Darunavir/cobicistat/emtricitabine/tenofovir alafenamide versus dolutegravir /abacavir/lamivudine in antiretroviral-naïve adults (SYMTRI): a multicenter randomized open-label study (PReEC/RIS-57)

D/C/F/TAF is the reference for combination therapy based on protease inhibitors but has not been compared with regimens containing integrase inhibitors as initial ART. We could not demonstrate D/C/F/TAF noninferiority relative to DTG/ABC/3TC, although both regimens were similarly well tolerated. Background Darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) is the reference for combination therapy based on protease inhibitors due to its efficacy, tolerability, and convenience. Head-to-head randomized comparisons between D/C/F/TAF and combination therapy based on integrase inhibitors in antiretroviral-naive patients are lacking. Methods Adult (>18 years old) human immunodeficiency virus-infected antiretroviral-naive patients (HLA-B*5701 negative and hepatitis B virus negative), with viral load (VL) >= 500 c/mL, were centrally randomized to initiate D/C/F/TAF or dolutegravir/abacavir/lamivudine (DTG/3TC/ABC) after stratifying by VL and CD4 count. Clinical and analytical assessments were performed at weeks 0, 4, 12, 24, and 48. The primary endpoint was VL 100 000 copies/mL, and 13% had <200 CD4 cells/mu L. Median weight was 73 kg and median body mass index was 24 kg/m(2). At 48 weeks, 79% (D/C/F/TAF) versus 82% (DTG/3TC/ABC) had VL <50 c/mL (difference, -2.4%; 95% confidence interval [CI], -11.3 to 6.6). Eight percent versus four percent experienced virologic failure but no resistance-associated mutations emerged. Four percent versus six percent had drug discontinuation due to adverse events. In the per-protocol analysis, 94% versus 96% of patients had VL <50 c/mL (difference, -2%; 95% CI, -8.1 to 3.5). There were no differences in CD4 cell count or weight changes. Conclusions We could not demonstrate the noninferiority of D/C/F/TAF relative to DTG/ABC/3TC as initial antiretroviral therapy, although both regimens were similarly well tolerated

Choice of the initial antiretroviral treatment for HIV-positive individuals in the era of integrase inhibitors

BACKGROUND: We aimed to describe the most frequently prescribed initial antiretroviral therapy (ART) regimens in recent years in HIV-positive persons in the Cohort of the Spanish HIV/AIDS Research Network (CoRIS) and to investigate factors associated with the choice of each regimen. METHODS: We analyzed initial ART regimens prescribed in adults participating in CoRIS from 2014 to 2017. Only regimens prescribed in >5% of patients were considered. We used multivariable multinomial regression to estimate Relative Risk Ratios (RRRs) for the association between sociodemographic and clinical characteristics and the choice of the initial regimen. RESULTS: Among 2874 participants, abacavir(ABC)/lamivudine(3TC)/dolutegavir(DTG) was the most frequently prescribed regimen (32.1%), followed by tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC)/elvitegravir(EVG)/cobicistat(COBI) (14.9%), TDF/FTC/rilpivirine (RPV) (14.0%), tenofovir alafenamide (TAF)/FTC/EVG/COBI (13.7%), TDF/FTC+DTG (10.0%), TDF/FTC+darunavir/ritonavir or darunavir/cobicistat (bDRV) (9.8%) and TDF/FTC+raltegravir (RAL) (5.6%). Compared with ABC/3TC/DTG, starting TDF/FTC/RPV was less likely in patients with CD4100.000 copies/mL. TDF/FTC+DTG was more frequent in those with CD4100.000 copies/mL. TDF/FTC+RAL and TDF/FTC+bDRV were also more frequent among patients with CD4<200 cells//muL and with transmission categories other than men who have sex with men. Compared with ABC/3TC/DTG, the prescription of other initial ART regimens decreased from 2014-2015 to 2016-2017 with the exception of TDF/FTC+DTG. Differences in the choice of the initial ART regimen were observed by hospitals' location. CONCLUSIONS: The choice of initial ART regimens is consistent with Spanish guidelines' recommendations, but is also clearly influenced by physician's perception based on patient's clinical and sociodemographic variables and by the prescribing hospital location

Regulation of the pyrimidine biosynthetic pathway by lysine acetylation of E. coli OPRTase

© 2022 The Authors. The FEBS Journal published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. http://creativecommons.org/licenses/by /4.0/ This document is the Accepted version of a Published Work that appeared in final form in The FEBS Journal. To access the final edited and published work see https://doi.org/10.1111/febs.1659

Impact of an enhanced screening program on the detection of non-AIDS neoplasias in patients with human immunodeficiency virus infection

Background: The incidence of non-AIDS defining cancer (NADC) is higher in people living with HIV (PLWH) than in the general population, and it is already one of the leading causes of death in the HIV-infected population. It is estimated that the situation will be aggravated by the progressive aging of PLWH. Early diagnosis through intensive cancer screening may improve the ability for therapeutic interventions and could be critical in reducing mortality, but it might also increase expenditure and harms associated with adverse events. The aim of this study is to evaluate an enhanced screening program for early diagnosis of cancer in PLWH compared to standard practice. The specific objectives are (1) to compare the frequency of cancer diagnosed at an early stage, (2) to analyze safety of the enhanced program: adverse events and unnecessary interventions, (3) to analyze the cost-utility of the program, and (4) to estimate the overall and site-specific incidence of NADC in PLWH. Methods: We will conduct a multicenter, non-blinded, randomized, controlled trial, comparing two parallel arms: conventional vs enhanced screening. Data will be recorded in an electronic data collection notebook. Conventional intervention group will follow the standard of care screening in the participating centers, according to the European AIDS Clinical Society recommendations, and the enhanced intervention group will follow an expanded screening aimed to early detection of lung, liver, anal, cervical, breast, prostate, colorectal, and skin cancer. The trial will be conducted within the framework of the Spanish AIDS Research Network Cohort (CoRIS). Discussion: The trial will evaluate the efficacy, safety, and efficiency of an enhanced screening program for the early diagnosis of cancer in HIV patients compared to standard of care practice. The information provided will be relevant since there are currently no studies on expanded cancer screening strategies in patients with HIV, and available data estimating cost effectiveness or cost-utility of such as programs are scarce. An enhanced program for NADC screening in patients with HIV could lead to early diagnosis and improve the prognosis of these patients, with an acceptable rate of unnecessary interventions, but it is critical to demonstrate that the benefits clearly outweigh the harms, before the strategy could be implemented

Outcomes by sex following treatment initiation with darunavir/cobicistat in a large Spanish cohort of the CODAR study (GeSIDA 9316)

[Background] Few women have been included in darunavir/cobicistat clinical development studies, and hardly any of them were antiretroviral experienced or treated with anything other than triple-based therapies.[Objectives] Our aim was to increase our knowledge about women living with HIV undergoing darunavir/cobicistat-based regimens.[Methods] A multicentre (21 hospitals), retrospective study including a centrally selected random sample of HIV-1 patients starting a darunavir/cobicistat-based regimen from June 2014 to March 2017 was planned. Baseline characteristics, 24 and 48 week viral load response (<50 copies/mL), CD4+ lymphocyte count increase, time to change darunavir/cobicistat and adverse event occurrence were all compared by sex. The study was approved by each of the 21 ethics committees, and patients signed informed consent.[Results] Out of 761 participants, 193 were women. Similar characteristics were found for both sexes, except that the women had a longer duration of HIV infection (P = 0.001), and were less frequently pre-treated with darunavir/cobicistat in their previous regimen (P = 0.02). The main reason for using a darunavir/cobicistat-based regimen was simplification, without differences by sex, while monotherapy seems to be more frequently prescribed in women than in men (P = 0.067). The main outcomes, HIV viral load response, CD4+ lymphocyte count increase at 24 or 48 weeks, occurrence of adverse events, main reasons for changing and time to the modify darunavir/cobicistat regimen, did not show differences between the sexes.[Conclusions] No sex disparities were found in the main study outcomes. These results support the use of a darunavir/cobicistat-based regimen in long-term pre-treated women. Clinical Trial.gov No. NCT03042390.The CODAR study (Gesida Study no. 9316) was sponsored by SEIMC-GESIDA with support from Janssen. Other contributors were the RD12/0017/0017 project as part of Plan Nacional R + D + I and co-funded by Instituto de Salud Carlos III (ISCIII)-Subdirección General de Evaluación and Fondo Europeo de Desarrollo Regional (FEDER).Peer reviewe

Laboratory Cross-Comparison and Ring Test Trial for Tumor BRCA Testing in a Multicenter Epithelial Ovarian Cancer Series: The BORNEO GEICO 60-0 Study

Germline and tumor BRCA testing constitutes a valuable tool for clinical decision-making in the management of epithelial ovarian cancer (EOC) patients. Tissue testing is able to identify both germline (g) and somatic (s) BRCA variants, but tissue preservation methods and the widespread implementation of NGS represent pre-analytical and analytical challenges that need to be managed. This study was carried out on a multicenter prospective GEICO cohort of EOC patients with known gBRCA status in order to determine the inter-laboratory reproducibility of tissue sBRCA testing. The study consisted of two independent experimental approaches, a bilateral comparison between two reference laboratories (RLs) testing 82 formalin-paraffin-embedded (FFPE) EOC samples each, and a Ring Test Trial (RTT) with five participating clinical laboratories (CLs) evaluating the performance of tissue BRCA testing in a total of nine samples. Importantly, labs employed their own locally adopted next-generation sequencing (NGS) analytical approach. BRCA mutation frequency in the RL sub-study cohort was 23.17%: 12 (63.1%) germline and 6 (31.6%) somatic. Concordance between the two RLs with respect to BRCA status was 84.2% (gBRCA 100%). The RTT study distributed a total of nine samples (three commercial synthetic human FFPE references, three FFPE, and three OC DNA) among five CLs. The median concordance detection rate among them was 64.7% (range: 35.3–70.6%). Analytical discrepancies were mainly due to the minimum variant allele frequency thresholds, bioinformatic pipeline filters, and downstream variant interpretation, some of them with consequences of clinical relevance. Our study demonstrates a wide range of concordance in the identification and interpretation of BRCA sequencing data, highlighting the relevance of establishing standard criteria for detecting, interpreting, and reporting BRCA variants

Anales de Edafología y Agrobiología Tomo 38 Número 1-2

Suelos: Suelos volcánicos españoles. (ll. Olot (Gerona). Características morfológicas y químicas, por C. Vizcayno Muñoz, J. García Vicente y M. T. García González.-- Suelos volcánicos españoles. IV. Olot (Gerona). Mineralogía de la fracción arcilla, por C. Vizcayno Muñoz, M. T. García González y J. García Vicente.-- Suelos del Norte de la Sierra de Francia, por J. F. Gallardo y J. A. Egida.-- Caracterización de un suelo desarrollado sobre cenizas volcánicas de la Sierra Ecuatoriana, por Juan L. de Olmedo y Luis Mejía.-- Evolución de los minerales de la arcilla en cuatro perfiles de la Sierra de Francia (Salamanca), por M. Ledesma, M. A. Vicente, J. Gallardo y J. A. Egida.--Calores de adsorción de fosfatos de trialquilo por montmorillonita, por G. Dios Cancela y S. González García.-- Interacción del 1-2 propilén carbonato con montmorillonita. l. Estudio rontgenográfico y térmico, por G. Dios Cancela.-- Acción de la hidrólisis ácida sobre los ácidos húmicos. Componente proteica, por J. Cegarra y F. Costa.-- Evaluación del peso molecular-promedio ponderal (Mw) de ácidos húmicos por un método combinado de gel-filtración y difusión, por F. l. González Vila y F. Martín Martínez.-- Estudio de la distribución vertical de Eumycetes en los Andosoles de Tenerife: Perfil Izaña, por G. Vivancos Gallego y A. M. Borges Alvarez.-- Ecological importance of antibiotics in soil: Production of antibiotics by species of Penicillium in an Andosol in the province of Navarra, Spain, by A. T. Mortínez and C. Ramírez.--Fertilidad de Suelos.-- Effect of iron-nickel interacti ons on the availability of copper and manganese, by Hi S. G. Misra and R. S. Dwivedi.-- Efecto del uso del suelo sobre algunos indicadores de fertilidad en dos subórdenes (Andept y Tropet) del Altiplano de Pasto, Colombia. l. Materia orgánica y bases cambiables, por Ricardo Guerrero, Alvaro Dávila y Carlos Torres.-- Efecto del uso del suelo sobre algunos indicadores de fertilidad en dos subórdenes (Andept y Tropet) del Altiplano de Pasto, Colombia. II Disponibilidad de Cu, Zn, Fe y B, por Ricardo Guerrero, Alvaro Dávila y Carlos Torres.-- Efecto de la fertilización de soja con distintas formas de azufre, por C. Lluch, M. Gómez y J. Olivares.-- Equipo automático para cultivo hidropónico con solución circulante, por Mª P. Sánchez Conde y P. Azuara.-- Influencia del pH, arcilla y mecanismos de reacción del fósforo en el suelo sobre la capacidad tampón del ion fosfato, por J. A. Díez.-- Nutrición y Fisiología Vegetal.-- Efecto de la interacción NaCl- P sobre el contenido foliar de Fe, Mn, Zn, Cu y B, en plantas, por A. Cerda y F. T. Bingham.-- Crecimiento y metabolismo nitrogenado en plantas de Nicotiana rustica L. irradiadas con UV cercano. l. Caracteres vegetativos y aminoácidos, por MªT. Piñal, J. Barceló y C. Morales.-- Crecimiento y metabolismo nitrogenado en plantas de Nicotiana rustica L. irradiadas con UV cercano.II. Acidos nucleicos: ADN y ARN, por Mª T. Piñol y C. Morales.-- Interacciones entre K, Ca y Mg a nivel de su absorción y distribución en plantas de tomate, por l. Agüi, M. Gómez y L. Recalde Efecto de la proporción K, Ca y Mg en la solución nutritiva sobre la absorción y distribución de micronutrientes, por l. Agüi, M. C. Alvarez-Tinaut y L. Recalde Martínez.-- Evolución del proceso de biosíntesis proteica a través de la composición de aminoácidos libres en savia de tomatera por V. Hernando, P. Buenadicha y M. Torres- Correlaciones entre bioelementos en especies pratenses bajo los efectos de la madurez. l. Leguminosas, por A. Valdés Amado, B. García Criado y J. M. Gómez Gutiérrez. Los efectos del régimen hídrico y de distintos niveles de fertilidad .sobre el rendimiento, calidad y tamaño del tomate de invierno. V Efectos del régimen hídrico y del PK sobre el tamaño del fruto, por V. Hernando y B. Orihuel Gasque.-- Notas.--Aviso importantePeer reviewe

Spatiotemporal Characteristics of the Largest HIV-1 CRF02_AG Outbreak in Spain: Evidence for Onward Transmissions

Background and Aim: The circulating recombinant form 02_AG (CRF02_AG) is the predominant clade among the human immunodeficiency virus type-1 (HIV-1) non-Bs with a prevalence of 5.97% (95% Confidence Interval-CI: 5.41-6.57%) across Spain. Our aim was to estimate the levels of regional clustering for CRF02_AG and the spatiotemporal characteristics of the largest CRF02_AG subepidemic in Spain. Methods: We studied 396 CRF02_AG sequences obtained from HIV-1 diagnosed patients during 2000-2014 from 10 autonomous communities of Spain. Phylogenetic analysis was performed on the 391 CRF02_AG sequences along with all globally sampled CRF02_AG sequences (N = 3,302) as references. Phylodynamic and phylogeographic analysis was performed to the largest CRF02_AG monophyletic cluster by a Bayesian method in BEAST v1.8.0 and by reconstructing ancestral states using the criterion of parsimony in Mesquite v3.4, respectively. Results: The HIV-1 CRF02_AG prevalence differed across Spanish autonomous communities we sampled from (p < 0.001). Phylogenetic analysis revealed that 52.7% of the CRF02_AG sequences formed 56 monophyletic clusters, with a range of 2-79 sequences. The CRF02_AG regional dispersal differed across Spain (p = 0.003), as suggested by monophyletic clustering. For the largest monophyletic cluster (subepidemic) (N = 79), 49.4% of the clustered sequences originated from Madrid, while most sequences (51.9%) had been obtained from men having sex with men (MSM). Molecular clock analysis suggested that the origin (tMRCA) of the CRF02_AG subepidemic was in 2002 (median estimate; 95% Highest Posterior Density-HPD interval: 1999-2004). Additionally, we found significant clustering within the CRF02_AG subepidemic according to the ethnic origin. Conclusion: CRF02_AG has been introduced as a result of multiple introductions in Spain, following regional dispersal in several cases. We showed that CRF02_AG transmissions were mostly due to regional dispersal in Spain. The hot-spot for the largest CRF02_AG regional subepidemic in Spain was in Madrid associated with MSM transmission risk group. The existence of subepidemics suggest that several spillovers occurred from Madrid to other areas. CRF02_AG sequences from Hispanics were clustered in a separate subclade suggesting no linkage between the local and Hispanic subepidemics