Resistencia genotípica del HIV a los antirretrovirales en niños de Argentina entre 2006 y 2021 / HIV genotypic drug resistance to antiretrovirals in children in Argentina between 2006 and 2021

Introducción: La resistencia del HIV a los antirretrovirales (ARVs) es una de las principales causas de fallo terapéutico en niños, niñas y adolescentes que conviven con el virus. Desde el año 2006, el Laboratorio de Biología Celular y Retrovirus del Hospital Garrahan realiza el estudio genotípico de resistencia (ER) del HIV-1 a los ARVs a fin de identificar mutaciones que disminuyen la susceptibilidad del virus a los fármacos que componen el tratamiento ARV. Objetivos: El objetivo del trabajo fue estudiar el tipo y frecuencia de resistencia del HIV a los ARVs, a través de un análisis de 371 ER realizados entre los años 2006 y 2021 en niños, niñas y adolescentes con HIV-1 adquirido por transmisión vertical y con solicitud médica de ER por presentar fallo terapéutico. Resultados: Entre los años 2006 y 2013 la proporción de casos con resistencia a al menos una clase de fármaco ARV fue mayor al 90%, sugiriendo una asociación directa entre el fallo virológico y la disminución en la susceptibilidad del HIV-1 a uno o más componentes del TARV. A partir del año 2012, se observa una disminución progresiva del nivel de resistencia de HIV-1, llegando al 50% en 2021 (p<0.0001). La frecuencia de mutaciones de resistencia fue diferente para cada una de las clases de ARVs. Mientras que la resistencia a INNTR no sufrió cambios significativos a lo largo del período de estudio, oscilando entre 27% y 75%. La proporción de mutaciones a IPs en pacientes con fallo virológico disminuyó de 87% en 2006 a 17% en 2021 y para los INTR, disminuyó de 79% en 2006 a 45% en 2021. Conclusión: El nivel de resistencia a los ARVs ha disminuido de manera sustancial a lo largo de los últimos 16 años, probablemente por el uso de nuevos fármacos ARV con alta potencia que posibilitaron la intensificación de los tratamientos ARV y la implementación de criterios de fallo terapéutico más estrictos tanto a nivel clínico como virológico (AU)

Introduction: HIV resistance to antiretroviral (ARV) drugs is one of the main causes of therapeutic failure in children and adolescents living with the virus. Since 2006, the Cell Biology and Retrovirus Laboratory of the Garrahan Hospital has been performing the genotypic study of HIV-1 resistance to ARV drugs in order to identify mutations that reduce the susceptibility of the virus to the drugs that constitute ARV treatment. Objectives: The aim of this study was to assess the type and frequency of HIV resistance to ARV drugs through an analysis of 371 genotype studies performed between 2006 and 2021 in children and adolescents with HIV-1 acquired through motherto-child transmission and with medical request for genotype study due to therapeutic failure. Results: Between 2006 and 2013, the proportion of cases with resistance to at least one ARV drug class was greater than 90%, suggesting a direct association between virologic failure and decreased susceptibility of HIV-1 to one or more components of ART. From 2012 onwards, a progressive decrease in the level of HIV-1 resistance was observed, reaching 50% in 2021 (p<0.0001). The frequency of resistant mutations was different for each of the ARV classes, while resistance to non-nucleoside reverse transcriptase inhibitors (NNRTIs) did not change significantly over the study period, ranging from 27% to 75%. The proportion of drug-resistant mutations to protease inhibitors (PI) in patients with virologic failure decreased from 87% in 2006 to 17% in 2021 and for NNRTIs from 79% in 2006 to 45% in 2021. Conclusion: The level of resistance to ARV drugs has decreased substantially over the last 16 years, probably due to the use of new ARV drugs with high potency that allowed the intensification of ARV treatments and the implementation of stricter criteria for therapeutic failure both clinically and virologically (AU)

Molecular identification of aviadenoviruses in broiler chickens suspected to inclusion body hepatitis in Golestan province, Iran.

BACKGROUND: Fowl adenoviruses (FAdVs) are distributed widely throughout the world, and domestic avian species of all ages are susceptible. Fowl aviadenoviruses (FAdVs) can be separated into 5 different species (A-E) with various genotypes and 12 serotypes. Some geno- or serotypes induce hepatitis-hydropericardium syndrome (HPS), inclusion body hepatitis (IBH), and adenoviral gizzard erosion (AGE). AIMS: Detect FAdVs serologically and molecularly and sequencing of FAdVs in broiler flocks in Golestan province. METHODS: From December 2017 to June 2018 liver tissues and blood samples were collected from 31 broiler flocks suspected of IBH. Polymerase chain reaction (PCR) was applied on liver samples and the positive samples were sequenced and antibody against FAdVs was measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: Out of 31 flocks, the titers of 29 flocks (93.5%) were high in ELISA test for FAdVs and 22 flocks (70.96%) were positive in PCR test. Sequence analysis indicated the isolates belonged to D and E genotype of adenovirus. CONCLUSION: Inclusion body hepatitis caused by FAdVs, are spreading increasingly in broiler flocks of Golestan province and more attention and surveillance programs of breeder and broiler farms are needed to develop preventive measures. Moreover, vaccination of poultry farms in Iran should be considered by more complement studies.

Evaluación del proceso de transición de adolescentes con infección por VIH/Sida / Evaluation of the transition process of adolescents with HIV infection/AIDS

El desarrollo de nuevas opciones terapéuticas para el manejo de la infección VIH ha mejorado la sobrevida de los niños con infección perinatal. Estos avances llevaron a preparar a los adolescentes para la transición desde una institución pediátrica hacia un centro de adultos. Población: Se incluyeron pacientes con infección por VIH de 16 años o mayores. Fueron excluidos aquellos pacientes con infecciones oportunistas activas que requerían internación y ante ausencia de consentimiento/asentimiento informado. Objetivo, material y método: Evaluar el proceso de transición de adolescentes con infección VIH/SIDA desde un hospital pediátrico a centros de atención de adultos. Se realizó un estudio de intervención que incluyó la aplicación y análisis del proceso de transición interinstitucional. La transición incluyó la preparación y evaluación del paciente con asistencia a una serie de talleres, prevenir conductas de riesgo y favorecer el bienestar físico-social-emocional. Se analizó el estado de preparación del paciente en una etapa inicial y en el transcurso del programa, el cumplimiento del plan establecido y el tiempo requerido para la transición exitosa. Los objetivos centrales del proyecto fueron: preparación del paciente, concretar etapas del programa de transición, establecer indicadores clínicos y psicosociales que permitieron realizar una transición exitosa. Resultados: De un total de 50 pacientes, sexo femenino 52%. Escolarizados 92%. La mediana de carga viral fue de 289 y de recuento de CD4 de 23.35. En el 52% de la población el diagnóstico fue develado antes de los 13 años de edad. Este grupo presentó en un 48% autonomía adecuada. El 54% realizó adecuado seguimiento clínico. Durante el periodo del estudio, 17 pacientes lograron la transición. La edad promedio de los pacientes transicionados fue de 18 años, en su mayoría mujeres (59%). Conclusiones: La transición es un proceso multifacético, que involucra al paciente, su familia y al equipo de salud tratante de niños y de adultos. Para que sea exitosa hay que conocer todos los aspectos propios del paciente y la situación (AU)

The development of new treatment options for the management of HIV infection has increased survival of perinatally infected children. These advances have led to the need to prepare adolescents for the transition from a pediatric institution to a center for adult care. Population: Patients 16 years or older with HIV infection were included in the study. Patients with active opportunistic infections that required hospital admission and those who did not provide written informed consent/assent were excluded. Aim, material, and method: To evaluate the process of transition of adolescents with HIV infection/AIDS from a pediatric hospital to an adult care center. An intervention was performed including application and analysis of the process of interinstitutional transition. The transition included the preparation and evaluation of the patient through the participation in a series of workshops, prevention of risk behaviors, and encouragement of physical-social-emotional well-being. The state of preparation of the patient in the initial stage and throughout the program, compliance with the established plan, and the time needed for successful transition were analyzed. The main aims of the project were: preparation of the patient, carry out the stages of the transition program, establish clinical and psychosocial markers for a successful transition. Results: Of a total of 50 patients, 52% were female; 92% was attending school. Median viral load was 289 and CD4 count was 23.35. In 52% of the cohort, the diagnosis was disclosed before 13 years of age. Autonomy was adequate in 48% of the children. Overall, 54% complied with the clinical follow-up. Over the study period, 17 patients successfully transitioned. Mean age of the transitioned patients was 18 years, with a majority of girls (59%). Conclusions: Transition is a multifaceted process involving the patient, their family, and the health-care teams for children and adults. For a successful transition, all patient- and situation-related aspects should be known (AU)

Genetic variants in genes related to lipid metabolism and atherosclerosis, dyslipidemia and atorvastatin response.

OBJECTIVE: Using candidate gene approach, we have investigated the effect of single nucleotide polymorphism (SNP) in genes related to lipid metabolism and atherosclerosis on dyslipidemia and atorvastatin response. METHODS: The study included 157 patients treated with atorvastatin and 145 controls. Genomic DNA was isolated and genotyped using SNPlex technology. RESULTS: Allele and genotype disease association test revealed that APOB rs693 (OR: 2.2 [1.5-3.2], p=0.0001) and CD36 rs1984112 (OR: 3.7 [1.9-7.0], p=0.0002) SNPs were independent risk factors for hypercholesterolemia. Only APOB rs693 T variant allele was associated with increased LDL cholesterol levels (>160mg/dL). After atorvastatin treatment (10mg/day/4weeks), LIPC -514T allele was positively associated with LDL cholesterol reduction. CONCLUSION: The current study reinforces the current knowledge that carrying APOB rs693 is an independent risk factor for dyslipidemia and higher LDL levels. Furthermore, we found that a variant of CD36 was associated with dyslipidemia as a risk (rs1984112) factor. Finally, atorvastatin response could be predicted by LIPC -514C>T SNP and physical activity. In conclusion, our data evidences the contribution of genetic markers and their interaction with environmental factor in the variability of statin response.

Polimorfismos no receptor Scavenger classe B tipo I e sua relação com perfil lipídico sérico e resposta a atorvastatina em indivíduos brasileiros / Scavenger receptor class B type I polymorphisms and its relation with serum lipids profile and response to atorvastatin in Braszilian individuals

O receptor scavenger BI (SR-BI) é um componente chave do transporte reverso do colesterol. Polimosfismos no gene SCARB1 foram associados com variações no perfil lipídico e outros de risco cardiovascular. Os polimosfismos de nucleotídeo único In5C>T e Ex8C>T no SCARB1 e medidas de lípides e apolipoproteínas foram avaliadas em 79 hipercolesterolêmicos (HC) e 173 normolipidêmicos (NL) provenientes do Brasil. Pacientes HC foram tratados com atorvastatina (10mg/dia/4semanas). Os polimosfismos foram identificados por PCR-RFLP. Os indivíduos HC portadores dos genótipos In5CC+TT mostraram concentrações mais elevadas de LDL-C, apoB, e menores da relação apoAI/apoB. No grupo NL, os genótipos In5CC+TT foram associados com concentrações maiores de LDL-C. Os indivíduos HC portadores de genótipo Ex8CC tiveram uma variação menor da razão apoAI/apoB em resposta à atorvastatina (p<0,05). Nos Hc portadores do haplótipo Ex8CC+CT/In5CT+TT tiveram valores basais elevados de LDL-C e relação apoAI/apoB diminuída. Após o tratamento com atorvastatina, os indivíduos Hc portadores do haplótipo Ex8CC/In5CC tiveram uma variação menor na relação apoAI/apoB. Os genótipos In5CT+TT no SCANB1 conferem um perfil lipídico mais aterogênico. O genótipo Ex8CC e o haplótipo Ex8CC estão associados com uma resposta à atorvastatina menor da razão apoAI/apoB na nossa população.