RESUMO Diante da cronificação da infecção pelo HIV, fatores psicossociais surgem como potencializadores para elevação dos níveis de estresse nas PVHIV, bem como para o desequilíbrio imunológico e elevação da carga viral. O objetivo da presente pesquisa foi avaliar o nível de estresse, a contagem de linfócitos TCD4 + e a carga viral de pessoas vivendo com HIV submetidas a TARV, atendidas em um hospital público universitário. Tratou-se de um estudo observacional, transversal com 25 pacientes (40,76 anos± 9,88 anos) que vivem com HIV atendidos no ambulatório de um hospital público do Rio de Janeiro. Foi utilizado um questionário sociodemográfico para caracterização da amostra, o estresse foi avaliado através do Inventário de Sintomas de Stress de LIPP e observados exames laboratoriais recentes. Foi identificado estresse em 68% dos participantes, com predomínio de sintomas físicos e fase de resistência. Houve maior prevalência de estresse em pessoas com baixo nível socioeconômico, desemprego e diagnóstico recente. Não foram observados menores níveis de linfócitos TCD4 + ou maior carga viral nas pessoas com estresse.

ABSTRACT Given the chronicity of HIV infection, psychosocial factors emerge as potentiators for the elevation of stress levels in PLHIV, as well as for the immunological imbalance and elevation of the viral load. The present research objective was to evaluate the stress level, TCD4+ lymphocyte count and viral load of people living with HIV undergoing ART, treated at a public university hospital. This was an observational, cross-sectional research with 25 patients (40.76 years± 9.88 years) living with HIV treated at the outpatient clinic of a public hospital in Rio de Janeiro. A sociodemographic questionnaire was used to characterise the sample. Stress was evaluated through the LIPP Stress Symptom Inventory and observed in recent laboratory tests. Stress was identified in 68% of the participants, with a predominance of physical symptoms and a resistance phase. There was a higher prevalence of stress in people with low socioeconomic status, unemployment and recent diagnosis. Lower levels of CD4+ T lymphocytes or higher viral load were not observed in people with stress.

A recuperação imunológica reflete condições de saúde. Nosso objetivo foi estimar o tempo até a recuperação imunológica e fatores associados em pessoas vivendo com HIV (PVHIV) após de iniciar a terapia antirretroviral (TARV). Foi conduzida uma coorte histórica de PVHIV (> 18 anos) no Estado de Minas Gerais, Brasil, usando bancos de serviços públicos de saúde. Foram incluídos pacientes que iniciaram a TARV entre 2009 e 2018, com linfócitos T-CD4+ e carga viral registrados antes e depois do início da TARV. O desfecho foi a recuperação imunológica, definida como a primeira contagem de T-CD4+ > 500 cel/µL após o início da TARV. As variáveis explanatórias foram idade, sexo, local de residência, ano de início de TARV, carga viral basal, T-CD4+ na linha de base e carga viral e adesão à TARV no seguimento. Foi realizada uma análise descritiva com estimativa de incidência acumulada e taxa de incidência (pessoa-ano). O tempo mediano até a recuperação imunológica foi estimado pelo método Kaplan-Meier. Fatores associados à recuperação imune foram avaliados por meio de regressão de Cox. Entre as 26.430 PVHIV, 8.014 (30%) foram elegíveis. A maioria era do sexo masculino (67%), com média de idade = 38,7 anos, residência em regiões fora da região metropolitana, mediana de T-CD4+ baseline = 228 células/µL (< 200 células/µL = 43%) e mediana de carga viral baseline = 4,7 log10 cópias/mL (carga viral detectável = 99%). Tempo de seguimento = 15.872 pessoas-ano. A incidência acumulativa e a taxa de incidência foram foram 58% (IC95%: 57-58) (n = 4.678) e 29,47 casos/100 pessoas-ano, respectivamente. Tempo mediano até recuperação imune = 22,8 meses (IC95%: 21,9-24,0). Os fatores independentemente associados com recuperação imunológica foram sexo feminino, idade < 38 anos, T-CD4+ basal > 200 células/µL, carga viral detectável (linha de base), adesão à TARV e carga viral indetectável (no seguimento). O tempo até a recuperação imunológica ainda é longo e impactado pelo tratamento precoce e da adesão à TARV.

La recuperación inmunológica refleja condiciones de salud. Nuestra meta fue estimar el tiempo y los factores asociados a la recuperación inmunológica en personas que viven con VIH (PVVIH), tras iniciar una terapia antirretroviral (TAR). Se realizó sobre una cohorte histórica entre PVVIH (> 18 años de edad) en Minas Gerais, Brasil, usando datos de las bases de datos del sistema de salud. Se incluyeron a pacientes que comenzaron una TAR entre 2009-2018, con T-CD4+ linfocitos y carga viral, registrada antes/después de TAR. El resultado fue el logro de recuperación inmunológica, definida como la primera T-CD4+ > 500 células/µL tras la iniciación TAR. Las variables explicatorias fueron: edad, género, lugar de residencia, año de iniciación TAR, base de referencia de carga viral, base de referencia de T-CD4+ y estatus de la carga viral y adherencia al TAR en el seguimiento. Se estimó: análisis descriptivo, acumulativo e incidencias persona-tiempo de recuperación inmunológica. La media de tiempo para la recuperación inmunológica se estimó usando el método Kaplan-Meier. Los factores asociados con la recuperación inmunológica se evaluaron mediante la regresión de Cox. Entre las 26.430 PVVIH, 8.014 (30%) fueron elegibles. La mayoría eran hombres (67%), media de edad = 38,7 años, residentes en una región no central, media de base de referencia T-CD4+ = 228 células/µL (< 200 células/µL = 43%) y carga viral media de base de referencia = 4,7 log10 copias/mL (carga viral detectable = 99%). El tiempo de seguimiento = 15.872 persona-años. La tasa acumulativa y de incidencia fue 58% (95%CI: 57-58) (n = 4.678) y 29,47 casos/100 persona-años, respectivamente. El tiempo de media para la recuperación inmunológica = 22,8 meses (95%CI: 21,9-24,0). Género femenino, PVVIH < 38 años de edad, T-CD4+ base de referencia > 200 células/µL, carga viral detectable (base de referencia), adherencia al TAR e carga viral indetectable (seguimiento) estuvieron independientemente asociadas con la recuperación inmunológica. El tiempo para la recuperación inmunológica sigue siendo largo y depende de un tratamiento temprano y de adherencia a la TAR.

Immune recovery reflects health conditions. Our goal was to estimate the time it takes to achieve immune recovery and its associated factors, in people living with HIV (PLHIV), after antiretroviral therapy (ART) initiation. A historical cohort study was performed among PLHIV (> 18 years-old) in Minas Gerais State, Brazil, using data from healthcare databases. Patients initiating ART between 2009-2018, with T-CD4+ lymphocytes and viral load recorded before and after antiretroviral therapy were included. The outcome is achievement of immune recovery, defined as the first T-CD4+ > 500 cells/µL after ART initiation. Explanatory variables were age, gender, place of residence, year of ART initiation, baseline viral load and T-CD4+, viral load status, and adherence to ART at follow-up. Descriptive analysis, cumulative, and person-time incidences of immune recovery were estimated. Median-time to immune recovery was estimated using Kaplan-Meier method. Factors associated with immune recovery were assessed by Cox regression. Among 26,430 PLHIV, 8,014 (30%) were eligible. Most were male (67%), mean age 38.7 years, resided in non-central region, median-baseline T-CD4+ = 228 cells/µL (< 200 cells/µL = 43%) and viral load median-baseline = 4.7 log10 copies/mL (detectable viral load = 99%). Follow-up time = 15,872 person-years. Cumulative and incidence rate were 58% (95%CI: 57-58) (n = 4,678) and 29.47 cases/100 person-years, respectively. Median-time to immune recovery was of 22.8 months (95%CI: 21.9-24.0). Women living with HIV, younger than 38 years of age, with T-CD4+ baseline > 200 cells/µL, detectable viral load (baseline), antiretroviral therapy-adherence and undetectable viral load (follow-up) were independently associated with immune recovery. Time to immune recovery remains long and depends on early treatment and antiretroviral therapy-adherence.

Abstract Purpose: Comparing survival rates of rats subjected to spleen procedures after fecal peritonitis induction. Assessing changes in TCD4 and CD8 lymphocyte rates before and after the procedures. Correlating animal survival with CD4 and CD8 lymphocytes. Methods: Thirty male Wistar rats were distributed into 3 groups of ten: spleen manipulation (SM); total splenectomy (TS); subtotal splenectomy with preservation of the inferior pole (IP). Rats were subjected to surgical procedure depending on the group. Seven days after surgery they underwent induction of peritonitis and survival time was recorded. All animals were subjected to two blood collections: before surgery and 70 days after it for TCD4/TCD8 lymphocyte counting. Results: Mean survival time was longer in the IP and SM groups and shorter in the TS group; there was significant difference between them. The comparison of the median number of CD4 did not present changes, whereas the comparison of the median number of CD8 decreased in the SM and IP groups. The correlation between the median number of TCD4 and TCD8 lymphocytes and the animals’ survival was not significant. Conclusion: The maintenance of splenic tissue contributed to increase the survival of rats and there was a change in the number of TCD8 lymphocytes.

Resumen Las células T reguladoras (Treg) son mediadoras fundamentales de la respuesta inmune, cuentan con una serie de mecanismos supresores que les permite controlar tanto clonas autorreactivas como linfocitos T convencionales. Si bien esta población corresponde únicamente al 5-10% de las células CD4+, su ausencia se ha relacionado con el desarrollo de patologías autoinmunes, condiciones proinflamatorias e incluso con abortos. Las células Treg pueden originarse tanto en el timo como en la periferia, sin embargo, aquellas originadas en el timo se caracterizan por su fenotipo estable y por su capacidad para reconocer autoantígenos. El objetivo de esta revisión es ofrecer al lector una visión general de las características de las células Treg así como su importancia en el contexto de diversas patologías; nos enfocaremos especialmente en los mecanismos y moléculas involucradas en la ontogenia de las células Treg de origen tímico.

Abstract Regulatory Т cells (Tregs) are key mediators of the immune response; they have a collection of suppressive mechanisms that allow them to control both, self-reactive lymphocytes and conventional T cell clones. Although this population corresponds only to 5-10% of the CD4Tcells compartment, their absence has been related to the development of autoimmunity, the worsening of proinflammatory conditions and even abortions. Tregs can originate at the thymus or the periphery, however thymic Tregs are characterized by their stable phenotype and their capacity to recognize auto-antigens. In this review, we aim to provide a general understanding of the characteristics of Tregs and their importance within pathologies with a special focus on thymic Tregs; we offer herein a general picture of T cell ontogeny emphasizing the mechanisms and molecules involved in Treg generation.

La obesidad es un problema de salud pública creciente a nivel mundial. Se ha clasificado como una enfermedad ocasionada por acumulación excesiva de triglicéridos en el tejido adiposo (TA). El TA visceral (TAV), se considera un factor importante en el desarrollo de enfermedades crónicas no transmisibles. Esto principalmente porque el adipocito aumenta en tamaño y número, lo cual lleva a hipoxia, liberación de ácidos grasos, movilización y activación de subpoblaciones leucocitarias (linfocitos T, B, macrófagos, neutrófilos y eosinófilos), liberación de mediadores proinflamatorios (factor de necrosis tumoral- α (TNF-α), interleucina (IL)-6, resistina) y disminución en la secreción de antiinflamatorios (adiponectina, IL-10, IL-4 e IL-13). Estos cambios en el TAV generan un estado de inflamación crónica de baja intensidad, que se ha relacionado con resistencia a la insulina (RI). La RI es el signo fundamental para el desarrollo del Síndrome Metabólico (SM), que inicialmente se presenta localmente en el TAV y después se vuelve sistémica. En la investigación de la obesidad y el desarrollo de sus comorbilidades, la trascendencia del TAV en la interacción entre células adiposas e inmunitarias, así como de liberación de mediadores para desencadenar el proceso inflamatorio crónico, es clave para el desarrollo de RI y SM; sin embargo, se ha observado que la masa músculo-esquelética está implicada en este proceso, aparte de las células y mediadores de los que se sabe su participación. De esta manera a los linfocitos T CD4 y T CD8 se les señala como proinflamatorios, en cambio a los eosinófilos y a la adiponectina se les clasifica como protectores del proceso.

Obesity is a widespread public health problem worldwide. This disease has been classified as a condition caused by excessive accumulation of triglycerides in adipose tissue (TA). Visceral TA is an important factor in the development of several chronic diseases, since the adipocyte increases in size and number, leading to hypoxia, fatty acid release, mo-bilization and activation of leukocyte subpopulations (macrophages, neutrophils, eosinophils, NK cells, T lymphocytes and B); release of pro-inflammatory mediators (TNF-á, IL-6, PAI-1, resistin and visfatin), and decreased secretion of anti-inflammatory cytokines (adiponectin, IL-10, IL-4 and IL-13). These changes in TAV generate a chronic inflammation state of low inten-sity, that has been linked to insulin resistance (IR), initially local and then becomes systemic, which represents the determining factor for the development of metabolic syndrome (SM). The transcendence of TAV in the interaction between adipose and immune cells, as well as the release of mediators that trigger the chronic inflammatory process, is key for the development of IR and SM. However, in the investigation of obesity and the development of its comorbidities, it has been observed that the skeletal-muscle mass is involved in this process, apart from the cells and mediators of which their participation is known. In this way, TCD4 and TCD8 lymphocytes are recognized as pro-inflammatory. In contrast, eosinophils and adiponectin are considered as protective of the process.

Introducción: Las manifestaciones orales en pacientes que viven con el Virus de la inmunodeficiencia humana (VIH) pueden ser el primer signo de la enfermedad, y hablar del deterioro del sistema inmune. Objetivo: Determinar la frecuencia de manifestaciones orales en personas que viven con VIH (PVVIH), estableciendo la asociación con el conteo de linfocitos TCD4 y la carga Viral. Materiales y métodos: Se estudiaron 177 pacientes que viven con VIH en control y/o tratamiento del Hospital Base de Valdivia en Chile, a los cuales se les realizó un examen clínico bucal y se recolectaron los valores del último conteo de linfocitos TCD4 y carga viral. Resultados: La muestra estaba formada por un 78,5% de varones; la edad promedio fue de 40,1±12,02 años y el 92,7% estaba bajo terapia antirretroviral. Las lesiones bucales se presentaron en el 93,8% de los pacientes, de las cuales el 39,2% pertenecían a manifestaciones orales de la Clasificación CEE. Se observó que los pacientes con manifestaciones bucales tenían valores de linfocitos TCD4 más bajos (427,40 ± 224,51) que los que no las presentaron (530,8 ± 222,7); encontrando que ambos valores son independiente de la carga viral. Conclusión: Las lesiones orales en PVVIH están asociadas mayormente a un conteo de linfocitos TCD4 bajo, independientemente de la terapia antirretroviral que reciben y la carga viral que presenten al momento del examen bucal.

Introduction: Oral Manifestations in patients living with Human Immunodeficiency Virus (HIV) may be the first sign of the disease, and talk about the deterioration of the immune system. Objective: Determine the frequency of oral manifestations in people living with HIV (PLHIV), establishing the association with CD4 lymphocyte count and viral load. Materials and methods: 177 patients living with HIV in control and / or treatment of the Base Hospital of Valdivia in Chile, where he underwent an oral examination and values of the last count of CD4 lymphocytes and viral load were collected were studied. Results: The sample consisted of 78.5% males; the average age was 40.1±12.02 years, and 92.7% were on antiretroviral therapy. The oral lesions occurred in 93.8% of patients, of which 39.2% belonged to oral manifestations of the EEC Classification. It was observed that patients with oral manifestations had values lower CD4 lymphocytes (427.40 ± 224.51) than those who did not submit (530.8 ± 222.7); finding that both values are independent of viral load. Conclusion: Oral lesions in people living with HIV are mostly associated with a low CD4 lymphocyte count, regardless of receiving antiretroviral therapy and viral load at the time of presenting oral exam.

Resumo A gestação é um estado fisiológico que exige adaptações imunológicas para que transcorra normalmente. Nesse período a mãe e o feto apresentam uma relação imunológica, ou seja, a interface materno fetal. A enzima indoleamina 2,3 dioxigenase (IDO) desempenha um papel importante na tolerância materno fetal, por ser responsável pela metabolização do triptofano, impedindo por diversas vias a proliferação principalmente de linfócitos TCD8. Diversos tipos celulares estão presentes na interface materno fetal e vários deles podem expressar a IDO. Os leucócitos com perfil Th1 produzem uma citocina conhecida: o interferon γ que estimula a expressão da IDO em vários tipos celulares. Os linfócitos são divididos em subpopulações de acordo com sua função e fenótipo. Seus tipos incluem linfócitos T, linfócitos B e as células natural killer (NK). Hormônios também atuam nesse processo a progesterona que exerce função determinante sobre a resposta imunológica materna podendo alterar o prognóstico gestacional e o estrógeno essencial para a tolerância materno fetal e manutenção da prenhez. Dessa maneira este trabalho tem por objetivo principal identificar os linfócitos presentes na placenta bovina em cultivo que expressam IDO (linfócitos T, linfócitos B e células NK), frente a estimulação por progesterona, estrógeno e interferon γ nas diversas fases gestacionais utilizando a citometria de fluxo. Segundo os resultados no período de 67,5 a 77, 5 dias com a adição de interferon γ a expressão da enzima IDO aumentou discretamente nos linfócitos TCD3, TCD4, e diferente dos linfócitos T CD8 apresentaram uma elevada expressão da enzima (4,48 ± 2,12 - 8,65± 4,91). No período de 92,5 a 172, 5 dias os linfócitos TCD4, TCD8 e TCD25 apresentaram uma diminuição da IDO. No período final de 195 a 222,5 dias, os linfócitos TCD3, TCD4 e os BCD25 aumentaram a expressão da IDO quando submetidos ao interferon γ, no entanto, os linfócitos T CD8 e as células NK não apresentaram alterações significativas. Com base nos resultados apresentados pode-se concluir que todos os tipos celulares foram capazes de expressar a IDO mediante a suplementação com interferon γ, sendo que o linfócito T CD8 apresentou uma diferença bastante significativa quanto ao aumento da IDO, já o estrógeno elevou a expressão da IDO somente nos linfócitos B (CD25) e a progesterona diminuiu a expressão da enzima nos linfócitos T (CD3 e CD4) e nas células NK. Estes resultados sugerem um mecanismo de regulação do sistema imunológico desempenhado pelos hormônios esteroides presentes durante o processo gestacional, particularmente pela modulação da expressão da IDO.

Abstract Pregnancy is a physiological state that requires immune adaptation in order to be successfully carried on. During this period, mother and fetus establish an immune tolerance status at the maternal fetal interface. Indoleamine 2,3-dioxygenase (IDO) plays an important role in maternal-fetal tolerance by metabolizing tryptophan, impairs by several pathways, mainly T CD8 cells proliferation. Several cell types are present in the maternal fetal interface and several of them can express IDO. Leucocytes with Th1 produce a cytokine known as interferon γ that stimulates the expression of IDO in several cell types. Lymphocytes are divided into sub-populations according to their function and phenotype: T lymphocytes, B lymphocytes and natural killer cells (NK). Hormones also involved in this process where progesterone exerts decisive role on maternal immune response that may change gestational outcome and estrogen is essential for fetal maternal tolerance and maintenance of pregnancy. Therefore, the main objective of this study was to identify lymphocytes in the bovine placental cell culture that are sensitive to progesterone, estrogen and interferon γ, IDO expression in various gestational stages using flow cytometry. According to the results in the gestational period from 67.5 to 77.5 days with the addition of interferon γ expression IDO was slightly increased in TCD3 lymphocytes, CD4, and differently from the other T cells CD8 displayed an higher expression of the enzyme (4.48±2.12 to 8.65±4.91). In the period from 92.5 to 172. 5 days the CD4 lymphocytes, CD8 and TCD25 showed a significant decrease of IDO expression (p<0.05). At the final stages between 195 and 222, 5 days TCD3 lymphocytes, CD4 and BCD25 increased expression when subjected to interferon γ supplementation; however, CD8 T cells and NK cells showed no significant changes. Based on the results presented we can conclude that all cell types were able to express IDO by supplementation with interferon γ, and that T CD8 lymphocyte showed an highly significant increase of IDO expression, whereas estrogen increased the expression of IDO only in B lymphocytes (CD25), and progesterone decreased enzyme expression in T lymphocytes (CD3 and CD4) and in NK cells. These results suggest a regulatory mechanism of the immunological system by steroidal hormones during gestation, particularly by modulating IDO expression.

Background: Pharmaceutical follow-up consists on the detection, prevention, and resolution of drug-related problems (DRP) in a continuous, systematized, and documented way. DRP is a health problem connected to pharmacotherapy, which can interfere with the expected health outcomes in the patient. Aim: To make a pharmacotherapeutic surveillance in HIV/AIDS inpatients attended at "Hospital San Juan de Dios" throughout a year prospective study (January to December 2012). Results: 88.6% (93/105) of patients were in stage AIDS with a median of CD4+ lymphocytes of 29 cells/mm³ and a viral load of 107,000 RNA copies/mL. The 16.2% were admitted to a intensive care unit ICU. 296 DRP (DRP 2.8 per patient) were detected, 72% of DRP (n; 213) were associated with treatment safety, 94 were adverse reactions, 19 required dose adjustments, and 6 interactions had a negative clinical impact; 23.3% (n: 69) experimented the necessity to add or remove a drug and 4.7% (n: 14) presented problems associated with effectiveness. A statistically significant relation was observed when associating the number of DRP with admittance to the ICU and the use of more than six drugs. Conclusion: The results allow the conclusion that inpatients present drug-related problems mainly related to toxicity, becoming risk factors for the development of them admittance to ICU, and concomitant use of more than 6 drugs.

Introducción: El seguimiento farmacoterapéutico, consiste en la detección, prevención y resolución de los problemas relacionados con los medicamentos (PRM), en forma continua, sistematizada y documentada. Un PRM es un problema de salud vinculado con la farmacoterapia, que interfiere o puede interferir con los resultados de salud esperados en el paciente. Objetivo y Métodos: Realizar un seguimiento farmacoterapéutico a pacientes hospitalizados con infección por VIH/SIDA del Hospital San Juan de Dios, a través de un estudio prospectivo de un año (enero a diciembre 2012). Resultados: El 88,6% (93/105) de los pacientes se encontraba en etapa SIDA, con una mediana de linfocitos TCD4+ de 29 céls/mm³ y una carga viral de 107.000 copias ARN/mL. El 16,2% de los pacientes ingresó a una unidad de paciente crítico. Se detectaron 296 PRM (2,8 PRM por paciente); el 72% de los PRM (n: 213) estuvieron asociados a seguridad del tratamiento, objetivándose 94 reacciones adversas, 19 eventos con necesidad de ajustes de dosis y seis interacciones con repercusión clínica negativa; 23,3% (n: 69) a la necesidad de incorporar o eliminar algún fármaco y 4,7 % (n: 14) a problemas asociados a efectividad. Se observó una relación estadísticamente significativa al asociar el N° de PRM con la unidad de pacientes críticos y uso de más de seis fármacos. Conclusión: Los resultados permiten concluir que los pacientes hospitalizados presentan problemas relacionados al uso de medicamentos, principalmente asociado a toxicidad, encontrándose como factores de riesgo para el desarrollo de éstos la permanencia en una unidad de paciente crítico y el uso concomitante de más de seis fármacos.

El curso de la infección por HIV se caracteriza principalmente por una depleción grave de los linfocitos TCD4+ y una activación inmune marcada, hallazgos centrales que conducen a variaciones numéricas y fenotípicas de las poblaciones linfocitarias TCD4+. El tratamiento antirretroviral (TARV) combinado ha modificado sustancialmente el curso de la infección por HIV, y la correcta adherencia al mismo resulta en una disminución de la carga viral a niveles indetectables, y a un incremento significativo en la repoblación de los linfocitos T periféricos. En este trabajo se evaluó en 28 niños HIV (+) la relación entre los cambios en los niveles de las poblaciones linfocitarias y la adherencia al TARV, luego de 9 meses en promedio de iniciado el mismo. El grupo de 18 niños con buena adherencia, superior al 95%, presentó un aumento significativo en los porcentajes de células naive CD4+CD45RA+CD62L+ y un descenso en las células de memoria central CD4+CD45RA-CD62L+, entre ambos momentos del seguimiento. Por el contrario, los 10 niños con fallas en la adherencia no mostraron diferencias significativas en los niveles de tales poblaciones. La buena adherencia al TARV produce el rápido y significativo descenso de la replicación viral lo cual se asocia a la progresiva reconstitución cuantitativa y funcional del sistema inmune.

Human immunodeficiency virus infection causes a severe depletion of TCD4+ lymphocytes and a sustained immune activation state, hallmarks findings that led to numerical and phenotypic changes in the TCD4+ subsets. Highly active anti-retroviral therapy has substantially modified the course of HIV infection. Correct adherence to the treatment results in a decrease in viral load at undetectable levels and a significant increase in the number of peripheral T cell lymphocytes. In the present study association between changes in T cell subsets and treatment adherence was evaluated in 28 HIV (+) infected children, before and after 9 months on average, from starting anti-retroviral therapy. The group of 18 patients with good adherence, above 95%, showed a significant increase in CD4+CD45RA+CD62L+ naive cells percentual levels and a decrease in the CD4+CD45RA-CD62L+ central memory subset, between the two points of the follow-up period. Conversely, 10 children with failure in the adherence did not show significant differences in the percentual levels of both subsets. Improvement in the percentage of adherence among paediatric population, optimizing antiretroviral treatment, allows a quick and significant reduction of viral replication. This feature is associated with the progressive reconstitution of the immune system.

Antecedentes: El fortalecimiento de la política de productos competidores (genéricos) se puede acompañar de interrogantes sobre la calidad y, por tanto, sobre la efectividad de algunos de estos medicamentos. Los estudios fase IV son una opción válida para valorar la efectividad y seguridad de estos medicamentos. Objetivos: Valorar la efectividad y seguridad del esquema genérico Lamivudina/Zidovudina/Efavirenz en pacientes con VIH/SIDA que no han recibido terapia antirretroviral, que son atendidos en un programa de atención integral ambulatoria especializada, y comparar estos resultados con los datos de eficacia y seguridad reportados en un estudio de referencia (que utiliza el mismo esquema de medicamentos innovadores y fue realizado con pacientes con condiciones similares). Métodos: Se realizó un estudio clínico abierto no controlado del tipo fase IV. Se valoró la efectividad (disminución de carga viral en plasma y aumento de linfocitos CD4+) y seguridad (reacciones adversas) del esquema genérico Lamivudina/ Zidovudina/Efavirenz durante 12 meses en pacientes mayores de 18 años VIH (+), que no habían recibido terapia antirretroviral y con indicación para recibirla. Los seguimientos clínicos y el seguimiento farmacoterapéutico fueron utilizados como estrategias de valoración y recolección de datos. Los resultados fueron comparados con los resultados reportados en un estudio referencia, contrastando la hipótesis de no inferioridad de dichos resultados. Resultados: El estudio incluyó 47 pacientes, de los cuales 33 estuvieron presentes hasta el final del estudio. Al año de tratamiento, en 28 pacientes (el 85%) la carga viral (valorada por indetectabilidad de las copias de RNAm viral/mL) alcanzó una disminución estadísticamente significativa, mientras que en 30 pacientes (el 91%) el recuento de linfocitos T-CD4+ mayor a 200 células/mm³ alcanzó un aumento progresivo y estadísticamente significativo. Para la comparación se halló un artículo que cumplió con los criterios definidos y se contrastó la hipótesis de no inferioridad. En comparación con el estudio referencia, las proporciones de pacientes [intervalo de confianza del 95%] que lograron indetectabilidad no fueron estadísticamente diferentes: 0,85 [0,69-0,93] versus 0,90 [0,81-0,93], p = 0,7; similarmente, no se encontró diferencias en el incremento promedio [desviación estándar] de linfocitos CD4+: 179 [142] versus 201 [21], p = 0,08. Tampoco se encontró diferencias notorias en el perfil de seguridad. Conclusiones: El esquema genérico evaluado, Lamivudina/Zidovudina/Efavirenz, muestra resultados de efectividad no inferiores a los reportados en un estudio de referencia diseñado para valorar el mismo esquema de medicamentos innovadores.

Background: The strengthening of generic drugs policy may be accompanied by reservations about their quality, and therefore, also about effectiveness of some of these products. Phase IV clinical trials are a proper design to evaluate the effectiveness and safety of these drugs. Objective: Assess the effectiveness and the safety data of generic drug scheme Lamivudine/Zidovudine/Efavirenz in HIV (+) naïve patients who are served in a specialized comprehensive ambulatory care program, and compare these results with efficacy and safety data reported in reference studies (using the same therapeutic scheme of innovator drugs and conducted in patients with the same conditions). Methods: An open-label and non-controlled phase IV clinical trial was conducted. Effectiveness (measured as viral load reduction to undetectable level and lymphocytes CD4 + increase) and safety (adverse reactions) of the generic drug scheme Lamivudine/Zidovudine + Efavirenz were assessed. Antiretroviral therapy was used during 12 months in HIV (+) naïve patients over 18 years old who had the indication to treatment. Clinical follow-up and Pharmacotherapy follow-up were used as assessment strategies and data collection. Non-inferiority hypothesis was contrasted against the study results and those reported in a reference study. Results: The study included 47 patients, of which 33 completed the study. After one year of treatment, 28 patients (85%) achieved a statistically significant reduction in viral load (assessed by undetectable mRNA copies/mL), and 30 of them (91%) had a progressive and statistically significant increase in T- CD4 + lymphocyte count greater than 200 cells/mm³. The comparison was performed using an article that met the defined criteria, and non-inferiority hypothesis was proven. The proportions of patients [CI 95%] achieving undetectability was not statistically different when comparing with reference study: 0.85 [0.69 to 0.93] versus 0.90 [0.81 to 0.93], p = 0.7. Similarly, there was no difference in the average increase of CD4 + [SD]: 179 ± 142 versus 201 ± 21, p = 0.08. Likewise, No important differences in the safety profile were found. Conclusions: The generic drug scheme Lamivudine/Zidovudine/Efavirenz is effective and safe, and effectiveness outcomes achieved were not lower than those reported in reference studies designed to assess the same scheme of innovator drugs.

Introducción. Se han desarrollado modelos para la predicción de la tasa de disminución de células CD4 en pacientes con VIH/sida con base en redes neurales y, también, en la variabilidad de la disminución de los recuentos de CD4 en pacientes seropositivos y seronegativos, con el recurso de métodos epidemiológicos. Objetivo. Predecir la población de linfocitos T CD4, a partir de la información del cuadro hemático sobre leucocitos y linfocitos, mediante la teoría de la probabilidad. Métodos. Se evaluaron los cuadros hemáticos de siete casos particulares, determinando la cantidad total de leucocitos y linfocitos, y la cantidad de linfocitos CD4 por medio de citometría de flujo. A partir de un trabajo previo, se desarrolló una inducción con la que se determinaron los conjuntos A, B, C y D, con base en los cuales se calculó la probabilidad de aparición de combinaciones específicas de valores de leucocitos, linfocitos y CD4, en rangos de 1.000 leucocitos para 128 casos. Resultado. Se predice que los rangos de leucocitos inferiores a 5.000 y 4.000 por mm3 de sangre periférica se asocian a menos de 570 linfocitos CD4 por µl con una probabilidad de 0,92 y 1, respectivamente. A medida que disminuye la cantidad de las poblaciones de leucocitos, el porcentaje de aciertos entre las tres medidas es más efectivo. Conclusión. La teoría de la probabilidad reveló una autoorganización matemática de las poblaciones celulares estudiadas, que permitió desarrollar predicciones clínicas para el número de células CD4 a partir del cuadro hemático, disminuyendo los costos y deduciendo los resultados de la citometría de flujo.

Background: Models for the prediction of the CD4 decrease rate in VIH/AIDS patients have been developed with neural networks, and also for the prediction of the variability in CD4 counts decrease in seropositive and seronegative patients with epidemiological models. Objective: to predict the TCD4 lymphocyte population, beginning with the Complete Blood Count (CBC) information of leucocytes and lymphocytes, through probabilistic theories. Methods: Seven CBC of particular cases were evaluated, by determining the total count of leucocytes and lymphocytes, and the proportion of CD4 Lymphocytes by flow cytometry. Based on a previous work an induction was developed; with that induction the sets A, B, C and D were determined. Based on that sets we established the probability of aparition of specific combinations of leucocytes, Lymphocytes ans CD4 values, in ranges of 1.000 leucocytes, in 128 cases. Results: it is predicted that the leucocytes ranges lower than 5,000 and 4,000 per cubic milimeter of peripheral blood are associated with less than 570 CD4 per microliter with a probability of 0.92 and 1 respectively. As the quantity of populations diminishes, the success percentage between the three measures is more effective. Conclusion: The probability theory revealed a mathematical self-organization of the studied cellular populations, allowing the development of predictions in a clinical level for the CD4 number from the CBC, diminishing costs and deducting the results of the flow cytometry.

En la infección por el virus de la inmunodeficiencia humana (VIH) el deterioro del sistema inmune por una disminución de los linfocitos TCD4 aumenta la susceptibilidad a padecer diferentes patologías en la cavidad oral y entre ellas las del periodonto. Fueron objetivos de esta investigación determinar la prevalencia y gravedad de la enfermedad periodontal de las PVIH/sida, así como su asociación a los factores como el conteo de TCD4, el uso de terapia antirretroviral y el índice de higiene bucal simplificado. Se determinaron además los factores de riesgo locales de enfermedad periodontal. Para ello, se realizó un estudio descriptivo y transversal en 207 personas viviendo con VIH/sida pertenecientes a la provincia de Pinar del Río en el año 2008, los cuales asistieron al control serológico en el momento de la investigación. Se utilizaron los índices de higiene bucal simplificado y el índice periodontal de Russell revisado. Se usaron las frecuencias absolutas y relativas y para describir la asociación entre variables las pruebas de Bartholomew y ji cuadrado al 95 % de confianza. Se determinó una alta prevalencia de la enfermedad obteniéndose un 78,3 %. Los factores de riesgo locales en la enfermedad periodontal más frecuentes son la placa dentobacteriana, caries y dientes ausentes no restituidos. Se identificó una relación significativa entre los resultados de los TCD4 y el estado periodontal, así como con la higiene bucal. No se encontró asociación con la enfermedad periodontal y el tratamiento antirretroviral.

In the infection by the Human Immune Deficiency Virus (HIV) the deterioration of the immune system due to a diminution of the TCD4 lymphocytes increases the sensitivity of suffering from different pathologies in oral cavity and among them those in periodontal region. This research paper was aimed at determining the prevalence and severity of periodontal diseases in people living with HIV/AIDS and the association with factors such as: TCD4 counting, the use of antiretroviral therapy and the Rate of Simplified Oral Health. Local risk factors for periodontal diseases were determined. To carry it out, a descriptive and cross sectional study taking 207 people living with HIV/AIDS in Pinar del Rio (2008), who underwent to a serological control at the research time. Both, Rates of Simplified Oral Health and Russell Periodontal Rate were verified. Absolute and relative frequencies and to describe the association among variables, Bartholomew and chi-square tests up to 95% of confidence were applied. A high prevalence of periodontal disease was observed (78,3%). Most frequent local risk factors were dento-bacterial plaque, caries and non-existence of teeth without restitution. A significant relation between the results of TCD4 and periodontal status was observed as well as oral hygiene, where no association with periodontal disease and retroviral treatment was found.

Estudos em populações de leucócitos e linfócitos do sistema imunológico evidenciam a perda de linfócitos CD4 através do tempo no desenvolvimento da AIDS, que tem implicações no inicio e acompanhamento do tratamento, bem como na predição de mortalidade. Foram desenvolvidas algumas predições sobre a variabilidade e a contagem de CD4. O objetivo deste trabalho é predizer as populações de CD4 com base na informação de leucócitos e linfócitos do quadro hemático, mediante a teoría de conjuntos. Para isso, a partir de 7 triplas de dados da quantidade de leucócitos/ ml3, linfócitos/ml3 e a subpopulação de CD4/μL mediante citometria de fluxo de pacientes específicos, desenvolveu-se uma indução que gerou quatro conjuntos A, B, C e D. Baseando-se nestes quantificaram-se 103 quadros hemáticos, estabelecendo sua atribuição a cada conjunto de acordo com as diferentes distribuições das três populações com respeito a intervalos de 1.000 leucócitos/ml3. Posteriormente avaliou-se A∪C, B∪D e a intersecção entre as duas uniões. Finalmente estabeleceu-se o número de elementos componentes destes conjuntos, bem como a porcentagem de atribuição com respeito à totalidade de casos de cada intervalo. Estabeleceu-se uma porcentagem de acerto superior a 80% para 5 dos 8 intervalos medidos, e que os intervalos de leucócitos inferiores a 5.000 e 4.000/ml3 podem ser associados a menos de 570 CD4/μL com uma porcentagem de efetividade de 90% e 100% respectivamente, de tal modo que a medida que diminui a quantidade de leucócitos desde o intervalo de 6.000 a porcentagem de acertos da predição entre as três medidas é mais efetiva. Conclui-se que a teoría de conjuntos aplicada às populações de leucócitos, linfócitos, e CD4 revela uma auto-organização matemática objetiva, reproduzível e de aplicação clínica para a predição de intervalos de CD4/μl, cujo uso pode reduzir recursos e custos.

Estudios en poblaciones de leucocitos y linfocitos del sistema inmune evidencian la pérdida de linfocitos CD4 a través del tiempo en el desarrollo de SIDA, lo cual tiene implicaciones en el inicio y seguimiento del tratamiento, así como en la predicción de mortalidad. Se han desarrollado algunas predicciones sobre la variabilidad y el conteo de CD4. El objetivo de este trabajo es predecir las poblaciones de CD4 con base en la información de leucocitos y linfocitos del cuadro hemático, mediante la teoría de conjuntos. Para ello, a partir de 7 triplas de datos de la cantidad de leucocitos/ml3, linfocitos/ml3 y la subpoblación de CD4/μL mediante citometria de flujo de pacientes específicos, se desarrolló una inducción que generó cuatro conjuntos A, B, C y D. Basándose en éstos se cuantificaron 103 cuadros hemáticos, estableciendo su pertenencia a cada conjunto de acuerdo con las diferentes distribuciones de las tres poblaciones respecto a rangos de 1.000 leucocitos/ml3. Posteriormente se evaluó A∪C, B∪D y la intersección entre las dos uniones. Finalmente se estableció el número de elementos componentes de estos conjuntos, así como el porcentaje de pertenencia respecto a la totalidad de casos de cada rango. Se estableció un porcentaje de acierto superior al 80% para 5 de los 8 rangos medidos, y que los rangos de leucocitos inferiores a 5.000 y 4.000/ml3 se pueden asociar a menos de 570 CD4/µL con un porcentaje de efectividad de 90% y 100% respectivamente, de tal modo que a medida que disminuye la cantidad de leucocitos desde el rango de 6.000 el porcentaje de aciertos de la predicción entre las tres medidas es más efectiva. Se concluye que la teoría de conjuntos aplicada a las poblaciones de leucocitos, linfocitos, y CD4 revela una autoorganización matemática objetiva, reproducible y de aplicación clínica para la predicción de rangos de CD4/µl, cuyo uso puede reducir recursos y costos.

Studies on the immune system leukocytes and lymphocytes populations evidence the loss of CD4 lymphocytes over time in the development of AIDS which has implications on the treatment start and follow-up as well as on the mortality prediction. A number of predictions have been developed regarding the CD4 variability and count. The aim of this paper is to predict the CD4 populations based on the information about the leukocytes and lymphocytes in the complete blood count through the set theory. With this purpose, starting from 7 data triplets of the amount of leukocytes/ml3, lymphocytes/ml3 and the CD4/μL sub-population through flux cytometry in specific patients, an induction that generated four A, B, C and D sets was developed. Based on those sets, 103 complete blood counts were quantified, by setting their belonging to each set according to the different distributions of the three populations with respect to ranges of 1000 leukocytes/ml3. Subsequently, A∪C, B∪D and the intersection between the two bonds were assessed. Finally, the number of elements composing these sets was determined as well as the belonging percentage in reference to the totality of cases in each range. A percentage of higher than 80% success for 5 of the 8 measured ranges became established, and the fact that the leukocytes ranges below 5000 a 4000/ml3can be associated to less than 570 CD4/ μL, with 90% and 100% effectiveness percentage, respectively, so that, as the amount of leukocytes decreases from the range of 6000, the percentage of correct forecasts between the three measures is more effective. In conclusion, the set theory applied to the leukocytes, lymphocytes, and CD4 populations reveals an objective mathematical auto-organization, which is reproducible and has clinical application for predicting CD4/μl ranges, whose use can reduce resources and costs.

This study was designed to assess the effect of GB virus (GBV)-C on the immune response to human immunodeficiency virus (HIV) in chronically HIV-infected and HIV- hepatitis C virus (HCV)-co-infected patients undergoing antiretroviral therapy. A cohort of 159 HIV-seropositive patients, of whom 52 were HCV-co-infected, was included. Epidemiological data were collected and virological and immunological markers, including the production of interferon gamma (IFN-γ) and interleukin (IL)-2 by CD4, CD8 and Tγδ cells and the expression of the activation marker, CD38, were assessed. A total of 65 patients (40.8%) presented markers of GBV-C infection. The presence of GBV-C did not influence HIV and HCV replication or TCD4 and TCD8 cell counts. Immune responses, defined by IFN-γ and IL-2 production and CD38 expression did not differ among the groups. Our results suggest that neither GBV-C viremia nor the presence of E2 antibodies influence HIV and HCV viral replication or CD4 T cell counts in chronically infected patients. Furthermore, GBV-C did not influence cytokine production or CD38-driven immune activation among these patients. Although our results do not exclude a protective effect of GBV-C in early HIV disease, they demonstrate that this effect may not be present in chronically infected patients, who represent the majority of patients in outpatient clinics.