Éditeur(s) : HAL CCSD Lippincott, Williams & Wilkins
Résumé : International audience
Among 103 patients with multidrug-resistant HIV who initiated raltegravir, etravirine, and darunavir/ritonavir-containing regimen in the ANRS 139 TRIO trial, 100 participated in extended follow-up and continued study treatment until week 96. Among them, 87 (87%) received an optimized background therapy including either nucleoside reverse transcriptase inhibitors or enfuvirtide, they were 78 (78%) at week 96. At week 96, 88% achieved durable virologic response (<50 copies/mL). CD4 response was maintained (median change of +150 cells/mm(3)). No major toxicity was reported. This triple drug combination showed sustained efficacy and thus should be strongly considered for patients with multiclass-resistant virus.
ISSN: 1525-4135

hal-00875207
https://hal.archives-ouvertes.fr/hal-00875207
DOI : 10.1097/QAI.0b013e31824bb720
PUBMED : 22293546

Éditeur(s) : HAL CCSD WB Saunders
Résumé : International audience
OBJECTIVE: We hypothesized that, in Human Immunodeficiency Virus and Hepatitis C Virus (HIV/HCV) co-infected patients who did not respond to peg-interferon and ribavirin, a maintenance therapy with peg-interferon could induce fibrosis regression. METHODS: This was a randomized study with two parallel groups. HIV/HCV co-infected patients received peg-interferon α-2a at 180 μg/week or remained on observation for 96 weeks. The primary endpoint was the percentage of patients who experienced a decrease of at least one point in their Metavir fibrosis score between initial and final liver biopsies. Secondary endpoints included plasma fibrosis markers at week 96, occurrence of HCV-related complications, and survival. RESULTS: A total of 52 patients were randomized (peg-interferon: 25; control: 27) including 18 with cirrhosis. The median (interquartile range) age was 44 (40-46) years, and 69% were male. A total of 64% had ALT levels >1.5 normal values, and the CD4 cell count was 391 (296-537) cells/mm(3); 67% of patients had HIV RNA <200 copies/mL at entry. The main endpoint was assessed in 41 patients. Response rates were 3/20 (15%) and 4/21 (19%) in the peg-interferon and control groups, respectively (p = 0.99). There was no significant difference between peg-interferon and control groups on plasma fibrosis markers at the final visit. Severe liver-related complications were observed in 2 and 5 patients in peg-interferon and control groups, respectively. Three deaths were observed, all in the control group. CONCLUSIONS: A maintenance therapy with peg-interferon α-2a over 96 weeks in HIV/HCV co-infected patients, who were non-responders to HCV treatment, did not change liver fibrosis. ClinicalTrials.gov Identifier: NCT00122616.
ISSN: 0163-4453

hal-00875067
https://hal.archives-ouvertes.fr/hal-00875067
DOI : 10.1016/j.jinf.2013.05.007
PUBMED : 23800784

Éditeur(s) : HAL CCSD Oxford University Press (OUP)
Résumé : International audience
Retreatment with pegylated interferon (peg-IFN) and ribavirin (RBV) results in poor sustained virological response (SVR) rates in human immunodeficiency virus (HIV)/hepatitis C virus (HCV)-coinfected patients. There are limited data regarding the use of telaprevir plus peg-IFN/RBV in this population. HIV type 1-infected patients who previously failed ≥12 weeks of peg-IFN/RBV for HCV genotype 1 coinfection were enrolled in a single-arm, phase 2 trial. Patients with cirrhosis and previous null response were excluded. Authorized antiretrovirals were tenofovir, emtricitabine, efavirenz, atazanavir, and raltegravir. All patients received peg-IFN alfa-2a (180 µg/week) plus RBV (1000-1200 mg/day) for 4 weeks, followed by telaprevir (750 mg or 1125 mg every 8 hours with efavirenz) plus peg-IFN/RBV for 12 weeks and peg-IFN/RBV for 32-56 weeks according to virological response at week 8. The primary endpoint was the SVR rate at 24 weeks after the end of treatment (SVR24). Sixty-nine patients started treatment; SVR24 was achieved in 55 (80% [95% confidence interval, 68%-88%). SVR24 was not influenced by baseline fibrosis stage, IL28B genotype, antiretroviral regimen, HCV subtype, CD4 cell count, previous response to HCV treatment, HCV RNA level, or HCV RNA decline at week 4. HCV treatment was discontinued for adverse events (AEs) in 20% of patients, including cutaneous (4%), psychiatric (4%), hematological (6%), and other AEs (6%). Peg-IFN or RBV dose reduction was required in 23% and 43% of patients, respectively. Seventy percent of patients required erythropoietin, blood transfusions, or RBV dose reduction for anemia. Two patients died during the study. No HIV breakthrough was observed. Despite a high discontinuation rate related to toxicity, a substantial proportion of treatment-experienced HIV-coinfected patients achieved SVR24 with a telaprevir-based regimen. Clinical Trials Registration. NCT01332955.
ISSN: 1058-4838

hal-01118447
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01118447
PUBMED : 25139963
DOI : 10.1093/cid/ciu659

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
A new portable sampling system was developed to extract Radium isotopes from large volumes (up to 300 L) of fresh surface- and ground-waters of low Ra-activities (<5 mBq/L). Ra is quantitatively adsorbed on a small amount (6.5 g) of MnO2-coated acrylic fibers, which are then dried and burned at 600 °C in the laboratory. The resulting Mn-oxide powder (about 2 cm3 when compacted) is then analyzed through gamma-ray spectrometry which allows measurement of the whole Ra quartet (226Ra, 228Ra, 224Ra and 223Ra) in a single counting of a few days. The usual relative standard combined uncertainties (1σ) are 2–3% for 226Ra, 228Ra and 224Ra; and less than 10% for 223Ra. This method was applied to the analysis of Ra in karstic waters of the Lez aquifer, and surface- and ground-waters of the upper and middle Vidourle watershed (South of France). The analyzed waters have relatively low 226Ra activities (1–4 mBq/L) in both cases, regardless of the contrasted geology (Mesozoic limestone vs crystalline Variscan basement), but clearly distinct (228Ra/226Ra) ratios in agreement with the differences in Th/U ratios of the two drained areas. Short-lived Ra isotopes (224Ra and 223Ra) appear to be mainly influenced by near-surface desorption/recoil processes for most of the sampling sites.
ISSN: 0969-8043

hal-01491281
https://hal.archives-ouvertes.fr/hal-01491281
DOI : 10.1016/j.apradiso.2016.12.010

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
We present in this study the first data on Ra isotopes, 222Rn, and 210Pb in waters from the Lez karst system, one of the main ground-water resources in the South of France. The low Ra isotope activities of the Lez system waters (from 0.35 to 3.45 mBq/L of 226Ra) were measured by gamma spectrometry using the method developed in our previous work. Our data reveal the coherent behavior of 226Ra in Lez spring waters, well correlated to other major and trace elements, like Cl, Na, K, Mg, Li, Rb and Ba. The (228Ra/226Ra) ratios are distinct between the Lez spring (0.60 to 0.72) and two neighboring springs (0.52 to 0.65), showing the spatial variability in karst systems. In spite of their small variations in the Lez spring, it was possible to trace different water components and mixing processes from Lower-Cretaceous, Upper-Jurassic and Middle Jurassic end-members, in agreement with previous studies based on major and trace elements. Data obtained on waters derived from the Upper-Jurassic karst reveal that their (228Ra/226Ra) ratios are not related to the Th/U ratio of the Jurassic limestone, but are rather influenced by the soil and alterite cover of the recharge area.222Rn activities in the Lez spring are relatively low (0.5 to 3.7 Bq/L) compared to other karst regions. The highest 222Rn activities are found in diluted waters following heavy rainfall episodes, suggesting a subsurface origin of Rn. Soil and alterite samples that have much higher 226Ra activities (from 51 to 130 Bq/kg), compared to those from the main aquifer rocks (from 2.9 to 16 Bq/kg), are probably the main source of Rn, rather than the rocks of the karst itself. The study of several flood episodes reveals the correlation between Rn peak-values or total activity discharged at the spring with cumulative rainfall. Finally, 222Rn dissolved in water decays to 210Pb, and our data show that constraints on transfer times of underground waters can potentially be obtained from their coupled measurement.
ISSN: 0009-2541

hal-01622749
https://hal.archives-ouvertes.fr/hal-01622749
DOI : 10.1016/j.chemgeo.2017.06.022