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Descamps D.,University Paris Diderot | Descamps D.,French Institute of Health and Medical Research | Descamps D.,Laboratoire Of Virologie | Peytavin G.,University Paris Diderot | And 20 more authors.
Clinical Infectious Diseases | Year: 2015

Background. Dolutegravir has shown in vitro activity against human immunodeficiency virus type 2 (HIV-2). We report safety and efficacy data of regimens containing dolutegravir (50 mg twice daily) in antiretroviral-experienced, HIV-2-infected patients. Methods. HIV-2-infected patients experiencing virological failure to raltegravir received dolutegravir with optimized background antiretroviral combinations within the French Named Patient Program (NPP). Plasma HIV-2 RNA (pVL) was assessed at time of dolutegravir initiation (baseline), month 3, and month 6. Antiretroviral trough plasma concentrations (C12h) were determined using liquid chromatography coupled with tandem mass spectrometry. Results. Thirteen HIV-2-infected-patients, with a median duration of 15 years' infection and given 16 previous antiretroviral regimens, were included in NPP. Median follow-up was 9 months (min-max, 3-15 months). Median baseline pVL and CD4 cell count were 9544 copies/mL (inter quartile range [IQR], 3096-23 120 copies/mL) and 100 cells/μL (IQR, 77-171 cells/μL), respectively. Available integrase genotypic resistance patterns were Y143C/G/H/R (n = 5), Q148R/K (n = 2), and N155H (n = 4). Optimized background antiretroviral regimens conferring a genotypic sensitivity score ≤2 in 10 patients included nucleoside reverse transcriptase inhibitors associated with darunavir/ritonavir (n = 12), saquinavir/ritonavir (n = 2), and maraviroc (n = 3). At months 3 and 6, pVL was undetectable in 6 of 13 and 4 of 12 patients, respectively, and median CD4 count was 161 (101-188) cells/μL and 167 (135-1353) cells/μL, respectively. Median dolutegravir C12h was 4086 (1756-5717 ng/mL) ng/mL in 9 patients. No serious events were notified except 1 death from progressive multifocal leukoencephalopathy at month 4. Conclusions. Optimized dolutegravir-containing antiretroviral regimens supported by good plasma exposure provide a substantial initial efficacy rate for salvage therapy in heavily antiretroviral-experienced HIV-2-infected patients with virus harboring resistance to first-generation integrase inhibitors. Larger numbers of patients and longer follow-up are needed to confirm these findings. © 2015 The Author.

Achour S.,Laboratoire Central dAnalyses Medicales | Achour S.,Universite Ibn Tofail | Rhalem N.,Center Antipoison Et Of Pharmacovigilance Du Maroc | Rhalem N.,Universite Ibn Tofail | And 6 more authors.
Therapie | Year: 2012

Peganum harmala L. is commonly used in traditional medicine in Morocco for its sedative and emmenagogue properties but expose to the risk of overdose and poisoning. The aim of our study was to analyze a series of 200 cases of poisoning collected in poison control and pharmacovigilance center of Morocco in order to describe the epidemiological, clinical, therapeutic features and outcome of patients and indicate the toxicity of this plant used primarily for therapeutic purposes. Methods. This retrospective study performed over a period of twenty four years from January 1984 to December 2008. Results. The mean age of patients was 24.4±16.8 years with a female predominance (167 women against 33 men). Therapeutic circumstance was found in 32.5%, followed by suicide (28.5%) and abortion (13.5%). The symptomatology was dominated by neurological, gastrointestinal and cardiovascular signs respectively 34.4%, 31.9 % and 15.8%. The evolution has been specified in 114 cases, 7 deaths have been deplored with a fatality rate of 6.2%. © 2012 Société Française de Pharmacologie et de Thérapeutique.

Cazanave C.,University of Bordeaux 1 | Cazanave C.,French National Institute for Agricultural Research | Reigadas S.,University of Bordeaux 1 | Mazubert C.,University of Bordeaux 1 | And 15 more authors.
Open Forum Infectious Diseases | Year: 2015

Background. The purpose of this study was to assess the efficacy and tolerability of combined antiretroviral therapy (cART) in human immunodeficiency virus (HIV)-1 virologically suppressed patients who switched to rilpivirine (RPV)/tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC) as a single-tablet regimen (STR). Methods. A retrospective multicenter cohort study was performed between September 2012 and February 2014 in Bordeaux University Hospital-affiliated clinics. Patients with a plasma HIV viral load (VL) lower than 50 copies/ mL and switching to STR were evaluated at baseline, 3, 6, 9, and 12 months from switch time (M3, M6, M9, M12) for VL and other biological parameters. Change from baseline in CD4 cell counts was evaluated at M6 and M12. Virological failure (VF) was defined as 2 consecutive VL >50 copies/mL. Results. Three hundred four patients were included in the analysis. Single-tablet regimen switch was proposed to 116 patients with adverse events, mostly efavirenz (EFV)-based (n = 59), and to 224 patients for cART simplification. Thirty of 196 patients with available genotype resistance test results displayed virus with ≥1 drug resistance mutation on reverse-transcriptase gene. After 12 months of follow-up, 93.4% (95.5% confidence interval, 89.9-96.2) of patients remained virologically suppressed. There was no significant change in CD4 cell count. During the study period, 5 patients experienced VF, one of them harboring RPV resistance mutation. Clinical cART tolerability improved in 79 patients overall (29.9%) at M6, especially neurological symptoms related to EFV. Fasting serum lipid profiles improved, but a significant estimated glomerular function rate decrease (-11 mL/min/1.73 m2; P < 10-4) was observed. Conclusions. Overall, virologic suppression was maintained in patients after switching to RPV/TDF/ FTC. This STR strategy was associated with improved tolerability. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Societyof America.

Desnoyer A.,Bichat Claude Bernard Hospital | Desnoyer A.,Laboratoire Of Pharmaco Toxicologie | Pospai D.,Bichat Claude Bernard Hospital | Le M.P.,Bichat Claude Bernard Hospital | And 19 more authors.
Journal of Hepatology | Year: 2016

Background & Aims Hepatitis C virus (HCV) infection is an independent risk factor for chronic kidney disease and leads to faster liver disease progression in patients requiring hemodialysis than in those with normal renal function. Little is known about the use of a sofosbuvir-containing regimen for infected patients on hemodialysis. We aimed to describe the pharmacokinetics, safety and efficacy of sofosbuvir in 2 dosing regimens and associated antiviral agents in HCV-infected patients requiring hemodialysis. Methods Multicenter, prospective and observational study of patients receiving sofosbuvir, 400 mg once daily (n = 7) or 3 times a week (n = 5), after hemodialysis with simeprevir, daclatasvir, ledipasvir or ribavirin was conducted. Drug plasma concentrations were determined by liquid chromatography-tandem mass spectrometry before and after a 4 h hemodialysis and 1.5 h after last drug intake at the end of hemodialysis. Results Plasma concentrations of sofosbuvir or its inactive metabolite sofosbuvir-007 did not accumulate with either regimen between hemodialysis sessions or throughout the treatment course. Sofosbuvir-007 extraction ratio (52%) was consistent with historical data. In one patient receiving the once daily regimen, sofosbuvir-007 half-life was slightly higher (38 h) than for patients with normal renal function receiving a full dose. Hemodialysis did not remove any other associated anti-HCV agents. Clinical and biological tolerance was good for all patients. Two relapses occurred with the 3 times a week regimen and none with the once daily. Conclusions A regimen including sofosbuvir, 400 mg once daily, could be proposed for HCV-infected patients requiring hemodialysis and should be associated with close clinical, biological, cardiovascular, and therapeutic drug monitoring. Lay summary Hepatitis C Virus (HCV) infection in hemodialysis patients is prevalent and aggressive. Effective anti-HCV treatment in these patients may stabilize their renal disease. However, sofosbuvir, the cornerstone of most anti-HCV-containing regimens, should not be administered to these patients until more data is available. In this pharmacokinetic study, sofosbuvir full dose (400 mg once daily) administered every day with another direct antiviral agent did not accumulate in hemodialysis patients and was safe and effective. © 2016 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Peytavin G.,Laboratoire Of Pharmaco Toxicologie | Peytavin G.,University Paris Diderot | Joly V.,Service de Maladies Infectieuses et Tropicales | Joly V.,University Paris Diderot | And 2 more authors.
Journal des Anti-Infectieux | Year: 2014

Once-daily single-tablet regimen (STR) represents a significant recent advance in the simplification of antiretroviral therapy, facilitating adherence to complex and chronic treatments, and improving the quality of life of HIV-infected patients. The STR reduces the risk of treatment errors, particularly in situations of selective non-compliance and therefore, limits the risk of emergence of HIV resistance mutations. Galenic researches and pharmaceutical industry collaborations may allow STR combining drugs with favorable pharmacokinetic profiles as HIV-1 non-nucleosidic reverse transcriptase inhibitors (efavirenz or rilpivirine), integrase inhibitors (cobicistat-boosted elvitegravir or dolutegravir), and protease inhibitors (cobicistat-boosted darunavir) associated with either tenofovir disoproxil fumarate/emtricitabine or abacavir/lamivudine. With the exception of renal or liver dysfunctions or drug-drug interactions requiring dose adjustments, the preferential use of STR should be recommended by guidelines in many antiretroviral-naïve or -experienced HIV-infected patients. © 2014 Elsevier Masson SAS.

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