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Llibre J.M.,Autonomous University of Barcelona | Pulido F.,Institute Investigacion Hospital 12 Of Octubre I12 | Garcia F.,Hospitales Universitarios Of Granada | Garcia Deltoro M.,Consorcio Hospital General Universitario Of Valencia | And 2 more authors.
AIDS reviews | Year: 2015

Dolutegravir is a novel integrase strand-transfer inhibitor that displays potent in vitro activity and a remarkably different resistance profile. Its robust pharmacokinetic/pharmacodynamic properties - long plasma t1/2, high plasma inhibition quotient, and slow dissociation rate from the integrase complex - suggest it should present a high barrier to resistance development. This has been confirmed in pivotal phase III studies of initial therapy, with none out of 1,118 treated individuals selecting resistance-associated mutations at the integrase or reverse transcriptase. In integrase-naive subjects with virological failure, a rescue intervention with dolutegravir has shown significantly higher rates of virological suppression than raltegravir, as well as significantly lower rates of selection of resistance both at the integrase and against the optimized background. Unexpectedly, a mutation rarely selected in this scenario (R263K) induces a fitness cost that prevents HIV-1 from evading drug pressure, and accumulation of further secondary mutations does not occur and has not been able to compensate the replication capacity deficit in the aftermath of the appearance of a single drug resistance mutation. Therefore, both in vitro and in vivo, it leads the virus to a previously unnoticed evolutionary pathway with low chances to develop resistance to both dolutegravir and other families of antiretrovirals present in the background. This high genetic barrier to resistance development in early stages of antiretroviral treatment can help preserve future treatment options in patients who fail antiretroviral therapy.


Llibre J.M.,University Hosp Germans Trias jol | Llibre J.M.,Autonomous University of Barcelona | Pulido F.,Institute Investigacion Hospital | Garcia F.,Hospitales Universitarios Of Granada | And 3 more authors.
AIDS Reviews | Year: 2014

Dolutegravir is a novel integrase strand-transfer inhibitor that displays potent in vitro activity and a remarkably different resistance profile. Its robust pharmacokinetic/pharmacodynamic properties - long plasma t1/2, high plasma inhibition quotient, and slow dissociation rate from the integrase complex - suggest it should present a high barrier to resistance development. This has been confirmed in pivotal phase III studies of initial therapy, with none out of 1,118 treated individuals selecting resistance-associated mutations at the integrase or reverse transcriptase. In integrase-naive subjects with virological failure, a rescue intervention with dolutegravir has shown significantly higher rates of virological suppression than raltegravir, as well as significantly lower rates of selection of resistance both at the integrase and against the optimized background. Unexpectedly, a mutation rarely selected in this scenario (R263K) induces a fitness cost that prevents HIV-1 from evading drug pressure, and accumulation of further secondary mutations does not occur and has not been able to compensate the replication capacity deficit in the aftermath of the appearance of a single drug resistance mutation. Therefore, both in vitro and in vivo, it leads the virus to a previously unnoticed evolutionary pathway with low chances to develop resistance to both dolutegravir and other families of antiretrovirals present in the background. This high genetic barrier to resistance development in early stages of antiretroviral treatment can help preserve future treatment options in patients who fail antiretroviral therapy.


Molina-Barea R.,Hospital Universitario San Cecilio | Rios-Peregrina R.M.,Hospitales Universitarios Of Granada | Slim M.,University of Granada | Calandre E.P.,University of Granada | And 2 more authors.
Breast Care | Year: 2014

Background: Metastases of lobular breast cancer are commonly encountered at the level of lungs, bones, brain and liver, whereas lesions in the gastrointestinal tract are rarely seen. Case Report: A case of a patient with metastases in the right colon and gallbladder originating from an invasive lobular carcinoma is described. Conclusion: Adequate diagnostic procedures should be performed in patients with a history of breast cancer and who show gastrointestinal symptoms to rule out the potential presence of gastrointestinal metastases. © 2014 S. Karger GmbH, Freiburg.


Miro O.,Area de Urgencias | Fernandez-Guerrero I.M.,Grupo de Investigacion Urgencias Procesos y Patologias | Fernandez-Guerrero I.M.,Hospitales Universitarios Of Granada | Burillo-Putze G.,Hospital Universitario Of Canarias | Martin-Sanchez F.J.,Complutense University of Madrid
Emergencias | Year: 2015

A journal is generally considered to be of higher quality to the extent that it publishes articles that are cited. A journal’s articles are not all cited equally, however; rather, citations of only a select group of titles accounts for most of a journal’s impact factor. This study aimed to identify the characteristics of Emergencias’s most highly cited articles and compare their impact to that of papers by other authors in Spain, in Spanish, and internationally in the field of emergency medicine. Between 2008 and 2015, Emergencias published 975 articles, which received 2207 citations. The most-cited article received 52, and the group of 20 most-cited articles accumulated a total of 519 cites (23.5%). Even though Emergencias is published in Spanish and was included in Journal Citation Reports only recently (2008), some of the published articles have had considerable impact. The most-cited article (EVADUR Study) was in the top 2% (98th percentile) of all publications by authors in Spain, and in the top 1% of articles published in Spanish or in emergency medicine. © 2015, Grupo Saned. All rights reserved.


Monge S.,Institute Salud Carlos III | Diez M.,Institute Salud Carlos III | Alvarez M.,Hospitales Universitarios Of Granada | Guillot V.,Hospitales Universitarios Of Granada | And 9 more authors.
Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases | Year: 2015

Prevalence of transmitted drug resistance (pTDR) to antiretroviral drugs in Spain (2007-2012) was estimated using the CoRIS cohort, adjusting its territorial distribution and transmission route to the reference population from the Spanish Information System on New human immunodeficiency virus diagnoses. A total of 2702 patients from ten autonomous communities and with naive FASTA sequence within 6 months of human immunodeficiency virus diagnosis were selected. Weighted pTDR, estimated using the inverse probability of selection in the sample by autonomous communities and transmission group, was 8.12% (95% CI 6.44-9.80), not significantly different from unweighted pTDR. We illustrate how proportional weighting can maximize representativeness of cohort-based data, and its value to monitor pTDR at country level. Copyright © 2014 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

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