K65R in Subtype C HIV-1 Isolates from Patients Failing on a First-Line Regimen Including d4T or AZT: Comparison of Sanger and UDP Sequencing Data

BACKGROUND: We and others have shown that subtype C HIV-1 isolates from patients failing on a regimen containing stavudine (d4T) or zidovudine (AZT) exhibit thymidine-associated mutations (TAMs) and K65R which can impair the efficacy of Tenofovir (TDF) at second line. Depending on the various studies, the prevalence of K65R substitution as determined by the Sanger method ranges from 4 to 30%. Our aim was to determine whether ultra-deep pyrosequencing (UDPS) could provide more information than the Sanger method about selection of K65R in this population of patients. METHODS: 27 subtype C HIV-1 isolates from treated patients failing on a regimen with d4T or AZT plus lamivudine (3TC) plus nevirapine (NVP) or efavirenz (EFV) and who had been sequenced by Sanger were investigated by UDPS at codon 65 of the reverse transcriptase (RT). 18 isolates from naïve patients and dilutions of a control K65R plasmid were analysed by Sanger plus UDPS. RESULTS: Analysis of Sanger sequences of subtype C HIV-1 isolates from naïve patients exhibited expected polymorphic substitutions compared to subtype B but no drug resistance mutations (DRMs). Quantitation of K65R variants by UDPS ranged from <0.4% to 3.08%. Sanger sequences of viral isolates from patients at failure of d4T or AZT plus 3TC plus NVP or EFV showed numerous DRMs to nucleoside reverse transcriptase inhibitors (NRTIs) including M184V, thymidine-associated mutations (TAMs) plus DRMs to non- nucleoside reverse transcriptase inhibitors (NNRTIs). Two K65R were observed by Sanger in this series of 27 samples with UDPS percentages of 27 and 87%. Other samples without K65R by Sanger exhibited quantities of K65R variants ranging from <0.4% to 0.80%, which were below the values observed in isolates from naïve patients. CONCLUSIONS: While Sanger sequencing of subtype C isolates from treated patients at failure of d4T or AZT plus 3TC plus NVP or EFV exhibited numerous mutations including TAMs and 8% K65R, UDPS quantitation of K65R variants in the same series did not provide any more information than Sanger

Quelques racines objectives des variations internationales dans le maintien des jeunes au domicile parental : L’inégale durée de la cohabitation parent-enfant en Europe à la lumière des modèles multiniveaux

International audienc

Quelques racines objectives des variations internationales dans le maintien des jeunes au domicile parental : L’inégale durée de la cohabitation parent-enfant en Europe à la lumière des modèles multiniveaux

International audienc

Observation d'états excitoniques à température ambiante dans les semiconducteurs à puits quantiques de type InGaAs/InP (Applications)

Les structures à base de semiconducteurs constituant des puits quantiques présentent de remarquables propriétés électroniques et optiques. En particulier les états excitoniques peuvent être observés à température ambiante et les propriétés optiques qui leur sont attachées permettent de concevoir l'utilisation de tels composants dans le domaine du traitement optique de l'information. Dans ce cadre, des éléments logiques commandés par voie purement optique ou assistés sous champ électrique peuvent constituer un des éléments de base devant être pris en compte pour la conception des futurs ordinateurs. Cet article présente les caractéristiques optiques de transmission de structures de type multi-puits quantiques réalisées à partir de matériaux III-V InGaAs/InP. Les effets non linéaires associés à l'existence d'un effet collectif des excitons sont démontrés et l'emploi de ces effets en optique surfacique ou en optique guidée est évoqué au travers de deux exemples (bistabilité et coupleur non linéaire)

Failure of Calcineurin Inhibitor (Tacrolimus) Weaning Randomized Trial in Long-Term Stable Kidney Transplant Recipients

International audienceLong-term renal transplant outcome is limited by side effects of immunosuppressive drugs, particularly calcineurin inhibitor (CNI). We assumed that some patients selected for a “low immunological risk of rejection” could be eligible and benefit from a CNI weaning strategy. We designed a prospective, randomized, multicenter, double-blind placebocontrolled clinical study (Eudract: 2010-019574-33) to analyze the benefit–risk ratio of tacrolimus weaning on highly selected patients (≥4 years of transplantation, normal histology, stable graft function, no antiHLA immunization). The primary endpoint was improvement of renal function. Fifty-two patients were scheduled in each treatment arm, placebo compared to the CNI maintenance arm. Only 10 patients were eligible and randomized. Five patients were assigned to the placebo arm and five were assigned to the tacrolimus maintenance arm. In the tacrolimus maintenance arm, all patients maintained stable graft function and no immunological events occurred.Contrastingly, in the placebo arm, all five patients had to reintroduce a full dose of tacrolimus since three of them presented an acute rejection episode (one humoral, one mixed, and one borderline) and two displayed anti-HLA antibodies without histological lesion (one donor-specific antibodies [DSA] and one non-DSA). Clearly, tacrolimus withdrawal must be avoided even in long-term highly selective stable kidney recipients