Analysis of the reasons for requesting HIV serology in the emergency department other than those defined in the targeted screening strategy of the "Urgències VIHgila" program and its potential inclusion in a future consensus document.

OBJECTIVE: To describe other reasons for requesting HIV serology in emergency departments (ED) other than the 6 defined in the SEMES-GESIDA consensus document (DC-SEMES-GESIDA) and to analyze whether it would be efficient to include any of them in the future. METHODS: Review of all HIV serologies performed during 2 years in 20 Catalan EDs. Serologies requested for reasons not defined by the DC-SEMES-GESIDA were grouped by common conditions, the prevalence (IC95%) of seropositivity for each condition was calculated, and those whose 95% confidence lower limit was >0.1% were considered efficient. Sensitivity analysis considered that serology would have been performed on 20% of cases attended and the remaining 80% would have been seronegative. RESULTS: There were 8044 serologies performed for 248 conditions not recommended by DC-SEMES-GESIDA, in 17 there were seropositive, and in 12 the performance of HIV serology would be efficient. The highest prevalence of detection corresponded to patients from endemic countries (7.41%, 0.91-24.3), lymphopenia (4.76%, 0.12-23.8), plateletopenia (4.37%, 1.20-10.9), adenopathy (3.45%, 0.42-11.9), meningoencephalitis (3.12%, 0.38-10.8) and drug use (2.50%, 0.68-6.28). Sensitivity analysis confirmed efficiency in 6 of them: endemic country origin, plateletopenia, drug abuse, toxic syndrome, behavioral-confusional disorder-agitation and fever of unknown origin. CONCLUSION: The DC-SEMES-GESIDA targeted HIV screening strategy in the ED could efficiently include other circumstances not previously considered; the most cost-effective would be origin from an endemic country, plateletopenia, drug abuse, toxic syndrome, behavioral-confusional-agitation disorder and fever of unknown origin.

Detección en urgencias de infección por VIH en pacientes que consultan por condiciones potencialmente relacionadas con infección oculta: Resultados iniciales del programa “Urgències VIHgila” / Emergency detection of HIV infection in patients consulting for conditions potentially related to occult infection: Initial results of the “Urgències VIHgila” program

Objective: To estimate the prevalence of unknown HIV infection in patients who consulted in hospital emergency services (ED) for conditions defined in the SEMES-GESIDA Consensus Document (DC), evaluate the efficiency of its im-plementation and investigate the efficiency of HIV serology determination in other conditions. Methods: Results were reviewed in 10 Catalan EDs for 12 months (July-21-June-22) after implementing CD recommendations: request HIV serology in case of suspected sexually transmitted infection, chemsex, post-exposure prophylaxis (PEP), mononucleosis syndrome, community pneumonia (18-65 y-o) or herpes zoster (18-65 y-o). Other reasons for request were included. Prevalence (%) of global seropositivity and for each circumstance was calculated, with a 95% confidence interval (95%CI). The efficient strategy was considered if the lower limit of the CI95%>0.1%. Results: A total of5,107 HIV serologies were performed: 2,847(56%) in situations specified in CD, and 2,266 (44%) in other 138 circumstances. Forty-eight unknown HIV infections were detected (prevalence=0.94%;95%CI=0.69-1.24). The prevalence was somewhat higher in DC requests (30 cas-es 1.12%) than the rest (18 cases 0.71%; p=0.16). The individualized prevalence of CD reasons ranged between 7.41% (95%CI=0.91-24.3) in chemsex and 0.42% 95%CI=0.14-0.98) in PPE, always efficient except herpes zoster (0.76%; CI95%=0.02-4.18). In other reasons, cases were detected in 12 circumstances, and in four the determination could be efficient: lymphopenia (10%;CI95%=0.25-44.5), fever with polyarthralgia-polyarthritis (7.41%;CI95% =0.91-24.3), behavioral alteration-confusion-encephalopathy (3.45%;95%CI=0.42-11.9) and fever of unknown origin (2.50%;95%CI=0.82-5.74). (AU)

Objetivo: Estimar la prevalencia de infección por VIH des-conocida en pacientes que consultan en servicios de urgencias hospitalarios (SUH) por las condiciones definidas en el Documento de Consenso (DC) de SEMES-GESIDA, evaluar la eficiencia de su implementación e investigar si en otras condiciones la determinación de serología VIH puede resultar eficiente.Método: Se revisaron los resultados obtenidos en 10 SUH catalanes durante los 12 meses (julio-21 a junio-22) siguientes a implementar las recomendaciones del DC de solicitar serología VIH a pacientes con sospecha de infección de transmisión sexual, práctica de chemsex, solicitud profilaxis post-exposición (PPE), síndrome mononucleósico, neumonía comunitaria (18-65 años) o herpes zóster (18-65 años). Se consignaron también otros motivos de solicitud. Se calculó la prevalencia (%) de seropositividad global y para cada circunstancia, con su intervalo de confianza del 95% (IC95%). Se consideró la estrategia eficiente si el límite inferior del IC95% era >0,1%.Resultados: Se realizaron 5.107 serologías VIH: 2.847 (56%) en situaciones especificadas en el DC, y 2.266 (44%) en otras 138 circunstancias. Se detectaron 48 infecciones por VIH desconocidas (prevalencia=0,94%; IC95%=0,69-1,24). La preva-lencia fue algo superior en las solicitudes ajustadas al DC (30 ca-sos, 1,12%) que en las que no (18 casos, 0,71%; p=0,16). La prevalencia individualizada para los motivos especificados en el DC osciló entre 7,41% IC95%=0,91-24,3) en práctica de chemsex y 0,42% (IC95%=0,14-0,98) en PPE, y siempre resultó eficiente, con excepción de herpes zóster (0,76%, IC95%=0,02-4,18). Respecto al resto de motivos de solicitud, se detectaron casos en 12 circunstancias, y en cuatro la determinación podría ser eficiente: linfopenia (10%, IC95%=0,25-44,5), fiebre con poliartralgias-poliartritis (7,41%, IC95%=0,91-24,3), alteración conductual-confusión-encefalopatía (3,45%,IC95%=0,42-11,9) y fiebre de origen desconocido(2,50%,IC95%=0,82-5,74)(AU)

Pulmonary embolism in patients with COVID-19: incidence, risk factors, clinical characteristics, and outcome.

AIMS: We investigated the incidence, risk factors, clinical characteristics, and outcomes of pulmonary embolism (PE) in patients with COVID-19 attending emergency departments (EDs), before hospitalization. METHODS AND RESULTS: We retrospectively reviewed all COVID-19 patients diagnosed with PE in 62 Spanish EDs (20% of Spanish EDs, case group) during the first COVID-19 outbreak. COVID-19 patients without PE and non-COVID-19 patients with PE were included as control groups. Adjusted comparisons for baseline characteristics, acute episode characteristics, and outcomes were made between cases and randomly selected controls (1:1 ratio). We identified 368 PE in 74 814 patients with COVID-19 attending EDs (4.92‰). The standardized incidence of PE in the COVID-19 population resulted in 310 per 100 000 person-years, significantly higher than that observed in the non-COVID-19 population [35 per 100 000 person-years; odds ratio (OR) 8.95 for PE in the COVID-19 population, 95% confidence interval (CI) 8.51-9.41]. Several characteristics in COVID-19 patients were independently associated with PE, the strongest being D-dimer >1000 ng/mL, and chest pain (direct association) and chronic heart failure (inverse association). COVID-19 patients with PE differed from non-COVID-19 patients with PE in 16 characteristics, most directly related to COVID-19 infection; remarkably, D-dimer >1000 ng/mL, leg swelling/pain, and PE risk factors were significantly less present. PE in COVID-19 patients affected smaller pulmonary arteries than in non-COVID-19 patients, although right ventricular dysfunction was similar in both groups. In-hospital mortality in cases (16.0%) was similar to COVID-19 patients without PE (16.6%; OR 0.96, 95% CI 0.65-1.42; and 11.4% in a subgroup of COVID-19 patients with PE ruled out by scanner, OR 1.48, 95% CI 0.97-2.27), but higher than in non-COVID-19 patients with PE (6.5%; OR 2.74, 95% CI 1.66-4.51). Adjustment for differences in baseline and acute episode characteristics and sensitivity analysis reported very similar associations. CONCLUSIONS: PE in COVID-19 patients at ED presentation is unusual (about 0.5%), but incidence is approximately ninefold higher than in the general (non-COVID-19) population. Moreover, risk factors and leg symptoms are less frequent, D-dimer increase is lower and emboli involve smaller pulmonary arteries. While PE probably does not increase the mortality of COVID-19 patients, mortality is higher in COVID-19 than in non-COVID-19 patients with PE.

HCV eradication with IFN-based therapy does not completely restore gene expression in PBMCs from HIV/HCV-coinfected patients.

OBJECTIVE: To evaluate the impact of hepatitis C virus (HCV) elimination via interferon (IFN)-based therapy on gene expression profiles related to the immune system in HIV/HCV-coinfected patients. METHODS: We conducted a prospective study in 28 HIV/HCV-coinfected patients receiving IFN-based therapy at baseline (HIV/HCV-b) and week 24 after sustained virological response (HIV/HCV-f). Twenty-seven HIV-monoinfected patients (HIV-mono) were included as a control. RNA-seq analysis was performed on peripheral blood mononuclear cells (PBMCs). Genes with a fold-change (FC) ≥ 1.5 (in either direction) and false discovery rate (FDR) ≤ 0.05 were identified as significantly differentially expressed (SDE). RESULTS: HIV/HCV-b showed six SDE genes compared to HIV-mono group, but no significantly enriched pathways were observed. For HIV/HCV-f vs. HIV/HCV-b, we found 58 SDE genes, 34 upregulated and 24 downregulated in the HIV/HCV-f group. Of these, the most overexpressed were CXCL2, PDCD6IP, ATP5B, IGSF9, RAB26, and CSRNP1, and the most downregulated were IFI44 and IFI44L. These 58 SDE genes revealed two significantly enriched pathways (FDR < 0.05), one linked to Epstein-Barr virus infection and another related to p53 signaling. For HIV/HCV-f vs. HIV-mono group, we found 44 SDE genes that revealed 31 enriched pathways (FDR < 0.05) related to inflammation, cancer/cell cycle alteration, viral and bacterial infection, and comorbidities associated with HIV/HCV-coinfection. Five genes were overrepresented in most pathways (JUN, NFKBIA, PIK3R2, CDC42, and STAT3). CONCLUSION: HIV/HCV-coinfected patients who eradicated hepatitis C with IFN-based therapy showed profound gene expression changes after achieving sustained virological response. The altered pathways were related to inflammation and liver-related complications, such as non-alcoholic fatty liver disease and hepatocellular carcinoma, underscoring the need for active surveillance for these patients.

Frequency, Risk Factors, Clinical Characteristics, and Outcomes of Spontaneous Pneumothorax in Patients With Coronavirus Disease 2019: A Case-Control, Emergency Medicine-Based Multicenter Study.

BACKGROUND: Recent reports of patients with coronavirus disease 2019 (COVID-19) developing pneumothorax correspond mainly to case reports describing mechanically ventilated patients. The real incidence, clinical characteristics, and outcome of spontaneous pneumothorax (SP) as a form of COVID-19 presentation remain to be defined. RESEARCH QUESTION: Do the incidence, risk factors, clinical characteristics, and outcomes of SP in patients with COVID-19 attending EDs differ compared with COVID-19 patients without SP and non-COVID-19 patients with SP? STUDY DESIGN AND METHODS: This case-control study retrospectively reviewed all patients with COVID-19 diagnosed with SP (case group) in 61 Spanish EDs (20% of Spanish EDs) and compared them with two control groups: COVID-19 patients without SP and non-COVID-19 patients with SP. The relative frequencies of SP were estimated in COVID-19 and non-COVID-19 patients in the ED, and annual standardized incidences were estimated for both populations. Comparisons between case subjects and control subjects included 52 clinical, analytical, and radiologic characteristics and four outcomes. RESULTS: We identified 40 occurrences of SP in 71,904 patients with COVID-19 attending EDs (0.56‰; 95% CI, 0.40‰-0.76‰). This relative frequency was higher than that among non-COVID-19 patients (387 of 1,358,134, 0.28‰; 95% CI, 0.26‰-0.32‰; OR, 1.93; 95% CI, 1.41-2.71). The standardized incidence of SP was also higher in patients with COVID-19 (34.2 vs 8.2/100,000/year; OR, 4.19; 95% CI, 3.64-4.81). Compared with COVID-19 patients without SP, COVID-19 patients developing SP more frequently had dyspnea and chest pain, low pulse oximetry readings, tachypnea, and increased leukocyte count. Compared with non-COVID-19 patients with SP, case subjects differed in 19 clinical variables, the most prominent being a higher frequency of dysgeusia/anosmia, headache, diarrhea, fever, and lymphopenia (all with OR > 10). All the outcomes measured, including in-hospital death, were worse in case subjects than in both control groups. INTERPRETATION: SP as a form of COVID-19 presentation at the ED is unusual (< 1‰ cases) but is more frequent than in the non-COVID-19 population and could be associated with worse outcomes than SP in non-COVID-19 patients and COVID-19 patients without SP.

Effects of Hepatitis C Virus (HCV) Eradication on Bone Mineral Density in Human Immunodeficiency Virus/HCV-Coinfected Patients.

BACKGROUND: Little is known about the effects of eradication of hepatitis C virus (HCV) on bone mineral density (BMD) and biomarkers of bone remodeling in human immunodeficiency virus (HIV)/HCV-coinfected patients. METHODS: We prospectively assessed standardized BMD (sBMD) at the lumbar spine and femoral neck, World Health Organization BMD categories at both sites, and plasma concentrations of soluble receptor activator of NF-κß ligand (sRANKL), and osteoprotegerin (OPG) at baseline (the date of initiation of anti-HCV therapy) and at 96 weeks. RESULTS: A total of 238 patients were included. The median age was 49.5 years, 76.5% were males, 48.3% had cirrhosis, 98.3% were on antiretroviral therapy, median CD4+ cell count was 527 cells/µL, and 86.6% had HIV-1 RNA <50 copies/mL. The prevalence of osteoporosis at baseline at the lumbar spine (LS) and femoral neck (FN) was 17.6% and 7.2%, respectively. Anti-HCV therapy comprised pegylated interferon (peg-IFN) and ribavirin (RBV) plus 1 direct-acting antiviral in 53.4%, peg-IFN/RBV in 34.5%, and sofosbuvir/RBV in 12.2%. A total of 145 (60.9%) patients achieved sustained virologic response (SVR). No significant effect of SVR was observed on sBMD for the interaction between time and SVR either in the LS (P = .801) or the FN (P = .911). Likewise, no significant effect of SVR was observed in plasma levels of sRANKL (P = .205), OPG (P = .249), or sRANKL/OPG ratio (P = .123) for the interaction between time and SVR. No significant correlation was found between fibrosis by transient elastography, and LS and FN sBMD, at baseline and week 96. CONCLUSIONS: SVR was not associated with significant changes in BMD nor biomarkers of bone remodeling in HIV/HCV-coinfected persons.

Evaluación de las características clínicas y evolución de pacientes con COVID-19 a partir de una serie de 1000 pacientes atendidos en servicios de urgencias españoles / Analysis of clinical characteristics and outcomes in patients with COVID-19 based on a series of 1000 patients treated in Spanish emergency departments

OBJETIVO: Describir las características clínicas de los pacientes con COVID-19 atendidos en los servicios de urgencias hospitalarios (SUH) españoles y evaluar su asociación con los resultados de su evolución. MÉTODOS: Estudio multicéntrico, anidado en una cohorte prospectiva. Participaron 61 SUH que incluyeron pacientes seleccionados aleatoriamente de todos los diagnosticados de COVID-19 entre el 1 de marzo y el 30 de abril de 2020. Se recogieron características basales, clínicas, de exploraciones complementarias y terapéuticas del episodio en los SUH. Se calcularon las odds ratio (OR) asociadas a la mortalidad intrahospitalaria y al evento combinado formado por el ingreso en unidad de cuidados intensivos (UCI), la intubación orotraqueal o ventilación mecánica invasiva (IOT/ VMI), crudas y ajustadas con modelos de regresión logística para tres grupos de variables independientes: basales, clínicas y de exploraciones complementarias. RESULTADOS: La edad media fue de 62 años (DE 18). La mayoría manifestaron fiebre, tos seca, disnea, febrícula y diarrea. Las comorbilidades más frecuentes fueron las enfermedades cardiovasculares, seguidas de las respiratorias y el cáncer. Las variables basales que se asociaron independientemente y de forma directa a peores resultados evolutivos (tanto a mortalidad como a evento combinado) fueron edad y obesidad; las variables clínicas fueron disminución de consciencia y crepitantes a la auscultación pulmonar, y de forma inversa cefalea; y las variables de resultados de exploraciones complementarias fueron infiltrados pulmonares bilaterales y cardiomegalia radiológicos, y linfopenia, hiperplaquetosis, dímero-D > 500 mg/dL y lactato-deshidrogenasa > 250 UI/L en la analítica. CONCLUSIONES: Conocer las características clínicas y la comorbilidad de los pacientes con COVID-19 atendidos en urgencias permite identificar precozmente a la población más susceptible de empeorar, para prever y mejorar los resultados

OBJECTIVES: To describe the clinical characteristics of patients with coronavirus disease 2019 (COVID-19) treated in hospital emergency departments (EDs) in Spain, and to assess associations between characteristics and outcomes. METHODS: Prospective, multicenter, nested-cohort study. Sixty-one EDs included a random sample of all patients diagnosed with COVID-19 between March 1 and April 30, 2020. Demographic and baseline health information, including concomitant conditions; clinical characteristics related to the ED visit and complementary test results; and treatments were recorded throughout the episode in the ED. We calculated crude and adjusted odds ratios for risk of in-hospital death and a composite outcome consisting of the following events: intensive care unit admission, orotracheal intubation or mechanical ventilation, or in-hospital death. The logistic regression models were constructed with 3 groups of independent variables: the demographic and baseline health characteristics, clinical characteristics and complementary test results related to the ED episode, and treatments. RESULTS: The mean (SD) age of patients was 62 (18) years. Most had high- or low-grade fever, dry cough, dyspnea, and diarrhea. The most common concomitant conditions were cardiovascular diseases, followed by respiratory diseases and cancer. Baseline patient characteristics that showed a direct and independent association with worse outcome (death and the composite outcome) were age and obesity. Clinical variables directly associated with worse outcomes were impaired consciousness and pulmonary crackles; headache was inversely associated with worse outcomes. Complementary test findings that were directly associated with outcomes were bilateral lung infiltrates, lymphopenia, a high platelet count, a D-dimer concentration over 500 mg/dL, and a lactate-dehydrogenase concentration over 250 IU/L in blood. CONCLUSION: This profile of the clinical characteristics and comorbidity of patients with COVID-19 treated in EDs helps us predict outcomes and identify cases at risk of exacerbation. The information can facilitate preventive measures and improve outcomes

Analysis of clinical characteristics and outcomes in patients with COVID-19 based on a series of 1000 patients treated in Spanish emergency departments. / Evaluación de las características clínicas y evolución de pacientes con COVID-19 a partir de una serie de 1000 pacientes atendidos en servicios de urgencias españoles.

OBJECTIVES: To describe the clinical characteristics of patients with coronavirus disease 2019 (COVID-19) treated in hospital emergency departments (EDs) in Spain, and to assess associations between characteristics and outcomes. MATERIAL AND METHODS: Prospective, multicenter, nested-cohort study. Sixty-one EDs included a random sample of all patients diagnosed with COVID-19 between March 1 and April 30, 2020. Demographic and baseline health information, including concomitant conditions; clinical characteristics related to the ED visit and complementary test results; and treatments were recorded throughout the episode in the ED. We calculated crude and adjusted odds ratios for risk of in-hospital death and a composite outcome consisting of the following events: intensive care unit admission, orotracheal intubation or mechanical ventilation, or in-hospital death. The logistic regression models were constructed with 3 groups of independent variables: the demographic and baseline health characteristics, clinical characteristics and complementary test results related to the ED episode, and treatments. RESULTS: The mean (SD) age of patients was 62 (18) years. Most had high- or low-grade fever, dry cough, dyspnea, and diarrhea. The most common concomitant conditions were cardiovascular diseases, followed by respiratory diseases and cancer. Baseline patient characteristics that showed a direct and independent association with worse outcome (death and the composite outcome) were age and obesity. Clinical variables directly associated with worse outcomes were impaired consciousness and pulmonary crackles; headache was inversely associated with worse outcomes. Complementary test findings that were directly associated with outcomes were bilateral lung infiltrates, lymphopenia, a high platelet count, a D-dimer concentration over 500 mg/dL, and a lactate-dehydrogenase concentration over 250 IU/L in blood. CONCLUSION: This profile of the clinical characteristics and comorbidity of patients with COVID-19 treated in EDs helps us predict outcomes and identify cases at risk of exacerbation. The information can facilitate preventive measures and improve outcomes.

OBJETIVO: Describir las características clínicas de los pacientes con COVID-19 atendidos en los servicios de urgencias hospitalarios (SUH) españoles y evaluar su asociación con los resultados de su evolución. METODO: Estudio multicéntrico, anidado en una cohorte prospectiva. Participaron 61 SUH que incluyeron pacientes seleccionados aleatoriamente de todos los diagnosticados de COVID-19 entre el 1 de marzo y el 30 de abril de 2020. Se recogieron características basales, clínicas, de exploraciones complementarias y terapéuticas del episodio en los SUH. Se calcularon las odds ratio (OR) asociadas a la mortalidad intrahospitalaria y al evento combinado formado por el ingreso en unidad de cuidados intensivos (UCI), la intubación orotraqueal o ventilación mecánica invasiva (IOT/ VMI), crudas y ajustadas con modelos de regresión logística para tres grupos de variables independientes: basales, clínicas y de exploraciones complementarias. RESULTADOS: La edad media fue de 62 años (DE 18). La mayoría manifestaron fiebre, tos seca, disnea, febrícula y diarrea. Las comorbilidades más frecuentes fueron las enfermedades cardiovasculares, seguidas de las respiratorias y el cáncer. Las variables basales que se asociaron independientemente y de forma directa a peores resultados evolutivos (tanto a mortalidad como a evento combinado) fueron edad y obesidad; las variables clínicas fueron disminución de consciencia y crepitantes a la auscultación pulmonar, y de forma inversa cefalea; y las variables de resultados de exploraciones complementarias fueron infiltrados pulmonares bilaterales y cardiomegalia radiológicos, y linfopenia, hiperplaquetosis, dímero-D > 500 mg/dL y lactato-deshidrogenasa > 250 UI/L en la analítica. CONCLUSIONES: Conocer las características clínicas y la comorbilidad de los pacientes con COVID-19 atendidos en urgencias permite identificar precozmente a la población más susceptible de empeorar, para prever y mejorar los resultados.

Rapid decrease in titer and breadth of neutralizing anti-HCV antibodies in HIV/HCV-coinfected patients who achieved SVR.

The main targets for neutralizing anti-hepatitis C virus (HCV) antibodies (HCV-nAbs) are the E1 and E2 envelope glycoproteins. We have studied the characteristics of HCV-nAbs through a retrospective study involving 29 HIV/HCV-coinfected patients who achieved sustained virological response (SVR) with peg-IFNα + ribavirin anti-HCV therapy. Plasma samples at baseline and week 24 after SVR were used to perform neutralization assays against five JFH1-based HCV recombinant viruses coding for E1 and E2 from genotypes 1a (H77), 1b (J4), 2a (JFH1), 3a (S52) and 4a (ED43). At baseline, the majority of plasma samples neutralized 1a, 1b, 2a, and 4a, but not 3a, genotypes. Twenty-four weeks following SVR, most neutralizing titers declined substantially. Furthermore, titers against 3a and 2a were not detected in many patients. Plasma samples with high HCV-nAb titers neutralized all genotypes, and the highest titers at the starting point correlated with the highest titers at week 24 after SVR. In conclusion, high titers of broad-spectrum HCV-nAbs were detected in HIV/HCV-coinfected individuals, however, those titers declined soon after SVR.

Prevalence of hepatitis E infection in HIV/HCV-coinfected patients in Spain (2012-2014).

Hepatitis E virus (HEV) has emerged as a relevant pathogen for HIV-infected patients. However, there is scarce data on HEV infection in HIV/HCV-coinfected individuals with advanced fibrosis, which seems to increase the risk of HEV infection and worsen the prognosis of liver disease. We aimed to determine the prevalence of anti-HEV antibodies, acute hepatitis E, resolved hepatitis E, and exposure to HEV in HIV/HCV-coinfected patients and to evaluate associations with clinical and epidemiological characteristics. We performed a cross-sectional study on 198 HIV/HCV-coinfected patients, 30 healthy controls and 36 HIV-monoinfected patients. We found a low concordance between techniques used for detection of anti-HEV antibodies (ELISA versus Immunoblot), particularly in HIV/HCV-coinfected patients. HIV/HCV-coinfected patients showed the highest prevalence of IgG against HEV, resolved hepatitis E, and exposure to HEV (19.2%, 17.2%, and 22.2% respectively). However, we did not find any samples positive for HEV-RNA nor significant differences between groups. Moreover, HIV/HCV-coinfected patients with CD4 T-cells <350 cells/mm3 had higher prevalence for anti-HEV IgG antibodies, resolved hepatitis E, and exposure to HEV than healthy controls or those with CD4 T-cells ≥ 350 cells/mm3 (p = 0.034, p = 0.035, and p = 0.053; respectively). In conclusion, HIV/HCV-coinfected patients in Spain have a high prevalence for IgG anti-HEV antibodies, resolved hepatitis E, and exposure to HEV; particularly patients with CD4+T-cells <350 cells/mm3.

Dysregulation of the Immune System in HIV/HCV-Coinfected Patients According to Liver Stiffness Status.

BACKGROUND: Advanced cirrhosis is related to alterations in immunity. We aimed to evaluate the levels of peripheral CD4⁺ T cells (Tregs) and plasma cytokine in patients coinfected with human immunodeficiency virus and hepatitis C virus (HIV/HCV) according to liver fibrosis stages [evaluated as liver stiffness measure (LSM)] and their linear relationship. METHODS: We performed a cross-sectional study on 238 HIV/HCV-coinfected patients (119 had <12.5 kPa, 73 had 12.5⁻25 kPa, and 46 had >25 kPa). Peripheral T-cell subsets were phenotyped by flow cytometry, plasma biomarkers were assessed by multiplex immunoassays, and LSM was assessed by transient elastography. Results: We found HIV/HCV-coinfected patients had higher values of CD4⁺ Tregs (p < 0.001), memory Tregs (p ≤ 0.001), and plasma cytokine levels [IFN-γ (p ≤ 0.05) and IL-10 (p ≤ 0.01)] compared with healthy donors and HIV-monoinfected patients. In the multivariate analysis, higher LSM values were associated with reduced levels of IL-10 (adjusted arithmetic mean ratio (aAMR) = 0.83; p = 0.019), IL-2 (aAMR = 0.78; p = 0.017), TNF-α (aAMR = 0.67; p < 0.001), and IL-17A (aAMR = 0.75; p = 0.006). When we focus on HIV/HCV-coinfected patients analyzed by LSM strata, patients with ≥25 kPa had lower values of IL-2 (aAMR = 0.66; p = 0.021), TNF-α (aAMR = 0.565; p = 0.003), and IL-17A (aAMR = 0.58; p = 0.003) than patients with <12.5 kPa. CONCLUSION: HIV/HCV-coinfected patients showed an immunosuppressive profile compared to healthy controls and HIV-monoinfected patients. Additionally, HIV/HCV-coinfected patients with advanced cirrhosis (LSM ≥ 25 kPa) had the lowest plasma values of cytokines related to Th1 (IL-2 and TNF-α) and Th17 (IL-17A) response.

Elevated liver stiffness is linked to increased biomarkers of inflammation and immune activation in HIV/hepatitis C virus-coinfected patients.

OBJECTIVES: Immune dysregulation is a hallmark of HIV and hepatitis C virus (HCV) infections. We aimed to evaluate the relationship between liver stiffness measurement (LSM) and biomarkers of T-cell activation, bacterial translocation, inflammation, endothelial dysfunction, and coagulopathy in HIV/HCV-coinfected patients. DESIGN: Cross-sectional study. METHODS: We studied 238 HIV/HCV-coinfected patients, 32 healthy controls, and 39 HIV-monoinfected patients. Patients were stratified according to LSM into four groups: less than 12.5, 12.5-25, 25-40, and more than 40 kPa. T-cell subsets were measured using flow cytometry and plasma biomarkers using immunoassays. RESULTS: HIV/HCV-coinfected patients had higher biomarker levels of immune activation in peripheral blood [T-cell activation (CD4CD38 and CD8CD38), bacterial translocation (soluble CD14), inflammation [IL-1b, IL-6, IL-8, IL-18, IFN-γ-inducible protein 10 (IP-10)] endothelial dysfunction [soluble vascular cell adhesion molecule 1 (sVCAM1), soluble intercellular cell adhesion molecule 1 (sICAM1), and soluble tumor necrosis factor receptor 1 (sTNFR1)], and coagulopathy (plasminogen activator inhibitor-1)] than healthy controls and HIV-monoinfected patients. Moreover, in HIV/HCV-coinfected patients, a direct relationship between LSM and immune activation [T-cell activation (CD8CD38 bacterial translocation (lipopolysaccharide), inflammation (IL-8, IP-10), endothelial dysfunction (sVCAM1, sICAM1, and sTNFR1), and coagulopathy (D-dimer)] was found. Subsequently, patients were stratified into different fibrosis stages, finding that patients with cirrhosis who had LSM at least 40 kPa showed higher biomarker values of immune activation [T-cell activation (CD4CD38 and CD8CD38), bacterial translocation (lipopolysaccharide), inflammation (IL-8, IL-6, IP-10), endothelial dysfunction (sVCAM1, sICAM1, and sTNFR1), and coagulopathy (D-dimer)] than patients from the other three groups (<12.5, 12.5-25, and 25-40 kPa). CONCLUSION: T-cell activation, bacterial translocation, inflammation, endothelial dysfunction, and coagulopathy increased with the severity of liver fibrosis in HIV/HCV-coinfected patients, particularly in patients who had LSM at least 40 kPa.

Human Immunodeficiency Virus/Hepatits C Virus Coinfection in Spain: Elimination Is Feasible, but the Burden of Residual Cirrhosis Will Be Significant.

BACKGROUND: We assessed the prevalence of antibodies against hepatitis C virus (HCV-Abs) and active HCV infection in patients infected with human immunodeficiency virus (HIV) in Spain in 2016 and compared the results with those of similar studies performed in 2002, 2009, and 2015. METHODS: The study was performed in 43 centers during October-November 2016. The sample was estimated for an accuracy of 2% and selected by proportional allocation and simple random sampling. During 2016, criteria for therapy based on direct-acting antiviral agents (DAA) were at least significant liver fibrosis, severe extrahepatic manifestations of HCV, and high risk of HCV transmissibility. RESULTS: The reference population and the sample size were 38904 and 1588 patients, respectively. The prevalence of HCV-Abs in 2002, 2009, 2015, and 2016 was 60.8%, 50.2%, 37.7%, and 34.6%, respectively (P trend <.001, from 2002 to 2015). The prevalence of active HCV in 2002, 2009, 2015, and 2016 was 54.0%, 34.0%, 22.1%, and 11.7%, respectively (P trend <.001). The anti-HCV treatment uptake in 2002, 2009, 2015, and 2016 was 23.0%, 48.0%, 59.3%, and 74.7%, respectively (P trend <.001). In 2016, HCV-related cirrhosis was present in 7.6% of all HIV-infected individuals, 15.0% of patients with active HCV, and 31.5% of patients who cleared HCV after anti-HCV therapy. CONCLUSIONS: Our findings suggest that with universal access to DAA-based therapy and continued efforts in prevention and screening, it will be possible to eliminate active HCV among HIV-infected individuals in Spain in the short term. However, the burden of HCV-related cirrhosis will continue to be significant among HIV-infected individuals.

Eradication of hepatitis C virus and non-liver-related non-acquired immune deficiency syndrome-related events in human immunodeficiency virus/hepatitis C virus coinfection.

We assessed non-liver-related non-acquired immunodeficiency syndrome (AIDS)-related (NLR-NAR) events and mortality in a cohort of human immunodeficiency virus (HIV)/hepatitis C virus (HCV)-coinfected patients treated with interferon (IFN) and ribavirin (RBV), between 2000 and 2008. The censoring date was May 31, 2014. Cox regression analysis was performed to assess the adjusted hazard rate (HR) of overall death in responders and nonresponders. Fine and Gray regression analysis was conducted to determine the adjusted subhazard rate (sHR) of NLR deaths and NLR-NAR events considering death as the competing risk. The NLR-NAR events analyzed included diabetes mellitus, chronic renal failure, cardiovascular events, NLR-NAR cancer, bone events, and non-AIDS-related infections. The variables for adjustment were age, sex, past AIDS, HIV transmission category, nadir CD4+ T-cell count, antiretroviral therapy, HIV RNA, liver fibrosis, HCV genotype, and exposure to specific anti-HIV drugs. Of the 1,625 patients included, 592 (36%) had a sustained viral response (SVR). After a median 5-year follow-up, SVR was found to be associated with a significant decrease in the hazard of diabetes mellitus (sHR, 0.57; 95% confidence interval [CI], 0.35-0.93; P = 0.024) and decline in the hazard of chronic renal failure close to the threshold of significance (sHR, 0.43; 95% CI, 0.17-1.09; P = 0.075). CONCLUSION: Our data suggest that eradication of HCV in coinfected patients is associated not only with a reduction in the frequency of death, HIV progression, and liver-related events, but also with a reduced hazard of diabetes mellitus and possibly of chronic renal failure. These findings argue for the prescription of HCV therapy in coinfected patients regardless of fibrosis stage. (Hepatology 2017;66:344-356).

Aportaciones de la reducción de riesgos y daños en un contexto de regulación / No disponible

Esta revisión trata sobre los beneficios de la regulación respecto a la prohibición, la guerra a las drogas, sus costes y consecuencias negativas no previstas, la ley de seguridad ciudadana, la nueva política de drogas, la regulación del mercado de cannabis, las asociaciones cannábicas y sus buenas prácticas para la prevención de riesgos. Se concluye que en el ámbito de las drogas es necesaria la regulación responsable y la información veraz

This review discusses the benefits of regulation regarding prohibition, the war on drugs, their costs and unintended negative consequences, the Spanish law of public safety, the new drug policy, market regulation of cannabis, cannabis associations and best practices for risk prevention. We conclude that in the field of drugs responsible regulation and accurate information is needed

IFNL4 rs368234815 polymorphism is associated with innate resistance to HIV-1 infection.

The interferon (IFN)L4 polymorphism rs368234815 is associated with hepatitis C virus (HCV) spontaneous clearance and response to IFN-based treatments. The role of this polymorphism in HIV-1 infection is controversial. We investigated whether genetic variation at IFNL4 is associated to HIV-1 acquisition. The HCV protective allele TT was associated with decreased likelihood of HIV-1 infection in male intravenous drug users [odds ratio (OR): 0.3; P = 0.006], and this association was not modified by the genotype of CCR5. These results suggest that genetic susceptibility to HCV and HIV-1 infection shares common molecular pathways.

Prevalence and detection of neuropsychiatric adverse effects during hepatitis C treatment.

BACKGROUND: Current treatment combinations for chronic hepatitis C virus infection still include pegylated interferon and ribavirin despite the new therapeutic options available. Interferon-based treatments are associated with a high incidence of adverse effects. Central nervous system events are among the most frequent adverse drug reactions and their influence on treatment adherence and effectiveness is controversial. OBJECTIVE: The aim of the study was to evaluate neuropsychiatric adverse effects of interferon-based treatment for chronic hepatitis C in standard multidisciplinary clinical practice. Risk factors for these adverse effects and their impact on adherence and sustained viral response were also evaluated. Setting Ambulatory care pharmacy in coordination with the liver unit and the infectious diseases unit at a 650-bed tertiary university hospital. METHODS: We included all consecutive patients with chronic hepatitis C who completed treatment with pegylated interferon and ribavirin between 2005 and 2013. All patients underwent a multidisciplinary follow-up during treatment. MAIN OUTCOME MEASURES: Neuropsychiatric adverse effects were evaluated in relation to severity, management and outcome. The presence of anxiety and depression was evaluated by means of specific tests. RESULTS: A total of 717 treatments in 679 patients were included. During treatment, we detected 1679 neuropsychiatric adverse effects in 618 patients (86.2 %), generating 1737 clinical interventions. Fifty-seven (3.3 %) neuropsychiatric adverse effects were severe and 2 (0.1 %) were life-threatening (suicidal attempts). Most neuropsychiatric adverse effects (1555 events, 92.6 %) resolved without sequelae. Psychiatric medication was required in 289 patients (40.3 %). Sustained viral response was achieved in 400 cases (55.8 %) and was associated with adherence (OR = 1.942, 95 % CI = 1.235-3.052, p = 0.004). A multivariate analysis did not show any relationship between neuropsychiatric adverse effects and treatment adherence or sustained viral response. A psychiatric history was a strong risk factor for depression, anxiety and other psychiatric disorders during treatment. CONCLUSION: Neuropsychiatric adverse effects during interferon-based treatments in patients with chronic hepatitis C were common but mostly mild or moderate. Early detection and accurate multidisciplinary management avoided treatment discontinuation, ensuring adherence and attaining sustained viral response. The identified risk factors could be used to determine patients eligible for interferon-free combinations, thus optimizing health system economics.

Association of baseline CD4+ cell count and HIV-RNA on sustained virologic response to interferon-ribavirin in HIV/HCV coinfected patients.

UNLABELLED: BACKGROUND AND RATIONALE FOR THE STUDY: We assessed the association of CD4+ T-cell counts and HIV-RNA on sustained viral response (SVR) after therapy with pegylated interferon and ribavirin (PR) in HIV/HCV coinfected patients. We examined two large cohorts of coinfected patients treated with PR in Spain between 2000 and 2008. SVR was defined as undetectable HCV-RNA at 24 weeks after the end of PR. RESULTS: We studied 1682 patients, of whom 38% achieved SVR. Baseline factors independently associated with reduced odds of SVR included genotype 1 or 4, HCV-RNA > 500,000 IU/mL, advanced liver fibrosis, CDC clinical category C, and detectable HIV-RNA. By multivariate logistic regression analysis, we found that, in comparison with patients with combination antiretroviral therapy (cART) and undetectable HIV-RNA, the odds ratio [95% confidence interval (CI)] of SVR was 0.56 (0.41-0.78) for cART and detectable HIV-RNA, 0.86 (0.56-2.57) for no-cART and detectable HIV-RNA, and 1.38 (0.74-2.57) for no-cART and undetectable HIV-RNA. CONCLUSIONS: Detectable HIV-RNA, but not CD4+ T-cell count, was associated with reduced odds of SVR. However, this finding was only confirmed for cART and detectable HIV-RNA, raising the question as whether this represents a true association of HIV-RNA on response to PR or a spurious association due to poor adherence to treatment.

Faldaprevir and pegylated interferon α-2a/ribavirin in individuals co-infected with hepatitis C virus genotype-1 and HIV.

OBJECTIVE: Faldaprevir is a potent, once-daily hepatitis C virus (HCV) NS3/4A protease inhibitor. STARTVerso4 assessed the efficacy and safety of faldaprevir and response-guided pegylated interferon α-2a/ribavirin (PegIFN/RBV) in individuals with HCV/HIV co-infection. DESIGN: A phase 3 open-label study (NCT01399619). METHODS: Individuals (N = 308) co-infected with HCV genotype 1 (treatment-naive or prior interferon relapsers) and HIV [96% on antiretroviral therapy (ART)] received faldaprevir 120 mg (N = 123) or 240 mg (N = 185) and PegIFN/RBV. Those receiving a protease inhibitor or efavirenz ART were assigned to faldaprevir 120 or 240 mg, respectively. Individuals achieving early treatment success (ETS; HCV RNA <25 IU/ml at week 4 and undetectable at week 8) were randomized to 24 or 48 weeks of PegIFN/RBV. The primary endpoint was sustained virologic response 12 weeks after treatment (SVR12). RESULTS: SVR12 was achieved in 221 (72%) individuals, and the rates were comparable across faldaprevir doses. ETS was achieved in 80%, and of these 86% achieved SVR12, with comparable rates with 24 and 48 weeks of PegIFN/RBV (87 and 94%, respectively). In multivariate analysis, age below 40 years, IL28B CC genotype, and baseline HCV RNA below 800 000 IU/ml were associated with SVR12 (P = 0.027, P < 0.0001, and P = 0.0002, respectively), whereas treatment (ART regimen and faldaprevir dose), liver cirrhosis, and genotype 1 subtype were not. The safety profile was comparable to that of faldaprevir in HCV-monoinfected individuals. CONCLUSIONS: High SVR12 rates were achieved with faldaprevir and PegIFN/RBV in HIV/HCV co-infected individuals, regardless of faldaprevir dose and background ART, HCV genotype 1 subtype, or cirrhosis status. SVR rates mirrored those obtained with similar regimens in HCV monoinfected individuals.

Comparison of the prognostic value of liver biopsy and FIB-4 index in patients coinfected with HIV and hepatitis C virus.

BACKGROUND: We compared the prognostic value of liver biopsy (LB) and FIB-4 index in patients with human immunodeficiency virus (HIV)/hepatitis C virus (HCV) coinfection. METHODS: We studied patients from the Grupo de Estudio del SIDA 3603 study cohort, in whom fibrosis was evaluated at baseline using both LB (Metavir score) and FIB-4 index. We assessed overall death (OD) and liver-related events (LREs), defined as decompensation or hepatocellular carcinoma, whichever occurred first. We used receiver operating characteristic (ROC) curves to determine the ability of LB and FIB-4 to predict outcomes. We also assessed the association between advanced fibrosis-LB (F3 or greater) or FIB-4 (≥3.25)-and outcomes using multivariate Cox regression analysis. RESULTS: The study sample comprised 903 patients (328 with sustained virologic response [SVR]). Baseline fibrosis by LB was as follows: F0, n = 71; F1, n = 242; F2, n = 236; F3, n = 236; F4, n = 118. Fibrosis by FIB-4 was as follows: ≤1, n = 148; >1 to <3.25, n = 597; ≥3.25, n = 158. After a median follow-up of 62 months, there were 46 deaths and 71 LREs. The area under the ROC curves for OD/LREs was 0.648 and 0.742 for LB and FIB-4, respectively (P = .006). Similar results were found for patients without SVR and for OD and LREs separately. The adjusted hazard ratios of OD or LRE were 1.740 (95% confidence interval [CI], 1.119-2.7.06; P = .014) for advanced fibrosis assessed by LB and 3.896 (95% CI, 2.463-6.160; P < .001) assessed by FIB-4. CONCLUSIONS: FIB-4 outperformed LB as a predictor of OD and LRE. These findings are of relevance for clinical practice and research and call into question the role of LB as a gold standard for assessing prognosis in HIV/HCV coinfection.