Centro Nacional de Microbiología (CNM)

Permanent URI for this collectionhttps://hdl.handle.net/20.500.12105/19609

El Centro Nacional de Microbiología (CNM) es uno de los centros pertenecientes al Instituto de Salud Carlos III que proporciona apoyo científico-técnico a la Administración General del Estado, a las Comunidades Autónomas y al Sistema Nacional de Salud (SNS), tal y como se recoge en La Ley General de Sanidad (Ley 14/1986, de 25 de abril) y el Estatuto del Instituto de Salud Carlos III (RD 375/2001, de 6 abril y su posterior reforma, RD 1672/2009, de 6 de noviembre). La función específica del CNM es el control de las enfermedades infecciosas para lo que ofrece servicios de diagnóstico y referencia, manteniendo además programas de investigación, tanto básica como orientada, relacionados con la prevención, el diagnóstico y el tratamiento de estas enfermedades. Dispone de un sistema de gestión de calidad conforme a la norma UNE-EN ISO 9001, certificado por AENOR, para la recepción de muestras biológicas, así como varias técnicas y servicios acreditados por ENAC según la norma UNE-EN ISO 15189.

Browse

Now showing 1 - 20 of 2017

Sex and age-related differences in humoral and cellular responses to the recombinant zoster vaccine in people living with HIV.
(Elsevier, 2025-11) Díez, Cristina; Pita-Martínez, Carlos; Quero-Delgado, Marta; Gómez-Tórtola, Aurora; Fanciulli, Chiara; Marchan, Ana; Aldámiz-Echevarría, Teresa; Sepulveda-Crespo, Daniel; Tejerina, Francisco; Pérez-Latorre, Leire; Gutiérrez, Isabel; López, Juan Carlos; Martinez, Isidoro; Resino, Salvador; Agencia Estatal de Investigación (España); Centro de Investigación Biomédica en Red - CIBERINFEC (Enfermedades Infecciosas); Instituto de Salud Carlos III; Unión Europea. Comisión Europea. NextGenerationEU
Background: Data on the immunogenicity of the recombinant zoster vaccine (RZV) in people living with HIV (PLWH) are limited, despite their high risk for herpes zoster. This study aimed to characterize the humoral (Varicella-zoster virus (VZV)-specific IgG) and cellular (VZV-specific IFN-γ/IL-2 T-cell) immune responses to RZV in PLWH on suppressive antiretroviral therapy (ART), stratified by sex and age. Methods: This prospective study enrolled 207 PLWH on suppressive ART who received two doses of RZV. VZV-specific IgG antibody titers were quantified by in-house ELISA at baseline and post-vaccination and T-cell responses using FluoroSpot assays post-vaccination. We estimated geometric mean titers (GMTs), geometric mean fold rises (GMFRs), and adjusted arithmetic mean ratios (aAMRs) using generalized linear models. Results: RZV vaccination induced a significant humoral response, with an overall GMFR of 16.7 and a 71 % positive response rate (≥4-fold rise in IgG titers). Females < 60 years old exhibited a markedly higher GMFR (43.8) than all other subgroups (p < 0.05). The vaccine also induced robust VZV-specific T-cell responses, with GMTs being comparable across all groups. Notably, a strong positive association was found between humoral and T-cell responses, particularly with IL-2-secreting cells (aAMR=1.6, p < 0.001). This association was most pronounced in participants < 60 years, especially females, and was attenuated in older individuals. Conclusions: RZV vaccination effectively induces both humoral and T-cell immunity in PLWH. However, host factors, such as sex and age, critically modulate immunogenicity. Females < 60 years showed a superior humoral response and the strongest association between immune compartments, highlighting important variability in vaccine responsiveness.
Identification and functional insights into new phage tail-like bacteriocins targeting as new antimicrobials.
(American Society for Microbiology (ASM), 2026-03-24) Ibarguren-Quiles, Clara; Blasco, Lucía; López-Causape, Carla; Bleriot, Inés; Fernández-García, Laura; Arman, Lucia; Barrio-Pujante, Antonio; Ortiz-Cartagena, Concha; Aracil, Belen; Menéndez-Rodriguez, Olaya; Mariñas-Pardo, Luis; Cantón, Rafael; Oliver, Antonio; Tomás, María; Instituto de Salud Carlos III; Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF); Centro de Investigación Biomédica en Red - CIBERINFEC (Enfermedades Infecciosas); Ministerio de Ciencia, Innovación y Universidades (España); Unión Europea. Comisión Europea. NextGenerationEU; Xunta de Galicia (España)
The current health crisis caused by multidrug-resistant (MDR) pathogens is one of the health problems of most concern globally. Infections caused by these pathogens, such as , lead to high rates of complications, particularly in compromised patients such as cystic fibrosis (CF) patients. The need to counteract and minimize the forecast future impact has led to the rescue of phage therapy. The use of bacteriophages has important advantages, including highly specific targeting, self-amplification at the infection site, minimal disruption of the microbiome, safety, and biocompatibility. However, the capacity of bacteria to escape these entities results in a form of resistance that compromises the effectiveness of the therapy. This involves the search for potential alternatives, such as the phage tail-like bacteriocins (PTLBs), also named as tailocins. These high-molecular-weight particles resemble the tail structure of bacteriophages and are characterized by the absence of genetic material, avoiding the development of resistance, one of the major handicaps associated with phage therapy. In this study, we detected 34 different PTLBs in 75 genomes, with different serotypes and sequence types, 11 of which were characterized as novel F-type PTLB subtypes (F13-F24). Furthermore, we report that four selected PTLBs (R1, F15, F19, and R3-F24) can deal with bacterial infection, with the R1 and the F15 PTLBs being the most efficient in clearing infection , yielding a survival rate of more than 75% in the larvae model. This reaffirms the potential of PTLBs to control infections, which can cause chronic infections in some patients, such as people with CF, due to its strong impact as a MDR bacterium.IMPORTANCEThe 75 genomes from people with cystic fibrosis in the study collection included at least one phage tail-like bacteriocins (PTLB) cluster. From the 34 different PTLBs detected in the study collection, 7 were R-type, 10 were complex (R- and F-type encoded), and 14 were F-type PTLBs. Eleven new F-type PTLBs were described in the collection under study. An association between the O-antigen present on the surface of the isolate and the encoded PTLB subtype was detected. The R1 and F15 PTLB subtypes display high antimicrobial activity both in vitro and in vivo (Galleria mellonella).
Advances in Nanotechnology-Enabled Optical Biosensors for Dengue Virus Detection: A Systematic Review.
(Wiley, 2025-07-29) Quero-Delgado, Marta; Codina Márquez, Helena; Gómez, Rafael; Terán, Francisco José; Muñoz-Fernández, M A; Jiménez, José Luis; Resino, Salvador; Sepulveda-Crespo, Daniel; Martinez, Isidoro; Instituto de Salud Carlos III; Centro de Investigación Biomédica en Red - CIBERINFEC (Enfermedades Infecciosas); Centro de Investigación Biomédica en Red - CIBERBBN (Bioingeniería, Biomateriales y Nanomedicina); Comunidad de Madrid (España)
The dramatic surge in dengue cases in early 2024, endangering half the global population, urgently necessitates faster diagnostic methods. Nanotechnology-enabled optical biosensors offer a promising avenue, leveraging nanomaterial properties for highly sensitive detection of dengue virus (DENV), potentially surpassing conventional techniques in terms of simplicity, speed, and cost-effectiveness. This systematic review analyzes recent advancements in these biosensors for DENV diagnosis. Following PRISMA 2020 guidelines, we systematically searched PubMed, Embase, Scopus, Web of Science, and Cochrane Library databases (2010-June 1, 2025; OSF: https://osf.io/3gmey/). The methodological quality of the 98 included studies was assessed using a modified CASP checklist. Diverse nanotechnology-based optical biosensors were identified. SPR (36.7%) was the most common transducer, followed by fluorescence (24.5%), colorimetry (15.3%), and SERS (8.2%). Gold-based nanomaterials (35.7%) were most frequently employed, with silver nanomaterials (15.3%), quantum dots (15.3%), and graphene-based materials (15.3%) also showing promise. DENV NS1 protein was the primary target analyte (21.4%). Importantly, almost half of the studies (44.9%) used clinically relevant human samples. While many optical biosensors show promise, challenges hinder their demonstration of the true potential for point-of-care use in their current format; however, they offer high specificity and faster results, laying a strong foundation for cost-effective clinical diagnostics. Nanotechnology-driven optical biosensors offer a transformative approach for DENV detection. Advances in computational design and green synthesis of novel nanomaterials are key to addressing stability and field-deployment challenges. These innovations are crucial for developing robust, sensitive, and user-friendly tools to manage dengue and improve patient outcomes globally.
From Management to Cure: The Shifting Paradigm in HIV and Chronic Viral Hepatitis.
(Multidisciplinary Digital Publishing Institute (MDPI), 2025-07-11) Sepulveda-Crespo, Daniel; Resino, Salvador
The management of human immunodeficiency virus (HIV) and chronic viral hepatitis (HBV, HCV, and HDV) infections continues to pose a significant global health challenge [...].
Prevalence and risk factors of active hepatitis C infection among at-risk migrant populations in Madrid, Spain, 2019 to 2023.
(European Centre for Disease Prevention and Control (ECDC), 2025-07) Ryan, Pablo; Valencia, Jorge; Pérez-García, Felipe; Quero-Delgado, Marta; Cuevas, Guillermo; Manzano, Samuel; Estévez, Samuel; Martinez, Isidoro; Sepulveda-Crespo, Daniel; Resino, Salvador; Gilead Sciences (Spain); Instituto de Salud Carlos III; AbbVie; Asociación Española para el Estudio del Hígado; Centro de Investigación Biomédica en Red - CIBERINFEC (Enfermedades Infecciosas)
Background: Hepatitis C virus (HCV) microelimination among at-risk migrants supports global elimination goals.AIMTo evaluate risk factors, prevalence and trends of active HCV infection among at-risk migrants screened for HCV in Madrid from 2019-23. Methods: At-risk migrants (born outside Spain, living in country < 10 years regardless of legal status), were screened for HCV via mobile units with rapid antibody testing, and confirmed by RNA testing. Recruitment of this convenience sample focused on migrant centres, shelters, harm reduction centres and social service sites. Primary outcome was active HCV prevalence. Risk factors analysed included origin, alcohol use, no stable income, drug use and sexual behaviour. Data were analysed using general linear models with negative binomial distribution and p values adjusted for multiple comparisons (q values). Results: TSAmong 2,288 migrants, 6.5% (149/2,288) had anti-HCV antibodies, 47.0% (70/149) of whom tested positive for HCV-RNA; 81.4% (57/70) began antiviral therapy. Overall prevalence of active HCV infection was 3.1% (70/2,288). Injection drug use (non-active vs never used (aIRR: 7.3; 95% CI: 2.7-12.7) and active (aIRR: 14.7; 95% CI: 6.7-32.1)), European origin (vs non-European; aIRR: 5.8; 95% CI: 2.7-12.7) and alcohol misuse (vs no misuse; aIRR: 1.8; 95% CI: 1.1-2.9) were main risk factors. Prevalence showed no significant change during 2019-23 in the overall population and across risk groups. Conclusion: At-risk migrants screened in Madrid had a high prevalence of active HCV infection. This is higher than reported estimates for the general Spanish population and supports the need to enhance targeted HCV prevention, screening and treatment strategies among migrant populations.
Persistent Low Anti-HIV Neutralizing Antibody Titers in HIV/HCV Coinfection Despite HCV Cure: A 5-Year Longitudinal Analysis.
(Multidisciplinary Digital Publishing Institute (MDPI), 2025-05-19) Sepulveda-Crespo, Daniel; Sánchez-Merino, Víctor; Amigot-Sánchez, Rafael; Rubio-Pérez, Almudena; Díez, Cristina; Hontañón, Víctor; Berenguer, Juan; González-García, Juan; García, Felipe; Martinez, Isidoro; Yuste, Eloísa; Resino, Salvador; Instituto de Salud Carlos III; Centro de Investigación Biomédica en Red - CIBERINFEC (Enfermedades Infecciosas)
Background: Anti-HIV neutralizing antibodies (anti-HIV-nAbs) play a critical role in the immune defense against HIV by preventing viral entry and limiting replication. This study longitudinally evaluated the titers and variability of anti-HIV-nAbs in individuals coinfected with HIV and HCV. Samples were collected at three time points: before starting HCV treatment, one year after completion, and five years post-treatment. Methods: A retrospective analysis was conducted on 71 HIV/HCV-coinfected patients who achieved a sustained virologic response following antiviral therapy for HCV. A control group of 41 HIV-monoinfected individuals was also included. Anti-HIV-nAb titers were evaluated by HIV neutralization assays using a panel of six recombinant HIV viruses representing multiple genetic subtypes. Generalized Linear Mixed Models and Generalized Linear Models were used for statistical analysis. p-values were adjusted using the Benjamini-Hochberg procedure (q-value). Results: HIV-neutralizing antibody responses in HIV/HCV-coinfected individuals remained stable over five years following HCV therapy without significant changes (q-value > 0.05). The mean neutralization scores remained stable, with baseline scores of 6.1 (95% CI: 5.4-6.7), 6.2 (95% CI: 5.5-6.8) at one year post-HCV therapy, and 6.0 (95% CI: 5.3-6.7) at five years post-HCV therapy. HIV/HCV-coinfected individuals consistently showed lower neutralization scores compared to the control group throughout the follow-up (q-value < 0.05). Regression analyses adjusted for age, gender, nadir CD4+, and baseline CD4+ counts confirmed that the observed differences between HIV-monoinfected and HIV/HCV-coinfected individuals persisted (q-value < 0.05) at both the baseline and after HCV therapy completion. Conclusions: Successful HCV eradication in HIV/HCV-coinfected individuals did not normalize anti-HIV-nAb titers, which remained consistently lower than those in HIV-monoinfected controls over five years.
Antibody Response Against SARS-CoV-2 Spike Protein in People with HIV After COVID-19 Vaccination.
(Multidisciplinary Digital Publishing Institute (MDPI), 2025-04-29) Muñoz-Gómez, María José; Ryan, Pablo; Quero-Delgado, Marta; Martin-Vicente, Maria; Cuevas, Guillermo; Valencia, Jorge; Jiménez, Eva; Blanca-López, Natalia; Manzano, Samuel; Lazo, Juan Ignacio; Mas, Vicente; Vázquez, Mónica; Sepulveda-Crespo, Daniel; Torres-Macho, Juan; Martinez, Isidoro; Resino, Salvador; Instituto de Salud Carlos III; Centro de Investigación Biomédica en Red - CIBERINFEC (Enfermedades Infecciosas)
People with HIV (PWH) often have a suboptimal response to vaccines, raising concerns regarding the efficacy of coronavirus disease 2019 (COVID-19) vaccines in this population. We aimed to evaluate the humoral immune response to the B.1 lineage and Omicron variant in PWH on antiretroviral therapy (ART) following COVID-19 vaccination. : We conducted a prospective study of 19 PWH on ART who received a two-dose series of the COVID-19 mRNA vaccine and a booster six months later. Participants without HIV infection (n = 25) were included as a healthy control (HC) group. The humoral response to the COVID-19 vaccine (anti-SARS-CoV-2 S IgG levels and ability to block ACE2-S interaction) against both the original B.1 lineage and the Omicron variant was assessed using immunoassays. : The humoral response in PWH was very strong (geometric mean fold rise, GMFR > 8) after the second dose and strong (GMFR > 4) after the booster dose for both the B.1 lineage and the Omicron variant. We found comparable humoral responses to the B.1 lineage and Omicron variant between PWH and HC groups after the second and booster doses (q-value > 0.05). The COVID-19 vaccine generated a significantly weaker humoral response against the Omicron variant compared to the B.1 lineage in both groups (q-value < 0.05). However, this response improved after the booster dose, although it remained weaker in PWH. : PWH showed a strong humoral response to the COVID-19 vaccine against B.1 and Omicron, though the Omicron response was weaker than B.1. Booster doses in PWH improved the Omicron response, but it stayed lower than B.1. Findings confirm vaccine effectiveness in PWH, stressing the critical role of boosters and potential need for updated vaccines for variants like Omicron.
Diagnostic performance of dried blood spot hepatitis C virus core antigen testing for hepatitis C screening: A systematic review and meta-analysis.
(Wiley, 2024-10) Treviño-Nakoura, Ana; Sepulveda-Crespo, Daniel; Bellon, José M; Codina, Helena; Amigot-Sánchez, Rafael; Quero-Delgado, Marta; Ryan, Pablo; Martinez, Isidoro; Resino, Salvador; Instituto de Salud Carlos III; Gilead Sciences (Spain); Centro de Investigación Biomédica en Red - CIBERINFEC (Enfermedades Infecciosas)
Dried blood spot (DBS) sampling is increasingly used for hepatitis C virus (HCV) screening. HCVcAg testing offers a faster and more streamlined approach to diagnosing HCV infection. We conducted a systematic review and meta-analysis to assess the diagnostic performance of the Abbott ARCHITECT HCV Ag assay for screening active HCV infection using DBS samples. Eight studies (n = 1229) were selected among all published studies available up to October 4, 2024, in different databases with a search strategy registered (PROSPERO: CRD42022363975). The gold standard method was the HCV PCR test. Data were analyzed using the MIDAS module in STATA with a random effects model. Combined diagnostic accuracy measures were as follows: sensitivity 85%, specificity 100%, positive likelihood ratio (PLR) 233.1, negative likelihood ratio (NLR) 0.15, and summary receiver operating characteristic (SROC) 0.99. Likelihood ratios and Fagan's nomogram suggested that the HCVcAg assay with DBS samples can confirm or rule out active HCV infection with over 92% accuracy in high-prevalence settings (≥5%). However, in low-prevalence settings (≤1%), a confirmatory test must be required for positive results. The ability of the test to identify people without HCV infection was high regardless of HCV prevalence, with an error rate of less than 3%. This meta-analysis is subject to limitations, particularly due to the number of included studies and significant heterogeneity among them. HCV screening using the Abbott ARCHITECT HCV Ag assay with DBS samples showed excellent diagnostic performance, but its external validity may be limited when HCV prevalence is low (≤1%).
IL7RA rs10491434 polymorphism is related to spontaneous HIV infection control in naïve HIV-infected patients: A retrospective study.
(Wiley, 2023-11) Sepulveda-Crespo, Daniel; Jimenez-Sousa, Maria Angeles; Fernandez-Rodriguez, Amanda; Muñoz-Fernández, María A; Jiménez, José L; Caraciolo, Begoña B; Reus Bañuls, Sergio; Vilchez, Helem; Mothe, Beatriz; Martinez, Isidoro; Benito, José M; Rallón, Norma; Resino, Salvador; Instituto de Salud Carlos III; Ministerio de Ciencia, Innovación y Universidades (España); Redes Temáticas de Investigación Cooperativa en Salud (RETICS) (España); Centro de Investigación Biomédica en Red - CIBERINFEC (Enfermedades Infecciosas); Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF); Unión Europea. Comisión Europea. NextGenerationEU
Interleukin 7 receptor (IL7R) is vital in the adaptive immune response against human immunodeficiency viruses (HIV). We assessed IL7RA polymorphisms (SNPs) in antiretroviral therapy (ART)-naïve HIV patients for their association with spontaneous HIV infection control. We conducted a retrospective cohort study involving 667 ART-naïve patients categorized by HIV progression (ordinal variable): 150 rapid progressors, 334 moderate/typical progressors, 86 long-term nonprogressors elite controllers (LTNPs-EC), and 97 LTNPs-non-EC. We genotyped three IL7RA SNPs using Agena Bioscience's MassARRAY platform. The association between IL7RA SNPs and spontaneous HIV infection control was evaluated using ordinal logistic regression. Individuals carrying the rs10491434 G allele have a higher likelihood of spontaneous HIV infection control (adjusted odds ratio [aOR] = 1.33; p = 0.023). Moreover, the IL7RA GCT haplotype, consisting of three specific SNPs (rs6897932, rs987106, and rs10491434), demonstrated an association with the control of untreated HIV infection (aOR = 1.34; p = 0.050). Remarkably, the rs10491434 SNP and the IL7RA GCT haplotype exhibited similar aOR values, suggesting that rs10491434 may be primarily responsible for the observed effect of the haplotype. IL7RA rs10491434 G allele is associated with a higher likelihood of spontaneous HIV infection control, indicating its significant role in the pathogenesis of HIV, possibly influencing infection course and viral replication control.
IgG antibody levels against the SARS-CoV-2 spike protein in mother-child dyads after COVID-19 vaccination.
(Springer Nature, 2024-06) Muñoz-Gómez, María José; Martin-Vicente, Maria; Vigil-Vazquez, Sara; Carrasco, Itziar; Lobo, Alicia Hernanz; Mas, Vicente; Vázquez, Mónica; Manzanares, Angela; Cano, Olga; Zamora, Clara; Alonso, Roberto; Sepulveda-Crespo, Daniel; Tarancon-Diez, Laura; Muñoz-Fernández, María Ángeles; Muñoz-Chapuli, Mar; Resino, Salvador; Navarro, Maria Luisa; Martinez, Isidoro; Instituto de Salud Carlos III; Centro de Investigación Biomédica en Red - CIBERINFEC (Enfermedades Infecciosas); Centro de Investigación Biomédica en Red - CIBERBBN (Bioingeniería, Biomateriales y Nanomedicina)
Purpose: We aimed to assess IgG antibodies against the SARS-CoV-2 spike protein (anti-SARS-CoV-2 S IgG) in vaccinated mothers and their infants at delivery and 2-3 months of age. Methods: We conducted a prospective study on mothers who received at least one dose of the COVID-19 vaccine (Pfizer-BNT162b2, Moderna mRNA-1273, or Oxford-AstraZeneca ChAdOx1-S) during pregnancy and on their infants. The baseline was at the time of delivery (n = 93), and the end of follow-up was 2 to 3 months post-partum (n = 53). Serum anti-SARS-CoV-2 S IgG titers and ACE2 binding inhibition levels were quantified by immunoassays. Results: Mothers and infants had high anti-SARS-CoV-2 S IgG titers against the B.1 lineage at birth. However, while antibody titers were maintained at 2-3 months post-partum in mothers, they decreased significantly in infants (p < 0.001). Positive and significant correlations were found between anti-SARS-CoV-2 S IgG titers and ACE2-binding inhibition levels in mothers and infants at birth and 2-3 months post-partum (r > 0.8, p < 0.001). Anti-S antibodies were also quantified for the Omicron variant at 2-3 months post-partum. The antibody titers against Omicron were significantly lower in mothers and infants than those against B.1 (p < 0.001). Again, a positive correlation was observed for Omicron between IgG titers and ACE2-binding inhibition both in mothers (r = 0.818, p < 0.001) and infants (r = 0.386, p < 0.005). Previous SARS-CoV-2 infection and COVID-19 vaccination near delivery positively impacted anti-SARS-CoV-2 S IgG levels. Conclusions: COVID-19 mRNA vaccines induce high anti-SARS-CoV-2 S titers in pregnant women, which can inhibit the binding of ACE2 to protein S and are efficiently transferred to the fetus. However, there was a rapid decrease in antibody levels at 2 to 3 months post-partum, particularly in infants.
Recently acquired hepatitis C: Epidemiological characteristics and treatment response in a large cohort of MSM living with HIV in Madrid.
(Elsevier, 2024-10) Martín-Carbonero, Luz; Gutierrez, Ángela; Bisbal, Otilia; Vergas, Jorge; González-Baeza, Alicia; Rodríguez Martín, Carmen; Vivancos, María Jesús; Sanz, José; Álvarez, Beatriz; Palomar, Marina; de Los Santos, Ignacio; Sepulveda-Crespo, Daniel; Resino, Salvador; Berenguer, Juan; Cano-Smith, Joanna; González-García, Juan; Ryan, Pablo; Instituto de Salud Carlos III
Introduction: We analyzed epidemiological, clinical characteristics, and the response to treatment in people living with HIV (PLHIV) who recently acquired hepatitis C (RAHC) in a multicentre study in Madrid (Spain). Methods: Multicenter, ambispective, observational study of RAHC in men who have sex with men (MSM) infected with HIV. Clinical, epidemiological, and RAHC evolution were recorded prospectively in 2019 and 2020 and retrospectively in 2017 and 2018. In patients who received HCV treatment, sustained virological response (SVR) was provided 12 weeks after the end of treatment in an intention to treat analysis (ITT): all treated patients were included; and in analysis per-protocol (PP): missing patients were excluded. Results: Overall, 133 patients were included. Median (IQR) age was 40 (34.3-46.1) years, 90.9% had at least one previous sexual transmission disease (STD), and 33.6% had previously hepatitis C. More than half of the prospective sample included patients using chemsex related drugs (57.3%), 45.7% of them intravenously. The most prevalent genotype was G1a (66.2%), followed by G4 (11.3%). Ten of 90 patients evaluated for spontaneous cure (11%) cured the infection spontaneously, and 119 had treatment after a median time of 1.8 (0.7-4.6) months: sustained virological response (SVR) was achieved in 90.7% in the ITT and 94.7% in the PP analysis, with no differences regarding the direct-acting antiviral agents (DAA) combination used. Conclusions: MSM infected by HIV with a RAHC were exposed to high-risk sexual behavior. Spontaneous cure rate was low, while SVR after treatment was achieved by more than 90%.
IRF5-TNOP3 polymorphisms are associated with elite control of HIV infection: A retrospective study.
(Wiley, 2023-06) Sepulveda-Crespo, Daniel; Jimenez-Sousa, Maria Angeles; Fernandez-Rodriguez, Amanda; Muñoz-Fernández, María A; Jiménez, José Luis; Moreno, Santiago; Garcia, Felipe; Martinez, Isidoro; Benito, José M; Rallón, Norma; Resino, Salvador; Instituto de Salud Carlos III; Ministerio de Ciencia, Innovación y Universidades (España); Plan Nacional de I+D+i (España); Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF); Unión Europea. Comisión Europea. NextGenerationEU; Centro de Investigación Biomédica en Red - CIBERINFEC (Enfermedades Infecciosas); Redes Temáticas de Investigación Cooperativa en Salud (RETICS) (España)
IRF5-TNPO3 polymorphisms have previously been related to immune response, and TNPO3 plays a role in human immunodeficiency virus (HIV)-1 infection after nuclear import. Therefore, we analyzed the genetic association between IRF5-TNPO3 polymorphisms and the HIV elite control in long-term nonprogressors (LTNPs). We performed a retrospective cohort study on 183 LTNPs, who were antiretroviral therapy-naïve with CD4 ≥ 500 cells/mm , viral load ≤10 000 copies/mL, and asymptomatic over 10 years after HIV seroconversion. The primary outcome variable was HIV elite control (undetectable viral load in at least 90% of the measurements for at least 1 year). Seven IRF5-TNPO3 polymorphisms were genotyped using Agena Bioscience's MassARRAY platform. We found a significant association between specific IRF5-TNPO3 genotypes and HIV elite control: rs2004640 TT (aOR = 2.05; p = 0.041), rs10954213 AA (aOR = 1.95; p = 0.035), rs2280714 TT (aOR = 2.02; p = 0.031), and rs10279821 CC (aOR = 2.12; p = 0.017). We also found a significant association between IRF5-TNPO3 haplotype TATC composed of the favorable significant polymorphisms (rs2004640, rs10954213, rs2280714, and rs10279821) and the HIV elite control (aOR = 1.59; p = 0.048). IRF5-TNPO3 rs2004640, rs10954213, rs2280714, and rs10279821 polymorphisms were related to HIV elite control in LTNPs. Our data provide new knowledge about the impact of IRF5-TNPO3 polymorphisms on HIV pathogenesis to understand the phenomenon of natural HIV control.
High prevalence of azole resistance among environmental isolates from outdoor air in Madrid, Spain.
(Frontiers Media, 2026-01-23) Soto-Debrán, Juan Carlos; Sanchez Iñigo, Francisco Javier; Calvo-López, Alejandro B; Alguacil-Cuéllar, Laura; Hrynzovska, Anastasiia A; Mellado, Emilia; Garcia Dos Santos-Alves, Saul; Alastruey-Izquierdo, Ana; Instituto de Salud Carlos III
Introduction: Aspergillus fumigatus has been designated by the World Health Organization (WHO) as a critical fungal pathogen. Its spores are commonly present in the air and are inhaled daily. Azoles are the first-line treatment for Aspergillus infections, but the emergence of resistance is a growing concern. However, limited data exist on the occurrence of azole-resistant A. fumigatus in the outdoor environment in Spain. Methods: This study aimed to investigate the prevalence of azole-resistant A. fumigatus isolates in outdoor air at two distinct locations in Madrid. We characterized the isolates using TRESPERG genotyping and examined the underlying molecular mechanisms responsible for azole resistance development. Results: Azole-resistant A. fumigatus isolates were found in 55% of the 20 air samples collected. Among the 200 A. fumigatus isolates analyzed, 38.5% were azole resistant and were classified into 10 different genotypes. Notably, the TR34/L98H mutation in Cyp51A was found in 77% of the resistant isolates, while 23% showed no mutations in the screened targets (cyp51A, cyp51B, or hmg1). Discussion: This study revealed a high prevalence of azole-resistant A. fumigatus in outdoor environmental air, with the TR34/L98H mutation being the main mechanism of azole resistance. A close genetic relationship was observed among the resistant isolates. This research underscores the need for continued monitoring of environmental azole-resistant A. fumigatus isolates and highlights the importance of understanding genetic diversity and resistance mechanisms to develop effective strategies for fungal infection control.
Elevated Zonulin-1 is Associated With an Increased Risk of Non-AIDS-Defining Cancers in People With HIV With Suboptimal Immune Recovery: A Case-Cohort Study.
(Wiley, 2026-04) Pita-Martínez, Carlos; Muñoz-García, Paula; Martinez, Isidoro; Rava, Marta; Bautista Hernández, Azucena; Pérez-Somarriba, Juncal; Campins, Antoni; Novella Mena, María; Vera, Francisco; Montero-Alonso, Marta; Jimenez-Sousa, Maria Angeles; Resino, Salvador; Martín-Escolano, Rubén; CoRIS cohort; Instituto de Salud Carlos III; Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF); Agencia Estatal de Investigación (España); Centro de Investigación Biomédica en Red - CIBERINFEC (Enfermedades Infecciosas); Comunidad de Madrid (España); Centro de Investigación Biomédica en Red - CIBERBBN (Bioingeniería, Biomateriales y Nanomedicina)
People with HIV (PWH) on antiretroviral therapy (ART) exhibit a heightened risk of non-AIDS-defining cancers (NADCs), linked to chronic inflammation driven by microbial translocation. We investigated whether plasma biomarkers of gut barrier dysfunction are associated with NADC risk, hypothesizing this association is modified by immune status. We conducted a case-cohort study nested within the Spanish CoRIS cohort. Plasma levels of zonulin-1, lipopolysaccharide, LPS-binding protein, and flagellin were measured in 71 incident NADC cases and a 261-individuals subcohort. Multivariable Cox proportional hazards models were used to estimate NADC risk, testing for effect modification by baseline CD4 + T-cell count. Zonulin-1 was not independently associated with NADC risk. However, a strong statistical interaction with baseline CD4 + T-cell count was detected (p = 0.001). Among individuals with suboptimal immune recovery (defined as CD4 + T-cell count < 500 cells/mm³), higher zonulin-1 levels were associated with a nearly threefold increased NADC risk (aHR = 2.94 (1.28-6.76)). Conversely, no association was observed in those with robust immune reconstitution (≥ 500 cells/mm³; aHR= 0.84 (0.41-1.72)). Other biomarkers showed no association. This supports a "two-hit" model of carcinogenesis where a compromised gut barrier and impaired immune competence are associated with an increased risk of cancer. Zonulin-1 is a key biomarker for identifying this high-risk phenotype, suggesting targeted cancer prevention strategies restoring gut integrity.
Lipid and immune dysregulation and risk of metabolic disorders after HCV clearance in HIV/HCV-coinfected participants with cACLD: a retrospective study.
(Frontiers Media, 2026-01-12) Virseda-Berdices, Ana; Requena, Belen; Berenguer, Juan; González-García, Juan; Gonzalez-Riano, Carolina; Díez, Cristina; Hontañon, Victor; Fernandez-Rodriguez, Amanda; Barbas, Coral; Resino, Salvador; Martín-Escolano, Rubén; Jimenez-Sousa, Maria Angeles; Instituto de Salud Carlos III; Agencia Estatal de Investigación (España); Unión Europea. Comisión Europea. NextGenerationEU; Comunidad de Madrid (España)
Introduction: People with HIV and chronic hepatitis C may develop metabolic complications after sustained virologic response (SVR), possibly due to persistent molecular alterations induced by HCV. This study aimed to identify baseline (pre-treatment) lipid and immune biomarkers associated with post-SVR metabolic events in HIV/HCV-coinfected participants with compensated advanced chronic liver disease (cACLD) receiving long-term suppressive antiretroviral therapy. Methods: We conducted a retrospective study of 56 HIV/HCV-coinfected participants with cACLD. Untargeted lipidomic profiling was performed on baseline plasma samples using a liquid-chromatography-mass spectrometer. The outcome was the development of metabolic events (diabetes mellitus and/or hyperlipidemia) during follow-up, up to seven years post-HCV treatment. Statistical analyses included orthogonal partial least squares discriminant analysis (OPLS-DA), Cox regressions models, and Spearman correlations with inflammation-related biomarkers and immune checkpoint proteins, with multiple comparison corrections using the false discovery rate. Results: 25% participants developed metabolic events after SVR. OPLS-DA identified 163 lipid species (VIP scores≥1) associated with these events, and adjusted Cox regression confirmed significant associations for 24 of them. Lysophosphatidylcholines (LPCs) were the most prevalent, with higher baseline levels linked to increased metabolic risk. Participants who developed events also had higher levels of plasmalogens LPC (O-LPC), lysophosphatidylethanolamine (LPE), lysophosphatidylinositol (LPI), lysophosphatidic acid (LPA), and phosphosphatidylcholine (PC). Several lipid species correlated positively with the pro-inflammatory cytokine IL-18, the anti-inflammatory suppressor IL-1RA, and the immune checkpoint proteins IDO and S100A8/A9. Discussion: Pre-treatment lipid and immune dysregulation was associated with post-SVR metabolic events in HIV/HCV-coinfected participants, suggesting that HCV may leave a lasting metabolic imprint that contributes to adverse outcomes after viral clearance.
HIV status defines distinct immunological drivers of persistent portal hypertension after HCV cure in people with advanced cirrhosis.
(Frontiers Media, 2026-02-02) Martín-Escolano, Rubén; Fernandez-Rodriguez, Amanda; Tarancon-Diez, Laura; Berenguer, Juan; Codina Márquez, Helena; Amigot-Sánchez, Rafael; González-García, Juan; Hontañón, Víctor; Pérez-Latorre, Leire; Ibañez-Samaniego, Luis; Llop-Herrera, Elba; Olveira, Antonio; Díaz, Laura; Martinez, Isidoro; Jimenez-Sousa, Maria Angeles; Resino, Salvador; Instituto de Salud Carlos III; Agencia Estatal de Investigación (España); Unión Europea. Comisión Europea. NextGenerationEU; Centro de Investigación Biomédica en Red - CIBERINFEC (Enfermedades Infecciosas); Comunidad de Madrid (España)
Introduction: The immunological drivers of portal hypertension regression after hepatitis C virus (HCV) cure are poorly understood, particularly in the context of human immunodeficiency virus (HIV) coinfection We aimed to identify baseline immune signatures predicting the evolution of the hepatic venous pressure gradient (HVPG) in people with and without HIV (PWH/PWoH). Methods: We prospectively followed 41 individuals with advanced cirrhosis (18 PWoH, 23 PWH) who were cured of HCV with direct-acting antivirals (DAA). Baseline plasma and cellular immune markers were extensively profiled using multiplex assays and flow cytometry. We used mixed-effects modeling to test for associations between these baseline immune features and the change in HVPG over a 48-week follow-up period, with q-values controlling for false discoveries. Results: Two distinct immunological profiles of impaired HVPG regression emerged. In PWoH, impaired regression was linked to a broad proinflammatory profile [TNF-α (AMR = 1.13; q=0.012), IL17A (AMR = 1.28; q=0.012), and IL10 (AMR = 1.2; q=0.028)], a widespread total CD4+ T-cell activation [HLA-DR+ (AMR = 1.44; q<0.001) and CD38+HLA-DR+ (AMR = 1.3; q=0.007)], and robust activation across central memory (CM) and effector memory (EM) subsets. Conversely, in PWH, impaired HVPG regression was associated with sVCAM-1 (AMR = 1.58; q=0.096), and a more focused activation within EM (HLA-DR+, AMR = 1.08; q=0.030) and TemRA (CD38+HLA-DR+, AMR = 1.12; q=0.030) CD4+ T-cells. Discussion: HIV coinfection fundamentally reshapes the immunological landscape of post-cure portal hypertension recovery. The shift from systemic inflammation in PWoH to endothelial dysfunction and T-cell exhaustion in PWH reveals distinct pathological pathways. Understanding these signatures is a crucial step toward developing targeted therapies to promote complete hepatic recovery.
Long-term effects of HCV eradication on lipid profiles associated with MASLD among people with HIV with advanced fibrosis or cirrhosis.
(Elsevier, 2025-12) Virseda-Berdices, Ana; Requena, Belen; Berenguer, Juan; Gónzalez-García, Juan; Gonzalez-Riano, Carolina; Díez, Cristina; Hontañón, Victor; Muñoz-García, Paula; Fernandez-Rodriguez, Amanda; Barbas, Coral; Resino, Salvador; Martín-Escolano, Rubén; Jimenez-Sousa, Maria Angeles; the Marathon Study Group; Instituto de Salud Carlos III; Centro de Investigación Biomédica en Red - CIBERINFEC (Enfermedades Infecciosas); Unión Europea. Comisión Europea. NextGenerationEU; Comunidad de Madrid (España)
Background: Despite successful hepatitis C virus (HCV) clearance, some individuals continue to experience liver disease progression. Metabolic dysfunction-associated steatotic liver disease (MASLD) may play a key role in this ongoing progression. This study aims to characterize the lipidomic profiles associated with MASLD in individuals coinfected with human immunodeficiency virus (HIV) and HCV with advanced fibrosis or cirrhosis after sustained virologic response (SVR). Methods: We conducted cross-sectional studies in fifty-two HIV/HCV-coinfected individuals. Untargeted lipidomics was performed on plasma samples collected at 1 year and 6 years post-SVR using liquid chromatography-mass spectrometry. The primary outcome was MASLD. Statistical analyses included orthogonal partial least squares discriminant analysis (OPLS-DA) and generalized linear models (GLM), with corrections for multiple comparisons. Results: The prevalence of MASLD was 28.9 % one year after SVR, increasing to 44.8 % six years after SVR. OPLS-DA models identified 225 lipids at 1 year and 167 at 6 years, with a VIP score ≥ 1, distinguishing individuals based on MASLD status. Adjusted GLMs confirmed significant associations between MASLD and 116 lipids at 1 year and 49 at 6 years. At 1 year, most significant lipids were glycerophospholipids (GP), with increased phosphatidylcholines (PC) and phosphatidylethanolamines (PE), and decreased lysophosphatidylcholines (LPC) and lysophosphatidylethanolamines (LPE). By 6 years, LPC was the most abundant differential lipid, while triglycerides increased significantly. Conclusions: MASLD was common during follow-up, with changes in lipidomic profiles over time suggesting ongoing metabolic disturbances that may contribute to liver disease progression despite SVR. These findings highlight the need for long-term metabolic and liver health monitoring after HCV eradication in these individuals.
Immune and senescence profiles associated with non-AIDS-defining cancer risk in people with HIV: a case-cohort study.
(Frontiers Media, 2025-10-21) Pita-Martínez, Carlos; Jimenez-Sousa, Maria Angeles; Martinez-Picado, Javier; Rodríguez, Carmen Elena Gómez; Fariñas, Carmen; Galindo, Pepa; Roca-Oporto, Cristina; Santos, Jesús; Muñoz-García, Paula; Rava, Marta; Resino, Salvador; Martín-Escolano, Rubén; Instituto de Salud Carlos III; Agencia Estatal de Investigación (España); Unión Europea. Comisión Europea. NextGenerationEU; Comunidad de Madrid (España); Centro de Investigación Biomédica en Red - CIBERINFEC (Enfermedades Infecciosas)
Introduction: People with HIV (PWH) on effective antiretroviral therapy (ART) have an increased risk of developing Non-AIDS Defining Cancers (NADCs) compared to the general population, partly due to chronic inflammation and immune dysregulation. This study aimed to identify plasma biomarkers associated with the risk of developing NADCs in a cohort of PWH on ART. Methods: A case-cohort study was conducted within the Spanish CoRIS cohort, including 316 PWH on ART (71 cases and 245-individuals subcohort). Plasma levels of 24 immune regulation and senescence-associated secretory phenotype (SASP) biomarkers were quantified using Luminex technology. Cox proportional hazards regression models with Borgan II weights were used to assess the association between biomarker levels and the risk of NADC development (hazard ratios), adjusting for confounders. Effect modification by gender was also evaluated. Results: Higher baseline plasma levels of twelve biomarkers were significantly associated with increased NADC risk. The strongest associations were found for PD-L2 (aHR=3.33), PAI-1 (aHR=2.27), and MMP-1 (aHR=2.32). However, a distinct, gender-specific pattern was observed, with significant interactions found for nine biomarkers. Most interactions indicated a higher NADC risk increase in females, with the exception of CD80, TNF-β and IP-10, which indicated a relatively lower risk in females compared to males. Discussion: Plasma biomarkers of immune regulation and SASP are associated with NADC risk in PWH on long-term ART, highlighting the importance of gender-specific pathways in NADC development among PWH. Understanding these distinct profiles may guide future strategies for risk stratification, early detection, and personalized preventive care.
Low Specific T-Cell Immunity Against Mpox Elicited in People With HIV-1 and PrEP Users After Subcutaneous Vaccination Compared to Natural Infection.
(Wiley, 2025-07) Calle-Jiménez, Olivia de la; Casado-Fernández, Guiomar; Armenteros-Yeguas, Inés; Lemus-Aguilar, Luis; Baza, Begoña; Pérez-García, Jorge Alfredo; Rodríguez-Añover, Javier; Mateos, Elena; Homen, Reynaldo; Orviz-García, Eva; Cabello, Noemí; Negredo, Anabel; Sánchez-Seco, María Paz; Del Romero, Jorge; Estrada, Vicente; Torres, Montserrat; Coiras, Mayte; National Institutes of Health (Estados Unidos); Ministerio de Ciencia e Innovación (España); Agencia Estatal de Investigación (España); Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF); Instituto de Salud Carlos III; Centro de Investigación Biomédica en Red - CIBERINFEC (Enfermedades Infecciosas); Comunidad de Madrid (España)
In August 2024, the World Health Organization declared mpox infection a Public Health Emergency of International Concern for second time since 2022 and recommended vaccinating all people at-risk, such as people with HIV-1 (PWH) and prophylaxis pre-exposition (PrEP) users. We recruited PWH and PrEP users who received one or two doses of subcutaneous Imvanex® or Jynneos® and compared specific T-cell immunity with participants who passed mpox natural infection or were Nonexposed to mpox. CD4 + T cells from people who had mpox showed the highest capacity to produce IL-2 (1.8-fold, p = 0.0328), as well as IFNγ (2.5-fold, p = 0.0247), and IL-4 (1.8-fold, p = 0.0373) from naïve CD4 + T cells, in response to MHC-II-restricted mpox-related peptides, compared to vaccinated participants. CD8 + T cells from individuals who had mpox also showed the highest capacity to produce IFN (1.6-fold, p = 0.0321) and TNF (2.1-fold, p = 0.0084) against MHC-I-restricted peptides. Therefore, the most potent and robust T-cell responses were developed after mpox infection, while they were barely detectable after vaccination. These results support the need to explore booster doses or improved vaccines to enhance cellular immunity in at-risk populations. More studies are needed to evaluate the capacity of mpox vaccines to confer long-term protection.
Frequent carriage of resistance mechanisms to β-lactams and biofilm formation in Haemophilus influenzae causing treatment failure and recurrent otitis media in young children.
(https://doi.org/10.1093/jac/dku158, 2014-09) García-Cobos, Silvia; Moscoso, Miriam; Pumarola, Félix; Arroyo, Margarita; Lara Fuella, Noelia; Perez-Vazquez, Maria; Aracil, Belen; Oteo-Iglesias, Jesus; García, Ernesto; Campos, Jose
Objectives: Non-typeable Haemophilus influenzae are a major cause of acute otitis media (AOM), including chronic and recurrent otitis in young children. The objective of this study was to determine whether non-typeable H. influenzae isolates causing these infections produce biofilms and carry resistance mechanisms to β-lactams. Methods: A collection of 48 H. influenzae isolates was obtained by tympanocentesis or from otorrhoea samples from individual patients <3 years of age and diagnosed with recurrent or treatment failure AOM. Each isolate was surveyed for the presence of blaTEM genes, amino acid substitutions in the transpeptidase domain of penicillin-binding protein 3 (PBP3) and biofilm formation in microtitre plates. Results: In 43 of the 48 isolates (89.6%), at least one of the three tested conditions was identified: biofilm formation (83.3%) and resistance mechanisms to β-lactams (33.3%), modifications in the transpeptidase domain of PBP3 being the most prevalent (22.9%), followed by β-lactamase production (10.4%). Additionally, 13 (27.1%) isolates had two or more of these three traits. In relation to biofilm formation, those isolates with an amoxicillin MIC ≤ 0.5 mg/L had higher optical density values than isolates with an amoxicillin MIC ≥ 1 mg/L (Mann-Whitney U-test, P=0.048). Conclusions: These findings suggest that the successful treatment of non-typeable H. influenzae causing chronic and recurrent AOM in young children may be compromised by the high biofilm-forming capacity of the isolates and the presence of β-lactam resistance mechanisms, particularly PBP3 mutations.

Browse

Recent Submissions