Intracellular Efavirenz Levels in Peripheral Blood Mononuclear Cells from Human Immunodeficiency Virus-Infected Individuals▿

We describe a novel method for isolating plasma-free peripheral blood mononuclear cells retaining intracellular efavirenz. Quantification of efavirenz in 13 human immunodeficiency virus-infected patients by liquid chromatography-tandem mass spectrometry showed a higher correlation of intracellular levels with unbound plasma levels (accumulation ratio, 1,190) than with total plasma levels

Clinical efficacy of a combination of Percoll continuous density gradient and swim-up techniques for semen processing in HIV-1 serodiscordant couples

To evaluate the clinical efficacy of a procedure comprising a combination of Percoll continuous density gradient and modified swim-up techniques for the removal of human immunodeficiency virus type 1 (HIV-1) from the semen of HIV-1 infected males, a total of 129 couples with an HIV-1 positive male partner and an HIV-1 negative female partner (serodiscordant couples) who were treated at Keio University Hospital between January 2002 and April 2012 were examined. A total of 183 ejaculates from 129 HIV-1 infected males were processed. After swim-up, we successfully collected motile sperms at a recovery rate as high as 100.0% in cases of normozoospermia (126/126 ejaculates), oligozoospermia (6/6), and asthenozoospermia (36/36). The recovery rate of oligoasthenozoospermia was 86.7% (13/15). In processed semen only four ejaculates (4/181:2.2%) showed viral nucleotide sequences consistent with those in the blood of the infected males. After using these sperms, no horizontal infections of the female patients and no vertical infections of the newborns were observed. Furthermore, no obvious adverse effects were observed in the offspring. This protocol allowed us to collect HIV-1 negative motile sperms at a high rate, even in male factor cases. We concluded that our protocol is clinically effective both for decreasing HIV-1 infections and for yielding a healthy child

First report of safety and efficacy of a glycoPEGylated FVIII (N8-GP) in previously treated pediatric patients with severe hemophilia A-results from the international phase 3 pathfinder (TM) 5 trial

WOS: 00037994090017

Safety and efficacy of a glycoPEGylated rFVIII (turoctocog alpha pegol, N8-GP) in paediatric patients with severe haemophilia A

WOS: 000409564600007PubMed ID: 28692108Turoctocog alfa pegol (N8-GP, Novo Nordisk, Bagsvaerd, Denmark), an extended half-life glycoPEGylated recombinant factor VIII (rFVIII), is being developed for prophylaxis and treatment of bleeds in haemophilia A patients. pathfinder (TM) 5 is a multinational, open-label, single-arm trial to assess safety, efficacy and pharmacokinetics of N8-GP in paediatric (50 exposure days [ED] for patients aged 0-5 years [younger cohort]; >150 ED for patients aged 6-11 years [older cohort]) were included. For prophylaxis, N8-GP was dosed at 50-75 IU/kg twice weekly; bleeds were treated with 20-75 IU/kg. Half-life was estimated for the patients' previous FVIII product and for N8-G P. Sixty-eight patients received N8-GP; none developed inhibitors and no other concerns were identified. Median annualised bleeding rate was 1.95 (1.94 and 1.97 in the younger and older cohorts, respectively). Twenty-nine patients (42.6 %;15 younger and 14 older children, respectively) did not report any bleeding while on N8-GP prophylaxis; 39 patients (57.4 %; 19 younger and 20 older children, respectively) reported 70 bleeds (all mild/moderate). N8-GP treatment was successful for 78.6 % of bleeds in all patients, 80.0 % in younger and 77.5 % in older patients. Most bleeds (80.0 %) were treated with <= 2 injections. Half-life ratio between N8-GP and the patients' previous FVIII product was 1.85. N8-GP was well tolerated and provided effective prophylaxis and treatment of bleeds in paediatric patients with severe haemophilia A.Novo Nordisk A/S (Bagsvaerd, Denmark)Novo NordiskThis trial was sponsored by Novo Nordisk A/S (Bagsvaerd, Denmark). The sponsor was responsible for trial operations, including data analysis

Nonacog beta pegol (N9-GP) in haemophilia B: A multinational phase III safety and efficacy extension trial (paradigm™4)

Introduction Paradigm™4 was an international extension trial investigating the safety and efficacy of nonacog beta pegol, a recombinant glycoPEGylated factor IX (FIX) with extended half-life, in haemophilia B patients (FIX activity ≤ 2%; aged 13–70 years) who had previously participated in phase III pivotal (paradigm™2) or surgery (paradigm™3) trials. Methods Patients chose to continue treatment with nonacog beta pegol in either one of two once-weekly prophylaxis arms (10 IU/kg or 40 IU/kg), or an on-demand arm (40 IU/kg for mild/moderate bleeds; 80 IU/kg for severe bleeds). The primary objective was to evaluate immunogenicity; key secondary objectives included assessing safety and haemostatic efficacy in the treatment and prevention of bleeds. Results Seventy-one patients received prophylaxis or on-demand treatment. No patient developed an inhibitor and no safety concerns were identified. The success rate for the treatment of reported bleeds was 94.6%; most (87.9%) resolved with one injection. The median annualised bleeding rate for patients on prophylaxis was 1.36 (interquartile range [IQR] 0.00–2.23) and 1.00 (IQR 0.00–2.03) for the 10 and 40 IU/kg treatment arms, respectively. The mean FIX activity trough achieved for 10 and 40 IU once weekly was 9.8% and 21.3%, respectively. Fourteen patients on prophylaxis underwent 23 minor surgical procedures; haemostatic perioperative outcomes for all of those evaluated were ‘excellent’ or ‘good’. Conclusions Nonacog beta pegol showed a favourable tolerability profile (with no safety issues identified) with good prophylactic protection and control of bleeding in previously treated adult and adolescent haemophilia B patients