RESUMO
BACKGROUND: While a low CD4/CD8 ratio during HIV treatment correlates with immunosenescence, its value in identifying patients at an increased risk for clinical events remains unclear. METHODS: We analyzed data from the CoRIS cohort to determine whether CD4 count, CD8 count, and CD4/CD8 ratio at year two of antiretroviral therapy (ART) could predict the risk of serious non-AIDS events (SNAEs) during the next five years. These included major adverse cardiovascular events, non-AIDS-defining malignancies, and non-accidental deaths. We used pooled logistic regression with inverse probability weighting to estimate the survival curves and cumulative risk of clinical events. FINDINGS: The study included 4625 participants, 83% male, of whom 200 (4.3%) experienced an SNAE during the follow-up period. A CD4/CD8 ratio <0.3 predicted an increased risk of SNAEs during the next five years (OR 1.63, 95% CI 1.03-2.58). The effect was stronger at a CD4/CD8 ratio cut-off of <0.2 (OR 3.09, 95% CI 1.57-6.07). Additionally, low CD4 count at cut-offs of <500 cells/µL predicted an increased risk of clinical events. Among participants with a CD4 count ≥500 cells/µL, a CD8 count ≥1500 cells/µL or a CD4/CD8 ratio <0.4 predicted increased SNAE risk. INTERPRETATION: Our results support the use of the CD4/CD8 ratio and CD8 count as predictors of clinical progression. Patients with CD4/CD8 ratio <0.3 or CD8 count ≥1500/µL, regardless of their CD4 count, may benefit from closer monitoring and targeted preventive interventions. FUNDING: This work was supported by CIBER (CB 2021), Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación and Unión Europea-NextGenerationEU; by the Spanish AIDS Research Network (RIS) RD16/0025/0001 project as part of the Plan Nacional R + D + I, and cofinanced by Instituto de Salud Carlos III (ISCIII)- Subdirección General de Evaluación y el Fondo Europeo de Desarrollo Regional (FEDER), ISCIII projects PI18/00154, PI21/00141, and ERDF, "A way to make Europe", ICI20/00058.
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Síndrome da Imunodeficiência Adquirida , Humanos , Masculino , Feminino , Relação CD4-CD8 , Contagem de Linfócito CD4 , Europa (Continente) , Linfócitos T CD8-PositivosRESUMO
The aim of this report is to review the literature and shed light on the uncertainties surrounding the use of antiviral agents in general and remdesivir in COVID-19 patients. This review evaluated a battery of antiviral compounds and their effectiveness in the treatment of COVID-19 since the beginning of the pandemic. Remdesivir is the only antiviral approved by the EMA and FDA for the treatment of SARS-CoV-2 infection. This work extensively reviews remdesivir data generated from clinical trials and observational studies, paying attention to the most recent data, and focusing on outcomes to give readers a more comprehensive understanding of the results. This review also discusses the recommendations issued by official bodies during the pandemic in the light of the current knowledge. The use of remdesivir in the treatment of SARS-CoV-2 infection is justified because a virus is the causative agent that triggers the inflammatory responses and its consequences. More trials are needed to improve the management of this disease.
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Tratamento Farmacológico da COVID-19 , Monofosfato de Adenosina/análogos & derivados , Alanina/análogos & derivados , Antivirais/farmacologia , Antivirais/uso terapêutico , Humanos , SARS-CoV-2 , Replicação ViralRESUMO
BACKGROUND: COVID-19 survivors report residual lung abnormalities after discharge from the hospital. The aim of this study was to identify biomarkers in serum and induced sputum samples from patients after hospitalization for COVID-19. METHODS: Patients admitted to hospitals in Spain with laboratory-confirmed COVID-19 were recruited for this study. SARS-CoV-2-infected patients were divided into groups with mild/moderate and severe disease according to the severity of their symptoms during hospitalization. Levels of 92 biomarkers were measured in serum and induced sputum samples. RESULTS: A total of 108 patients (46.2% severe cases) were included in this study. The median number of days after the onset of symptoms was 104. A significant difference was observed in diffusing capacity for carbon monoxide (DLCO), an indicator of lung function, whereby DLCO <80% was significantly lower in severe cases (p <0.001). Differences in inflammatory biomarkers were observed between patients with mild/moderate and severe disease. For some biomarkers, correlations in serum and induced sputum levels were detected. Independent predictors of severe disease were DLCO <80% and the serum CDCP1 value. CONCLUSIONS: Higher levels of CDCP1 remain after hospital discharge and are associated with the severity of COVID-19. The possible prognostic implications warrant further investigation.
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Antígenos de Neoplasias/sangue , COVID-19/sangue , Moléculas de Adesão Celular/sangue , Antígenos de Neoplasias/análise , Biomarcadores/sangue , Moléculas de Adesão Celular/análise , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Índice de Gravidade de Doença , Escarro/químicaRESUMO
INTRODUCTION: About 25% of patients with COVID-19 develop acute respiratory distress syndrome (ARDS) associated with a high release of pro-inflammatory cytokines such as interleukin-6 (IL-6). The aim of the SARICOR study is to demonstrate that early administration of sarilumab (an IL-6 receptor inhibitor) in hospitalised patients with COVID-19, pulmonary infiltrates and a high IL-6 or D-dimer serum level could reduce the progression of ARDS requiring high-flow nasal oxygen or mechanical ventilation (non-invasive or invasive). METHODS AND ANALYSIS: Phase II, open-label, randomised, multicentre, controlled clinical trial to study the efficacy and safety of the administration of two doses of sarilumab (200 and 400 mg) plus best available therapy (BAT) in hospitalised adults with COVID-19 presenting cytokine release syndrome. This strategy will be compared with a BAT control group. The efficacy and safety will be monitored up to 28 days postadministration. A total of 120 patients will be recruited (40 patients in each arm). ETHICS AND DISSEMINATION: The clinical trial has been approved by the Research Ethics Committee of the coordinating centre and authorised by the Spanish Agency of Medicines and Medical Products. If the hypothesis is verified, the dissemination of the results could change clinical practice by increasing early administration of sarilumab in adult patients with COVID-19 presenting cytokine release syndrome, thus reducing intensive care unit admissions. TRIAL REGISTRATION NUMBER: NCT04357860.
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Anticorpos Monoclonais Humanizados/uso terapêutico , Infecções por Coronavirus/tratamento farmacológico , Síndrome da Liberação de Citocina/tratamento farmacológico , Pneumonia Viral/tratamento farmacológico , Síndrome do Desconforto Respiratório/tratamento farmacológico , Adolescente , Adulto , Idoso , Betacoronavirus , COVID-19 , Ensaios Clínicos Fase II como Assunto , Infecções por Coronavirus/imunologia , Síndrome da Liberação de Citocina/imunologia , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Humanos , Interleucina-6/imunologia , Masculino , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto , Pandemias , Pneumonia Viral/imunologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Respiração Artificial , Síndrome do Desconforto Respiratório/imunologia , SARS-CoV-2 , Adulto Jovem , Tratamento Farmacológico da COVID-19RESUMO
PURPOSE: In recent decades, the life expectancy of HIV-infected patients has increased considerably, to the extent that the disease can now be considered chronic. In this context of progressive aging, HIV-infected persons have a greater prevalence of comorbid conditions. Consequently, they usually take more non-antiretroviral drugs, and their drug therapy are more complex. This supposes a greater risk of drug interactions, of hospitalization, falls, and death. In the last years, deprescribing has gained attention as a means to rationalize medication use. METHODS: Review of the different therapeutic approach that includes optimization of polypharmacy and control and reduction of potentially inappropriate prescription. RESULTS: There are several protocols for systematizing the deprescribing process. The most widely used tool is the Medication Regimen Complexity Index, an index validated in HIV-infected persons. Anticholinergic medications are the agents that have been most associated with major adverse effects so, various scales have been employed to measure it. Other tools should be employed to detect and prevent the use of potentially inappropriate drugs. Prioritization of candidates should be based, among others, on drugs that should always be avoided and drugs with no justified indication. CONCLUSIONS: The deprescribing process shared by professionals and patients definitively would improve management of treatment in this population. Because polypharmacy in HIV-infected patients show that a considerable percentage of patients could be candidates for deprescribing, we must understand the importance of deprescribing and that HIV-infected persons should be a priority group. This process would be highly feasible and effective in HIV-infected persons.
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Desprescrições , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/prevenção & controle , Infecções por HIV/tratamento farmacológico , Prescrição Inadequada/prevenção & controle , Medicamentos sob Prescrição/uso terapêutico , Interações Medicamentosas , Humanos , Expectativa de VidaRESUMO
BACKGROUND: Extra virgin olive oil (EVOO) has shown beneficial effects on the lipid profile and inflammatory parameters in general population. Our goal is to analyze these changes together with those of intestinal microbiota in human immunodeficiency virus (HIV)-infected patients over 50 years of age. METHODS: Experimental single arm open study. HIV patients over the age of 50 with undetectable viral load were selected. EVOO was distributed among the patients so that each one consumed 50âg daily for 12 weeks. Lipid profile, C-reactive protein (CRP), and intestinal microbiota composition were analyzed at the beginning and at the end of the intervention. RESULTS: Total cholesterol decreased significantly (5âmg/dL), and a nonsignificant decrease in low-density lipoprotein cholesterol (12âmg/dL), triglycerides (21âmg/dL), and CRP (1.25âmg/dL) was observed. There was a significant increase in alpha diversity after the intervention in men and a decrease in proinflammatory genera such as Dethiosulfovibrionaceae was observed. Differences were also observed in the microbiota of men and women and according to the type of antiretroviral treatment. CONCLUSION: Sustained consumption of 50âg of EVOO in elderly HIV-infected patients might be associated with an improvement in lipid profile and alfa diversity of intestinal microbiota.
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Microbioma Gastrointestinal/efeitos dos fármacos , Infecções por HIV/sangue , Infecções por HIV/microbiologia , Lipídeos/sangue , Azeite de Oliva/administração & dosagem , Idoso , Antirretrovirais/uso terapêutico , Proteína C-Reativa/análise , Colesterol/sangue , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Dieta/métodos , Feminino , HIV , Humanos , Masculino , Pessoa de Meia-Idade , Triglicerídeos/sangueRESUMO
BACKGROUND AND OBJECTIVES: Cardiovascular disease is a major concern in HIV-infected patients. Lifetime risk estimations use the risk of developing it over the course of remaining lifetime, and are useful in communicating this risk to young patients. We aim to describe the prevalence of cardiovascular risk factors among a representative sample of HIV-infected subjects under antiretroviral therapy in Spain, and to estimate their lifetime risk of cardiovascular disease. METHODS: Cross-sectional survey about cardiovascular risk factors in 10 HIV units across Spain. Lifetime risk assessed according to Barry was classified in two major categories: low and high lifetime risk. RESULTS: We included 895 subjects, 72% men, median age 45.7âyears; median CD4 lymphocyte count 598âcells/µl, median time since HIV diagnosis 11âyears, median time on antiretroviral treatment 6.3âyears, 87% had undetectable HIV viral load. Tobacco smoking was the most frequent risk factor (54%), followed by dyslipidemia (48.6%) and hypertension (38.6%). Estimated 10-year coronary risk (Framingham/Regicor Risk Score) risk was low ( < 5%) in 78% of the patients, and intermediate (5-10%) in 20%. Lifetime risk estimation showed a high risk profile for 71.4% of the population studied, which was associated with increasing age, prolonged antiretroviral therapy and patient's place of origin. CONCLUSIONS: Modifiable cardiovascular risk factors in this population are very common. There are significant disparities between the low 10-year risk estimated with the Framingham/Regicor score and the higher lifetime risk in HIV patients on antiretroviral therapy. A more aggressive management of modifiable cardiovascular risk factors in these patients seems advisable.
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Antirretrovirais/uso terapêutico , Doenças Cardiovasculares/epidemiologia , Infecções por HIV/epidemiologia , Adulto , Idoso , Contagem de Linfócito CD4 , Doenças Cardiovasculares/complicações , Estudos Transversais , Dislipidemias , Feminino , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Humanos , Hipertensão , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Espanha/epidemiologia , Fumar TabacoAssuntos
Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , /tratamento farmacológico , Peptídeo 1 Semelhante ao Glucagon/análogos & derivados , Hipoglicemiantes/uso terapêutico , Biomarcadores/metabolismo , /metabolismo , Peptídeo 1 Semelhante ao Glucagon/uso terapêutico , Medição de RiscoRESUMO
BACKGROUND: Left ventricular hypertrophy (LVH) is a predictor of overall mortality in the general population. The most sensitive diagnostic method is transthoracic echocardiography (TTE). In this study, we describe the prevalence of LVH, and the factors associated with it, in a group of patients with HIV infection. METHODS: TTE was offered to all patients attending the outpatient clinic of the Hospital Costa del Sol (Marbella, Spain) between 1 December 2009 and 28 February 2011. The corresponding demographic and clinical data were obtained. The left ventricular mass (LVM) was calculated and indexed by height(2.7). LVH was defined as LVM >48g/m(2.7) in men or >44g/m(2.7) in women. RESULTS: We examined 388 individuals (75.5% male, mean age 45.38years). Of these, 76.1% were receiving HAART; 11.9% had hypertension, 6.2% had diabetes mellitus, 23.2% had dyslipidaemia and 53.6% were tobacco users. The risk of cardiovascular disease at 10years (RV10) was 12.15% (95%CI: 10.99-13.31%). 19.1% of these patients had a high RV10. A total of 69 patients (19.8%) presented high LVM. Age, hypertension, dyslipidaemia, RV10 and the use of nevirapine were associated with a greater presence of LVH in the univariate analysis. In the logistic regression analysis performed, the factors retained in the model were the presence of high RV10 (OR: 2.92, 95%CI: 1.39-6.15) and the use of nevirapine (OR 2.20, 95%CI: 1.18-4.14). CONCLUSIONS: In this group of patients, the use of nevirapine and the presence of high RV10 were associated with LVH. The use of nevirapine might be related to its prescription for patients with higher RV10.
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Infecções por HIV/complicações , Hipertrofia Ventricular Esquerda/complicações , Adenina/análogos & derivados , Adenina/uso terapêutico , Adulto , Alcinos , Fármacos Anti-HIV/uso terapêutico , Terapia Antirretroviral de Alta Atividade , Benzoxazinas/uso terapêutico , Carbamatos/uso terapêutico , Comorbidade , Estudos Transversais , Ciclopropanos , Diabetes Mellitus/epidemiologia , Combinação de Medicamentos , Dislipidemias/epidemiologia , Ecocardiografia , Feminino , Furanos , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Humanos , Hipertensão/epidemiologia , Hipertrofia Ventricular Esquerda/diagnóstico por imagem , Hipertrofia Ventricular Esquerda/epidemiologia , Lamivudina/uso terapêutico , Lopinavir/uso terapêutico , Masculino , Pessoa de Meia-Idade , Nevirapina/uso terapêutico , Organofosfatos/uso terapêutico , Organofosfonatos/uso terapêutico , Fatores de Risco , Ritonavir/uso terapêutico , Fumar/epidemiologia , Espanha/epidemiologia , Sulfonamidas/uso terapêutico , Tenofovir , Zidovudina/uso terapêuticoRESUMO
OBJECTIVE: Our aim was to study the proportion of healthcare workers with a positive serology for Influenza A(H1N1)2009 without having flu, in a Spanish hospital at the beginning of the pandemic. METHODS: A survey study carried out during August 2009 (before the peak of the pandemic in Spain) in the Hospital Costa del Sol, a second level hospital with almost 300 beds in the South of Spain. The participants were workers in the following hospital units: Emergencies, Medical Area (Internal Medicine, Chest Diseases), Surgical Area (General Surgery and Anaesthesia) of any professional category. A study was made of the proportion of healthcare workers in our hospital with positive serology for the new influenza A (H1N1)2009 virus, as determined by the haemagglutination inhibition technique (≥1/40). The subjects completed a health status questionnaire, and provided a blood sample for serology testing. RESULTS: A total of 239 workers participated, of whom 25.1% had positive serology. The hospital area in which most individuals had positive serology was the Emergency Department (36.6%), while the professional category in which most individuals with a positive serology worked was that of the orderlies (41.7%). CONCLUSION: Around 25% of healthcare workers in our hospital had positive serology before the peak of the pandemic, none of them had received vaccine for Influenza A (H1N1) 2009 or had been diagnosed of influenza previously.
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Anticorpos Antivirais/sangue , Pessoal de Saúde , Vírus da Influenza A Subtipo H1N1/imunologia , Influenza Humana/sangue , Influenza Humana/epidemiologia , Adulto , Estudos Transversais , Feminino , Humanos , Masculino , Pandemias , Estudos SoroepidemiológicosRESUMO
Background: Vascular risk is an important cause of morbidity and mortality in HIV infected patients. Aim: To study the value of the ankle-brachial index (ABI) in vascular risk stratification in a cohort of people with HIV infection. Patients and Methods: Vascular risk was calculated in all the patients that agreed to participate in the study and clinical reports were reviewed retrospectively. Ten year risk of fatal myocardial infarction was calculated according to Framingham equation, National Cholesterol Education Program (NCEP) III and Systematic Coronary Risk Evaluation (SCORE) project score. ABI was calculated measuring resting systolic blood pressure at the ankle, that was compared with the systolic brachial pressure. The ratio of the two pressures defined ABI, that was considered abnormal if it was d" 0.9 or e" 1.3. Results: A total of 231 HIV infected patients aged 23 to 82 years (80 percent males) were enrolled. Ten years risk according to Framingham equation was 8.4 percent, 95 percent confidence intervals (CI): 7.54-9.15 and according to SCORE scale was 0.8 percent, 95 percent CI: 0.62-1.01. According to NCEP III 9 percent of patients had a high or very high cardiovascular risk. Median ABI was 1.17 (95 percent CI intervals: 1.16-1.19) and 58 patients (25 percent) had an abnormal value. Using ABI results, approximately 20 percent of patients were re-classified as having a high vascular risk. Conclusions: ABI identified approximately 20 percent of this cohort of HIV infected subjects as having high vascular risk.