11 research outputs found
Controversies in the Design of Strategies for the Cure of HIV Infection
No full textThe cure for chronic human immunodeficiency virus (HIV) infections has been a goal pursued since the antiretroviral therapy that improved the clinical conditions of patients became available. However, the exclusive use of these drugs is not enough to achieve a cure, since the viral load rebounds when the treatment is discontinued, leading to disease progression. There are several theories and hypotheses about the biological foundations that prevent a cure. The main obstacle appears to be the existence of a latent viral reservoir that cannot be eliminated pharmacologically. This concept is the basis of the new strategies that seek a cure, known as kick and kill. However, there are other lines of study that recognize mechanisms of persistent viral replication in patients under effective treatment, and that would modify the current lines of research on the cure of HIV. Given the importance of these concepts, in this work, we propose to review the most recent evidence on these hypotheses, covering both the evidence that is positioned in favor and against, trying to expose what are some of the challenges that remain to be resolved in this field of research
Impact of the initial administration of an antiretroviral drug with latency reversal properties on the HIV reservoir size
No full textCoRIS Cohort:
Santiago Moreno, Inma Jarrín, David Dalmau, M. Luisa Navarro, M. Isabel González, Federico Garcia, Eva Poveda, Jose Antonio Iribarren, Félix Gutiérrez, Rafael Rubio, Francesc Vidal, Juan Berenguer, Juan González, M. Ángeles Muñoz-Fernández, Inmaculada Jarrín, Cristina Moreno, Marta Rava, Rebeca Izquierdo, Cristina Marco, Teresa Gómez-García, Mª Ángeles Muñoz-Fernández, Roxana Juárez, Joaquín Portilla, Irene Portilla, Esperanza Merino, Gema García, Iván Agea, José Sánchez-Payá, Juan Carlos Rodríguez, Livia Giner, Sergio Reus, Vicente Boix, Diego Torrus, Verónica Pérez, Julia Portilla, Héctor Pinargote, María Remedios Alemán, Ana López Lirola, Dácil García, Felicitas Díaz-Flores, M. Mar Alonso, Ricardo Pelazas, María Inmaculada Hernández, Lucia Romero, Abraham Bethencourt, Daniel Rodríguez, Víctor Asensi, María Eugenia Rivas-Carmenado, Rebeca Cabo Magadan, Javier Díaz-Arias, Federico Pulido, Rafael Rubio, Otilia Bisbal, M. Asunción Hernando, David Rial, María de Lagarde, Adriana Pinto, Laura Bermejo, Mireia Santacreu, Roser Navarro, Juan Martín Torres, José Antonio Iribarren, M. José Aramburu, Xabier Camino, Miguel Ángel Goenaga, M. Jesús Bustinduy, Harkaitz Azkune, Maialen Ibarguren, Xabier Kortajarena, Ignacio Álvarez-Rodriguez, Leire Gil, Francisco Carmona-Torre, Ana Bayona Carlos, Maialen Lekuona Sanz, Félix Gutiérrez, Catalina Robledano, Mar Masiá, Sergio Padilla, Araceli Adsuar, Rafael Pascual, Marta Fernández, Antonio Galiana, José Alberto García, Xavier Barber, Javier García Abellán, Guillermo Telenti, Lucía Guillén, Ángela Botella, Paula Mascarell, Mar Carvajal, Alba de la Rica, Carolina Ding, Lidia García-Sánchez, Nuria Ena, Leandro López, Jennifer Vallejo, Nieves Gonzalo-Jiménez, Montserrat Ruiz, Christian Ledesma, Santiago López, María Espinosa, Ana Quiles, María Andreo, Juan Carlos López Bernaldo de Quirós, Isabel Gutiérrez, Juan Berenguer, Margarita Ramírez, Paloma Gijón, Teresa Aldamiz-Echevarría, Francisco Tejerina, Cristina Diez, Leire Pérez, Chiara Fanciulli, Saray Corral, Joaquín Peraire, Anna Rull, Anna Martí, Consuelo Viladés, Beatriz Villar, Lluïsa Guillem, Montserrat Olona, Graciano García-Pardo, Frederic Gómez-Bertomeu, Verónica Alba, Silvia Chafino, Alba Sánchez, Marta Montero, María Tasias, Eva Calabuig, Miguel Salavert, Juan Fernández, Rosa Blanes, Juan González-García, Ana Delgado-Hierro, José Ramón Arribas, Víctor Arribas, José Ignacio Bernardino, Carmen Busca, Joanna Cano-Smith, Julen Cadiñanos, Juan Miguel Castro, Luis Escosa, Iker Falces, Pedro Herranz, Víctor Hontañón, Alicia González-Baeza, M. Luz Martín-Carbonero, Mario Mayoral, Rafael Micán, Rosa de Miguel, Rocío Montejano, Mª Luisa Montes, Luis Ramos-Ruperto, Berta Rodés, Talía Sainz, Elena Sendagorta, Eulalia Valencia, M. del Mar Arcos, Alejandro de Gea Grela, Carlos Oñoro López, David Dalmau, Marina Martinez, Angels Jaén, Mireia Cairó, Javier Martinez-Lacasa, Roser Font, Laura Gisbert, Ignacio de los Santos, Alejandro de los Santos, Lucio García-Fraile, Enrique Martín, Ildefonso Sánchez-Cerrillo, Marta Calvet, Ana Barrios, Azucena Bautista, Carmen Sáez, Marianela Ciudad, Ángela Gutiérrez, María Aguilera García, Santiago Moreno, Santos del Campo, José Luis Casado, Fernando Dronda, Ana Moreno, M. Jesús Pérez, Sergio Serrano-Villar, Mª Jesús Vivancos, Javier Martínez-Sanz, Alejandro Vallejo, Matilde Sánchez, José Antonio Pérez-Molina, José Manuel Hermida, Erick De La Torre Tarazona, Elena Moreno, Laura Martín Pedraza, Claudio Díaz García, Jorge Díaz, Alejandro García, Raquel Ron, Enrique Bernal, Antonia Alcaraz, Joaquín Bravo, Ángeles Muñoz, Cristina Tomás, Eva Oliver, David Selva, Eva García, Román González, Elena Guijarro, Rodrigo Martínez, María Dolores Hernández, Federico García, Clara Martínez, Leopoldo Muñoz Medina, Marta Álvarez, Natalia Chueca, David Vinuesa, Adolfo de Salazar, Ana Fuentes, Emilio Guirao, Laura Viñuela, Andrés Ruiz-Sancho, Francisco Anguita, Naya Faro, José Peregrina, Lucia Chaves, Marta Illescas, Valme Sánchez, Jorge Del Romero, Montserrat Raposo, Carmen Rodríguez, Teresa Puerta, Juan Carlos Carrió, Mar Vera, Juan Ballesteros, Oskar Ayerdi, Begoña Baza, Eva Orviz, Melchor Riera, María Peñaranda, MAngels Ribas, Antoni A. Campins, Mercedes Garcia-Gazalla, Francisco J. Fanjul, Javier Murillas, Francisco Homar, Helem H. Vilchez, Luisa Martin, Antoni Payeras, Jesús Santos, María López, Cristina Gómez, Isabel Viciana, Rosario Palacios, Luis Fernando López-Cortés, Nuria Espinosa, Cristina Roca, Silvia Llaves, Juan Manuel Tiraboschi, Arkaitz Imaz, María Saumoy, Julián Olalla, Javier Pérez, Alfonso del Arco, Javier de la Torre, José Luis Prada, Onofre Juan Martínez, Lorena Martinez, Francisco Jesús Vera, Josefina García, Begoña Alcaraz, Antonio Jesús Sánchez Guirao, Álvaro Mena, Berta Pernas, Pilar Vázquez, Soledad López, Brais Castelo, Carlos Galera, Marian Fernández, Helena Albendin, Antonia Castillo, Asunción Iborra, Antonio Moreno, M. Angustias Merlos, Inmaculada Chiclano, Inés Suarez-García, Eduardo Malmierca, Patricia González-Ruano, M. Pilar Ruiz, José Francisco Pascual, Luz Balsalobre, Ángela Somodevilla, José Sanz, Alberto Arranz, Cristina Hernández, María Novella, María José Galindo, Sandra Pérez Gómez, Ana Ferrer, Antonio Rivero Román, Inma Ruíz, Antonio Rivero Juárez, Pedro López, Isabel Machuca, Mario Frias, Ángela Camacho, Ignacio Pérez, Diana Corona, Javier Manuel Caballero, Rafael Rodríguez-Rosado Martinez-Echevarría, Rafael Torres, Juan Macías Sánchez, Pilar Rincón, Luis Miguel Real, Anais Corma, Alejandro González-Serna, Eva Poveda, Alexandre Pérez, Luis Morano, Celia Miralles, Antonio Ocampo, Guillermo Pousada, María Gallego, Jacobo Alonso & Inés MartínezThe elimination of the latent viral reservoir remains the main barrier in the quest for a cure for people with HIV (PWH). The administration of latency reversal agents (LRA) at antiretroviral treatment (ART) initiation could improve the effectiveness of strategies aimed at HIV remission. This study assessed the impact of maraviroc (MVC), an antiretroviral drug with HIV latency reversal properties, on the viral reservoir size when it is administered at ART initiation. We conducted a longitudinal observational study in PWH initiating ART with a regimen including (MVC-initiation, n = 12) or not including MVC (non-MVC-initiation, n = 22), or switching to an MVC-containing regimen after achieving an undetectable viral load (VL) (MVC-switch, n = 9). The HIV reservoir size was determined via Alu-LTR and Intact Proviral DNA Assay (IPDA) methods, and cell-associated HIV-RNA (ca-HIV-RNA) by nested-qPCR. Comparative analyses employed mixed multivariate linear models. After a median of 90 weeks, the MVC-initiation group showed a greater reduction in integrated and IPDA-total (7.1- and 4.0-fold, respectively), but not IPDA-intact, HIV-DNA reservoir compared to the non-MVC-initiation group. The reductions in integrated, IPDA-total, and IPDA-intact HIV-DNA levels in the MVC-initiation group were also greater compared to the MVC-switch group (from 5.4 to 13.8-fold). Moreover, no significant differences in the HIV transcriptional activity, assessed by ca-HIV-RNA levels or HIV-RNA/HIV-DNA ratios, were observed between the MVC-initiation and non-MVC-initiation groups. In conclusion, starting ART with a drug with HIV latency reversing activity at detectable VL phase may contribute to a greater reduction in the HIV-DNA reservoir. These findings could inform the design of future trials targeting HIV remission via a "kick and kill" strategy.This study was funded by the Instituto de Salud Carlos III (ISCIII) through the projects PI20/00945, PI20/00676, PI23/01896 and CIBERINFEC INFECG30 S.N./ 2024, and co-funded by the European Union.Peer reviewe
Eficacia en vida real del cambio a bictegravir/ emtricitabina/tenofovir alafenamida en pacientes previamente tratados con pautas triples que contienen rilpivirina
No full textOBJECTIVE: To analyze the efficacy and tolerability of the strategy to change from rilpivirine (RPV) based regimens to bictegravir / emtricitabine / tenofovir alafenamide (B/F/TAF). METHODS: Single-center, observational and retrospective study. Patients who made the change to B/F/TAF before February 2020 were selected, analyzing the results after 24 and 48 weeks. The percentage that remained with an undetectable viral load was determined, as well as the changes in CD4 + lymphocytes, metabolic parameters and renal function. RESULTS: A total of 42 patients were included. Thirty-two of the 35 patients (91.4%) who completed the 48 weeks of follow-up had an undetectable viral load. The CD4 + lymphocyte count remained stable at 24 and 48 weeks. The response to B/F/TAF was not influenced by the two analogs previously received. CONCLUSION: Switching from triple therapy with RPV to B/F/TAF is a safe and effective strategy in real life
Human intestinal spirochetosis: an entity associated with sexual transmitted infections
No full text[ES] Introducción: La espiroquetosis intestinal humana (EIH) es una entidad clínica poco estudiada. No obstante, en los últimos años está cobrando una especial relevancia dado que se han descrito un número creciente de casos en personas que viven con virus de inmunodeficiencia humana (VIH) (PVIH) y en pacientes con historia de infecciones de transmisión sexual (ITS) o inmunosupresión. Métodos: Estudio retrospectivo de todos los casos identificados de EIH en un hospital de tercer nivel (Hospital Universitario la Paz, Madrid) entre los años 2014-2021. Resultados: Se identificaron 36 casos de EIH, la mayoría en varones (94%) y con una mediana de edad de 45 años. Diez pacientes eran PVIH (29,4%) y 20 (56%) eran hombres que mantenían sexo con hombres. Si bien las manifestaciones clínicas fueron muy heterogéneas, la más frecuente fue la diarrea crónica (47%), y 25% tuvieron clínica de proctitis; 39% de los pacientes fueron diagnosticados de una ITS en los dos años previos, siendo este hecho más frecuente en PVIH (90 vs. 28%; p < 0,01) que en pacientes sin infección por VIH. La ITS más frecuentemente asociada al diagnóstico de EIH fue la sífilis (31%). Conclusión: La EIH se diagnostica frecuentemente con otras ITS y afecta mayoritariamente a hombres que tienen sexo con hombres, lo cual apoyaría que esta entidad pudiera considerarse como una nueva ITS. [EN] Introduction: Human intestinal spirochetosis (HIE) is a poorly studied clinical entity with variable clinical manifestations. However, in recent years it has gained special relevance because an increasing number of cases have been described in people living with HIV (PWH) and in patients with a history of sexually transmitted infections (STI) or immunosuppression. Methods: retrospective review of all HIE cases identified in a tertiary level hospital(Hospital Universitario la Paz, Madrid) between 2014-2021. Results: 36 cases of HIE were identified. Most cases corresponded to males (94%) with a median age of 45 years. 10 patients (29.4%) were PWH and 20 (56%) were men who had sex with men. Although the clinical manifestations were very heterogeneous, the most frequent was chronic diarrhea (47%), and up to 25% of the subjects had clinical proctitis. 39% percent of patients had been diagnosed with an STI in the previous two years, this characteristic being more frequent in PWH (90% vs 28%; p < 0.01) than in patients without HIV infection. The STI most frequently associated with a diagnosis of HIE was syphilis (31%). Conclusión: HIE is frequently diagnosed with other STIs and affects mostly men who have sex with men, which supports that this entity could be considered as a new STI.S
Clinical Cure of a Difficult-to-Treat Resistant Pseudomonas aeruginosa Ventriculitis Using Cefiderocol: A Case Report and Literature Review
No full textVentriculitis is a complication of meningitis (community-acquired or nosocomial) or other central nervous system (CNS) infections such as brain abscess. They are associated with a different spectrum of microorganisms, from resistant gram-negative bacilli to staphylococci, that can lead serious illness with high mortality. Difficult-to-treat resistance (DTR) gram-negative bacilli may increase to 20% of deaths respective to susceptible isolates of the same bacteria. We present the first report of a clinical cured case of DTR Pseudomonas aeruginosa ventriculitis in which cefiderocol penetration into the CNS has been confirmed in blood and cerebrospinal fluid. Cefiderocol might be considered for difficult-to-treat CNS infections in view of the recent new cases published as well as our case
A Comparison of the Efficacy of Treatment With Fidaxomicin Versus Vancomycin in Clostridioides difficile Infection.
No full text20.500.12530/87857Background Clostridioides difficile infection (CDI) is a major cause of diarrhea in hospitalized adult patients. This study aims to evaluate the clinical characteristics, clinical cure, recurrence and mortality in patients with CDI treated with either fidaxomicin or vancomycin. Methods A retrospective case-control study was conducted on patients with CDI treated with either fidaxomicin or vancomycin at a hospital from January 2019 to March 2022. Results We assessed 140 patients with CDI episodes, 70 patients treated with fidaxomicin and 70 with vancomycin. Seventy (50%) were male. Median age was 70 years old (IQR: 56-81). Fidaxomicin group had more recurrent CDI episodes within six months (59% vs 11%, p ≤ 0.001), more severity (43% vs 16%, p ≤ 0.001) and less treatment response (84% vs 100%, p ≤ 0.002) compared with vancomycin group. Recurrence and mortality rates in the follow-up period did not differ in both groups. Conclusions Our study found fidaxomicin treatment had worse outcomes due to restricted usage, potentially impacting its effectiveness in CDI. This finding is especially significant for patients with severe or recurrent CDI, as prescribing of the drug was limited until May 2022 in Spain with the lifting of this restriction, further research is necessary to better understand the potential benefits of fidaxomicin in treating CDI
Partial Recovery of Telomere Length After Long-term Virologic Suppression in Persons With HIV-1
No full textBackground: People with HIV-1 (PWH) age differently than the general population. Blood telomere length (BTL) attrition is a surrogate biomarker of immunosenescence and aging in PWH. BTL is reduced immediately after HIV-1 infection and recovers in PWH with long-term virologic suppression, but the extent of this recovery is unknown. Methods: This prospective 6-year observational study assessed the evolution of BTL in PWH who were virologically suppressed. A cross-sectional analysis additionally compared BTL with age- and sex-matched blood donors and sex-matched persons older than 60 years from a general population cohort. DNA from whole blood was isolated, and relative BTL was determined by monochrome quantitative multiplex polymerase chain reaction assay and expressed as the ratio of telomere to single-copy gene (T/S). Results: A total of 128 PWH were included in the prospective 6-year observational study. These same 128 PWH (median age, 55 years; 27.3% women) were compared cross-sectionally at 6-year follow-up with 128 age- and gender-matched blood donors (median age, 55 years) and 128 gender-matched individuals older than 60 years from a general population cohort (median age, 70 years). An inverse correlation between age and BTL was observed. The median BTL of PWH was shorter than their matched blood donors (T/S, 1.07 [IQR, 0.95-1.17] vs 1.28 [IQR, 1.12-1.48]; P <. 001) but longer than the elderly population (T/S, 0.89 [IQR, 0.77-0.98], P <. 001). PWH experienced a BTL increase at 6 years of 2.9% (T/S, 1.04 vs 1.07; P = .002). In PWH, age was associated with a shorter BTL (coefficient, -0.007 45, SE = 0.002 04, P = .002) and baseline lower CD4 count with a gain in BTL (coefficient, -0.000 06, SE = 0.000 02, P = .004). Shorter baseline BTL (odds ratio, 0.91 [95% CI,. 87-.94]; P <. 001) and higher glucose levels (odds ratio, 1.04 [95% CI, 1.02-1.07]; P = .003) were associated with a greater similarity of BTL to the elderly population. Conclusions: PWH with long-term virologic suppression experience a trend toward an increased BTL after 6 years of follow-up. Middle-aged people with long-term controlled HIV-1 have a shorter BTL than expected for their chronologic age but longer than that of people 15 years older in the general populatio
Impact of preexisting nucleos(t)ide reverse transcriptase inhibitor resistance on the effectiveness of bictegravir/emtricitabine/tenofovir alafenamide in treatment experience patients
No full textINTRODUCTION: Few clinical trials and cohort studies have evaluated the efficacy of bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) in people with HIV (PWH) with preexisting M184V/I or other nucleos(t)ide reverse transcriptase inhibitor (NRTI) resistance-associated mutations (RAMs). Real-world data are also scarce. METHODS: Retrospective review of treatment-experienced patients who started B/F/TAF in a cohort of PWH. HIV-RNA less than 50 copies/ml was analyzed at 48 weeks in an intention-to-treat (ITT) analysis (missing=failure) and per protocol analysis (patients with missing data or changes for reasons other than virological failure were excluded). Results were compared in patients with and without previous NRTI-RAMs. RESULTS: Five hundred and six PWH were included (16.2% women). Median age and time with HIV infection were 52.3 and 18.9 years, respectively. At baseline, viral load was less than 50 copies/ml in 440 patients (86.6%). Overall, 69 (13.6%) participants had documented preexisting NRTI-RAMs: 57 (11.2%) M184V/I and 30 (5.9%) tenofovir RAMs. In the ITT analysis, 83% (420/506) had HIV-RNA less than 50 copies/ml [82.2% (359/437) and 88.4% (61/69) in persons without and with NRTI-RAMs, respectively (P = 0.2)]. In the per protocol analysis 94.2% (420/445) had HIV-RNA less than 50 copies/ml [94.4% (359/380) vs. 93.8% (61/65); P = 0.2]. A total of 61 participants were excluded from the per protocol analysis (23 missing data, 19 discontinued B/F/TAF because of toxicity, 13 for other reasons, and 6 died). CONCLUSION: Switching to B/F/TAF is well tolerated and effective in the real-world setting, even in patients with preexisting NRTI RAMs, such as M184V and RAMs conferring resistance to tenofovir. These results confirm the robustness of this combination
Healthcare workers hospitalized due to COVID-19 have no higher risk of death than general population. Data from the Spanish SEMI-COVID-19 Registry
No full textAim To determine whether healthcare workers (HCW) hospitalized in Spain due to COVID-19 have a worse prognosis than non-healthcare workers (NHCW). Methods Observational cohort study based on the SEMI-COVID-19 Registry, a nationwide registry that collects sociodemographic, clinical, laboratory, and treatment data on patients hospitalised with COVID-19 in Spain. Patients aged 20-65 years were selected. A multivariate logistic regression model was performed to identify factors associated with mortality. Results As of 22 May 2020, 4393 patients were included, of whom 419 (9.5%) were HCW. Median (interquartile range) age of HCW was 52 (15) years and 62.4% were women. Prevalence of comorbidities and severe radiological findings upon admission were less frequent in HCW. There were no difference in need of respiratory support and admission to intensive care unit, but occurrence of sepsis and in-hospital mortality was lower in HCW (1.7% vs. 3.9%; p = 0.024 and 0.7% vs. 4.8%; p<0.001 respectively). Age, male sex and comorbidity, were independently associated with higher in-hospital mortality and healthcare working with lower mortality (OR 0.211, 95%CI 0.067-0.667, p = 0.008). 30-days survival was higher in HCW (0.968 vs. 0.851 p<0.001). Conclusions Hospitalized COVID-19 HCW had fewer comorbidities and a better prognosis than NHCW. Our results suggest that professional exposure to COVID-19 in HCW does not carry more clinical severity nor mortality
