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BACKGROUND: Antiretroviral therapy has increased the life expectancy of people living with HIV. However, this increase is not free of comorbidities, and metabolic syndrome is one of the most prevalent. Berberine is an alkaloid nutraceutical that has been shown to ameliorate metabolic disorders such as prediabetes, polycystic ovary syndrome, and non-alcoholic fatty liver disease. However, it has not been tested in HIV infection. Therefore, we conducted a randomized controlled trial to evaluate the efficacy of berberine in improving metabolic syndrome. METHODS AND RESULTS: In this double-blind, placebo-controlled trial, adults living with HIV under virological suppression and metabolic syndrome received either berberine 500 mg TID or placebo for 20 weeks. The primary outcomes were a composite of weight reduction, insulin resistance decrease, and lipid profile improvement. A total of 43 participants were randomized (22 in the berberine group and 21 in the placebo group); 36 participants completed the follow-up and were analyzed. The berberine group showed a reduction in weight and body mass index, lower insulin resistance, and a reduction in TNF-alpha. The control group had higher total cholesterol, c-LDL, and IL-6 concentration. CONCLUSION: In people living with HIV under virological suppression, berberine was safe and improves clinical and biochemical components of metabolic syndrome. However, further studies with more participants and longer intervention periods need to be explored.

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Resumen Con el advenimiento de la terapia antirretroviral (ART), la infección por el virus de inmunodeficiencia humana (VIH) se ha convertido en una enfermedad crónica con complicaciones metabólicas importantes más acentuadas que en la población general. Mientras no se tenga una vacuna que erradique las tasas de infección y no exista una cura para esta pandemia, se debe ser más incisivo en el controlar las comorbilidades, entre las que destacan las alteraciones en el perfil de lípidos pues aumentan el riesgo cardiovascular.

Abstract With the advent of antiretroviral therapy (ART), infection with the human immunodeficiency virus (HIV) has become a chronic disease with major metabolic complications more pronounced than in the general population. While there is no vaccine to eradicate infection rates and there is no cure for this pandemic, it should be more incisive in controlling comorbidities, among which alterations in the lipid profile stand out as they increase cardiovascular risk.

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BACKGROUND: The role of vitamin D in the pathophysiology of human immunodeficiency virus type 1 (HIV-1) infection is still unclear. OBJECTIVE: To evaluate the associations between vitamin D and immunological, virological, and oxidative stress biomarkers in individuals with human immunodeficiency virus type 1 (HIV-1) infection. METHODS: The serum levels of 25 hydroxyvitamin D [25(OH)D] were determined in 314 HIV-1- infected individuals and 127 controls and the values ≥30 ng/mL defined a vitamin D sufficient (VDS) status, and <30 ng/mL defined the presence of hypovitaminosis D (HD). Oxidative stress was evaluated with plasma levels of lipid hydroperoxides, advanced oxidation protein products (AOPP), carbonyl protein, nitric oxide metabolites (NOx), total radical-trapping antioxidant parameter (TRAP), and sulfhydryl groups of proteins. Plasma HIV-1 viral load and CD4+/CD8+ T cells were quantified. RESULTS: The 25(OH)D levels and vitamin D status did not differ between HIV-1-infected individuals and controls. Hydroperoxides and AOPP were higher (p<0.0001 and p=0.002, respectively), whereas TRAP, carbonyl protein, and NOx were lower in HIV-1-infected individuals than controls (p<0.0001). HIV-1-infected individuals with HD showed higher hydroperoxide levels than those with a VDS status (p=0.012) and controls (p=0.022), independent of ethnicity and antiretroviral therapy. A positive correlation between 25(OH)D ≥30 ng/mL and viral load was observed when expressed as the number of copies/mL (r=0.178, p=0.039), as well as log10 copies/mL (r=0.183, p=0.033). CONCLUSION: These results suggest the bimodal influence of vitamin D in the modulation of immune response in HIV-1 infection, considering its differential susceptibility to modulation of the various immune targets and pathways.

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Plasmablastic lymphoma is a rare and aggressive subtype of diffuse large B cell non-Hodgkin lymphoma, originally described in the oral cavity of male adults with acquired immune deficiency syndrome. It is composed of neoplastic ceils which resemble immunoblasts but present immunophenotype distinctive of plasma cell and Epstein-Barr virus latent infection. In children, it is an even rarer disease. We present a case of oral plasmablastic lymphoma in a vertically transmitted human immunodeficiency virus-positive five-year-old child.

El linfoma plasmablástico es un subtipo raro y agresivo de linfoma no Hodgkin de células grandes B, descrito inicialmente en la cavidad oral de adultos varones con enfermedad por virus de inmunodeficiencia humana/síndrome de inmunodeficiencia adquirida. Se compone de una proliferación de células neoplásicas que se asemejan a los inmunoblastos, pero presentan inmunofenotipo característico de célula plasmática e infección latente por el virus de Epstein-Barr. En la población pediátrica, es una entidad excepcional. Presentamos el caso de una niña de 5 años de edad, con enfermedad por virus de inmunodeficiencia humana / síndrome de inmunodeficiencia adquirida de transmisión vertical con linfoma plasmablástico de cavidad oral.

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El linfoma plasmablástico es un subtipo raro y agresivo de linfoma no Hodgkin de células grandes B, descrito inicialmente en la cavidad oral de adultos varones con enfermedad por virus de inmunodeficiencia humana/síndrome de inmunodeficiencia adquirida. Se compone de una proliferación de células neoplásicas que se asemejan a los inmunoblastos, pero presentan inmunofenotipo característico de célula plasmática e infección latente por el virus de Epstein-Barr. En la población pediátrica, es una entidad excepcional. Presentamos el caso de una niña de 5 años de edad, con enfermedad por virus de inmunodeficiencia humana / síndrome de inmunodeficiencia adquirida de transmisión vertical con linfoma plasmablástico de cavidad oral.

Plasmablastic lymphoma is a rare and aggressive subtype of diffuse large B cell non-Hodgkin lymphoma, originally described in the oral cavity of male adults with acquired immune deficiency syndrome. It is composed of neoplastic ceils which resemble immunoblasts but present immunophenotype distinctive of plasma cell and Epstein-Barr virus latent infection. In children, it is an even rarer disease. We present a case of oral plasmablastic lymphoma in a vertically transmitted human immunodeficiency virus-positive five-year-old child.

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Notificamos un caso de microangiopatía trombótica, caracterizado por un proceso de agregación plaquetaria amenazante para la vida, que presentó afectación multisistémica y rápida evolución en una paciente con infección por el VIH. En este caso exponemos ampliamente los síntomas, la evolución y, finalmente, la necropsia clínica. Esta enfermedad es ahora infrecuente tras la llegada de los antirretrovirales de gran actividad, no obstante, se presenta con síntomas inespecíficos y evoluciona rápidamente a la afectación multisistémica y muerte. En consecuencia, un diagnóstico precoz con base en criterios clínicos y analíticos es fundamental para instaurar el tratamiento adecuado y mejorar la supervivencia.

We report on a case of thrombotic microangiopathy, defined as an extensive and dangerous intravascular platelet aggregation disorder, which progressed to multisystem involvement in a patient with HIV infection. For this clinical case, we detail the symptoms, evolution and, ultimately, the clinical autopsy. This disease is now uncommon due to the arrival of highactivity antiretroviral drugs; however, it can appear with nonspecific symptoms and rapidly progress to multisystem involvement and death. An accurate diagnosis on the basis of clinical and analytical criteria is essential to starting treatment and improving survival.

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The availability of highly potent antiretroviral treatment during the last decades has transformed human immunodeficiency virus (HIV) infection into a chronic disease. Children that were diagnosed during the first months or years of life and received treatment, are living longer and better and are presently reaching adolescence and adulthood. Perinatally HIV-infected adolescents (PHIV) and young adults may present specific clinical, behavior and social characteristics and demands. We have performed a literature review about different aspects that have to be considered in the care and follow-up of PHIV. The search included papers in the MEDLINE database via PubMed, located using the keywords "perinatally HIV-infected" AND "adolescents". Only articles published in English or Portuguese from 2003 to 2014 were selected. The types of articles included original research, systematic reviews, and quantitative or qualitative studies; case reports and case series were excluded. Results are presented in the following topics: "Puberal development and sexual maturation", "Growth in weight and height", "Bone metabolism during adolescence", "Metabolic complications", "Brain development, cognition and mental health", "Reproductive health", "Viral drug resistance" and "Transition to adult outpatient care". We hope that this review will support the work of pediatricians, clinicians and infectious diseases specialists that are receiving these subjects to continue treatment.

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Clinical presentation of primary human immunodeficiency virus (HIV) infection includes a wide spectrum of manifestations from asymptomatic infection to a symptomatic and severe illness. Central nervous system involvement should be always considered as a severe clinical form of primary HIV infection. Physicians should be aware to the broad clinical spectrum of primary HIV infection. We report a case of a female with diagnosis of mononucleosis-like syndrome and acute aseptic meningoencephalitis during primary HIV infection.

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Oral hairy leukoplakia (OHL) is a disease associated with Epstein-Barr virus and human immunodeficiency virus infections. OHL is usually an asymptomatic lesion, but in some cases treatment is recommended to reestablish the normal characteristics of the tongue, to eliminate pathogenic microorganisms, to improve patient comfort and for cosmetic reasons. Proposed treatments for this condition include surgery, systemic antiviral treatment and topical management. Topical treatment is an inexpensive and safe therapy that is easy to apply, noninvasive, free of systemic adverse effects and effective over a long period of time. The aim of this study was to present a review of the literature for topical therapy for OHL. Gentian violet, retinoids, podophyllin, acyclovir and podophyllin associated with topical antiviral drugs were used to treat OHL. Reports with this focus are limited, and since 2010, no new studies have been published that discuss the efficacy of topical treatments for OHL. Podophyllin with acyclovir cream was found to be effective, causing regression of lesions with no recurrences. Additional searches are necessary to provide clinical evidence of topical management effectiveness.

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Para el 2015 >50% de la población con infección por el virus de inmunodeficiencia humana será >50 años, proponiéndose diversos retos en su atención. En el presente estudio se planteó como objetivo evaluar la respuesta a la terapia antirretroviral altamente activa, características epidemiológicas y clínicas en pacientes con infección del virus de inmunodeficiencia humana/síndrome de inmunodeficiencia adquiridad >50 años. Se realizó estudio descriptivo, retrospectivo, observacional, no experimental, con diseño de casos y controles (pacientes >50 años, casos; y <50 años, controles), comparando sus evaluaciones basales, a los 6 y a los 12 meses, entre enero 2005 y junio 2009. Se incluyeron 311 pacientes, 99 casos (>50 años) y 121 controles (<50 años), representado el género femenino un tercio de la población. Más del 65% consultaron en etapas avanzadas de la enfermedad, 47% correspondieron con síndrome de inmunodeficiencia adquirida estadio C3. La medida del lapso entre diagnóstico e inicio de la terapia antirretroviral altamente activa fue >1 año, en los grupos. Los regímenes de terapia antirretroviral altamente activa más usados fueron AZT/3TC/EFV y AZT/3TC+LOP/RIT. No se encontraron diferencias significativas en la respuesta inmunológica ni virológica a la terapia antirretroviral altamente activa a los 6 y 12 meses entre los grupos; valores promedio de carga viral a los 6 meses: 58221,08 copias de ARN/mm³ (2,21 log) y 6081,92 copias de ARN/mm³ (2,28 log) para adultos mayores y jóvenes, respectivamente. En adultos mayores , el incremeto de valores promedio de linfocitos TCD4+pos-terapia antirretroviral altamente activa fue significativa (P<0,05) comparando niveles basales y a los 12 meses; en los jóvenes dicha significancia se alcanzó a los 6 meses. Más del 85% de los pacientes tuvieron carga viral indetectable por 12 meses. En los pacientes >50 años se observó buena respuesta inmunológica y virológica similar a los jóvenes, a los 6 y 12 meses de la terapia....

For the year 2015 >50% of the population living with the human immunodeficiency virus infection will be >50 years old, facing it diverse challenges in their attention. In the current study the objetive to assess the response to the highly active antiretroviral therapy (HAART), epidemiological and clinical characteristics in patients with human immnodeficiency virus infection/acquired immunodeficiency syndrome >50 years old, was proposed. A descriptive, retrospective, observational, non-experimental, cases and control desing study (patients >50 years old, cases; and <50 years old, controls), comparing their basal, at 6 months and t 12 months evalutions, between january 2005 and june 2009, was done. A total 311 patients, 99 cases (>50 years old) and 212 controls (<50 years old) were included. Females represented a third of the population. More than 65% of the patients consulted in advanced stages of diseases, 47% corresponded with acquired immnodeficiency syndrome stage C3. Mean time between diagnosis and beginning of highly active antiretroviral therapy was >1 year, in both groups. Most used highly active antiretroviral therapy schemes were AZT/3TC/EFV and AZT/3TC+LOP/RIT. No significant differences between immunological and virological responce to highly active antiretroviral therapy at 6 and 12 months between both groups were found; mean values of viral load at 6 months: 5,821.08 RNA copies/mm³ (2.21 log) and 6,081.92 RNA copies/mm³ (2.28 log) for mayor adults and young patients, respectively. In mayor adults, increase in mean values of TCD4 + lymphocyte counts post-highly active antiretroviral therapy were significant (P<0.05) when compared basal with 12 months moments. In young patients that significant change was reached at 6 months. More than 85% of the patients had undetectable viral at 12 months. In patients >50 years old a good immunological and virological responce was observed, being similar to that seen in young patients, at 6 and 12 months.....

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Introducción: La infección por el VIH/sida es considerada un problema de la salud pública a nivel mundial. Los primeros diagnósticos ocurrieron en 1981 y desde entonces el número de infectados se ha incrementado. Cuba no está ajena a este fenómeno y se continúa trabajando para detener el avance de la epidemia en el país. Objetivo: Caracterizar el comportamiento de la epidemia de VIH en Cuba y elaborar un modelo pronóstico para los próximos años. Métodos: El universo estuvo constituido por todos los diagnósticos de personas de nacionalidad cubana infectadas por el VIH desde 1986 hasta 2010. La información fue obtenida de la base de datos de VIH/sida del Ministerio de Salud Pública de Cuba. Se analizó la epidemia tomando en cuenta los componentes de la serie cronológica. Para la modelación del pronóstico se empleó el alisamiento exponencial con dos parámetros. Para el procesamiento y análisis se utilizaron los paquetes estadísticos SPSS versión 11.5, Statistic versión 6.0, Econometric Views versión 4.0 y el programa MapInfo Profesional versión 7.5. Resultados: Se consideró que no existió aleatoriedad en la serie cronológica, pero sí que existía un patrón cíclico. La tasa de incidencia de VIH presentó una tendencia ascendente, aumentando un 90,70 % con respecto a los años extremos de la serie. La relación hombre/mujer se presentó como una mujer diagnosticada por cada 4 hombres. El 56,87 % de los diagnosticados eran homobisexuales, la mayoría del sexo masculino. El grupo de edades más afectado fue el de 20-24 años. La capital del país reportó la mayor tasa de incidencia de casos. Los municipios más afectados son urbanos y de alta densidad poblacional. Conclusiones: La incidencia del diagnóstico de personas VIH positivas mantiene una tendencia ascendente a expensas de los hombres que tienen sexo con otros hombres. El grupo de edades con mayor incidencia corresponden al de 20 a 24 años. La mayor cantidad de casos generalmente provenía de regiones urbanas y densamente pobladas.

Introduction: The HIV/AIDS infection is considered a public health problem around the world. The firsts diagnostics were made in 1981, and since that the number of infected persons has increased. Cuba is not free from to this phenomenon and we continue working to stop the advance of the epidemics in the country. Objective: Characterizing the behavior of the HIV epidemics in Cuba and making a prognostic model for the following years. Methods: The universe was formed by all the diagnoses of Cuban people infected with the HIV between 1986 and 2010. Data were obtained from the HIV/AIDS data base of the Public health Ministry of Cuba. We analyzed the epidemics taking into account the components of the chronologic series. For making the model of the prognostic we used the exponential smoothening with two parameters. For processing and analyzing data we used the statistic packages SPSS version 11.5, Statistic version 6.0, Econometric Views version 4.0 and the program MapInfo Professional Version 7.5. Results: We considered that there was not any randomization in the chronologic series, but there it was a cyclic pattern. The HIV incidence rate showed a growing tendency, increasing 90,70 % with respect of the extreme years of the series. The relation man/woman was one woman diagnosed per four men. The 56,87 % of the diagnosed people were homo-bisexual ones, most of them male. The most affected age group was the 20-24 years-old group. The capital of the country reported the biggest incidence rate of cases. The most affected municipalities were urban and had a high population density. Conclusions: The incidence of the HIV positive people's diagnosis maintains an increasing tendency due to the men having sex with other men. The age group with higher incidence is the 20-24 years-old one. The bigger quantity of the cases stems from urban and densely populated regions.

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The 24-h heart rate variability and QT-interval adaptation was investigated in perinatally HIV-infected preschool children classified according to immunological status in order to assess autonomic function at early stages of infection. Thirty-five perinatally HIV-infected and clinically stable children (4.8 ± 0.3 years) were enrolled after approval of the study by the University Hospital Pedro Ernesto Ethics Committee and written informed parental consent was obtained. The children were classified according to peripheral CD4+ count (cells/µL) as follows: group 1, N = 11 (≥1000); group 2, N = 7 (≥500 and <1000); group 3, N = 17 (<500). Left ventricular ejection fraction (>55%), 24-h RR interval variability (RRV) indexes (NN, SDANN, SDNN index, r-MSSD) and 24-h QT and Bazett-corrected QT (QTc) were determined, and groups were matched for age, body surface area, and left ventricular ejection fraction, reducing biases in RRV. The peak differences (∆) between the highest and lowest RRV and QT indexes were extracted from nocturnal (1 am-6 am) and daytime (1 pm-6 pm) hourly assessed segments, respectively. Pearson’s correlation (r) and Kruskal-Wallis ANOVA were used to compare groups. CD4+ count correlated positively with ∆NN (r = 0.45; P = 0.003). There were no significant differences in daytime NN among groups. Nighttime SDNN index (P = 0.01), nighttime r-MSSD (P = 0.003), ∆NN (P = 0.01), ∆SDNN index (P = 0.03) and ∆r-MSSD (P = 0.004) were significantly lower in group 3 than in the other groups. Expected nighttime QTc-interval lengthening was not observed in all groups. In perinatally HIV-infected preschool children with preserved left ventricular systolic function, parasympathetic-mediated autonomic dysfunction parallels immune status, impairing both RRV and circadian QTc interval adaptation.

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La diarrea crónica por causa infecciosa es una complicación extremadamente común en pacientes con infección por VIH. El tubo digestivo es el órgano principalmente afectado por infecciones oportunistas. Se puede determinar la presencia de un agente etiológico en aproximadamente 50% de los pacientes con síndrome de inmunodeficiencia humana (SIDA) con contaje de linfocitos CD4 menor a 200 cel/mm3 (SIDA C3). Los pacientes con inmunosupresión severa son susceptibles de desarrollar histoplasmosis diseminada, de los cuales, más del 75% tienen enfermedad del tubo digestivo y cursan con diarrea. A continuación se presenta un caso de histoplasmosis duodenal y colónica en un paciente con VIH.

Chronic diarrhea by infectious causes is an extremely common complication in patients with human immunodeficiency virus infection (HIV). The digestive tract is the first affected organ by opportunist infections. In approximately 50 % of the patients it can be established the infection agent involved with acquired immunodeficiency syndrome (AIDS) with a CD4 count of less than 200 cells/mm3 (AIDS C3). Severe inmunosupresion patients are susceptible to develop disseminate histoplasmosis and more than 75 % have digestive tract disease and diarrhea as a mainly symptom. The following case is a 40-year-old male with HIV and duodenal and colonic histoplasmosis.

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Given that highly active antiretroviral therapy (HAART) has been demonstrated useful to restore immune competence in type-1 human immunodeficiency virus (HIV-1)-infected subjects, we evaluated the specific antibody response to influenza vaccine in a cohort of HIV-1-infected children on HAART so as to analyze the quality of this immune response in patients under antiretroviral therapy. Sixteen HIV-1-infected children and 10 HIV-1 seronegative controls were immunized with a commercially available trivalent inactivated influenza vaccine containing the strains A/H1N1, A/H3N2, and B. Serum hemagglutinin inhibition (HI) antibody titers were determined for the three viral strains at the time of vaccination and 1 month later. Immunization induced a significantly increased humoral response against the three influenza virus strains in controls, and only against A/H3N2 in HIV-1-infected children. The comparison of post-vaccination HI titers between HIV-1+ patients and HIV-1 negative controls showed significantly higher HI titers against the three strains in controls. In addition, post vaccination protective HI titers (defined as equal to or higher than 1:40) against the strains A/H3N2 and B were observed in a lower proportion of HIV-1+ children than in controls, while a similar proportion of individuals from each group achieved protective HI titers against the A/H1N1 strain. The CD4+ T cell count, CD4/CD8 T cells ratio, and serum viral load were not affected by influenza virus vaccination when pre- vs post-vaccination values were compared. These findings suggest that despite the fact that HAART is efficient in controlling HIV-1 replication and in increasing CD4+ T cell count in HIV-1-infected children, restoration of immune competence and response to cognate antigens remain incomplete, indicating that additional therapeutic strategies are required to achieve a full reconstitution of immune functions.

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