Search

Copyright of Complutum is the property of Universidad Complutense de Madrid and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Objectives: To investigate resistance-associated substitutions (RASs) as well as retreatment efficacies in a large cohort of European patients with failure of glecaprevir/pibrentasvir.Methods: Patients were identified from three European Resistance Reference centres in Spain, Italy and Germany. Sequencing of NS3, NS5A and NS5B was conducted and substitutions associated with resistance to direct antiviral agents were analysed. Clinical and virological parameters were documented retrospectively and retreatment efficacies were evaluated.Results: We evaluated 90 glecaprevir/pibrentasvir failures [3a (n = 36), 1a (n = 23), 2a/2c (n = 20), 1b (n = 10) and 4d (n = 1)]. Ten patients were cirrhotic, two had previous exposure to PEG-interferon and seven were coinfected with HIV; 80 had been treated for 8 weeks. Overall, 31 patients (34.4%) failed glecaprevir/pibrentasvir without any NS3 or NS5A RASs, 62.4% (53/85) showed RASs in NS5A, 15.6% (13/83) in NS3 and 10% (9/90) in both NS5A and NS3. Infection with HCV genotypes 1a and 3a was associated with a higher prevalence of NS5A RASs. Patients harbouring two (n = 34) or more (n = 8) RASs in NS5A were frequent. Retreatment was initiated in 56 patients, almost all (n = 52) with sofosbuvir/velpatasvir/voxilaprevir. The overall sustained virological response rate was 97.8% in patients with end-of-follow-up data available.Conclusions: One-third of patients failed glecaprevir/pibrentasvir without resistance. RASs in NS5A were more prevalent than in NS3 and were frequently observed as dual and triple combination patterns, with a high impact on NS5A inhibitor activity, particularly in genotypes 1a and 3a. Retreatment of glecaprevir/pibrentasvir failures with sofosbuvir/velpatasvir/voxilaprevir achieved viral suppression across all genotypes. [ABSTRACT FROM AUTHOR]

Editorial. Introduces a series of articles on artificial intelligence adapted from the Ibero-American Conference on Artificial Intelligence, IBERAMIA 2002 in Seville, Spain.

To assess the effect of hydroxychloroquine (HCQ) and Tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) as pre-exposure prophylaxis on COVID-19 risk. EPICOS is a double-blind, placebo-controlled randomized trial conducted in Spain, Bolivia, and Venezuela. Healthcare workers with negative SARS-CoV-2 IgM/IgG test were randomly assigned to the following: daily TDF/FTC plus HCQ for 12 weeks, TDF/FTC plus HCQ placebo, HCQ plus TDF/FTC placebo, and TDF/FTC placebo plus HCQ placebo. Randomization was performed in groups of four. Primary outcome was laboratory-confirmed, symptomatic COVID-19. We also studied any (symptomatic or asymptomatic) COVID-19. We compared group-specific 14-week risks via differences and ratios with 95% CIs. Of 1002 individuals screened, 926 (92.4%) were eligible and there were 14 cases of symptomatic COVID-19: 220 were assigned to the TDF/FTC plus HCQ group (3 cases), 231 to the TDF/FTC placebo plus HCQ group (3 cases), 233 to the TDF/FTC plus HCQ placebo group (3 cases), and 223 to the double placebo group (5 cases). Compared with the double placebo group, 14-week risk ratios (95% CI) of symptomatic COVID-19 were 0.39 (0.00–1.98) for TDF + HCQ, 0.34 (0.00–2.06) for TDF, and 0.49 (0.00–2.29) for HCQ. Corresponding risk ratios of any COVID-19 were 0.51 (0.21–1.00) for TDF + HCQ, 0.81 (0.44–1.49) for TDF, and 0.73 (0.41–1.38) for HCQ. Adverse events were generally mild. The target sample size was not met. Our findings are compatible with both benefit and harm of pre-exposure prophylaxis with TDF/FTC and HCQ, alone or in combination, compared with placebo. [ABSTRACT FROM AUTHOR]

Abstract: At Sima de las Palomas del Cabezo Gordo (Murcia, Spain) remains of several Neanderthals have been excavated recently. From about 50,000 years ago articulated parts of 3 adult skeletons (including skulls with mandibles, vertebral column, rib cages, shoulder blades, hip bones, upper and lower limbs, hands and feet, often in anatomical connexion) were excavated from the lower part of a cemented accumulation of scree and large stones (éboulis) sloping downwards and inwards into the cavity, along with burnt bones of large mammals and Mousterian implements. The excavation of the skeletons is the subject of this paper (palaeoanthropological skeletal descriptions are soon to be published elsewhere). Behind the cemented scree there accumulated a layer of finer sediment containing burnt animal bones, followed by more fine sediment that filled the cavity up to the overhanging rock roof and contained isolated teeth and unburnt bone fragments of Neanderthals, including 3 mandibles, as well as Mousterian implements and faunal remains, all dating from before 40,000 years ago. Altogether, at least 9 Neanderthals are represented by finds from the site (including 3 unstratified mandibles), ranging from babies to adults. Dating methods include radiocarbon, uranium-series, and optical luminescence. Pollen analysis implies conditions less severe than those of the Heinrich 4 cold oscillation at 40,000 years ago. [Copyright &y& Elsevier]