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1.
Proc Natl Acad Sci U S A ; 119(21): e2200413119, 2022 05 24.
Artículo en Inglés | MEDLINE | ID: mdl-35576468

RESUMEN

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection fatality rate (IFR) doubles with every 5 y of age from childhood onward. Circulating autoantibodies neutralizing IFN-α, IFN-ω, and/or IFN-ß are found in ∼20% of deceased patients across age groups, and in ∼1% of individuals aged <70 y and in >4% of those >70 y old in the general population. With a sample of 1,261 unvaccinated deceased patients and 34,159 individuals of the general population sampled before the pandemic, we estimated both IFR and relative risk of death (RRD) across age groups for individuals carrying autoantibodies neutralizing type I IFNs, relative to noncarriers. The RRD associated with any combination of autoantibodies was higher in subjects under 70 y old. For autoantibodies neutralizing IFN-α2 or IFN-ω, the RRDs were 17.0 (95% CI: 11.7 to 24.7) and 5.8 (4.5 to 7.4) for individuals <70 y and ≥70 y old, respectively, whereas, for autoantibodies neutralizing both molecules, the RRDs were 188.3 (44.8 to 774.4) and 7.2 (5.0 to 10.3), respectively. In contrast, IFRs increased with age, ranging from 0.17% (0.12 to 0.31) for individuals <40 y old to 26.7% (20.3 to 35.2) for those ≥80 y old for autoantibodies neutralizing IFN-α2 or IFN-ω, and from 0.84% (0.31 to 8.28) to 40.5% (27.82 to 61.20) for autoantibodies neutralizing both. Autoantibodies against type I IFNs increase IFRs, and are associated with high RRDs, especially when neutralizing both IFN-α2 and IFN-ω. Remarkably, IFRs increase with age, whereas RRDs decrease with age. Autoimmunity to type I IFNs is a strong and common predictor of COVID-19 death.


Asunto(s)
Anticuerpos Neutralizantes , Autoanticuerpos , Autoinmunidad , COVID-19 , Interferón Tipo I , SARS-CoV-2 , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Anticuerpos Neutralizantes/sangre , Autoanticuerpos/sangre , COVID-19/inmunología , COVID-19/mortalidad , Femenino , Humanos , Interferón Tipo I/inmunología , Masculino , Persona de Mediana Edad , Riesgo
2.
J Antimicrob Chemother ; 79(3): 595-607, 2024 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-38267266

RESUMEN

BACKGROUND: Switching strategy with bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) has become a gold standard for people living with HIV (PLWH), achieving high efficacy and safety rates. However, data regarding immune status in long-term real-life cohorts of pretreated patients are needed. METHODS: We performed a multicentre, non-controlled, retrospective study in virologically suppressed PLWH switching to B/F/TAF. We evaluated CD4+, CD8+ and CD4+/CD8+ ratio, efficacy and safety at weeks 48 and 96. RESULTS: The study comprised 1966 PLWH from 12 hospitals in Spain, of whom 80% were men, and the median age was 51.0 [42.0-57.0] years. The median time of HIV infection was 18.0 [10.0-27.0] years. No significant changes in CD4+, CD8+ T cells, or CD4+/CD8+ were observed after 96 weeks. Nevertheless, in women at weeks 48 and 96, we found a significant increase of CD4+ T cells and a significant decrease in CD8+ T cells. In patients ≥60 years at week 96, CD4 T cells significantly increased and CD8+ T cells significantly decreased at week 48. The on-treatment analysis revealed HIV-RNA <50 copies/mL in 95.6% (1700/1779) and 96.7% (1312/1356) of patients at weeks 48 and 96, respectively. The rates increased to 99.2% (1765/1779) and 99.7% (1352/1356) when considering HIV-RNA <200 copies/mL. No resistance mutations were detected in virologic failures. B/F/TAF discontinuations accounted for 10.2% (200). Simplification was the most common reason for discontinuation in 3.8% (74) of patients. CONCLUSION: In long-term virologically controlled PLWH, B/F/TAF achieved high efficacy rates and slightly improved immune status in women and individuals aged 60 and over after 48 and 96 of switching.


Asunto(s)
Alanina , Amidas , Infecciones por VIH , Compuestos Heterocíclicos con 3 Anillos , Piperazinas , Piridonas , Tenofovir/análogos & derivados , Masculino , Humanos , Femenino , Persona de Mediana Edad , Anciano , Infecciones por VIH/tratamiento farmacológico , Emtricitabina/uso terapéutico , Estudios Retrospectivos , Adenina/uso terapéutico , Resultado del Tratamiento , Combinación de Medicamentos , Compuestos Heterocíclicos de 4 o más Anillos/uso terapéutico , ARN
3.
J Antimicrob Chemother ; 78(11): 2696-2701, 2023 11 06.
Artículo en Inglés | MEDLINE | ID: mdl-37725999

RESUMEN

OBJECTIVES: To evaluate the efficacy and safety of the two-pill regimen bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) plus darunavir/cobicistat as a switching strategy in heavily treatment-experienced people living with HIV (PLWH). METHODS: Multicentre, prospective, single-arm pilot clinical trial. Participants were virologically suppressed adults receiving a stable antiretroviral regimen of at least three pills from at least three drug families due to previous virological failures and/or toxicities with no documented resistance to integrase strand transfer inhibitors or darunavir (≥15 points, Stanford). Clinical and laboratory assessments were performed at 0, 4, 12, 24, 36 and 48 weeks. HIV-1 proviral DNA was amplified and sequenced by Illumina at baseline. Plasma bictegravir concentrations were determined in 22 patients using UHPLC-MS/MS. The primary study endpoint was viral load (VL)< 50 copies/mL at Week 48 (ITT). RESULTS: We enrolled 63 participants (92% men) with median baseline CD4 count of 515 cells/mm3 (IQR: 334.5-734.5), 24 years on ART (IQR: 15.9-27.8). The median number of pills was 4 (range: 3-10). At baseline, proviral DNA was amplified in 39 participants: 33/39 had resistance mutations. Three participants discontinued owing to toxicity. At 48 weeks, 95% had VL < 50 copies/mL by ITT and 100% by PP analysis. A modest increase was observed in the bictegravir plasma concentration, and a significant decrease in estimated glomerular filtration rate was observed only at Week 4, probably related to interaction with renal transporters. CONCLUSIONS: Our data suggest that BIC/FTC/TAF + darunavir/cobicistat is an effective, well-tolerated regimen that may improve convenience and, potentially, long-term success in stable heavily pre-treated PLWH.


Asunto(s)
Fármacos Anti-VIH , Infecciones por VIH , Adulto , Femenino , Humanos , Masculino , Adenina/uso terapéutico , Alanina/uso terapéutico , Fármacos Anti-VIH/efectos adversos , Antirretrovirales/uso terapéutico , Cobicistat/uso terapéutico , Darunavir/uso terapéutico , ADN/uso terapéutico , Emtricitabina/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Estudios Prospectivos , Espectrometría de Masas en Tándem
4.
Liver Int ; 42(2): 309-319, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-34767680

RESUMEN

BACKGROUND AND AIMS: People who inject drugs (PWID) and other marginalized populations with high hepatitis C virus (HCV) infection rates represent a unique challenge for treatment initiation due to health, administrative and social barriers. We analysed the HCV cascade of care (CoC) in some vulnerable subpopulations in Madrid, Spain, when using a mobile point-of-care (PoC). METHODS: From 2019 to 2021, a mobile unit was used to screen active HCV using a linkage-to-care and two-step PoC-based strategy. Viremic participants were grouped into four subgroups: PWID, homeless individuals and people with a mental health disorder (MHD) and alcohol use disorder (AUD). Logistic regression, and Cox and Aalen's additive models were used to analyse associated factors and differences between groups. RESULTS: A prospectively recruited cohort of 214 HCV-infected individuals (73 PWID, 141 homeless, 57 with a MHD and 91 with AUD) participated in the study. The overall HCV CoC analysis found that 178 (83.1%) attended a hospital, 164 (76.6%) initiated direct-acting antiviral therapy and 141 (65.8%) completed therapy, of which 99 (95.2%) achieved sustained virological response (SVR). PWID were significantly less likely to initiate treatment, whereas individuals with AUD waited longer before starting the treatment. Both people with AUD and PWID were significantly less likely to complete HCV treatment. CONCLUSIONS: Overall, SVR was achieved in the majority of the participants treated. However, PWID need better linkage to care and treatment, whereas PWID and AUD need more support for treatment completion.


Asunto(s)
Hepatitis C Crónica , Hepatitis C , Abuso de Sustancias por Vía Intravenosa , Antivirales/uso terapéutico , Hepacivirus , Hepatitis C/tratamiento farmacológico , Hepatitis C/epidemiología , Hepatitis C Crónica/tratamiento farmacológico , Humanos , Sistemas de Atención de Punto , Abuso de Sustancias por Vía Intravenosa/complicaciones , Abuso de Sustancias por Vía Intravenosa/epidemiología
5.
AIDS Care ; 34(10): 1297-1304, 2022 10.
Artículo en Inglés | MEDLINE | ID: mdl-34482777

RESUMEN

Our objective was to evaluate the effectiveness of initiated or reinitiated antiretroviral therapy (ART) in HIV-positive active drug users receiving integrated HIV and addiction care in a harm reduction setting. We performed a study of HIV-positive persons who use drugs (PWUD) in a harm reduction unit in Madrid, Spain. Participants received HIV care integrated into addiction care and received at least one dose of observed ART based on medication-assisted treatment between January 2013 and December 2019. Individuals newly diagnosed with HIV (n = 13) had a greater median CD4 cell count at baseline were less likely to be late presenters, had a greater CD4 cell count increase, and were less likely to have AIDS in comparison to those who were aware of their HIV status (n = 87) at initiation or reinitiation of ART. The overall VS was 73% in the intention-to-treat (ITT) analysis and 92.4% in the modified intention-to-treat (mITT) analysis. People who were engaged in OST, people with >90% adherence to ART, and older people were positively associated with VS in the multivariate analysis. An HIV care model integrated into a harm reduction facility demonstrated a high uptake of HIV treatment, retention in care, improvement in adherence, and achievement of VS.


Asunto(s)
Consumidores de Drogas , Infecciones por VIH , Anciano , Recuento de Linfocito CD4 , Infecciones por VIH/diagnóstico , Infecciones por VIH/tratamiento farmacológico , Humanos , España
6.
J Clin Immunol ; 41(5): 914-922, 2021 07.
Artículo en Inglés | MEDLINE | ID: mdl-33851338

RESUMEN

BACKGROUND: In a recent study, autoantibodies neutralizing type I interferons (IFNs) were present in at least 10% of cases of critical COVID-19 pneumonia. These autoantibodies neutralized most type I IFNs but rarely IFN-beta. OBJECTIVES: We aimed to define the prevalence of autoantibodies neutralizing type I IFN in a cohort of patients with severe COVID-19 pneumonia treated with IFN-beta-1b during hospitalization and to analyze their impact on various clinical variables and outcomes. METHODS: We analyzed stored serum/plasma samples and clinical data of COVID-19 patients treated subcutaneously with IFN-beta-1b from March to May 2020, at the Infanta Leonor University Hospital in Madrid, Spain. RESULTS: The cohort comprised 47 COVID-19 patients with severe pneumonia, 16 of whom (34%) had a critical progression requiring ICU admission. The median age was 71 years, with 28 men (58.6%). Type I IFN-alpha- and omega-neutralizing autoantibodies were found in 5 of 47 patients with severe pneumonia or critical disease (10.6%), while they were not found in any of the 118 asymptomatic controls (p = 0.0016). The autoantibodies did not neutralize IFN-beta. No demographic, comorbidity, or clinical differences were seen between individuals with or without autoantibodies. We found a significant correlation between the presence of neutralizing autoantibodies and higher C-reactive protein levels (p = 5.10e-03) and lower lymphocyte counts (p = 1.80e-02). No significant association with response to IFN-beta-1b therapy (p = 0.34) was found. Survival analysis suggested that neutralizing autoantibodies may increase the risk of death (4/5, 80% vs 12/42, 28.5%). CONCLUSION: Autoantibodies neutralizing type I IFN underlie severe/critical COVID-19 stages in at least 10% of cases, correlate with increased C-RP and lower lymphocyte counts, and confer a trend towards increased risk of death. Subcutaneous IFN-beta treatment of hospitalized patients did not seem to improve clinical outcome. Studies of earlier, ambulatory IFN-beta treatment are warranted.


Asunto(s)
Anticuerpos Neutralizantes/sangre , Autoanticuerpos/sangre , COVID-19/inmunología , Interferón Tipo I/inmunología , SARS-CoV-2/inmunología , Adulto , Anciano , Anciano de 80 o más Años , Proteína C-Reactiva/análisis , Femenino , Hospitalización , Humanos , Masculino , Persona de Mediana Edad
7.
J Thromb Thrombolysis ; 51(1): 237-242, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-32648092

RESUMEN

Coronavirus disease 2019 (COVID-19) could predispose to both venous and arterial thromboembolism, in an exaggerated immune response to the virus, especially in severe patients. Even though aortic clots are a rare entity, the pro-coagulant nature of COVID-19 is associated with thrombosis in atypical locations and should be considered in patients with severe abnormalities in coagulation parameters. We describe a series of three cases of aortic thrombi diagnosed by computerized tomography (CT) angiography in patients with confirmed SARS-CoV-2 infection.


Asunto(s)
Anticoagulantes/administración & dosificación , Aorta/diagnóstico por imagen , Enfermedades de la Aorta , COVID-19 , Trombosis , Anciano , Anticoagulantes/clasificación , Enfermedades de la Aorta/diagnóstico , Enfermedades de la Aorta/etiología , Enfermedades de la Aorta/fisiopatología , COVID-19/sangre , COVID-19/complicaciones , COVID-19/diagnóstico , COVID-19/terapia , Angiografía por Tomografía Computarizada/métodos , Diagnóstico Diferencial , Productos de Degradación de Fibrina-Fibrinógeno/análisis , Humanos , Accidente Cerebrovascular Isquémico/diagnóstico , Accidente Cerebrovascular Isquémico/etiología , Accidente Cerebrovascular Isquémico/fisiopatología , Masculino , Persona de Mediana Edad , Embolia Pulmonar/diagnóstico por imagen , Embolia Pulmonar/etiología , Embolia Pulmonar/terapia , SARS-CoV-2/aislamiento & purificación , Índice de Severidad de la Enfermedad , Trombosis/sangre , Trombosis/diagnóstico , Trombosis/tratamiento farmacológico , Trombosis/etiología , Tomografía Computarizada por Rayos X/métodos , Resultado del Tratamiento
9.
Eur J Clin Microbiol Infect Dis ; 38(3): 423-426, 2019 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-30443683
12.
J Antimicrob Chemother ; 71(12): 3510-3514, 2016 12.
Artículo en Inglés | MEDLINE | ID: mdl-27591292

RESUMEN

OBJECTIVES: To describe the effectiveness and safety of an abacavir/lamivudine + rilpivirine regimen in naive HIV-1-infected patients, as there is a lack of data with this combination. METHODS: This was an observational, retrospective, multicentre study in eight Spanish hospitals. All antiretroviral-naive patients ≥18 years old and starting abacavir/lamivudine + rilpivirine were included. Effectiveness (ITT and on-treatment) and safety (adverse events and laboratory parameters) were assessed during follow-up. Values are expressed as n (%) or median (IQR). The Wilcoxon signed-rank test was used to compare baseline and 6 and 12 month values. RESULTS: Eighty-four patients were included [93% males, age = 36 (30-45) years]. Time since HIV diagnosis was 12 (4-35) months. Fifty-one per cent of patients had comorbidities. Baseline CD4+ was 425 (340-519) cells/mm3 and baseline HIV-RNA was 19 000 (9500-42 000) copies/mL. Median follow-up was 18 (9-22) months; 100% and 68% patients with at least 6 and 12 months, respectively. At 6 and 12 months effectiveness was 94% and 86% by ITT analysis and 96% and 97% by on-treatment analysis. At 12 months, there were significant increases in CD4+ (+262 cell/mm3) and HDL cholesterol (+4 mg/dL) and a significant decrease in the total cholesterol/HDL cholesterol ratio (-0.2). There were two (2.4%) virological failures (HIV-RNA 50-100 copies/mL); one patient later achieving virological suppression without changing the treatment. Six patients (7.1%) changed treatment due to reasons other than virological failure or side effects. One patient discontinued treatment due to gastrointestinal complaints attributed to abacavir/lamivudine. CONCLUSIONS: Abacavir/lamivudine + rilpivirine was an effective and safe option in a selected group of HIV-1-infected treatment-naive patients.


Asunto(s)
Fármacos Anti-VIH/administración & dosificación , Fármacos Anti-VIH/efectos adversos , Didesoxinucleósidos/administración & dosificación , Didesoxinucleósidos/efectos adversos , Infecciones por VIH/tratamiento farmacológico , Lamivudine/administración & dosificación , Lamivudine/efectos adversos , Rilpivirina/administración & dosificación , Rilpivirina/efectos adversos , Adulto , Combinación de Medicamentos , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/epidemiología , Femenino , VIH-1/efectos de los fármacos , Hospitales , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , España , Resultado del Tratamiento
13.
Postgrad Med J ; 96(1132): 114, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-31558685
14.
Comput Methods Programs Biomed ; 253: 108228, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38810378

RESUMEN

BACKGROUND AND OBJECTIVE: Comparative diagnostic in brain tumor evaluation makes possible to use the available information of a medical center to compare similar cases when a new patient is evaluated. By leveraging Artificial Intelligence models, the proposed system is able of retrieving the most similar cases of brain tumors for a given query. The primary objective is to enhance the diagnostic process by generating more accurate representations of medical images, with a particular focus on patient-specific normal features and pathologies. A key distinction from previous models lies in its ability to produce enriched image descriptors solely from binary information, eliminating the need for costly and difficult to obtain tumor segmentation. METHODS: The proposed model uses Artificial Intelligence to detect patient features to recommend the most similar cases from a database. The system not only suggests similar cases but also balances the representation of healthy and abnormal features in its design. This not only encourages the generalization of its use but also aids clinicians in their decision-making processes. This generalization makes possible for future research in different medical diagnosis areas with almost not any change in the system. RESULTS: We conducted a comparative analysis of our approach in relation to similar studies. The proposed architecture obtains a Dice coefficient of 0.474 in both tumoral and healthy regions of the patients, which outperforms previous literature. Our proposed model excels at extracting and combining anatomical and pathological features from brain Magnetic Resonances (MRs), achieving state-of-the-art results while relying on less expensive label information. This substantially reduces the overall cost of the training process. Our findings highlight the significant potential for improving the efficiency and accuracy of comparative diagnostics and the treatment of tumoral pathologies. CONCLUSIONS: This paper provides substantial grounds for further exploration of the broader applicability and optimization of the proposed architecture to enhance clinical decision-making. The novel approach presented in this work marks a significant advancement in the field of medical diagnosis, particularly in the context of Artificial Intelligence-assisted image retrieval, and promises to reduce costs and improve the quality of patient care using Artificial Intelligence as a support tool instead of a black box system.


Asunto(s)
Inteligencia Artificial , Neoplasias Encefálicas , Sistemas de Apoyo a Decisiones Clínicas , Humanos , Neoplasias Encefálicas/diagnóstico por imagen , Algoritmos , Bases de Datos Factuales
15.
Infect Dis Ther ; 13(3): 609-617, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38372897

RESUMEN

INTRODUCTION: The objective was to characterize real-world outcomes of drug-drug interactions (DDIs) between antiretrovirals (ARVs) and other drugs, including over-the-counter medications (OTC), and treatment outcomes in clinical practice. METHODS: www.clinicalcasesDDIs.com is an open-access website for healthcare providers to consult and briefly describe real-world clinical cases on DDI with ARVs. We reviewed all the clinical cases reported to the website between March 2019 and May 2023. RESULTS: A total of 139 cases were reported, mostly involving ritonavir or cobicistat (boosters; 74 cases), unboosted integrase inhibitors (InSTI; 29 cases), and non-nucleoside reverse transcriptase inhibitors (NNRTI; 23 cases). Central nervous system drugs (29 cases) and cardiovascular drugs (19 cases) were the most frequently described co-medications. Notably, OTC medications were implicated in 27 cases, including mineral supplements (11 cases), herbals (8 cases), weight loss drugs (4 cases), anabolic steroids (3 cases), and recreational drugs (1 case). OTC acted as the perpetrator drug in 21 cases, leading to loss of ARV efficacy in 17 instances (mineral supplements in 10 cases, weight loss drugs in 4 cases, herbals in 3 cases). Additionally, toxicity was reported in 4 out of 6 cases where OTC was considered the victim drug of the DDI (anabolic steroids in 3 cases, MDMA in 1 case). CONCLUSIONS: Frequent unwanted outcomes resulting from DDIs between ARVs and OTC medications underscore the importance of integrating non-prescription drugs into medication reconciliation. The real-world data available through www.clinicalcasesDDIs.com serves as a valuable resource for assessing the clinical relevance of DDIs.

16.
J Exp Med ; 221(2)2024 Feb 05.
Artículo en Inglés | MEDLINE | ID: mdl-38175961

RESUMEN

We found that 19 (10.4%) of 183 unvaccinated children hospitalized for COVID-19 pneumonia had autoantibodies (auto-Abs) neutralizing type I IFNs (IFN-α2 in 10 patients: IFN-α2 only in three, IFN-α2 plus IFN-ω in five, and IFN-α2, IFN-ω plus IFN-ß in two; IFN-ω only in nine patients). Seven children (3.8%) had Abs neutralizing at least 10 ng/ml of one IFN, whereas the other 12 (6.6%) had Abs neutralizing only 100 pg/ml. The auto-Abs neutralized both unglycosylated and glycosylated IFNs. We also detected auto-Abs neutralizing 100 pg/ml IFN-α2 in 4 of 2,267 uninfected children (0.2%) and auto-Abs neutralizing IFN-ω in 45 children (2%). The odds ratios (ORs) for life-threatening COVID-19 pneumonia were, therefore, higher for auto-Abs neutralizing IFN-α2 only (OR [95% CI] = 67.6 [5.7-9,196.6]) than for auto-Abs neutralizing IFN-ω only (OR [95% CI] = 2.6 [1.2-5.3]). ORs were also higher for auto-Abs neutralizing high concentrations (OR [95% CI] = 12.9 [4.6-35.9]) than for those neutralizing low concentrations (OR [95% CI] = 5.5 [3.1-9.6]) of IFN-ω and/or IFN-α2.


Asunto(s)
COVID-19 , Interferón Tipo I , Niño , Humanos , Interferón-alfa , Autoanticuerpos
17.
J Clin Med ; 12(3)2023 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-36769822

RESUMEN

BACKGROUND: Immune recovery in people living with HIV (PLWHIV) is a residual aspect of antiretroviral treatment (ART) in most patients, but in a non-negligible proportion of them, the CD4+ lymphocytes count, or CD4/CD8 ratio remains suboptimal. METHODS: We performed a model of the immune response after 24 weeks of switching to a 2DR with DTG plus 3TC in a retrospective multicenter cohort of undetectable and experienced patients using significant predictor variables associated with the parameters or situations defined as success and failure. Clinical variables studied were CD4+ and CD8+ lymphocyte count, percentage of CD4, and CD4/CD8 ratio. These parameters were assessed at baseline and 24 weeks after the switch. Based on the evolution of each variable, four categories of immune response and four categories of non-immune response were defined. Immune response was defined as CD4+ count > 500 cells/mm3, %CD4 > 30%, CD8+ count < 1000 cells/mm3 and CD4/CD8 ratio ≥ 0.9. Non-response is just the opposite. RESULTS: In our different models of immunological response, the presence of stage of AIDS (p = 0.035, p = 0.065) and current age over 50 years (p = 0.045) are postulated as statistically significative limiting factors in achieving an improvement in CD4, %CD4, CD8, and CD4/CD8 ratio. Late HIV diagnosis (p = 0.156), without statistical significance, enhanced late the previous variables. In contrast, conditions where patients start with CD4 > 500 cells/mm3 (p = 0.054); CD4 > 30% (p = 0.054, p = 0.084); CD8 < 1000 cells/mm3 (p = 0.018), and CD4/CD8 ≥ 0.9 (p = 0.013, p = 0.09) are detected as stimulating or conducive to DTG plus 3TC treatment success. CONCLUSION: These models represent a proof of concept that could become a valuable tool for clinicians to predict the effects of DTG plus 3TC on immunological responses prior to the switch in undetectable pre-treated PLWHIV with immune dysfunction. The main predictors for immunological failure were late HIV diagnosis, stage of AIDS, and current age over 50 years. In contrast, starting with a normalized immune status was detected as stimulating or conducive to DTG plus 3TC treatment success.

18.
Viruses ; 15(4)2023 04 10.
Artículo en Inglés | MEDLINE | ID: mdl-37112915

RESUMEN

BACKGROUND: The high effectiveness and safety of the two-drug (2DRs) strategy using dolutegravir (DTG) plus lamivudine (3TC) have led to international guidelines recommending their use for treatment-naive HIV patients. In virologically suppressed patients, de-escalating from 3DRs to DTG plus either rilpivirine (RPV) or 3TC has shown high rates of virological suppression. OBJECTIVES: This study aimed to compare the real-life data of two multicenter Spanish cohorts of PLWHIV treated with DTG plus 3TC (SPADE-3) or RPV (DORIPEX) as a switch strategy, not only in terms of virological suppression, safety, and durability but also in terms of immune restoration. The primary endpoint was the percentage of patients with virological suppression on DTG plus 3TC and DTG plus RPV at weeks 24 and 48. The secondary outcomes included the proportion of patients who experienced the protocol-defined loss of virological control by week 48; changes in immune status in terms of CD4+ and CD8+ T lymphocyte counts and the CD4+/CD8+ ratio; the rate, incidence, and reasons for discontinuation of treatment over the 48-week study period; and safety profiles at weeks 24 and 48. METHODS: We conducted a retrospective, observational, multicenter study of 638 and 943 virologically suppressed HIV-1-infected patients in two cohorts who switched to 2DRs with DTG plus RPV or DTG plus 3TC. RESULTS: The most frequent reasons for starting DTG-based 2DRs were treatment simplification/pill burden or drug decrease. The virological suppression rates were 96.9%, 97.4%, and 99.1% at weeks 24, 48, and 96, respectively. The proportion of patients with virological failure over the 48-week study period was 0.01%. Adverse drug reactions were uncommon. Patients treated with DTG+3TC increased CD4, CD8, and CD4/CD8 parameters at 24 and 48 weeks. CONCLUSIONS: We conclude that DTG-based 2DRs (combined with 3TC or RPV) in clinical practice were effective and safe as a switching strategy, with a low VF and high viral suppression rates. Both regimens were well tolerated, and ADR rates were low, including neurotoxicity and induced treatment discontinuations.


Asunto(s)
Fármacos Anti-VIH , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Infecciones por VIH , Seropositividad para VIH , VIH-1 , Humanos , Lamivudine/efectos adversos , Infecciones por VIH/tratamiento farmacológico , Fármacos Anti-VIH/efectos adversos , Estudios Retrospectivos , Rilpivirina/efectos adversos , Compuestos Heterocíclicos con 3 Anillos/efectos adversos , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/epidemiología
19.
J Clin Med ; 12(9)2023 Apr 23.
Artículo en Inglés | MEDLINE | ID: mdl-37176500

RESUMEN

BACKGROUND: The global myocardial work index (GWI), a novel, valid, and non-invasive method based on speckle-tracking echocardiography, could provide value for calculating left ventricular (LV) function and energy consumption in athletes. MATERIALS AND METHODS: We prospectively analyzed a single-center cohort of Spanish First-Division football players who attended a pre-participation screening program from June 2020 to June 2021, compared to a control group. All the individuals underwent an electrocardiogram and echocardiography, including two-dimensional speckle tracking and 4D-echo. The study aimed to evaluate the feasibility of myocardial work in professional football players and its correlations with other echocardiographic parameters. RESULTS: The study population comprised 97 individuals (49 professional players and 48 controls). The mean age was 30.48 ± 7.20 years old. The professional football players had significantly higher values of LVEDV (p < 0.001), LVESV (p < 0.001), LV-mass index (p = 0.011), PWTd (p = 0.023), and EA (p < 0.001) compared with the control group. In addition, the professional players had lower GCW (p = 0.003) and a tendency to show lower GWI values (p < 0.001). These findings could suggest that professional football players have more remodeling and less MW, related to their adaptation to intensive training. Significant differences in GLS (p = 0.01) and GWE (p = 0.04) were observed as a function of the septal thickness of the athletes. Irrespective of the MW variable, the parameters with better correlations across all the populations were SBP, DBP, and GLS. CONCLUSIONS: The GWI is a novel index to assess cardiac performance, with less load dependency than strain measurements. Future GWI analyses are warranted to understand myocardial deformation and other pathological differential diagnoses.

20.
J Clin Med ; 12(12)2023 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-37373818

RESUMEN

MPOX (monkeypox) is a zoonotic viral disease, endemic in some Central and West African countries. However, in May 2022, cases began to be reported in non-endemic countries, demonstrating community transmission. Since the beginning of the outbreak, different epidemiological and clinical behaviors have been observed. We conducted an observational study at a secondary hospital in Madrid to characterize suspected and confirmed cases of MPOX epidemiologically and clinically. Besides the general descriptive analysis, we compared data between HIV-positive and HIV-negative subjects; 133 patients were evaluated with suspected MPOX, of which 100 were confirmed. Regarding positive cases, 71.0% were HIV positive, and 99.0% were men with a mean age of 33. In the previous year, 97.6% reported having sex with men, 53.6% used apps for sexual encounters, 22.9% practiced chemsex, and 16.7% went to saunas. Inguinal adenopathies were significantly higher in MPOX cases (54.0% vs. 12.1%, p < 0.001), as the involvement of genital and perianal area (57.0% vs. 27.3% and 17.0% vs. 1.0%, p = 0.006 and p = 0.082 respectively). Pustules were the most common skin lesion (45.0%). In HIV-positive cases, only 6.9% had a detectable viral load, and the mean CD4 count was 607.0/mm3. No significant differences were observed in the disease course, except for a greater tendency towards the appearance of perianal lesions. In conclusion, the MPOX 2022 outbreak in our area has been related to sexual intercourse among MSM, with no severe clinical cases nor apparent differences in HIV and non-HIV patients.

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