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Papers by Benito Garcia

Clinical Infectious Diseases, Oct 5, 2021

Background. The pharmacokinetics of bictegravir (BIC) and its association with the decay of human... more Background. The pharmacokinetics of bictegravir (BIC) and its association with the decay of human immunodeficiency virus (HIV)-1 RNA in genital fluids and the rectum have not yet been addressed. Methods. We conducted a prospective, multicenter study of antiretroviral-naive people living with HIV-1 and initiating BIC/ emtricitabine (FTC)/tenofovir alafenamide (TAF). HIV-1 RNA was measured (limit of quantification, 40 copies/mL) in blood plasma (BP), seminal plasma (SP), rectal fluid (RF), and cervicovaginal fluid (CVF) at baseline; Days 3, 7, 14, and 28; and Weeks 12 and 24. Total and protein-unbound BIC concentrations at 24 hours postdose (C 24h) were quantified in BP, SP, CVF and rectal tissue (RT) on Day 28 and Week 12 using a validated liquid chromatography-tandem mass spectrometry assay. Results. The study population comprised 15 males and 8 females. In SP, RF, and CVF, the baseline HIV-1 RNA was >40 copies/mL in 12/15, 13/15, and 4/8 individuals, respectively, with medians of 3.54 (2.41-3.79), 4.19 (2.98-4.70), and 2.56 (1.61-3.56) log 10 copies/mL, respectively. The initial decay slope was significantly lower in SP than in RF and BP. The time to undetectable HIV-1 RNA was significantly shorter in SP and RF than in BP. All women achieved undetectable HIV-1 RNA in CVF at Day 14. The median total BIC concentrations in SP, RT, and CVF were 65.5 (20.1-923) ng/mL, 74.1 (6.0-478.5) ng/g, and 61.6 (14.4-1760.2) ng/mL, respectively, representing 2.7%, 2.6%, and 2.8% of the BP concentration, respectively, while the protein-unbound fractions were 51.1%, 44.6%, and 42.6%, respectively. Conclusions. BIC/FTC/TAF led to rapid decay of HIV-1 RNA in genital and rectal fluids. Protein-unbound BIC concentrations in SP, RT, and CVF highly exceeded the half-maximal effective concentration (EC50) value (1.1 ng/mL). clinical Trials Registration. EudraCT 2018-002310-12.

Clinical Infectious Diseases, 2020

BackgroundThe pharmacokinetics of bictegravir (BIC) and its association with the decay of human i... more BackgroundThe pharmacokinetics of bictegravir (BIC) and its association with the decay of human immunodeficiency virus (HIV)–1 RNA in genital fluids and the rectum have not yet been addressed.MethodsWe conducted a prospective, multicenter study of antiretroviral-naive people living with HIV-1 and initiating BIC/emtricitabine (FTC)/tenofovir alafenamide (TAF). HIV-1 RNA was measured (limit of quantification, 40 copies/mL) in blood plasma (BP), seminal plasma (SP), rectal fluid (RF), and cervicovaginal fluid (CVF) at baseline; Days 3, 7, 14, and 28; and Weeks 12 and 24. Total and protein-unbound BIC concentrations at 24 hours postdose (C24h) were quantified in BP, SP, CVF and rectal tissue (RT) on Day 28 and Week 12 using a validated liquid chromatography-tandem mass spectrometry assay.ResultsThe study population comprised 15 males and 8 females. In SP, RF, and CVF, the baseline HIV-1 RNA was >40 copies/mL in 12/15, 13/15, and 4/8 individuals, respectively, with medians of 3.54 (2....

Journal of Virology, 1984

The characteristics of human rotavirus-associated RNA polymerase activity have been examined in r... more The characteristics of human rotavirus-associated RNA polymerase activity have been examined in relation to the effects of ribonucleoside triphosphate analogs and S-adenosylmethionine. These effects were analyzed by testing two forms of activated virus particles: EDTA- and heat-treated virions. The former lack outer shell proteins, and activation by means of heat treatment does not introduce any apparent modification in virion structure. Virus-associated RNA polymerase shows similar properties in both preparations, suggesting that outer proteins are not directly involved in RNA synthesis. Transcription in this virus is specifically dependent on a hydrolyzable form of ATP. Such a requirement is not overcome by preincubation or by the addition of S-adenosylmethionine, suggesting a hypothetical mechanism that couples transcription to ATP hydrolysis. The addition of S-adenosylmethionine stimulated transcription and diminished the Km value not only for ATP but also for the other three ri...

The Journal of Infectious Diseases, 2019

We determined total and unbound concentrations of bictegravir (BIC) in cerebrospinal fluid (CSF) ... more We determined total and unbound concentrations of bictegravir (BIC) in cerebrospinal fluid (CSF) in 15 asymptomatic, virologically suppressed patients. The median plasma and CSF total BIC concentrations were 1837.1 ng/mL (interquartile range [IQR], 1237.2–2586.7) and 6.9 (IQR, 4.8–10.9), respectively. Median unbound BIC concentration was 2.48 ng/mL (IQR, 1.6–3.7). Total and unbound BIC CSF concentrations were above the half-maximal effective concentration value in all patients, and all subjects had human immunodeficiency virus viral suppression in plasma and CSF. Bictegravir may contribute to inhibit viral replication in this compartment.

DICP, 1989

mg but that they weretolerable. The patientwasafebrile and not septic at the time of the reaction... more mg but that they weretolerable. The patientwasafebrile and not septic at the time of the reaction. Because gentamicin itself has rarely been implicated in acute respiratory distress,' a more probable explanation for this patient's dyspnea is a hypersensitivity reaction to the sodium metabisulfite, a preservative in the gentamicin multidose vial,' rather than to the gentamicin itself. However, this was not confirmed by rechallenging the patient with preservative-free gentamicin. Sensitivity to gentamicin is rare, with only one reported case in the literature.' The mechanism by which a sulfite can induce asthmatic symptoms is unknown. It has been suggested that sulfite-induced ~spiratory problems may not involvea humoral allergic response but instead be the result of sulfite attack on cholinergic receptors in the lungs' and that sulfitescause bronchoconstriction through direct stimulation of afferent parasympathetic irritant receptors.' Sensitive patients will react to sulfiteconcentrations ranging from 5 to 100 mg.' The most frequent symptom of a sulfite reaction is difficulty in breathing. Other symptoms can include nausea, vomiting and diarrhea, abdominal pain and cramps, dizziness, wheezing, hives, itching, rash, difficulty in swallowing, headache, fainting, change in body temperature, chest pain, change in heart rate, unconsciousness, and coma.' Pharmacists should be aware that sulfiting agents are often used in drug products.v However, as drug manufacturers continue to make changes in their products it wouldbe wise to contact the manufacturer directly or consult the productpackage insert to determine if a product contains sulfites. An attempt to identify patients who exhibit sulfite hypersensitivity should be made when these types of reactions are observed. Sulfite-free products are often available as alternative choices for these patients. LISA M. DEZIEL-EVANS, Pharm.D.

Clinical Infectious Diseases, 2018

Background This study assessed the penetration and efficacy of tenofovir alafenamide (TAF) in the... more Background This study assessed the penetration and efficacy of tenofovir alafenamide (TAF) in the male genital tract (MGT) and the semen quality of individuals infected with human immunodeficiency virus (HIV)-1 who were treated with a TAF-containing regimen. Methods This was a prospective, open-label, single-arm study of 14 virologically-suppressed, HIV-1–infected men on stable antiretroviral therapy with elvitegravir, cobicistat, emtricitabine (E/C/F) and tenofovir disoproxil fumarate (TDF) who switched to E/C/F and TAF. At baseline (pre-switch) and at 12 weeks post-switch, we measured HIV-1 RNA in seminal plasma (SP) and blood plasma (BP), tenofovir (TFV) in SP and BP, and TFV-diphosphate (dp) in peripheral blood mononuclear cells (PBMCs) and seminal mononuclear cells (SMCs) at the end of the dosing interval (C24h). Semen quality was assessed before switching and after 12 weeks on TAF. Results With TAF, TFV C24 was 11.9-fold higher in SP than in BP. This concentration was signific...

Annals of Pharmacotherapy, 1995

Trimethoprimlsulfamethoxazole dosing during renal dysfunction TOTHE EDITOR: We have received seve... more Trimethoprimlsulfamethoxazole dosing during renal dysfunction TOTHE EDITOR: We have received several inquiriesregarding the dosage regimensof trimethoprimlsulfamethoxazole (TMP/SMX) in patients with renaldysfunction. In our reviewarticle published in The Annals,we providedgeneraldosageguidelines based on a patient's creatinine clearance (C(.,l.

El proyecto trata de utilizar la aplicación Packet Tracer, de Cisco, para emular los diferentes p... more El proyecto trata de utilizar la aplicación Packet Tracer, de Cisco, para emular los diferentes protocolos de enrutamiento, la creación de redes interconectadas entre ellas, su configuración y conocer los elementos de red que participan en las redes. Por otro lado, otro objetivo, no menos importante, es poner a disposición de los estudiantes una herramienta que les permite conocer y profundizar en el sistema operativo de línea de comandos de Cisco (Cisco IOS), para que se familiaricen con una tecnología que tendrán presente, la mayoría, en su vida laboral. Por lo que, principalmente está destinado a servir de formación práctica sobre los protocolos de enrutamiento existentes, el lenguaje del sistema operativo de Cisco en sus routers, y entender conceptos relacionados con redes y su interconexión.Benito Garcia, J. (2008). Enrutamiento IP con Packet Tracer. http://hdl.handle.net/10251/32483.Archivo delegad

Reales Sitios Revista Del Patrimonio Nacional, 1993

Value in Health, 2013

A395 months. Methods: In PRIME, 1183 patients with previously untreated mCRC were randomised. Usi... more A395 months. Methods: In PRIME, 1183 patients with previously untreated mCRC were randomised. Using data from an exploratory analysis conducted when 80% of patients had died, NNTs (Bender. Encyclopedia of Biostatistics, Second Edition; Volume 6, pp3752-61) were retrospectively calculated in patients with KRAS/NRAS WT (n= 505; exons 2-4 assessed) mCRC overall and in the ECOG performance score 0/1 (n= 473) subgroup. ORR and PFS events were defined using RECIST. Results: In the overall KRAS/NRAS WT population, 59.3% vs 45.6% of patients receiving panitumumab+FOLFOX4 vs FOLFOX4 alone, respectively, achieved an OR; NNT(95% CI) in the ORR analysis was 7.3(4.5-19.9). In the ECOG 0/1 subgroup, 61.3% vs 46.4% of those receiving panitumumab+FOLFOX4 vs FOLFOX4 alone, respectively, had an OR; the NNT(95% CI) was 6.7(4.2-16.5). For the PFS overall population analysis, the HR(95% CI) was 0.74(0.62-0.90); HR(95% CI) for the ECOG 0/1 subgroup was 0.72(0.59-0.88). NNTs(95% CI) in the overall population at 6 and 12 months were 12.8(8.3-34.1) and 9.2(5.7-25.9), respectively; corresponding values for the ECOG 0/1 subgroup were 11.9(7.9-27.8) and 8.4(5.3-20.8). For the OS overall population analysis, the HR(95% CI) was 0.76(0.63-0.93); HR(95% CI) for the ECOG 0/1 subgroup was 0.74(0.60-0.90). NNTs(95% CI) in the overall population at 12 and 24 months were 16.

Current opinion in investigational drugs (London, England : 2000), 2005

Nucleoside/nucleotide analogs (NAs) are essential components of most current antiretroviral regim... more Nucleoside/nucleotide analogs (NAs) are essential components of most current antiretroviral regimens. Although many dual NA combinations may be used as backbones, not all display optimal results. For instance, some associations should be avoided due to antagonism (eg, zidovudine plus stavudine), high rates of toxicity (eg, didanosine plus stavudine) and/or increased risk of virological failure (eg, didanosine plus tenofovir). Moreover, the knowledge of plasma and intracellular interactions between different NAs is important for choosing appropriate combinations and optimal doses in order to optimize antiviral efficacy and minimize toxicities.

Revista Panamericana de Salud Pública, 2003

Journal of Power Sources, 1999

Abstract Li x V 2 O 5 phase ( x =0.9, 1.16 and 1.6) has been prepared by chemical reduction of V ... more Abstract Li x V 2 O 5 phase ( x =0.9, 1.16 and 1.6) has been prepared by chemical reduction of V 2 O 5 using n -butyllithium. Electrochemical charge–discharge characteristics of fresh and aged compounds have been investigated. Lithium ions cannot be fully deintercalated during the charge due to a chemical oxidation in air. This effect is more pronounced when x increases and with ageing. New behavior and attractive properties are reported for Li 1.16 V 2 O 5 electrodes aged for a few days in air. A specific capacity of 300 Ah/kg is available in the range 1.8–3.8 V after the 20th cycle, which represents an improvement of 15–20% compared to V 2 O 5 .

Anales de la …, 1976

Información del artículo Bacterias del grupo coliforme en mejillones (Mytilus edulis L.) sin depu... more Información del artículo Bacterias del grupo coliforme en mejillones (Mytilus edulis L.) sin depurar.

British Journal of Clinical Pharmacology, 2002

Aims The purpose of this study was to describe the population pharmacokinetics of gentamicin in p... more Aims The purpose of this study was to describe the population pharmacokinetics of gentamicin in patients with cancer, to identify possible relationships between clinical covariates and population pharmacokinetic parameter estimates and to examine the relevance of existing dosage nomograms in light of the population model developed in these patients. Methods Data were collected prospectively from 210 patients with cancer and were analysed with package NONMEM. Data were split into two sets: a population data set and an evaluation set. Creatinine clearance was estimated using measured creatinine concentrations and using 'low' creatinines set to a minimum of 60 mmol l −1 , 70 mmol l −1 or 88.4 mmol l −1. Results A two compartment model was fitted to the concentration-time curve. Two best models were obtained, one that related clearance to estimated creatinine clearance (minimum creatinine value 60 mmol l −1) and the other that related clearance to age, creatinine concentration and body surface area. Volume of the central compartment was influenced by body surface area and albumin concentration. For both models 90% of measured concentrations lay within the 95% confidence interval of the simulated concentrations and the mean prediction errors were −7.2% and −6.6%, respectively. A final analysis performed in all patients identified the following relationship CL (l h −1)=0.88 ×(1+0.043 ×creatinine clearance) and central volume of distribution V 1 (l)=8.59 ×body surface area ×(albumin/34) −0.39. The mean population estimate of intercompartmental clearance (Q) was 1.30 l h −1 and peripheral volume of distribution (V 2) was 9.80 l. Coefficient of variation was 18.5% on clearance and 28.2% on Q. Residual error expressed as a standard deviation was 0.36 mg l −1 at 1.0 mg l −1 and 1.32 mg l −1 at 8.0 mg l −1. The mean population estimate of clearance was 4.2 l h −1 and volume of distribution (V ss) was 24.6 l (0.38 l kg −1). The mean population estimates of half-lives were 1.8 h and 8.0 h. Conclusions In the context of published nomograms this analysis indicated that both the traditional approach and the new, 'once daily' approach should achieve satisfactory concentrations in cancer patients although serum concentration monitoring is required to confirm optimal dosing in individual patients.

Endoscopia ( …, 1999

Base de dados : LILACS. Pesquisa : 276440 [Identificador único]. Referências encontradas : 1 [ref... more Base de dados : LILACS. Pesquisa : 276440 [Identificador único]. Referências encontradas : 1 [refinar]. Mostrando: 1 .. 1 no formato [Detalhado]. página 1 de 1, 1 / 1, LILACS, seleciona. para imprimir. Fotocópia. experimental, Documentos relacionados. Id: 276440. ...

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Journal of neurovirology, 2018

This study aimed to assess cerebrospinal fluid (CSF) drug concentrations and viral suppression in... more This study aimed to assess cerebrospinal fluid (CSF) drug concentrations and viral suppression in HIV-1-infected patients on ritonavir-boosted atazanavir (ATV/r) plus lamivudine (3TC) dual therapy. HIV-1-infected adults with suppressed plasma HIV-1 RNA who switched to ATV/r plus 3TC were studied. Total ATV and 3TC concentrations at the end of the dosing interval (C), using a validated LC-MS/MS method, and HIV-1 RNA were measured in paired CSF and plasma samples 12 weeks after switching. Ten individuals were included. Median (range) age was 42.5 (33-70) years, time on ART was 39.5 (11-197) months, and time with plasma HIV-1 RNA < 40 copies/mL was 15.5 (6-46) months. At baseline, CSF HIV-1 RNA was < 40 copies/mL in all patients. Twelve weeks after switching to ATV/r plus 3TC, HIV-1 RNA remained at < 40 copies/mL in both plasma and CSF in 9/10 patients. One patient with suboptimal adherence to ART had HIV-1 RNA rebound in both plasma and CSF. The median CSF-to-plasma concentra...