Éditeur(s) : HAL CCSD Lippincott, Williams & Wilkins
Résumé : International audience
The aim of the study was to investigate the impact of first-line combined antiretroviral therapy (cART) regimen on the course of CD8 + T-cell counts in human immunodeficiency virus (HIV)-infected patients. A retrospective observational study conducted on the French DAT'AIDS Cohort of HIV-infected patients. We selected 605 patients initiating a first-line cART between 2002 and 2009, and which achieved a sustained undetectable HIV plasma viral load (pVL) for at least 12 months without cART modification. The evolution of CD8 + T-cell counts according to cART regimen was assessed. CD8 + T-cell counts were assessed in 572 patients treated with 2NRTIs+1PI/r (n= 297), 2NRTIs+1NNRTI (n= 207) and 3NRTIs (n= 68). In multivariate analysis, after 12 months of follow-up, the 3NRTIs regimen was associated with a significantly smaller decrease of CD8 + T-cell count compared with NNRTI-containing regimens (–10.2 cells/mL in 3NRTIs vs –105.1 cells/mL; P=0.02) but not compared with PI-containing regimens (10.2 vs –60.9 cells/mL; P=0.21). After 24 months, the 3NRTIs regimen was associated with a smaller decrease of CD8 + T-cell count and % compared with PI/r-and NNRTI-containing regimens (0.2 in 3NRTIs vs –9.9 with PI/r-regimens, P=0.001, and vs –11.1 with NNRTI-regimens, p < 0.0001). A focus analysis on 11 patients treated with an INSTI-containing cART regimen during the study period showed after 12 months of follow-up, a median decrease of CD8 + T-cell count of –155 [inter quartile range: –302; –22] cells/mL. Our data highlight the fact that cART regimens have differential effects on CD8 pool down regulation. Abbreviations: cART = combined antiretroviral therapy, HIV = human immunodeficiency virus, INSTI = integrase strand transfer inhibitor, NNRTI = non-nucleotide reverse transcriptase inhibitor, NRTI = nucleotide reverse transcriptase inhibitor, PI/r = Ritonavir-boosted protease inhibitor, pVL = plasma viral load.
ISSN: 0025-7974

inserm-01408002
http://www.hal.inserm.fr/inserm-01408002
http://www.hal.inserm.fr/inserm-01408002/document
http://www.hal.inserm.fr/inserm-01408002/file/2016%2C%20Poizot-Martin%20-%20First-line%20cART%20regimen%20impacts%20the%20course%20of%20CD8%2B%20T-cell%20counts%20in%20HIV-infected%20patients.pdf
DOI : 10.1097/MD.0000000000005087

Éditeur(s) : HAL CCSD Oxford University Press (OUP)
Résumé : International audience
OBJECTIVES: To compare virological effectiveness in patients who continued on a virologically successful first-line boosted protease inhibitor (PI)-containing combination antiretroviral therapy (cART) regimen or who switched to a PI-free cART including efavirenz, nevirapine or abacavir. METHODS: From the French Hospital Database on HIV, we selected 439 patients with undetectable viral load (VL) on a first-line boosted PI-containing cART regimen who switched to a PI-free combination including efavirenz, nevirapine or abacavir. Each of these patients was matched with three patients who continued to take their first-line cART regimen, on the basis of gender, age, CD4 cell count, VL, date of cART initiation and the duration of VL undetectability. Time to virological failure (VF) was analysed with Kaplan-Meier curves and Cox models. RESULTS: The 12 month probabilities of VF were 3.7% and 5.7% in non-switch and switch patients, respectively, and 3.9%, 7.2% and 9.0% in patients switching to efavirenz-, nevirapine- and abacavir-containing cART, respectively. After adjustment, only patients switching to abacavir-containing cART had a higher risk of VF than non-switch patients (adjusted hazard ratio, 1.99; 95% confidence interval, 1.05-3.79). CONCLUSIONS: Switching from a virologically successful first-line boosted PI-containing cART regimen to a non-nucleoside reverse transcriptase inhibitor-containing cART regimen containing either efavirenz or nevirapine is virologically safe, while switching to abacavir-containing cART should be avoided.
ISSN: 0305-7453

hal-00875284
https://hal.archives-ouvertes.fr/hal-00875284
DOI : 10.1093/jac/dkr208
PUBMED : 21636583

Éditeur(s) : Ecole Nationale Supérieure Agronomique de Rennes
Résumé : Long-line fishing has been growing on the island of La Réunion since the beginning of the 1990s. The target species is the swordfish (Xiphias gladius), fished mainly in the tropical waters surrounding the island between longitudes 45 degree E and 60 degree E, and latitudes 17 degree S and 27 degree S. From 1998 to 2000, a finalised research programme enabled the collection of precise data concerning the lines' positions and the parameters of the fishing efforts: 3,602 nettings were thus informed by the catches (in numbers of individuals caught) and 12 descriptive variables of the effort. In parallel with this collection effort, satellite maps that described the ocean's landscape of this region of the Indian Ocean exploited by La Réunion's fisheries were made available to sailors and scientists. Extractions from these environmental variables were made at the fishing lines' positions, which allowed us to propose 20 variables describing the environmental conditions of swordfish catches applied to the nettings. In an early part of this study, after a descriptive analysis and a first selection of the variables, we used several GAM (Generalised Additive Models) to model the respective effects of effort and environmental variables on the variability of swordfish catches. We thus highlighted the predominance of factors linked to fishermen (fishing effort) on oceanographic factors in the explanation of this variability. Following these results, a summary on the biology and ecology of the swordfish was proposed in order to draw up hypotheses on the characteristics of this species' population in the Indian Ocean. The aspects linked to the individual behaviour and movements of the population were particularly highlighted. In a latter part of this study and in order to complete the empirical approach by an exploratory constructivist approach, we proposed a modelling tool in order to simulate the possible movements of individuals within the oceanic landscape described by the available satellite maps. After reading in the literature about the various forms of modelling the movements of the large pelagics, we developed an original computer modelling architecture of the multi-agent type that made it possible to manipulate in a dynamic way the satellite maps (and derived products), the individual movements of "animats" whose behaviours were based on this environmental information, and agents that clarify the process of long-line fishing in a geographical way. The computer model that was implemented (MUFINS, for MUlti-Fish INdian ocean Simulator) was next used by calibrating the behaviour of the animats on the real data originally from the analysis of commercial catches proposed in the first part, using robust techniques based on fuzzy logic. The results of the simulations were compared, on the one hand, with the large-scale hypotheses of movement proposed in the first part, and, on the other hand, to swordfish catches both real and corrected for the effect of the fishing effort modelled by the GAM models. Even if the results of these simulations in this study do not allow for proposing convincing interpretations of the underlying processes, the MUFINS tool showed its ability to address questions associated with the swordfish's behaviour in the tropical oceanic landscape and to the effects of scale transfers between the individual level and the collective level. We now envisage its use in a more operational framework, as an interface for dialogue between fishermen and scientists with a goal of sustainable management of the resource.
La peche palangriere s'est developpee a l'ile de La Reunion depuis le debut des annees 1990. L'espece cible est l'espadon (Xiphias gladius), principalement exploite dans les eaux tropicales autour de l'ile entre les longitudes 45 degree E et 60 degree E, et les latitudes 17 degree S et 27 degree S. De 1998 a 2000, un programme de recherche finalisee a permis de collecter des informations precises concernant les positions des lignes et les parametres de l'effort de peche : 3602 filages sont ainsi renseignes par les captures (en nombre d'individus captures) et 12 variables descriptives de l'effort. En parallele de cet effort de collecte, des cartes satellitales ont pu etre mises a la disposition des marins et des scientifiques, decrivant le paysage oceanique de cette region de l'ocean Indien exploitee par la pecherie reunionnaise. Des extractions de ces variables environnementales ont ete effectuees aux positions des lignes de peche, nous permettant de proposer 20 variables descriptives des conditions environnementales de captures d'espadon appliquees aux filages. Dans une premiere partie de ce travail, apres une analyse descriptive et une premiere selection des variables, on a modelise par plusieurs modeles GAM (Generalized Additive Models) les effets respectifs des variables d'effort et des variables environnementales sur la variabilite des captures d'espadon. On a ainsi mis en evidence la predominance des facteurs lies aux pecheurs (effort de peche) sur les facteurs oceanographiques dans le caractere explicatif de cette variabilite. A la suite de ces resultats, une synthese sur la biologie et l'ecologie de l'espadon a ete proposee afin de degager des hypotheses sur les caracteristiques de la population de cette espece dans l'ocean Indien. Les aspects lies au comportement individuel et aux deplacements de la population ont ete particulierement mis en evidence. Dans une deuxieme partie de ce travail et afin de completer l'approche empirique par une approche constructiviste exploratoire, nous avons propose un outil de modelisation afin de simuler les deplacements possibles d'individus au sein du paysage oceanique decrit par les cartes satellitales disponibles. Apres avoir passe en revue dans la litterature les differentes formes de modelisation des deplacements des grands, pelagiques, nous avons developpe une architecture originale de modelisation informatique de type multi-agents permettant de manipuler de maniere dynamique les cartes satellitales (et les produits derives), les mouvements individuels < d'animats >, dont les comportements sont bases sur cette information environnementale, et des agents qui explicitent le processus de capture palangriere de maniere geographique. Le modele informatique ainsi implemente (MUFINS, pour MUlti-Fish INdian ocean Simulator) a ensuite ete utilise en calibrant les comportements des animats sur les donnees reelles issues de l'analyse des captures commerciales proposee en premiere partie, a partir de techniques robustes basee sur la logique floue. Les resultats des simulations ont ete confrontes d'une part aux hypotheses de deplacement a grande echelle proposees en premiere partie, et d'autre part aux captures d'espadon reelles et corrigees de l'effet de l'effort de peche modelise par les modeles GAM. Meme si les resultats de simulations presentes dans ce travail ne permettent pas de proposer d'interpretations convaincantes des processus sous-jacents, l'outil MUFINS a demontre son aptitude a aborder les questions liees au comportement de l'espadon dans le paysage oceanique tropical et aux effets des transferts d'echelle entre le niveau individuel et le niveau collectif. On envisage desormais son utilisation dans un cadre plus operationnel, comme interface de dialogue entre les pecheurs et les scientifiques a des fins de gestion durable de la ressource.

Droits : info:eu-repo/semantics/openAccess
http://archimer.ifremer.fr/doc/2005/these-2592.pdf
http://archimer.ifremer.fr/doc/00000/2592/

Éditeur(s) : HAL CCSD Public Library of Science
Résumé : International audience
Cytomegalovirus (CMV) infection is common among HIV-infected patients but its repercussion on the course of CD4+ and CD8+ T cells after cART initiation remains elusive. The French Dat'AIDS cohort enrolled 5,688 patients on first-line cART, from which we selected patients who achieved HIV suppression for at least 12 months without modification of cART, and for whom CMV serostatus was available. Five hundred and three patients fulfilled the selection criteria (74% male, median age 43 yrs, 15.5% CDC stage C), of whom 444 (88.3%) were seropositive for CMV (CMV+). Multivariate analyses using mixed-linear models adjusted for the time from HIV suppression, sex, age, transmission risk group, duration of HIV follow-up, the interaction between time from HIV suppression and CMV+ serol-ogy, and the nadir CD4 count revealed a negative correlation between CMV+ and CD4: CD8 ratio (coeff. =-0.16; p = 0.001). This correlation was also observed among patients displaying optimal CD4 recovery (!500 cells/mm3 at M12; coeff. =-0.24; p = 0.002). Hence, CMV+ serostatus antagonizes normalization of the CD4:CD8 ratio, although further analyses of the impact of co-morbidities that associate with CMV serostatus, like HCV infection, are needed to elucidate this antagonism formally. However, this might reflect a premature T cell senescence, thus advocating for a close monitoring of T cells in CMV co-infected patients. In addition, our results raise the question of the benefit of treatment for asymptomatic CMV co-infection in HIV-infected patients.
ISSN: 1932-6203

inserm-01418700
http://www.hal.inserm.fr/inserm-01418700
http://www.hal.inserm.fr/inserm-01418700/document
http://www.hal.inserm.fr/inserm-01418700/file/journal.pone.0165774.PDF
DOI : 10.1371/journal.pone.0165774