistant HIV-1 infection: mechanisms and long-term outcome

<p>Abstract</p> <p>Background</p> <p>Primary-HIV-1-infection in newborns that occurs under antiretroviral prophylaxis that is a high risk of drug-resistance acquisition. We examine the frequency and the mechanisms of resistance acquisition at the time of infection in newborns.</p> <p>Patients and Methods</p> <p>We studied HIV-1-infected infants born between 01 January 1997 and 31 December 2004 and enrolled in the ANRS-EPF cohort. HIV-1-RNA and HIV-1-DNA samples obtained perinatally from the newborn and mother were subjected to population-based and clonal analyses of drug resistance. If positive, serial samples were obtained from the child for resistance testing.</p> <p>Results</p> <p>Ninety-two HIV-1-infected infants were born during the study period. Samples were obtained from 32 mother-child pairs and from another 28 newborns. Drug resistance was detected in 12 newborns (20%): drug resistance to nucleoside reverse transcriptase inhibitors was seen in 10 cases, non-nucleoside reverse transcriptase inhibitors in two cases, and protease inhibitors in one case. For 9 children, the detection of the same resistance mutations in mothers' samples (6 among 10 available) and in newborn lymphocytes (6/8) suggests that the newborn was initially infected by a drug-resistant strain. Resistance variants were either transmitted from mother-to-child or selected during subsequent temporal exposure under suboptimal perinatal prophylaxis. Follow-up studies of the infants showed that the resistance pattern remained stable over time, regardless of antiretroviral therapy, suggesting the early cellular archiving of resistant viruses. The absence of resistance in the mother of the other three children (3/10) and neonatal lymphocytes (2/8) suggests that the newborns were infected by a wild-type strain without long-term persistence of resistance when suboptimal prophylaxis was stopped.</p> <p>Conclusion</p> <p>This study confirms the importance of early resistance genotyping of HIV-1-infected newborns. In most cases (75%), drug resistance was archived in the cellular reservoir and persisted during infancy, with or without antiretroviral treatment. This finding stresses the need for effective antiretroviral treatment of pregnant women.</p

Expansion of the Human Phenotype Ontology (HPO) knowledge base and resources.

The Human Phenotype Ontology (HPO)-a standardized vocabulary of phenotypic abnormalities associated with 7000+ diseases-is used by thousands of researchers, clinicians, informaticians and electronic health record systems around the world. Its detailed descriptions of clinical abnormalities and computable disease definitions have made HPO the de facto standard for deep phenotyping in the field of rare disease. The HPO\u27s interoperability with other ontologies has enabled it to be used to improve diagnostic accuracy by incorporating model organism data. It also plays a key role in the popular Exomiser tool, which identifies potential disease-causing variants from whole-exome or whole-genome sequencing data. Since the HPO was first introduced in 2008, its users have become both more numerous and more diverse. To meet these emerging needs, the project has added new content, language translations, mappings and computational tooling, as well as integrations with external community data. The HPO continues to collaborate with clinical adopters to improve specific areas of the ontology and extend standardized disease descriptions. The newly redesigned HPO website (www.human-phenotype-ontology.org) simplifies browsing terms and exploring clinical features, diseases, and human genes

Time to Switch to Second-line Antiretroviral Therapy in Children With Human Immunodeficiency Virus in Europe and Thailand.

Background: Data on durability of first-line antiretroviral therapy (ART) in children with human immunodeficiency virus (HIV) are limited. We assessed time to switch to second-line therapy in 16 European countries and Thailand. Methods: Children aged <18 years initiating combination ART (≥2 nucleoside reverse transcriptase inhibitors [NRTIs] plus nonnucleoside reverse transcriptase inhibitor [NNRTI] or boosted protease inhibitor [PI]) were included. Switch to second-line was defined as (i) change across drug class (PI to NNRTI or vice versa) or within PI class plus change of ≥1 NRTI; (ii) change from single to dual PI; or (iii) addition of a new drug class. Cumulative incidence of switch was calculated with death and loss to follow-up as competing risks. Results: Of 3668 children included, median age at ART initiation was 6.1 (interquartile range (IQR), 1.7-10.5) years. Initial regimens were 32% PI based, 34% nevirapine (NVP) based, and 33% efavirenz based. Median duration of follow-up was 5.4 (IQR, 2.9-8.3) years. Cumulative incidence of switch at 5 years was 21% (95% confidence interval, 20%-23%), with significant regional variations. Median time to switch was 30 (IQR, 16-58) months; two-thirds of switches were related to treatment failure. In multivariable analysis, older age, severe immunosuppression and higher viral load (VL) at ART start, and NVP-based initial regimens were associated with increased risk of switch. Conclusions: One in 5 children switched to a second-line regimen by 5 years of ART, with two-thirds failure related. Advanced HIV, older age, and NVP-based regimens were associated with increased risk of switch

Hyperprotidémie au diagnostic d'infection à VIH en pédiatrie (étude rétrospective chez les patients nouvellement diagnostiqués à l' hôpital Trousseau de 2000 à 2011)

L infection à VIH est sous-diagnostiquée en pédiatrie alors même que le recours aux services de santé est très fréquent L'hypergammaglobulinémie polyclonale chez les enfants infectés est un phénomène biologique décrit qui est à l'origine d'une élévation du niveau des protides sériques totales ; en revanche, sa fréquence et son ampleur au diagnostic d'infection à VIH n'ont jamais été étudiées. Le but de l'étude menée est donc de décrire la proportion ainsi que les caractéristiques liées à l'hyperprotidémie au diagnostic des patients suivis à l'hôpital Trousseau.Une étude rétrospective monocentrique a été réalisée. Des données socio-démographiques, cliniques et biologiques d'enfants nouvellement diagnostiqués pour une infection à VIH entre 2000 et 2011 dont le sexe, l'âge, le pays de naissance, les signes cliniques de présentation, la protidémie, le niveau de charge virale VIH et la proportion de CD4+, ont été relevées.Une infection à VIH a été diagnostiquée pour 83 enfants au cours de la période 2000- 2011. Un dosage de protidémie était disponible avant traitement antirétroviral pour 52 enfants. 87 % des patients sont d'origine africaine (dont la moitié arrivés récemment en France). L'âge moyen est de 5,2 ans au diagnostic ; 32 patients ont plus de 2 ans (19 filles et 13 garçons) et 20 patients ont 2 ans ou moins (11 filles, 9 garçons). Pour les patients de plus de 2 ans, la protidémie moyenne est de 97,6 g/L [93-103]IC 95% et 94% (30 patients/32) présentent une hyperprotidémie. Pour les patients de moins de 2 ans, elle est de 78,4 g/L [71-86]IC 95% et 35% (7 patients/20) ont une hyperprotidémie.L'hyperprotidémie est fréquente, au diagnostic d'infection à VIH dans notre étude et plus constante et plus marquée chez les enfants de plus de 2 ans. Elle peut constituer un signal d'alerte intéressant, associée au contexte clinique pour proposer la réalisation d'une sérologie spécifiquePARIS6-Bibl.Pitié-Salpêtrie (751132101) / SudocSudocFranceF

Mobilité, territoire et pouvoirs en Himalaya : pour Philippe Sagant

À la fin des années 1950, la recherche sur les régions himalayennes connaît un tournant majeur : les enquêtes de terrain des premiers ethnologues professionnels prennent le pas sur les travaux textuels orientalistes. Le Népal, royaume himalayen jamais colonisé, vient de s’ouvrir au monde. Environné d’états dorénavant fermés où s’était illustrée la recherche britannique des administrateurs coloniaux de l’Asie du Sud, il devient un laboratoire centré sur l’ethnologie des minorités dites tibéto-birmanes prises sous la double influence du monde indien et du monde sino-tibétain, une configuration d’une infinie richesse. Engagé après la guerre d’Algérie dans le métier d’ethnologue, Philippe Sagant, à la mémoire duquel ce numéro des Ateliers d'anthropologie est consacré, est un acteur de ce moment pionnier. Ses travaux nouent les exigences de la collecte ethnographique, entièrement à faire au Népal, à une réflexion dépassant les clivages régionaux culturels ou religieux pour développer une anthropologie des sociétés des marges prises entre des forces centralisatrices où les domaines du politique et du religieux sont indissociables. Ils témoignent des réflexions à l’œuvre dans l’aire himalayenne et dans la discipline ethnologique, depuis la formation de Philippe Sagant au musée de l’Homme, sa participation aux RCP des années 1960 et aux institutions créées à cette époque, jusqu’à ses ambitions comparatives sur un modèle de pouvoir archaïque, « le chef élu des dieux ». Son engagement dans la formation à l’université de Nanterre et à l’Inalco a marqué toute une génération. Les écrits de Philippe Sagant, c’est aussi un style très personnel, une voix très moderne par l’importance qu’il attribua à la parole et au vécu de ses informateurs, à la forme en ethnologie, vecteur de l’ethnocentrisme. Cet élan fut brisé par une maladie terrible qui le coupa de la recherche en 1996 jusqu’à son décès en 2015. Pour renouer les fils de ce temps suspendu, ce recueil propose des contributions reprenant certains de ses travaux, qui dialoguent avec des pages inédites issues de ses archives sur le vécu des Limbu de l’est du Népal à la fin des années 1960, période marquante dans l’histoire de ce pays. Il offre aussi la traduction en anglais de deux textes sur le « chef élu des dieux » en milieu hindou et bouddhiste et des inédits tardifs destinés à un public plus large. In the late 1950s, research on the Himalayan regions reached a major turning point: field studies by the first professional ethnologists supplanted orientalist textual works. Nepal, a Himalayan kingdom that had never been colonised, had just opened to the world. Surrounded by previously closed states where British research by the colonial administrators of South Asia had been illustrated, it became a laboratory focused on the ethnology of so-called Tibeto-Burman minorities under the dual influence of the Indian and Sino-Tibetan worlds, an infinitely rich configuration. Philippe Sagant, to whom this issue of Ateliers d’anthropologie is dedicated, played a part in that pioneering moment, taking up the ethnological profession after the Algerian War. His works combine the rigors of ethnographic collection—something that needed to be done in its entirety in Nepal—with reflection that goes beyond regional cultural or religious divisions, to develop an anthropology of marginal societies caught between centralising forces in which the political and religious spheres are inseparable. They show the reflections pursued in the Himalayan area and in the ethnological discipline, from the time of Philippe Sagant’s training at the Musée de l’Homme and his participation in the RCPs of the 1960s and in institutions created at that time, to his comparative ambitions revolving around an archaic power model of “the gods’ chosen one”. His involvement in training at Paris-Nanterre University and Inalco influenced a whole generation. Philippe Sagant’s writings also have a very personal style, and a very modern voice because of the importance he attributed to the words and experiences of his informants, and to form in ethnology, a vehicle of ethnocentrism. This momentum was broken by a terrible illness that halted his research in 1996 until his death in 2015. To reconnect the threads of that suspended time, this collection offers contributions revisiting some of Sagant’s works. They establish a dialogue with unpublished pages from his archives on the lives of the Limbu in eastern Nepal in the late 1960, a striking period in the history of that country. It also offers English translations of two texts on the “gods’ chosen headman” in Hindu and Buddhist environments, and late unpublished texts intended for a broader readership

Trichosporon : another yeast-like organism responsible for immune reconstitution inflammatory syndrome in patients with hematological malignancy

International audienceTrichosporon has recently emerged as a life-threatening opportunistic fungal pathogen, notably in patients with hematological malignancy. Fungemia, sometimes associated with cu-taneous lesions and/or pneumonitis, is the major clinical form. Here, we report two cases of patients suffering from acute leukaemia who developed hepatic and/or splenic lesions apart from Trichosporon positive blood cultures. The appearance of hepatic and splenic lesions following the recovery from neutropenia is highly suggestive of a chronic disseminated infection , now considered as an immune reconstitution inflammatory syndrome. Treatment with corticosteroid therapy led to clinical improvement in both cases