Therapeutic drug monitoring and virological response at week 48 in a cohort of HIV-1-infected patients switching to dolutegravir/rilpivirine dual maintenance therapy (ANRS-MIE-BIRIDER study).

Aims: Dolutegravir (DTG) and rilpivirine (RPV) dual therapy is now recommended as a switch option in virologically suppressed HIV patients. Literature suggests that virological failure with dual therapy could possibly relate to subtherapeutic drug concentrations. In this study, we aimed at describing the DTG and RPV trough plasma concentrations (Cmin) and plasma HIV-1 RNA viral load (VL) during maintenance dual therapy.

Implementation and Comparison of Two Pharmacometric Tools for Model-Based Therapeutic Drug Monitoring and Precision Dosing of Daptomycin.

Daptomycin is a candidate for therapeutic drug monitoring (TDM). The objectives of this work were to implement and compare two pharmacometric tools for daptomycin TDM and precision dosing. A nonparametric population PK model developed from patients with bone and joint infection was implemented into the BestDose software.

Association between voriconazole exposure and Sequential Organ Failure Assessment (SOFA) score in critically ill patients.

Therapeutic drug monitoring (TDM) is essential for voriconazole to ensure optimal drug exposure, mainly in critically ill patients for whom voriconazole demonstrated a large variability. The study aimed at describing factors associated with trough voriconazole concentrations in critically ill patients and evaluating the impact of voriconazole concentrations on adverse effects. A 2-year retrospective multicenter cohort study (NCT04502771) was conducted in six intensive care units.

Pharmacokinetic/Pharmacodynamic Dosage Individualization of Suppressive Beta-Lactam Therapy Administered by Subcutaneous Route in Patients With Prosthetic Joint Infection.

Suppressive parenteral antibiotic therapy with beta-lactams may be necessary in patients with Gram-negative bone and joint infection (BJI). Subcutaneous drug administration can facilitate this therapy in outpatient setting, but there is limited information about this practice. We have developed an original approach for drug dosing in this context, based on therapeutic drug monitoring (TDM) and pharmacokinetic/pharmacodynamic (PK/PD) principles.

Concerns about pharmacokinetic (PK) and pharmacokinetic-pharmacodynamic (PK-PD) studies in the new therapeutic area of COVID-19 infection.

In the context of the COVID-19 pandemic, several drugs have been repurposed as potential candidates for the treatment of COVID-19 infection. While preliminary choices were essentially based on in vitro potency, clinical translation into effective therapies may be challenging due to unfavorable in vivo pharmacokinetic properties at the doses chosen for this new indication of COVID-19 infection. However, available pharmacokinetic and pharmacokinetic-pharmacodynamic studies suffer from severe limitations leading to unreliable conclusions, especially in term of dosing optimization.

Dolutegravir Population Pharmacokinetics in a Real-Life Cohort of People Living With HIV Infection: A Covariate Analysis.

Background: There are growing concerns about dolutegravir (DTG)-related neuropsychiatric adverse events and about differences in the characteristics of people living with HIV infection (PLWH) potentially associated with higher risks of said side effects. Several studies have shown that DTG was stopped more frequently among women, older PLWH, and PLWH who initiated abacavir (ABC) at the same time. This study aimed to clarify the factors affecting the pharmacokinetics (PKs) of DTG in a real-life cohort of PLWH using a population PK approach.

The Roche Total Mycophenolic Acid® assay: An application protocol for the ABX Pentra 400 analyzer and comparison with LC-MS in children with idiopathic nephrotic syndrome.

Background: For TDM of mycophenolate acid (MPA), the Roche Total Mycophenolic Acid® assay based on the inhibition of recombinant inosine monophosphate dehydrogenase (IMPDH) has been shown to be a simple and reliable alternative to chromatographic methods. We have adapted this assay on the ABX Pentra 400 analyzer (HORIBA).

Objective: To investigate the analytical performances of the Roche Total Mycophenolic Acid® assay on the ABX Pentra 400 and to compare it to an LC-MS method using samples from children with nephrotic syndrome treated with mycophenolate mofetil (MMF).

EVESOR, a model-based, multiparameter, Phase I trial to optimize the benefit/toxicity ratio of everolimus and sorafenib.

Aim: This novel multiparameter Phase I study aimed to optimize doses/dosing schedules of everolimus and sorafenib drug combination, based on modeling/simulation (NCT01932177).

Patients & Methods: About 26 patients with solid tumors were treated in four different dosing schedules. Everolimus once daily + sorafenib twice daily were given continuously in arms A and B, and intermittently in arms C (alternating every other week) and D (everolimus continuous and sorafenib 3 days on/4 days off).

Sofosbuvir-based antiviral therapy in hepatitis C virus patients with severe renal failure.

Background: Chronic hepatitis C virus (HCV) infection is the most common chronic liver disease in patients with end-stage renal disease (ESRD). Over the last few years, second-generation direct-acting antivirals have been revolutionary in the treatment of hepatitis C, and sofosbuvir (SOF) is the backbone of most modern treatment strategies. Since SOF is eliminated through the kidney, the aim of this multicentre retrospective study was to assess its antiviral efficacy and safety in HCV-infected patients with severe renal failure [including haemodialysis (HD) patients].

Sofosbuvir plus daclatasvir with or without ribavirin for chronic hepatitis C infection: Impact of drug concentration on viral load decay.

Background: Sofosbuvir (SOF) plus daclatasvir (DCV) with or without ribavirin is one of the currently recommended treatment option for chronic hepatitis C.

Aims: Our objectives were to identify factors associated with SOF/DCV plasma concentrations [C] variations and to evaluate their impact on viral kinetics.

Methods: 130 consecutive HCV patients initiating SOF/DCV therapy with or without ribavirin were enrolled.

Efficiency and Safety of an Early Dose Adjustment of Ribavirin in Patients Infected With Hepatitis C Underexposed to the Drug and Treated With Peginterferon Ribavirin.

Background: Ribavirin exposure after the first dose (D0AUC0-4h) >1755 mcg·h·L is predictive of sustained virological response (SVR) in patients with hepatitis C treated with peginterferon and ribavirin. The aim of this study was to test the benefit of ribavirin early dose adjustment based on this target in naïve patients infected with genotype 1.

Methods: A multicenter randomized controlled trial with two parallel groups; fixed-dose (FD) group: standard of care in 2010-2011, ie, peginterferon-α2a 180 mcg·wk and weight-based ribavirin 1000-1200 mg/d during 48 weeks; adapted-dose (AD) group: increase of ribavirin dose if D0AUC0-4h <1755 mcg·h·L.

Maraviroc/raltegravir simplification strategy following 6 months of quadruple therapy with tenofovir/emtricitabine/maraviroc/raltegravir in treatment-naive HIV patients.

Objective: We assessed the virological efficacy of a 6 month maraviroc/raltegravir simplification strategy following 6 months of quadruple therapy combining tenofovir disoproxil fumarate/emtricitabine with maraviroc/raltegravir.

Methods: HIV-1-infected naive patients were enrolled in an open label, single-arm, Phase 2 trial. All patients received maraviroc 300 mg twice daily, raltegravir 400 mg twice daily and tenofovir/emtricitabine for 24 weeks.

Pharmacokinetic Variability of Daptomycin during Prolonged Therapy for Bone and Joint Infections.

The interindividual and intraindividual variabilities in daptomycin pharmacokinetics were investigated in 23 patients (69 pharmacokinetic profiles) who were treated for several months for bone and joint infections. Population daptomycin clearance was significantly influenced by renal function and was significantly higher in male than in female patients. We observed significant intraindividual changes in daptomycin clearance, which were uncorrelated with changes in renal function, suggesting that therapeutic drug monitoring is important in patients receiving prolonged daptomycin therapy.

Daptomycin > 6 mg/kg/day as salvage therapy in patients with complex bone and joint infection: cohort study in a regional reference center.

Background: Even if daptomycin does not have approval for the treatment of bone and joint infections (BJI), the Infectious Diseases Society of America guidelines propose this antibiotic as alternative therapy for prosthetic joint infection. The recommended dose is 6 mg/kg/d, whereas recent data support the use of higher doses in these patients.

Methods: We performed a cohort study including consecutive patients that have received daptomycin >6 mg/kg/d for complex BJI between 2011 and 2013 in a French regional reference center.

Nilotinib and peginterferon alfa-2a for newly diagnosed chronic-phase chronic myeloid leukaemia (NiloPeg): a multicentre, non-randomised, open-label phase 2 study.

Background: Nilotinib is now recommended for patients with newly diagnosed chronic myeloid leukaemia in chronic phase and leads to important rates of molecular response 4·5 log (MR(4·5)), allowing the prospect of therapy cessation. However, most patients do not reach this criterion and nilotinib is taken for lengthy periods, resulting in chronic or late-onset adverse events. Nilotinib combined with interferon might further increase rates of MR(4·5), avoid late side-effects, and allow therapy cessation.

Persistent But Not Replicating HIV-1 Cell-Associated DNA in Semen of Long-Term ART Experienced Men.

Background: The semen of HIV-1 infected men represents the main vector of HIV-1 spread following sexual transmission of cell-free or cell-associated virions.

Objective: The present study aimed to assess the impact of HAART on HIV-1 RNA/DNA and on inflammatory environment in the semen of long-term HAART-experienced men.

Methods: Forty-five paired samples of semen and blood were obtained from 37 consenting men, 10 untreated and 27 under HAART.

UGT1A1 genotype and irinotecan therapy: general review and implementation in routine practice.

Irinotecan is a major drug in the treatment of advanced colorectal cancer. Its active form is the SN38 metabolite, which is cleared by the biliary route after glucuronidation by uridine diphosphate-glucuronosyltransferase 1A1 (UGT1A1). UGT1A1 activity exhibits a wide intersubject variability, in part related to UGT1A1 gene polymorphisms.