Search results for "Tenofovir"
showing 10 items of 30 documents
Transmission of HIV Drug Resistance and the Predicted Effect on Current First-line Regimens in Europe
2016
Transmitted human immunodeficiency virus drug resistance in Europe is stable at around 8%. The impact of baseline mutation patterns on susceptibility to antiretroviral drugs should be addressed using clinical guidelines. The impact on baseline susceptibility is largest for nonnucleoside reverse transcriptase inhibitors.
Effectiveness and safety of switching to entecavir hepatitis B patients developing kidney dysfunction during tenofovir
2019
Background and Aims: Tenofovir disoproxil fumarate (TDF) is recommended for chronic hepatitis B (CHB) treatment, but it may induce kidney dysfunction whose management is not yet known. This Italian, multicentre, retrospective study aimed to assess the efficacy and safety of switching to entecavir (ETV) patients who developed TDF-associated glomerular and/or tubular dysfunction. Methods: A total of 103 TDF-treated patients were included as follows: age 64 years, 83% male, 49% cirrhotics, 98% with undetectable HBV DNA, 47% with previous lamivudine resistance (LMV-R) and 71% previously treated with adefovir. Twenty-nine (28%) were switched to ETV because estimated glomerular filtration rate (e…
Effectiveness of dolutegravir-based regimens as either first-line or switch antiretroviral therapy: data from the Icona cohort
2019
Introduction: Concerns about dolutegravir (DTG) tolerability in the real-life setting have recently arisen. We aimed to estimate the risk of treatment discontinuation and virological failure of DTG-based regimens from a large cohort of HIV-infected individuals. Methods: We performed a multicentre, observational study including all antiretroviral therapy (ART)-naïve and virologically suppressed treatment-experienced (TE) patients from the Icona (Italian Cohort Naïve Antiretrovirals) cohort who started, for the first time, a DTG-based regimen from January 2015 to December 2017. We estimated the cumulative risk of DTG discontinuation regardless of the reason and for toxicity, and of virologica…
COVID-19 in people living with HIV: Clinical implications of dynamics of the immune response to SARS-CoV-2.
2020
ABSTRACT Background Little evidence on COVID‐19 in people living with HIV (PLWH) is currently available. Material and Methods We reported clinical and viro‐immunological data of all HIV‐positive patients admitted to our centre with COVID‐19 from March 1 to May 12,2020. Results Overall, five patients were included: all were virologically‐suppressed on antiretroviral therapy and CD4+ count was >350 cell/mm3 in all but two patients. Although all patients had evidence of pneumonia on admission, only one developed respiratory failure. SARS‐CoV‐2‐RNA was never detected from nasopharyngeal swabs in two patients, whereas, in the others, viral clearance occurred within a maximum of 43 days. IgG prod…
Differential Effects of Tenofovir/Emtricitabine and Abacavir/Lamivudine on Human Leukocyte Recruitment
2012
Background The association of abacavir (ABC) with cardiovascular disease has led to HIV treatment guidelines favouring the combination of tenofovir/emtricitabine (TDF/FTC) over that of ABC/lamivudine (ABC/3TC). We have analysed the effects of plasma-relevant concentrations of TDF, FTC, ABC and 3TC, individually and in clinically employed combinations, on human leukocyte accumulation. The effects of ABC, 3TC, TDF and FTC on the expression of adhesion molecules were also evaluated. Methods Interactions between human leukocytes – specifically peripheral blood polymorphonuclear or mono-nuclear cells – and human umbilical vein endothelial cells were evaluated in a flow chamber reproducing in viv…
An Efficient Synthesis of Tenofovir (PMPA): A Key Intermediate Leading to Tenofovir-Based HIV Medicines
2020
Abstract: Herein, we report further improvements to the synthesis of tenofovir 1, the precursor to tenofovir disoproxil fumarate and tenofovir alafenamide fumarate. Starting from acyclic precursor diaminomalononitrile 12, a four-step protocol to tenofovir 1 will allow for vertical integration for more manufacturers. The key transformation is a more convergent one step procedure from 6 as compared to the current commercial process, with an improved yield from 59% (two steps) to 70%. Further improvements include eliminating the need for problematic magnesium tert-butoxide (MTB) and significant solvent reduction by eliminating the need for an intermediate workup. With the costs of HIV/AIDS tre…
The Di-Tert-Butyl Oxymethylphosphonate Route to the Antiviral Drug Tenofovir
2020
<div>The present manuscript describes a simple, two step synthesis of tenofovir from HPA through phosphonomethalation with a novel doubly protected oxymethylphosphonate electrophile. The crystalline electrophile can be prepared in a simple reaction sequence and can be deblocked more easily than its ditehyl analogue involved in the current commercial process for making the drug.</div><div>The approach is general and can also be used for the preparation of related antivirals and the synthesis of adefovir is described as well.<br></div>
FP187MITOCHONDRIAL DYSFUNCTION INDUCED BY TENOFOVIR IN RENAL CELLS. POTENTIATION OF THE EFFECTS BY CO-STIMULATION WITH ANGIOTENSIN II
2015
Di-tert-butyl Phosphonate Route to the Antiviral Drug Tenofovir
2021
Di-tert-butyl oxymethyl phosphonates were investigated regarding their suitability for preparing the active pharmaceutical ingredient tenofovir (PMPA). First, an efficient and simple access to the crystalline di-tert-butyl(hydroxymethyl)phosphonate was developed. O-Mesylation gave high yields of the active phosphonomethylation reagent. For the synthesis of tenofovir, a two-step sequence was developed using Mg(OtBu)2 as the base for the alkylation of (R)-9-(2-hydroxypropyl)adenine. Subsequent deprotection could be achieved with aqueous acids. (Di-tert-butoxyphosphoryl)methyl methanesulfonate showed to be the most efficient electrophile tested, affording PMPA in 72% yield on a 5 g scale. The …
The implementation of pre-exposure prophylaxis in Spain without women
2018
El objetivo del presente artículo es la exposición sucinta de la exclusión de las mujeres en la resolución del 27 de Julio de 2017 en el que se explicita el convenio de colaboración entre la Dirección General de Salud Pública, Calidad e Innovación y la empresa Gilead Servicios S.L.U. Este convenio es la formalización de la entrada e implementación de la profilaxis preexposición ante el VIH en el territorio nacional. La profilaxis preexposición ante el VIH es una novedosa intervención biomédica de carácter preventivo aplicada en personas que no viven con el VIH, que contiene como parte fundamental la ingesta diaria de un medicamento llamado Truvada, formado por dos componentes farmacológicos…