Prevalence of HIV-1 drug resistance in treated patients with viral load >50 copies/mL in 2009: a French nationwide study

Background Surveillance of HIV-1 drug resistance in treated patients with plasma viral load (VL) >50 copies/mL. Methods The protease and reverse transcriptase (RT) genes were systematically sequenced in samples from 756 patients with VL >50 copies/mL in 2009. The genotyping results were interpreted for each antiretroviral drug (ARV) by using the ANRS algorithm v21. Weighted analyses were used to derive representative estimates of percentages of patients. Prevalence rates were compared with those obtained in 2004 among patients with VL >1000 copies/mL. Results Sequences were obtained for 506 patients. Sequencing was successful in 45%, 80% and 96% of samples with VL of 51-500, 501-1000 and >1000 copies/mL, respectively. Resistance or possible resistance to at least one ARV was observed in 59% of samples. Overall, 0.9% of samples contained viruses resistant to all drugs belonging to at least three drug classes. All resistance prevalence rates were significantly lower in 2009 than in 2004. Conclusion In France, where 86% of patients were receiving combination antiretroviral therapy in 2009, only 15.0% of patients had a VL >50 copies/mL, suggesting that only 8.9% of treated patients could potentially transmit resistant viruses. Only 0.08% of patients harboured viruses fully resistant to at least three antiretroviral drug classes. Further studies are needed to determine whether resistance continues to decline over tim

HIV-1-infected patients from the French National Observatory experiencing virological failure while receiving enfuvirtide

Objectives We studied gp41 mutations associated with failing enfuvirtide salvage therapy. Methods This multicentre study involved patients with HIV-1 plasma viral load (pVL) > 5000 copies/mL after at least 3 months of uninterrupted enfuvirtide therapy and with plasma samples available at inclusion (T0), at initial enfuvirtide failure (T1) and at last follow-up visit during continued failing enfuvirtide therapy (T2). The HR-1 and HR-2 domains of the gp41 gene were sequenced at T0, T1 and T2. Results Ninety-nine patients were enrolled. At baseline, the median pVL and CD4 cell count were 5.1 log copies/mL and 72 cells/mm3, respectively. Based on the ANRS Resistance Group algorithm, the proportion of patients harbouring viruses with enfuvirtide resistance mutations increased significantly between T0 and T1. In the HR-1 domain, the V38A/M, Q40H, N42T, N43D and L45M mutations wereselected (P < 0.02). In the HR-2 domain, no mutations were significantly selected during the follow-up. None of the mutations was associated with a CD4 cell count increment. Conclusions Mutations selected during failing enfuvirtide salvage therapy are mainly located in the HR-1 domain of the gp41 gene, between codons 38 and 45. No mutations were associated with an increase in the CD4 cell coun

Persisting Mixed Cryoglobulinemia in Chikungunya Infection

Chikungunya virus is present in tropical Africa and Asia and is transmitted by mosquito bites. The disease is characterized by fever, headache, severe joint pain and transient skin rash for about a week. Most patients experience persisting joint pain and/or stiffness for months to years. In routine practice, diagnosis is based upon serology. Since 2004 there has been an ongoing giant outbreak of Chikungunya fever in East Africa, the Indian Ocean Islands, India and East Asia. In parallel, more than 1,000 travelers were diagnosed with imported Chikungunya infection in most developed countries. Considering the clinical features of our patients (joint pain), we hypothesized that cryoglobulins could be involved in the pathophysiology of the disease as observed in chronic hepatitis C infection. Cryoglobulins, which are immunoglobulins that precipitate when temperature is below 37°C, can induce rheumatic and vascular disorders. From April 2005 through May 2007, we screened all patients with possible imported Chikungunya infection for cryoglobulins. They were present in over 90% of patients, and possibly responsible for the unexpected false negativity of serological assays. Cryoglobulin frequency and levels decreased with time in recovering patients

Characterization of the Molecular Determinants of Primary HIV-1 Vpr Proteins: Impact of the Q65R and R77Q Substitutions on Vpr Functions

Although HIV-1 Vpr displays several functions in vitro, limited information exists concerning their relevance during infection. Here, we characterized Vpr variants isolated from a rapid and a long-term non-progressor (LTNP). Interestingly, vpr alleles isolated from longitudinal samples of the LTNP revealed a dominant sequence that subsequently led to diversity similar to that observed in the progressor patient. Most of primary Vpr proteins accumulated at the nuclear envelope and interacted with host-cell partners of Vpr. They displayed cytostatic and proapoptotic activities, although a LTNP allele, harboring the Q65R substitution, failed to bind the DCAF1 subunit of the Cul4a/DDB1 E3 ligase and was inactive. This Q65R substitution correlated with impairment of Vpr docking at the nuclear envelope, raising the possibility of a functional link between this property and the Vpr cytostatic activity. In contradiction with published results, the R77Q substitution, found in LTNP alleles, did not influence Vpr proapoptotic activity

Autoantibodies against type I IFNs in patients with critical influenza pneumonia

In an international cohort of 279 patients with hypoxemic influenza pneumonia, we identified 13 patients (4.6%) with autoantibodies neutralizing IFN-alpha and/or -omega, which were previously reported to underlie 15% cases of life-threatening COVID-19 pneumonia and one third of severe adverse reactions to live-attenuated yellow fever vaccine. Autoantibodies neutralizing type I interferons (IFNs) can underlie critical COVID-19 pneumonia and yellow fever vaccine disease. We report here on 13 patients harboring autoantibodies neutralizing IFN-alpha 2 alone (five patients) or with IFN-omega (eight patients) from a cohort of 279 patients (4.7%) aged 6-73 yr with critical influenza pneumonia. Nine and four patients had antibodies neutralizing high and low concentrations, respectively, of IFN-alpha 2, and six and two patients had antibodies neutralizing high and low concentrations, respectively, of IFN-omega. The patients' autoantibodies increased influenza A virus replication in both A549 cells and reconstituted human airway epithelia. The prevalence of these antibodies was significantly higher than that in the general population for patients 70 yr of age (3.1 vs. 4.4%, P = 0.68). The risk of critical influenza was highest in patients with antibodies neutralizing high concentrations of both IFN-alpha 2 and IFN-omega (OR = 11.7, P = 1.3 x 10(-5)), especially those <70 yr old (OR = 139.9, P = 3.1 x 10(-10)). We also identified 10 patients in additional influenza patient cohorts. Autoantibodies neutralizing type I IFNs account for similar to 5% of cases of life-threatening influenza pneumonia in patients <70 yr old

Les gelures du militaire en fonction du phototype

AIX-MARSEILLE2-BU Méd/Odontol. (130552103) / SudocPARIS-Bib. Serv.Santé Armées (751055204) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Chirurgie cardiaque de l'octogénaire (suivi à 3 ans)

LYON1-BU Santé (693882101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Le mélanome cutané (Taux d'incidence de 2005 à 2007 dans les armées et évaluation des pratiques médicales de dépistage en médecine d'unité)

AIX-MARSEILLE2-BU Méd/Odontol. (130552103) / SudocPARIS-Bib. Serv.Santé Armées (751055204) / SudocSudocFranceF

Activité médicale en poste isolé dans les terres australes et antartiques françaises

AIX-MARSEILLE2-BU Méd/Odontol. (130552103) / SudocPARIS-Bib. Serv.Santé Armées (751055204) / SudocSudocFranceF