Placental transfer of Letermovir & Maribavir in the ex vivo human cotyledon perfusion model. New perspectives for in utero treatment of congenital cytomegalovirus infection

International audienceBackground: Congenital cytomegalovirus infection can lead to severe sequelae. When fetal infection is confirmed, we hypothesize that fetal treatment could improve the outcome. Maternal oral administration of an effective drug crossing the placenta could allow fetal treatment. Letermovir (LMV) and Maribavir (MBV) are new CMV antivirals, and potential candidates for fetal treatment.Methods: The objective was to investigate the placental transfer of LMV and MBV in the ex vivo method of the human perfused cotyledon. Term placentas were perfused, in an open-circuit model, with LMV or MBV at concentrations in the range of clinical peak plasma concentrations. Concentrations were measured using ultraperformance liquid chromatography coupled with tandem mass spectrometry. Mean fetal transfer rate (FTR) (fetal (FC) /maternal concentration), clearance index (CLI), accumulation index (AI) (retention of each drug in the cotyledon tissue) were measured. Mean FC were compared with half maximal effective concentrations of the drugs (EC50(LMV) and EC50(MBV)).Results: For LMV, the mean FC was (± standard deviation) 1.1 ± 0.2 mg/L, 1,000-fold above the EC50(LMV). Mean FTR, CLI and AI were 9 ± 1%, 35 ± 6% and 4 ± 2% respectively. For MBV, the mean FC was 1.4 ± 0.2 mg/L, 28-fold above the EC50(MBV). Mean FTR, CLI and AI were 10 ± 1%, 50 ± 7% and 2 ± 1% respectively.Conclusions: Drugs' concentrations in the fetal side should be in the range for in utero treatment of fetuses infected with CMV as the mean FC was superior to the EC50 for both molecules

A case of tuberculosis and black-grain eumycetoma co-infection in a non-endemic country: clinical presentation and therapeutic management

International audienceWe report a case of black-grain eumycetoma co-localized with Mycobacterium tuberculosis infection, presenting as a painless leg abscess and associated with vertebral tuberculosis. The rare association of these two pathogens raises several challenges regarding foreseeable drug interactions, side effects, the most appropriate management and the potential link between these two diseases

Concentration–response model of rilpivirine in a cohort of HIV-1-infected naive and pre-treated patients

International audienceRilpivirine is widely prescribed in people living with HIV. Although trough plasma concentrations have been associated with virological response, the drug pharmacodynamics remain incompletely characterized

Baseline characteristics of the 116 patients.

<p>ART: antiretroviral therapy, ATV: atazanavir, DRV: darunavir, EFV: efavirenz, ETR: etravirine, FTC: emtricitabine, IQR: interquartile range, LPV: lopinavir, MVC: maraviroc, NNRTI: non nucleoside reverse transcriptase inhibitors, NRTI: nucleoside reverse transcriptase inhibitors, NVP: nevirapine, PI: protease inhibitors, RAL: raltegravir, TDF: tenofovir, /r: boosted with ritonavir.</p><p>Baseline characteristics of the 116 patients.</p

Outbreak of Pneumocystis jirovecii Infection Among Heart Transplant Recipients: Molecular Investigation and Management of an Interhuman Transmission

International audienc

Comment on: Population pharmacokinetics of the rilpivirine long-acting formulation after intramuscular dosing in healthy subjects and people living with HIV

International audienc

Comment on: Population pharmacokinetics of the rilpivirine long-acting formulation after intramuscular dosing in healthy subjects and people living with HIV

International audienc

Comment on: Population pharmacokinetics of the rilpivirine long-acting formulation after intramuscular dosing in healthy subjects and people living with HIV

International audienc

Distribution of tenofovir, emtricitabine and rilpivirine plasma concentrations at different time-points.

<p>Distribution of tenofovir, emtricitabine and rilpivirine plasma concentrations at different time-points.</p

Distribution of plasma HIV-1 viral load at baseline (BL), Week (W)12, W24, W36, W48, W72 and W96.

<p>Distribution of plasma HIV-1 viral load at baseline (BL), Week (W)12, W24, W36, W48, W72 and W96.</p