Mobbing gegen Christoph Mörgeli am Medizinhisto- rischen Institut und Museum Gegen Christoph Mörgeli wurde speziell seit Februar 2010 und damit seit der Direktionsstellvertretung durch Iris Ritzmann und verstärkt seit Februar 2011 anlässlich der Direktionsübernahme von Flurin Condrau ein intensives Mob- bing betrieben. Die im folgenden nachgewiesenen systematischen, feindseli- gen und v
La proportion de personnes infectées avec des souches résistantes n'a pas augmenté ces dernières années.La proportion de personnes infectées avec des souches résistantes n'a pas augmenté ces dernières années.
Evolution des résistances VIH-1 au traitement
La proportion de personnes
infectées avec des souches
résistantes n'a pas augmenté
ces dernières années.
Date de mise en ligne : vendredi 10 juin 2005 Description :
Plusieurs laboratoires de virologie français viennent de publier dans le journal JAIDS les résultats d'une étude sur la fréquence des résistances pour le VIH-1 chez les patients français. L'étude conclut que cette fréquence n'est pas significativement plus élevée en 2001/02 que dans les études précédentes.
La proportion de personnes infectées avec des souches résistantes n'a pas augmenté ces dernières années.
Plusieurs laboratoires de virologie français viennent de publier dans le journal JAIDS les résultats d'une étude sur la fréquence des résistances pour le VIH-1 chez les patients français. L'étude conclut que cette fréquence n'est pas significativement plus élevée en 2001/02 que dans les études précédentes. Nous parlons ici des patients naïfs de tout traitement antirétroviral (non traités). Par ailleurs, la prévalence du sous-type non-B est en augmentation comme indiqué dans la surveillance virologique de la DO-VIH.
Par ailleurs, l'étude s'est penchée sur l'évolution de la prévalence des différentes souches VIH. Le pourcentage de personnes porteuses du sous-type non-B est en augmentation dans la cohorte primo-infection, ce qui implique une augmentation de l'exposition de la population d'origine européenne à cette souche. (17% en 2002 contre 14% en L'étude a été menée sur les cohortes Primo et Odyssee. La fréquence de résistance pour le VIH-1 à au moins 1 antirétroviral est de 12% chez les patients en primo-infection (cohorte Primo) et 1,7% chez ceux non traités (cohorte Pour les cas de primo infection, la résistance n'apparaît pas en plus grand nombre entre 1996 (10%) et 2002 (12%).
Pour les patients non traités, elle tombe de 5,6% à 1,7 % entre 1998 et 2001. Cette différence, d'après les auteurs de l'étude, peut s'expliquer du fait d'une durée plus courte de connaissance de la séropositivité dans l'étude actuelle par Les auteurs font observer qu'en France, la proportion de personnes infectées avec des souches VIH-1 résistantes n'a pas augmenté ces dernières années.
L'étude complète est disponible ci-dessous.
HIV Drug Resistance in France
"French National Sentinel Survey of Antiretroviral Drug Resistance in Patients With HIV-1 Primary Infection
and in Antiretroviral-Naive Chronically Infected Patients in 2001-2002"
JAIDS Journal of Acquired Immune Deficiency Syndromes : Volume 38(5) 15 April 2005. Author list at end of article.
Abstract Objective : To survey the frequency of genotypic antiretroviral resistance and the spread of non-B subtypes
in patients with primary HIV-1 infection (2001-2002) and in treatment-naive chronically HIV-1-infected patients Methods : Plasma samples from 303 patients with acute HIV-1 infection (Primo study) and 363 treatment-naive
patients with chronic HIV-1 infection (Odyssee study) were tested for genotypic resistance. Resistance mutations were identified from the International AIDS Society Resistance Testing-USA panel and resistant viruses were defined according to the French Agence Nationale de Recherches sur le SIDA (ANRS) resistance algorithm.
Results : In the Primo study, 14% of the patients had viruses with resistance mutations and 12% of patients had
viruses with mutations conferring resistance to least 1 antiretroviral drug. Thirty patients had viruses with mutations to La proportion de personnes infectées avec des souches résistantes n'a pas augmenté ces dernières années.
at least 1 antiretroviral drug in a single pharmacologic class. Six patients were infected by viruses resistant to 2 or 3 classes of drugs. In the Odyssee study, the prevalence of reverse transcript (RT) associated and major protease inhibitor-associated mutations was 6.1% (95% CI : 3.6-8.6). Six patients had viruses resistant to at least 1 antiretroviral drug and 3 patients had viruses resistant to 2 classes of antiretroviral drugs. Twenty-four percent of acutely infected patients harbored non-B subtype strains (19% in 1999-2000) and 33.2% of chronically infected patients (10% in 1998 ; P < 0.0001).
Conclusion : In France, the frequency of HIV-1 resistance in untreated patients was not significantly higher in
2001-2002 than in previous surveys while the prevalence of non-B subtypes is increasing.
Genotypic Drug Resistance In the Primo study, the RT gene was not amplified in 2 cases and the protease gene
was not amplified in another 2 cases. According to the IAS list, 14% (42/299) of the patients had viruses with resistance mutations. The prevalences of mutations associated with resistance to nucleoside reverse transcriptase inhibitors (NRTIs), nonnucleoside reverse transcriptase inhibitors (NNRTIs), and protease inhibitors (PIs) were 10.3% (31/301), 3.3% (10/301), and 4.3% (13/301), respectively. The classic amino acid substitution at codon 215 (T215Y) was present in 9 patients. Atypical mutated profiles at this position (T215C/D/E/H) were identified in 12 patients.
According to the French ANRS resistance algorithm, 12% of patients (36/299) had viruses with mutations associated with resistance to at least 1 antiretroviral drug. Thirty patients had viruses with mutations conferring resistance to at least 1 antiretroviral drug belonging to a single pharmacologic class (NRTI in 18 cases, NNRTI in 5 cases, and PI in 7 cases). Six patients harbored viruses resistant to 2 or 3 classes of antiretroviral drugs. Eight percent (24/301) had viruses resistant to NRTIs, 2.6% (8/301) to NNRTIs, and 4.3% (14/301) to PIs. Median plasma viral load was lower in patients with viruses with at least 1 resistance mutation than in patients with viruses without mutations (4.86 vs. 5.39 log copies/mL, P = 0.035), and CD4 cell counts were significantly higher (676 vs. 489 cells/mm3, P = 0.048).
In the Odyssee study, according to the IAS expert panel list of mutations, the global weighted prevalence of RT- and major PI-associated mutations was 6.1% (95% CI : 3.6-8.6). The weighted prevalence of NRTI and NNRTI resistance-associated mutations was 4.3% (95% CI : 2.2-6.4) and 0.8% (95% CI : 0.0-1.8), respectively. The duration of known seropositivity had no significant impact on the prevalence rate. The prevalence of major PI resistance-associated mutations was 1% (95% CI : 0.0-2.0), again with no significant influence of the duration of known seropositivity. Patients harboring mutations (unweighted results) are described in Table 3. The classic amino acid substitution at codon 215 (T215Y) was present in 1 patient. Atypical mutation profiles at this position (T215C/D/H/N) were observed in 4 patients. The weighted prevalence of these atypical substitutions at codon 215 was 1% (95% CI : 0-2). According to the French ANRS resistance algorithm, 6 patients (1.7%) had viruses resistant to at least 1 antiretroviral drug. Four patients (1.1%) had viruses resistant to NRTIs, 1 was resistant to NNRTIs (0.4%), and 4 to PIs (1.1%). Three patients had viruses resistant to 2 classes of antiretroviral drugs. No difference in median plasma viral load or the CD4 cell count was observed between patients with and patients without mutant More Author Discussion The definition of resistance varies among studies, and algorithms of interpretation evolve
over time. We used 2 definitions of resistance, ie, the IAS-USA list of mutations (used in many published studies) and the ANRS resistance algorithm (used routinely in France). The IAS list is not a resistance algorithm (although some use it as such), but simply a list of mutations associated with some degree of resistance. In the Primo study the prevalence of resistance was similar whether the IAS list or the ANRS algorithm was used. In contrast, the 2 definitions gave different results in the Odyssee study. This might be explained by the fact that isolated thymidine analogue resistance-associated mutations observed in the Odyssee study (eg, at positions 41, 70, 210, and 219 of the RT gene) do not alone confer antiretroviral resistance.
Patients with recent infection were more likely to harbor resistant HIV variants than were treatment-naive patients with chronic infection. This might be explained by a lower risk of initial infection by a resistant virus in past years. It is also noteworthy that the proportion of patients infected in sub-Saharan African countries with no access to La proportion de personnes infectées avec des souches résistantes n'a pas augmenté ces dernières années.
antiretroviral drugs was higher in the chronic infection cohort than in the primary infection cohort. Finally, when an individual is infected by a quasispecies containing both wild-type and mutant viruses, the wild-type strain may become predominant in the absence of drug pressure.34-36 However, recent evidence suggests that resistant strains may persist in an individual for long periods even without selective drug pressure.37-39 In any case, one might expect that the initial resistant quasispecies would still be present as archived provirus in resting cells of the We observed a higher proportion of atypical than classic substitutions at codon 215 of the RT gene. Viruses containing partial revertants at codon 215 are selected because they are fitter than their resistant counterparts.35,40,41 Subsequent treatment with thymidine analogues has been linked to the development of In primary infection, we found that the proportion of patients infected by non-B subtypes tended to increase from 1998 to 2002, probably owing to increasing exposure of the European population to such strains. Indeed, 17% of patients of European origin with primary infection harbored a non-B strain in the present survey (2002), while we observed a figure of 14% in 1999-2000, and Couturier et al23 reported a rate of 6% in 1996-1998 among chronically infected patients (17 vs. 6%, P < 0.05). A similar increase was also observed among homosexuals and bisexuals. In the Odyssee study, the prevalence of non-B subtypes increased from 10% in 1998 to 33% in 2001.14 This latter change in subtype distribution was mainly due to a higher proportion of patients originating from sub-Saharan countries (particularly women and patients whose disease was diagnosed at a late stage of infection), as also noted in the French Hospital Database on HIV.33 Initial data generated by mandatory reporting of new diagnoses of HIV infection in France, initiated in 2003, show that 19% of newly diagnosed infections involved non-B subtypes in French patients and 82% in patients from sub-Saharan Africa.42 Our is the first report of resistance among non-B subtypes infecting untreated patients in France. These results confirm the spread of non-B subtypes in France but do not address a potential difference in transmission rates between B and non-B strains.
In conclusion, the frequency of genotypic HIV-1 resistance in untreated patients in France was not higher in 2001-2002 than in previous years. The prevalence of non-B subtypes is on the increase.
RESULTS Characteristics of the Population The baseline characteristics of the 303 patients included in the Primo
study and the 363 patients included in the Odyssee study are shown in Table 1. About half the patients included in the 2 studies lived in the Paris area and the others were distributed in different regions of France including the French Phylogenetic Analyses In the Primo study, 24% of patients (73/303) harbored non-B subtype viruses, with a
predominance of CRF02 strains (11%) (Fig. 1). Four of the 36 resistant viruses were non-B subtypes (1D, 1A, 1 CRF02, 1 CRF11). Table 4 cross-tabulates the subtype distribution by sex, disease stage, race, and transmission group. Among patients infected through homosexual or bisexual contact, 11% were infected by a non-B strain.
Finally, 37 (17%) of the 218 European patients were infected by a non-B subtype. Seven of these 37 patients (19%) reported intercourse with a partner originating from sub-Saharan Africa, and 2 (5%) with a partner originating from Asia. The frequency of viral resistance was lower in patients infected by non-B subtypes (5.5%) than in patients infected by subtype B (13.9%) (P = 0.0524).
In the Odyssee study, 33% of the patients were infected by non-B subtype strains (CRF02 in 19.6%). Non-B subtypes infected 53.9% of women and 23.0% of men (P < 0.001). Patients at Centers for Disease Control stage C were more frequently infected by non-B subtypes (45.9 vs. 35.7% at stage B and 29.7% at stage A ; P = 0.033).
Patients with a duration of known seropositivity of <6 months were more frequently infected by non-B subtypes (43.2 vs. 23.2%, P < 0.001). The frequency of viral resistance tended to be lower in patients infected by non-B subtypes (3.4%) than in patients infected by subtype B (7.1%) (P = 0.117). On the basis of historical data, the proportion of La proportion de personnes infectées avec des souches résistantes n'a pas augmenté ces dernières années.
patients infected by non-B subtypes increased from 1998 to 2002.
PATIENTS AND METHODS Study Population
In the Primo study, 303 patients with acute HIV infection (<6 months since infection) were recruited in 2001-2002 as part of a national survey conducted by the French Network on HIV-1 Primary Infection (Primo Cohort study 135 patients, ANRS AC-11 Resistance Group Laboratories 134 patients, INTERPRIM study 32 patients, and Primstop study 2 patients). The inclusion criteria were a negative or indeterminate HIV enzyme-linked immunosorbent assay associated with positive antigenemia or plasma HIV RNA ; a Western blot profile compatible with ongoing seroconversion ; or an initially negative test for HIV antibodies followed, within 6 months, by positive HIV serologic results. Patients were recruited throughout France to make the survey as thorough and as representative as possible. In the Odyssee study, 363 treatment-naive chronically infected patients (20 consecutive patients in each laboratory with complete Western blot profiles) managed in 23 specialized AIDS centers throughout metropolitan France were enrolled from January 2001 to April 2002. All patients gave their written informed consent to the study.
Weighted analysis was used (see below) to derive representative estimates.
Genotypic Resistance Analyses Genotypic resistance studies were performed on plasma viral RNA by using the
consensus technique of the ANRS Resistance study group,28 the TruGene HIV-1 genotyping kit (Bayer Healthcare, Eragny, France), or the ViroSeq sequencing-based HIV-1 genotyping kit (Abbott, Rungis, France). Protease and RT mutations were identified from the consensus statement of the International AIDS Society Resistance Testing-USA Nationale de Recherches sur le SIDA (ANRS) resistance algorithm ( ). All 24 laboratories involved in these studies have participated in national quality control studies.
Phylogenetic Analyses Phylogenetic analyses were performed by estimating the relationships among pol
sequences and reference sequences of HIV-1 genetic subtypes and circulating recombinant forms obtained from the Los Alamos Database ( ). Nucleotide sequences were aligned with the CLUSTAL W program version 1.7.29 Phylogenetic reconstruction was performed using a Kimura 2-parameter model and the neighbor-joining method with 500 bootstrapped data sets.
Statistical Analyses The ?2 test or the Fisher exact test was used, as appropriate, to compare categorical variables,
and the Mann-Whitney U test was used to compare continuous variables. The 95% CIs were computed using a binomial distribution. Links between primary mutations and sex, age, risk factors, clinical stage, duration of known seropositivity, CD4 count, and viral load were tested, together with links between the HIV-1 subtype and the other factors. In the Odyssee study, weighted analyses were used to derive representative estimates of the percentage of patients with resistance mutations.30 The weight of each center was attributed on the basis of the number of patients treated in each center, as stated in the French Hospital Database on HIV infection.31 Statistical analyses were performed using SSPS software (SPSS, Inc., Chicago, IL).
Descamps, Diane MD, PhD* ; Chaix, Marie-Laure MD, PhD ; André, Patrice MD, PhD ; Brodard, Véronique PharmD§ ; Cottalorda, Jacqueline MD ; Deveau, Christiane MD ; Harzic, Martine MD# ; Ingrand, Didier MD** ; Izopet, Jacques MD, PhD ; Kohli, Evelyne MD ; Masquelier, Bernard PharmD, PhD§§ ; Mouajjah, Said MD ; Palmer, Pierre MD ; Pellegrin, Isabelle MD, PhD§§ ; Plantier, Jean-Christophe PharmD, PhD## ; Poggi, Cécile MD*** ; Rogez, Sylvie PharmD, PhD ; Ruffault, Annick PharmD ; Schneider, Véronique MD§§§ ; Signori-Schmück, Anne PharmD, PhD ; Tamalet, Catherine MD, PhD ; Wirden, Marc MD### ; Rouzioux, Christine MD, PhD ; Brun-Vezinet, Françoise MD, PhD* ; Meyer, Laurence MD, PhD ; Costagliola, Dominique PhD From the *Laboratoire de Virologie, CHU Bichat-Claude Bernard, Paris, France ; Laboratoire de Virologie, CHU Necker-Enfants Malades, Paris, France ; Laboratoire de Virologie, CHU Lyon, France ; §Laboratoire de Virologie, La proportion de personnes infectées avec des souches résistantes n'a pas augmenté ces dernières années.
CHU Reims, France ; Laboratoire de Virologie, CHU Nice, France ; INSERM U569, Service d'Epidémiologie, Le Kremlin-Bicêtre, France ; Laboratoire de Virologie, Hôpital de Versailles, Le Chesnay, France ; Laboratoire de Virologie, Hôpital Antoine Beclère, Clamart, France ; Laboratoire de Virologie, CHU Toulouse, France ; Laboratoire de Virologie, CHU Dijon, France ; Laboratoire de Virologie, CHU Bordeaux, France ; INSERM EMI0214, CHU Pitié Salpètrière, Paris, France ; Laboratoire de Virologie, CHU Saint-Louis, Paris, France ; Laboratoire de Virologie, CHU Rouen, France ; Laboratoire de Virologie, Hôpital de Toulon, Toulon, France ; Laboratoire de Virologie, CHU Dupuytren, Limoges, France ; Laboratoire de Virologie, CHU Pontchaillou, Rennes, France ; §§§Laboratoire de Virologie, CHU Tenon, Paris, France ; Laboratoire de Virologie, CHU Michalon, Grenoble, France ; Laboratoire de Virologie, CHU La Timone, Marseille, France ; and Laboratoire de Virologie, CHU Pitié-Salpètrière, Paris, France.
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Revised Syllabus for M. Sc. (Part – II) Semester III CH-361 : - Chemistry of Heterocycles and Biologically active Compounds- CH-362 :- Advance Analytical methods. CH-363: - Drug Development (Immunology and Microbiology) CH-364:- Stereo chemical Principles and applications. SemesterIV CH-461 - Synthetic Methods in Organic Chemistry. CH-462:- Chemotherapy. CH-463 : - Drug Design Pr