Diagnóstico microbiológico de la infección por el VIH

Producción CientíficaEn la actualidad se calcula que en España hay alrededor de 150.000 personas infectadas por el virus de la inmunodeficiencia humana (VIH). Este número, junto con el hecho de que esta enfermedad se haya convertido en una patología crónica gracias a los nuevos tratamientos antirretrovirales, condiciona una gran demanda asistencial en los laboratorios de microbiología de nuestros hospitales. Esta mayor demanda tiene lugar no sólo en el terreno del diagnóstico y tratamiento de las infecciones oportunistas, sino también en pruebas que ayudan en el diagnóstico y tratamiento terapéutico de la propia infección por el virus. Consciente de ello, la Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica ha realizado una actualización de su procedimiento sobre el diagnóstico microbiológico de la infección por VIH. En dicho procedimiento se realiza una revisión de las principales novedades en el terreno del diagnóstico serológico, de la carga viral plasmática y de la detección de resistencias a los distintos retrovirales

A randomized trial of the discontinuation of primary and secondary prophylaxis against Pneumocystis carinii pneumonia after highly active antiretroviral therapy in patients with HIV infection

Background: Prophylaxis against Pneumocystis carinii pneumonia is indicated in patients with human immunodeficiency virus (HIV) infection who have less than 200 CD4 cells per cubic millimeter and in those with a history of P. carinii pneumonia. However, it is not clear whether prophylaxis can be safely discontinued after CD4 cell counts increase in response to highly active antiretroviral therapy. Methods: We conducted a randomized trial of the discontinuation of primary or secondary prophylaxis against P. carinii pneumonia in HIV-infected patients with a sustained response to antiretroviral therapy, defined by a CD4 cell count of 200 or more per cubic millimeter and a plasma HIV type 1 (HIV-1) RNA level of less than 5000 copies per milliliter for at least three months. Prophylactic treatment was restarted if the CD4 cell count declined to less than 200 per cubic millimeter. Results: The 474 patients receiving primary prophylaxis had a median CD4 cell count at entry of 342 per cubic millimeter, and 38 percent had detectable HIV-1 RNA. After a median follow-up period of 20 months (388 person-years), there had been no episodes of P. carinii pneumonia in the 240 patients who discontinued prophylaxis (95 percent confidence interval, 0 to 0.85 episode per 100 person-years). For the 113 patients receiving secondary prophylaxis, the median CD4 cell count at entry was 355 per cubic millimeter, and 24 percent had detectable HIV-1 RNA. After a median follow-up period of 12 months (65 person-years), there had been no episodes of P. carinii pneumonia in the 60 patients who discontinued prophylaxis (95 percent confidence interval, 0 to 4.57 episodes per 100 person-years). Conclusions: In HIV-infected patients receiving highly active antiretroviral therapy, primary and secondary prophylaxis against P. carinii pneumonia can be safely discontinued after the CD4 cell count has increased to 200 or more per cubic millimeter for more than three months

Safety and vaccine-induced HIV-1 immune responses in healthy volunteers following a late MVA-B boost 4 years after the last immunization

Background: We have previously shown that an HIV vaccine regimen including three doses of HIV-modified vaccinia virus Ankara vector expressing HIV-1 antigens from clade B (MVA-B) was safe and elicited moderate and durable (1 year) T-cell and antibody responses in 75% and 95% of HIV-negative volunteers (n = 24), respectively (RISVAC02 study). Here, we describe the long-term durability of vaccine-induced responses and the safety and immunogenicity of an additional MVA-B boost. Methods: 13 volunteers from the RISVAC02 trial were recruited to receive a fourth dose of MVA-B 4 years after the last immunization. End-points were safety, cellular and humoral immune responses to HIV-1 and vector antigens assessed by ELISPOT, intracellular cytokine staining (ICS) and ELISA performed before and 2, 4 and 12 weeks after receiving the boost. Results: Volunteers reported 64 adverse events (AEs), although none was a vaccine-related serious AE. After 4 years from the 1st dose of the vaccine, only 2 volunteers maintained low HIV-specific T-cell responses. After the late MVA-B boost, a modest increase in IFN-γ T-cell responses, mainly directed against Env, was detected by ELISPOT in 5/13 (38%) volunteers. ICS confirmed similar results with 45% of volunteers showing that CD4+ T-cell responses were mainly directed against Env, whereas CD8+ T cell-responses were similarly distributed against Env, Gag and GPN. In terms of antibody responses, 23.1% of the vaccinees had detectable Env-specific binding antibodies 4 years after the last MVA-B immunization with a mean titer of 96.5. The late MVA-B boost significantly improved both the response rate (92.3%) and the magnitude of the systemic binding antibodies to gp120 (mean titer of 11460). HIV-1 neutralizing antibodies were also enhanced and detected in 77% of volunteers. Moreover, MVA vector-specific T cell and antibody responses were boosted in 80% and 100% of volunteers respectively. Conclusions: One boost of MVA-B four years after receiving 3 doses of the same vaccine was safe, induced moderate increases in HIV-specific T cell responses in 38% of volunteers but significantly boosted the binding and neutralizing antibody responses to HIV-1 and to the MVA vector

Safety and immunogenicity of a modified pox vector-based HIV/AIDS vaccine candidate expressing Env, Gag, Pol and Nef proteins of HIV-1 subtype B (MVA-B) in healthy HIV-1-uninfected volunteers: A phase I clinical trial (RISVAC02)

Clinical Trial, Phase ITo investigate the safety and immunogenicity of a modified vaccinia virus Ankara vector expressing HIV-1 antigens from clade B (MVA-B), a phase-I, doubled-blind placebo-controlled trial was performed.Peer reviewe

A phase I randomized therapeutic MVA-B vaccination improves the magnitude and quality of the T cell immune responses in HIV-1-infected subjects on HAART

Trial Design Previous studies suggested that poxvirus-based vaccines might be instrumental in the therapeutic HIV field. A phase I clinical trial was conducted in HIV-1-infected patients on highly active antiretroviral therapy (HAART), with CD4 T cell counts above 450 cells/mm3 and undetectable viremia. Thirty participants were randomized (2:1) to receive either 3 intramuscular injections of MVA-B vaccine (coding for clade B HIV-1 Env, Gag, Pol and Nef antigens) or placebo, followed by interruption of HAART. Methods The magnitude, breadth, quality and phenotype of the HIV-1-specific T cell response were assayed by intracellular cytokine staining (ICS) in 22 volunteers pre- and post-vaccination. Results MVA-B vaccine induced newly detected HIV-1-specific CD4 T cell responses and expanded pre-existing responses (mostly against Gag, Pol and Nef antigens) that were high in magnitude, broadly directed and showed an enhanced polyfunctionality with a T effector memory (TEM) phenotype, while maintaining the magnitude and quality of the pre-existing HIV-1- specific CD8 T cell responses. In addition, vaccination also triggered preferential CD8+ T cell polyfunctional responses to the MVA vector antigens that increase in magnitude after two and three booster doses

Novel genes and sex differences in COVID-19 severity

[EN] Here, we describe the results of a genome-wide study conducted in 11 939 coronavirus disease 2019 (COVID-19) positive cases with an extensive clinical information that were recruited from 34 hospitals across Spain (SCOURGE consortium). In sex-disaggregated genome-wide association studies for COVID-19 hospitalization, genome-wide significance (P < 5 × 10−8) was crossed for variants in 3p21.31 and 21q22.11 loci only among males (P = 1.3 × 10−22 and P = 8.1 × 10−12, respectively), and for variants in 9q21.32 near TLE1 only among females (P = 4.4 × 10−8). In a second phase, results were combined with an independent Spanish cohort (1598 COVID-19 cases and 1068 population controls), revealing in the overall analysis two novel risk loci in 9p13.3 and 19q13.12, with fine-mapping prioritized variants functionally associated with AQP3 (P = 2.7 × 10−8) and ARHGAP33 (P = 1.3 × 10−8), respectively. The meta-analysis of both phases with four European studies stratified by sex from the Host Genetics Initiative (HGI) confirmed the association of the 3p21.31 and 21q22.11 loci predominantly in males and replicated a recently reported variant in 11p13 (ELF5, P = 4.1 × 10−8). Six of the COVID-19 HGI discovered loci were replicated and an HGI-based genetic risk score predicted the severity strata in SCOURGE. We also found more SNP-heritability and larger heritability differences by age (<60 or ≥60 years) among males than among females. Parallel genome-wide screening of inbreeding depression in SCOURGE also showed an effect of homozygosity in COVID-19 hospitalization and severity and this effect was stronger among older males. In summary, new candidate genes for COVID-19 severity and evidence supporting genetic disparities among sexes are provided.S

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

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 &lt; 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

La política geoespacial en el ministerio de defensa

Geospatial information is a strategic resource for the accomplishment of the missions that have been commissioned to the Armed Forces in both National Territory and abroad. After an introduction to geospatial information, this paper presents a brief summary of the initiatives and regulations that rule the standardization and harmonization of the geospatial information procedures and the generation of application products on an European and National basis, followed by the specific study of our most relevant projects for defence purposes.La información geoespacial es un recurso estratégico para el cumplimiento de las misiones que las Fuerzas Armadas tienen encomendadas tanto en Territorio Nacional como en el exterior. Después de una introducción a la información geoespacial el documento presenta un breve resumen de las iniciativas y de la regulación que rigen la estandarización y armonización de los procedimientos de información geoespacial y la generación de productos de aplicación, sobre una base europea y nacional, seguido del estudio específico de los proyectos más relevantes para los propósitos de defensa