Global DNA methylation and telomere length as markers of accelerated aging in people living with HIV and non-alcoholic fatty liver disease.

Metabolic-dysfunction-associated fatty liver disease (MAFLD) is a comorbidity that generally increases in people living with HIV (PLWH). This condition is usually accompanied by persistent inflammation and premature immune system aging. In this prospective cohort study, we describe a straightforward methodology for quantifying biomarkers of aging, such as DNA methylation and telomere length, in PLWH and in the context of another relevant condition, such as MAFLD. Fifty-seven samples in total, thirty-eight from PLWH and nineteen from non-PLWH participants with or without MAFLD, were obtained and subjected to DNA extraction from peripheral blood mononuclear cells (PBMCs). Global DNA methylation and telomere length quantification were performed using an adapted enzyme-linked immunosorbent assay (ELISA) and qPCR, respectively. The quantification results were analysed and corrected by clinically relevant variables in this context, such as age, sex, and metabolic syndrome. Our results show an increased association of these biomarkers in PLWH regardless of their MAFLD status. Thus, we propose including the quantification of these age-related factors in studies of comorbidities. This will allow a better understanding of the effect of comorbidities of HIV infection and MAFLD and prevent their effects in these populations in the future.

Human Monkeypox in People With HIV: Transmission, Clinical Features, and Outcome.

We describe the first 25 persons with HIV diagnosed with human monkeypox virus (MPXV) in our hospital in an ongoing outbreak in Spain. Proctitis was the predominant finding in 52%, and MPXV DNA was detected in rectal swabs from 90%. Proctitis and demonstration of MPXV in rectal swabs support the sexual transmission of MPXV.

Use of Tenofovir Alafenamide/Emtricitabine/Elvitegravir-Cobicistat in HIV-Naive Patients with Advanced Disease: GENIS Study.

Objective: The primary endpoint of the study was to determine the proportion of patients with HIV RNA < 50 copies/mL at 48 weeks. Design: Phase IV, multicentric, open-label, single-arm clinical trial of participants recruited in 2018−2019 to evaluate the efficacy and safety of tenofovir alafenamide/emtricitabine/elvitegravir-cobicistat (TAF/FTC/EVG-c) as first-line treatment in HIV-1 infected naïve participants with advanced disease. Methods: Adverse events were graded according to the Division of AIDS scale version 2.0. Quantitative variables were recorded as median and interquartile range, and qualitative variables as absolute number and percentage. T-Student or Wilcoxon tests were used to analyze intragroup differences of the continuous variables. Results: Fifty participants were recruited with a baseline median CD4 lymphocyte count of 116 cells/µL and a viral load of 218,938 copies/mL. The proportion of patients with viral load <50 copies/mL at week 48 was 94% in the per-protocol analysis, with a median time of 1.9 months to achieve it. Three adverse events attributed to the study drug caused trial discontinuation. Conclusions: the use of TAF/FTC/EVG-c in patients with advanced HIV disease in our study demonstrated efficacy comparable to data from pivotal clinical trials with a good safety profile.

Severe Acute Respiratory Syndrome Coronavirus 2 Spreads to Lymph Nodes and Strongly Expands CD4+ Effector Memory RA Cells in a Patient With Mild Coronavirus Disease 2019.

A woman with mild coronavirus disease 2019 developed cervical adenopathy, being diagnosed of Epstein-Barr virus infectious mononucleosis. We performed fine needle aspiration, and demonstrate that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is found in lymph nodes even in mild disease along with a strong expansion of terminally differentiated effector memory CD4+ T cells, a cell population that is practically absent in lymph nodes.

CD4+:CD8+ T-cell ratio changes in people with HIV receiving antiretroviral treatment.

BACKGROUND: Cofactors associated with persistently abnormal CD4+:CD8+ T-cell ratio in people with HIV (PWH) on antiretroviral treatment (ART) might change over time as the population of people with HIV ages or as new ART drugs become available. The main objective of our study was to determine the long-term associations of baseline factors, including the CD4+ T-cell count and ratio, with ratio normalization (≥1). In addition to this, we explored whether the ratio remained associated with the risk of both AIDS and non-AIDS events among individuals on suppressive ART. METHODS: Clinic-based study in a tertiary, university hospital in Madrid. People with HIV starting a first-line ART regimen (January 2006-June 2017) were included in a prospective national multicentre cohort (CoRIS). People with controlled HIV-infection within the first year of ART initiation and complete CD4+ and CD8+ T-cell records were selected. Cox proportional hazard (PH) regression models were used to estimate the cumulative incidence of ratio normalization and to examine associations with socio-demographic and clinical variables. To investigate factors independently associated with the development of AIDS and non-AIDS events we used a time updated Poisson regression model. RESULTS: The study included 557 subjects. During follow-up (median 5.24 years), 44% of participants achieved a ratio of 1 within a median of 1.49 years. In a multivariate PH model, pre-ART factors negatively associated with ratio normalization were the pre-ART CD4+:CD8+ T-cell ratio and mode of HIV acquisition. For the secondary analysis, 1.3 events/100 person years of follow-up were observed. After adjustment, older age, HIV RNA >200 copies/ml and CD4+:CD8+ T-cell ratios over follow-up, remained significantly associated with the development of AIDS and non-AIDS events. In contrast, pre-ART ratio was not associated with the risk of AIDS and non-AIDS events. CONCLUSIONS: In summary, our study showed that higher pre-ART CD4+:CD8+ T-cell ratio is associated with rates of ratio normalization ≥1. In addition, the risk of AIDS and non-AIDS events seems to be predicted by the time updated CD4+:CD8+ T-cell ratio not by the pre-ART CD4+:CD8+ T-cell ratio. Therefore, CD4+:CD8+ T-cell ratio should be considered as a dynamic marker for translation into clinical practice.

Daclatasvir combined with sofosbuvir or simeprevir in liver transplant recipients with severe recurrent hepatitis C infection.

Daclatasvir (DCV) is a potent, pangenotypic nonstructural protein 5A inhibitor with demonstrated antiviral efficacy when combined with sofosbuvir (SOF) or simeprevir (SMV) with or without ribavirin (RBV) in patients with chronic hepatitis C virus (HCV) infection. Herein, we report efficacy and safety data for DCV-based all-oral antiviral therapy in liver transplantation (LT) recipients with severe recurrent HCV. DCV at 60 mg/day was administered for up to 24 weeks as part of a compassionate use protocol. The study included 97 LT recipients with a mean age of 59.3 ± 8.2 years; 93% had genotype 1 HCV and 31% had biopsy-proven cirrhosis between the time of LT and the initiation of DCV. The mean Model for End-Stage Liver Disease (MELD) score was 13.0 ± 6.0, and the proportion with Child-Turcotte-Pugh (CTP) A/B/C was 51%/31%/12%, respectively. Mean HCV RNA at DCV initiation was 14.3 × 6 log10 IU/mL, and 37% had severe cholestatic HCV infection. Antiviral regimens were selected by the local investigator and included DCV+SOF (n = 77), DCV+SMV (n = 18), and DCV+SMV+SOF (n = 2); 35% overall received RBV. At the end of treatment (EOT) and 12 weeks after EOT, 88 (91%) and 84 (87%) patients, respectively, were HCV RNA negative or had levels <43 IU/mL. CTP and MELD scores significantly improved between DCV-based treatment initiation and last contact. Three virological breakthroughs and 2 relapses occurred in patients treated with DCV+SMV with or without RBV. None of the 8 patient deaths (6 during and 2 after therapy) were attributed to therapy. In conclusion, DCV-based all-oral antiviral therapy was well tolerated and resulted in a high sustained virological response in LT recipients with severe recurrent HCV infection. Most treated patients experienced stabilization or improvement in their clinical status.

Does low-dose prolonged steroid therapy affect the natural history of chronic hepatitis C?

Chronic hepatitis C patients may require steroids due to other comorbidities. However, there is not enough information to consider steroids as beneficial or harmful drugs on natural history of chronic hepatitis C. The aim of the present study was to examine the effect of low-dose prolonged therapy with corticosteroids with or without azathioprine on these study patients. A retrospective-prospective observational study was established. Twenty-eight patients with chronic hepatitis C and treated with corticosteroids at low-dose (≤30 mg/day) with or without azathioprine for more than 6 months were included. AST, ALT, HCV RNA, and liver fibrosis were determined, and results were compared with a control group of non-treated chronic hepatitis C patients. The mean age was 47 ± 10 years. The male proportion was 43%. The mean dose of prednisone was 9 ± 5 mg/day (range: 2.5-30 mg/day). The mean treatment time was 76 ± 80 months (range: 7-349 months). Thirty six percent received concomitant azathioprine. Transaminases decreased significantly only within the first 3 months of treatment, with non-significant changes thereafter. Corticosteroids led to a non-significant increase in HCV RNA. Knodell Histology Activity Index decreased (from 8.5 ± 3.7 to 4.7 ± 1.7; P = 0.1). Fibrosis progression per year (final fibrosis stage-initial fibrosis stage/time between explorations, in years), was lower in treated cases than in control group (0.054 ± 0.25 units vs. 0.196 ± 0.6 units, P = 0.26). In conclusion, corticosteroid treatment caused a significant initial decrease in transaminases, non-significant changes in HCV RNA, and a trend to a slower fibrosis progression in comparison to a control group. Therefore, corticosteroids did not accelerate progression of chronic hepatitis C.

Hepatitis agudas, crónicas y fulminantes por virus de la hepatitis E: 7 años de experiencia (2004-2011) / Acute, chronic and fulminant hepatitis E: Seven years of experience (2004-2011)

OBJETIVO: Estudiar las características clínicas y epidemiológicas de 43 casos de hepatitis aguda, 5 casos de hepatitis fulminante y uno de hepatitis crónica causados por el virus de la hepatitis E (VHE), detectados en un periodo de 7 ańos. Pacientes Cuarenta y nueve (35 varones y 14 mujeres) pacientes atendidos entre 2004 y 2011 en el Hospital Ramón y Cajal, en la Comunidad de Madrid. El diagnóstico se realizó por detección de anticuerpos IgG e IgM anti-VHE y ARN VHE en suero. Se consideró el diagnóstico de hepatitis E aguda cuando el paciente presentaba un cuadro clínico compatible con hepatitis aguda y se detectó IgM anti-VHE y/o ARN VHE en suero; la hepatitis E crónica se definió por la presencia de ARN del VHE en suero por un periodo de tiempo mayor de 6 meses, y el fallo hepático fulminante E cuando se observó un deterioro severo de la función hepática asociado encefalopatía en presencia de IgM anti-VHE y/o ARN VHE en suero. RESULTADOS: La edad media fue de 46,67 y 49,6 ańos en los enfermos con hepatitis aguda y fulminante, respectivamente. Entre los antecedentes epidemiológicos, 13 referían viaje a zonas endémicas, 4 tenían contacto con animales, 4 tenían esteatosis hepática relacionada con consumo de alcohol, 3 consumían regularmente productos de herbolario y 2 bebían agua de arroyos. DISCUSIÓN: El VHE origina hepatitis aguda autolimitada, aunque el 36,73% requirieron hospitalización. Sin embargo, el 10,2% comenzaron con hepatitis fulminante, necesitando trasplante hepático. La hepatitis E crónica es excepcional en inmunocompetentes. El aumento de incidencia es debido a la mayor facilidad de diagnóstico en estos últimos ańos

OBJECTIVE: To study the clinical and epidemiological profiles of in 43cases of acute hepatitis, 5 cases of fulminant hepatitis, and one of chronic hepatitis due to hepatitis E virus (HEV), detected over a 7-year period. PATIENTS: Forty-nine individuals (33male and 10female) treated between 2004 and 2011 in the Hospital Ramón y Cajal (Comunidad de Madrid, Spain). The diagnosis was made by the detection of IgG and IgM anti-HEV and RNA HEV in serum samples. Acute hepatitis E was defined by the presence of IgM anti-HEV and/or RNA HEV in serum, and chronic hepatitis E if the ARN was detectable more than 6months. Fulminant hepatitis E was diagnosed if encephalopathy was observed in addition to IgM anti-HEV and/or RNA HEV in serum. RESULTS: The median age was 46.67 and 49.6years in acute hepatitis E and fulminant hepatitis E, respectively. The risk factors recorded were travel to endemic areas in 13 patients, 4 were in contact with animals, 4suffered from hepatic steatosis due to alcohol consumption, 3consumed uncontrolled foods, and 2drank water from streams. DISCUSSION: HEV is the cause of acute self-limited hepatitis, although 36.73% of the studied cases had to be hospitalised. However a small number of patients, 10.2%, had fulminant hepatitis requiring liver transplant. Chronic hepatitis E is very infrequent in immunocompetent individuals. The increase in incidence of hepatitis E is due to the introduction of better diagnostic tests in recent year

[Acute, chronic and fulminant hepatitisE: seven years of experience (2004-2011)]. / Hepatitis agudas, crónicas y fulminantes por virus de la hepatitisE: 7años de experiencia (2004-2011).

OBJECTIVE: To study the clinical and epidemiological profiles of in 43cases of acute hepatitis, 5cases of fulminant hepatitis, and one of chronic hepatitis due to hepatitis E virus (HEV), detected over a 7-year period. PATIENTS: Forty-nine individuals (33male and 10female) treated between 2004 and 2011 in the Hospital Ramón y Cajal (Comunidad de Madrid, Spain). The diagnosis was made by the detection of IgG and IgM anti-HEV and RNA HEV in serum samples. Acute hepatitisE was defined by the presence of IgM anti-HEV and/or RNA HEV in serum, and chronic hepatitisE if the ARN was detectable more than 6months. Fulminant hepatitisE was diagnosed if encephalopathy was observed in addition to IgM anti-HEV and/or RNA HEV in serum. RESULTS: The median age was 46.67 and 49.6years in acute hepatitisE and fulminant hepatitisE, respectively. The risk factors recorded were travel to endemic areas in 13patients, 4were in contact with animals, 4suffered from hepatic steatosis due to alcohol consumption, 3consumed uncontrolled foods, and 2drank water from streams. DISCUSSION: HEV is the cause of acute self-limited hepatitis, although 36.73% of the studied cases had to be hospitalised. However a small number of patients, 10.2%, had fulminant hepatitis requiring liver transplant. Chronic hepatitisE is very infrequent in immunocompetent individuals. The increase in incidence of hepatitisE is due to the introduction of better diagnostic tests in recent years.

Optimización de un medio de cultivo para el crecimiento de Gardnerella vaginalis / Optimization of a cultural medium for growing Gardnerella vaginalis

Se presenta una técnica para la optimización del medio de cultivo Caldo Triptona Soya suplementado con suero equino para el crecimiento de Gardnerella vaginalis. Se utilizó un diseño experimental 2² donde se evaluó la influencia de dos componentes del medio y un diseño compuesto central para mejorar los rendimientos celulares. Con la mejor variante de este estudio se realizaron corridas para caracterizar el crecimiento bacteriano empleando diferentes estimaciones. Se obtuvo que la dirección hacia los mayores crecimientos se localizó hacia mayores concentraciones de triptona soya y suero equino. La variación en la concentración de los componentes evaluados no influyó en la expresión de las proteínas antigénicas dado por los perfiles electroforéticos obtenidos.

The optimization of the cultural medium Soy Triptone Broth supplemented with equine serum to grow Gardnerella vaginalis is presented in this paper. An experimental design 2² was used in which the influence of two components of this medium was evaluated; and a central design aimed at improving cell performances. With the best variant of this study, the runs allowed characterize the bacterial growth using different estimations. The greatest growths were observed in higher concentrations of soy triptone and equine serum. The variation of the evaluated component concentrations did not have an impact on the expression of antigenic proteins given by the obtained electrophoretic profiles.

[Retrospective epidemiological study on the durability of the treatment of HIV infection or AIDS in Spain]. / Estudio epidemiológico retrospectivo sobre la duración del tratamiento de la infección por el virus de la inmunodeficiencia humana en España.

BACKGROUND AND OBJECTIVE: To know the durability of consecutive regimens of antiretroviral treatment is important to design a long-term therapy, but there is not much information about this subject. PATIENTS AND METHOD: Retrospective epidemiological study of a sample of 401 patients who began antiretroviral treatment between January 1997 and April 2000 at ten Spanish hospitals. The duration of each consecutive antiretroviral regimen was calculated and the reasons for modification and discontinuation were described. RESULTS: In the 3 years and 3 months covered by the study, 48.6% of the patients received more than one regimen of therapy. Seventy five of the initial prescribed combinations included protease inhibitors. Median duration of consecutive lines of therapy was decreasing: 560, 360, 330 and 202 days for the first, second, third and fourth regimens, respectively. The main reason to modification was intolerance or toxicity (46.2, 49.1 and 47.1% for the first, second and third modification). A fifth of changes was originated by difficulties to follow the therapy. Virological failure was the reason for modification in 21.8, 24.5 and 26.5% of first, second and third changes. CONCLUSIONS: Duration of consecutive antiretroviral regimens progressively decreases. Intolerance or drug toxicity were the main reasons conditioning the change of treatment.