Características clínicas, virológicas, inmunológicas y psicosociales de los adolescentes con infección por HIV: 15 años después de la implementación del programa de transición / Clinical, virological, immunological, and psychosocial characteristics of adolescents with HIV infection: 15 years after the implementation of the transition program

Desde 2007, el Servicio de Epidemiología e Infectología, ha implementado un programa de transición que busca optimizar la atención de los adolescentes con infección por el HIV durante el paso de la atención pediátrica a la de adultos. Objetivo: Describir las características clínicas, epidemiológicas, virológicas y psicosociales de los adolescentes con infección HIV atendidos en el Programa y analizar el proceso de transición. Materiales y Métodos: Estudio de cohorte retrospectivo. Se incluyeron a los adolescentes, atendidos en el Programa de Transición entre enero de 2019 y diciembre de 2023, en el Hospital Garrahan, con al menos un resultado de CV y CD4+ en ese período. Se obtuvo la información de la historia clínica electrónica y se analizaron variables clínicas, epidemiológicas, virológicas, terapéuticas y psicosociales. Resultados: Se incluyeron 124 pacientes. La vía de transmisión fue vertical en el 92,74% y el estadio clínico e inmunológico era avanzado. En el momento de la transición 77,4% se encontraban con supresión virológica y con recuperación inmunológica. El 55,6% ya realizó la transición a un centro de adultos, 31,4% continúan en el programa, 11,3% se perdieron en el seguimiento y 1,7% fallecieron. Se recopilaron los datos de 31 pacientes transferidos. La mediana de seguimiento fue de 2 años; 25 pacientes (80,6%) continúan en seguimiento. Conclusiones: A pesar de la pandemia de COVID-19, el programa logró la retención de los adolescentes con infección por HIV y una transferencia sostenida en el tiempo. Además de un programa de transición estructurado para garantizar una atención continua y de calidad, es necesario continuar evaluando la evolución postransición (AU)

Since 2007, the Epidemiology and Infectious Diseases Department has implemented a transition program to optimize the care of adolescents with HIV infection during their transition from pediatric to adult care. Objective: To describe the clinical, epidemiological, virological, and psychosocial characteristics of adolescents with HIV infection treated in the program and to analyze the transition process. Materials and Methods: A retrospective cohort study was conducted. Adolescents followed in the Transition Program at Garrahan Hospital between January 2019 and December 2023, with at least one viral load and CD4+ result during that period, were included. Information was obtained from electronic medical records, and clinical, epidemiological, virological, therapeutic, and psychosocial variables were analyzed. Results: A total of 124 patients were included. The route of transmission was vertical in 92.74%, and the clinical and immunologic stage was advanced. At the time of transition, 77.4% were virologically suppressed and had achieved immunologic recovery. Of the patients, 55.6% had already transitioned to an adult center, 31.4% were still in the program, 11.3% were lost to follow-up, and 1.7% died. Data were collected from 31 transferred patients, with a median follow-up of 2 years; 25 patients (80.6%) remain in follow-up. Conclusions: Despite the COVID-19 pandemic, the program successfully retained HIVinfected adolescents and ensured sustained transition over time. In addition to a structured transition program to ensure continuous and quality care, it is necessary to continue evaluating post-transition outcomes (AU)

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)

Características clínicas y epidemiológicas asociadas con internación en niños con COVID-19 en un hospital pediátrico de alta complejidad: Estudio de cohorte enero-marzo 2022 / Clinical and epidemiologic characteristics associated with hospital admission in children with COVID19 in a tertiary-care pediatric hospital: A January-March 2022 cohort study

Introducción: La proporción de casos reportados de niños y adolescentes con COVID-19 aumenta progresivamente. La hospitalización relacionada con COVID-19 en niños es infrecuente, pero causa morbilidad y sobrecarga al sistema de salud. Objetivos: Describir las características clínicas y evolutivas de los niños con diagnóstico de COVID-19 en un hospital pediátrico de alta complejidad. Comparar los pacientes que requirieron internación y los que no. Material y métodos: Cohorte prospectiva. Se incluyeron todos los pacientes con diagnóstico virológico de COVID-19 desde 1.1.2022 a 1.3.22 en un hospital pediátrico de alta complejidad. Se compararon los antecedentes, características clínicas y evolutivas de los pacientes según requirieran o no internación. Se utilizó STATA 16. Resultados: n: 1764 pacientes, de ellos 958 eran varones (54%). La mediana de edad fue 56 meses (RIC 17-116). Tenían enfermedad de base 789 pacientes (46%). Las más frecuentes fueron: enfermedad oncohematológica 215 (12%), neurológica 103 pacientes (6%) , enfermedad pulmonar crónica 68 (4%), cardiopatías congénitas 65 (4%) y síndrome genético 57 pacientes (3%). Eran inmunosuprimidos: 292 (17%). Presentaron síntomas relacionados con COVID-19 1319 pacientes (79%). Requirieron internación 591 (34%). Tuvieron coinfección con otros virus respiratorios 33 pacientes (2%). Ingresaron a Cuidados intensivos en relación a la COVID-19 22 pacientes (1.3%) y fallecieron en relación con la infección 8 (0.5%). En el análisis univariado, la presencia de comorbilidades, la coinfección viral y la inmunosupresión se asociaron estadísticamente con el requerimiento de internación. El antecedente de 2 o más dosis de vacuna para SARS-CoV-2 fue un factor protector para la internación en los mayores de 3 años. En el modelo multivariado, los pacientes menores de 3 años (OR 6.5, IC95% 1.2-36.8, p 0.03), con comorbilidades (OR 2.04, IC 95% 1.7- 3.3, p 0.00) y los huéspedes inmunocomprometidos (OR 2.89, IC95% 2.1-4.1, p 0.00) tuvieron más riesgo de internación. Ajustado por el resto de las variables, haber recibido dos o más dosis de vacuna fue un factor protector para la internación (OR 0.65, IC 95% 0.49-0.87, p<0.01). Conclusiones: En este estudio de cohorte prospectivo de niños con diagnóstico confirmado de COVID-19 predominó la enfermedad sintomática. Fueron admitidos en relación con el COVID-19, 34% de los pacientes. La vacunación con dos o más dosis fue un factor protector para la internación en el modelo multivariado. Además, se asociaron estadísticamente con la hospitalización, la edad menor de 3 años, las comorbilidades previas y la inmunosupresión (AU)

Introduction: The rate of reported cases of children and adolescents with COVID-19 is progressively increasing. COVID-19-related hospital admission in children is uncommon, but leads to morbidity and places a burden on the healthcare system. Objectives: To describe the clinical characteristics and outcome of children diagnosed with COVID-19 in a pediatric tertiary-care hospital and to compare patients who required hospital admission with those who did not. Material and methods: A prospective cohort study. All patients with a virological diagnosis of COVID-19 seen between 1.1.2022 and 1.3.22 in a tertiary-care pediatric hospital were included. We compared patient history, clinical characteristics, and outcome according to whether or not they required hospital admission. STATA 16 was used. Results: n: 1764 patients, 958 of whom were male (54%). The median age was 56 months (IQR, 17- 116). Overall, 789 patients had an underlying disease (46%), the most frequent of which were hematology-oncology disease in 215 patients (12%), neurological disease in 103 (6%), chronic lung disease in 68 (4%), congenital heart disease in 65 (4%), and a genetic syndrome in 57 (3%); 292 were immunosuppressed (17%). Overall, 1319 patients (79%) had COVID-19-related symptoms and 591 (34%) required hospital admission. A coinfection with other respiratory viruses was observed in 33 patients (2%). Intensive care admission due to COVID-19 was required in 22 patients (1.3%) and 8 (0.5%) died with COVID-19. In univariate analysis, the presence of comorbidities, viral coinfecton, and immunosuppression were statistically significantly associated with the need for hospitalization. A history of two or more doses of the SARSCoV2 vaccine was a protective factor against hospital admission in children older than 3 years. In the multivariate model, patients younger than 3 years (OR 6.5, 95% CI 1.2-36.8, p 0.03), with comorbidities (OR 2.04, 95%CI 1.7-3.3, p 0.00) and immunocompromised hosts (OR 2.89, 95% CI 2.1-4.1, p 0.00) had a higher risk of hospital admission. When adjusting for the remaining variables, having received two or more doses of the vaccine was found to be a protective factor against hospital admission (OR 0.65, 95% CI 0.49-0.87, p<0.01). Conclusions: In this prospective cohort study of children with a confirmed diagnosis of COVID-19, symptomatic disease predominated. Thirty-four percent of the patients were admitted for COVID-19. Vaccination with two or more doses was a protective factor against hospitalization in the multivariate model. In addition, age younger than 3 years, previous comorbidities, and immunosuppression were statistically associated with hospital admission (AU)

El rol del laboratorio de virología en la pandemia de COVID-19: diagnóstico de SARS-CoV-2 / The role of the virology laboratory in the COVID-19 pandemic: Diagnosis of SARS-CoV-2

Desde el inicio de la pandemia de COVID-19, el Laboratorio de Virología del Hospital Garrahan, implementó el diagnóstico molecular de SARS-CoV-2 mediante RT-PCR para dar respuesta rápida y de calidad a la creciente demanda. Al diagnóstico pediátrico se sumó el diagnóstico de los padres / acompañantes y personal de salud con criterio de caso sospechoso. Al inicio del 2021 se incorporó el test rápido de detección de antígeno para pacientes sintomáticos. Hasta junio de 2021 se procesó un total de 58 000 muestras para estudios moleculares. (AU)

Since the beginning of the COVID-19 pandemic, the Virology Laboratory of Garrahan Hospital has implemented molecular diagnosis of SARS-CoV-2 using RT-PCR in order to provide a rapid and high-quality response to the growing demand. In addition to the pediatric diagnosis, the diagnosis of parents/companions and healthcare personnel meeting the criteria of a suspected case was also added. At the beginning of 2021, the rapid antigen detection test for symptomatic patients was incorporated. Until June 2021, a total of 58,000 samples were analyzed by molecular studies. (AU)

Análisis de la características de los adolescentes con infección HIV en seguimiento en el consultorio de transición / Analysis of the characteristics of adolescents with HIV infection in follow-up at the transition clinic

Los avances en el manejo de los niños con infección HIV lograron mejoras importantes en la sobrevida por lo cual se plantea la necesidad de organizar un programa de transición de los adolescentes hacia un centro de adultos. La población de adolescentes atendidos en el Hospital de Pediatría Juan P. Garrahan presenta estadios de enfermedad avanzada y una larga historia de tratamientos. Se diseñó un programa de transición, con pasos definidos, que se implementó a partir del año 2007. Los objetivos de este estudio fueron: describir las características clínicas, epidemiológicas y virológicas de los adolescentes con infección VIH/ SIDA incluidos en el Programa de Transición, analizar la experiencia de los primeros 10 años de funcionamiento del programa de transición, y comparar las características de los jóvenes que han realizado la transición con los que se encuentran todavía en el programa. Entre junio de 2007 y diciembre de 2017, se incluyeron 420 pacientes, en 96% la transmisión vertical fue el modo de infección, la mayoría presentaba estadio clínico e inmunológico avanzado, la mediana de esquemas de tratamientos fue de 3 (RIC: 2-4) y 68,3% presentaron respuesta terapéutica adecuada. El análisis de las diferentes variables mostró que los pacientes que realizaron la transición en años previos se encontraban en estadios más avanzados de enfermedad, mientras que los jóvenes que todavía permanecían en el mismo, experimentaron menor número de rotaciones de esquemas de tratamiento antirretroviral y presentaban recuentos de linfocitos CD4+ >500/mm3 con mayor frecuencia (72,1% vs 61,6%, p=0,03). La transición se realizó en 276 pacientes (65,7%), 36 (8,5%) planeaban realizarla en los siguientes 4 meses y 80 (19,1%) se encontraban en el programa de transición para su preparación. Entre los pacientes no derivados, 4 fallecieron (1%) y en 24 se documentó la pérdida de seguimiento (AU)

Advances in the management of the infection in children with HIV infection have resulted in increased survival leading to a need to organize a transition program for adolescents to adult centers. The population of adolescents followed at Pediatric Hospital Juan P. Garrahan is in advanced stages of the disease and has a long treatment history. A transition program with well-defined steps was designed, which was implemented in 2007. The aims of this study were: To describe the clinical, epidemiological, and virological features of adolescents with HIV/AIDS infection included in the transition program, to analyze the experience of the program in the first 10 years, and to compare the characteristics of the youth who already transitioned with those who are still in the program. Between June 2007 and December 2017, 420 patients were included; in 96% mother-to-child transmission was the mode of infection, the majority was in advanced clinical and immunological stages, median treatment schemes used were 3 (IQR: 2-4), and 68,3% had a good response to therapy. Analysis of different variables showed that the patients who transitioned in previous years were in more advanced stages of the disease, while those who are currently in the program had received a lower number of rotations of antiretroviral treatment schemes and more often had normal CD4+ lymphocyte counts >500/mm3 (72,1% vs 61,6%, p=0,03). Overall, 276 patients transitioned (65,7%), 36 (8,5%) planned to transition in the next 4 months, and 80 (19,1%) were in the transition program to prepare for transitioning. Among the patients who were not referred, 4 died (1%) and 24 were lost to follow-up (AU)

Prevalence of HLA-B*57:01 allele in Argentinean HIV-1 infected patients.

Hypersensitivity reaction to abacavir (ABC hypersensitivity syndrome, AHS) is strongly associated with the presence of the HLA-B*57:01 allele. This study was designed to estimate the prevalence of HLA-B*57:01 allele in Argentinean HIV-1 infected patients. We analyzed the presence of HLA-B*57:01 allele in 1646 HIV-1 infected patients from different regions of Argentina. This allele was detected in 81 patients; most of them corresponded to patients living in the central region of the country. The prevalence of HLA-B*57:01 was 4.9%, similar to other Caucasian populations and higher than other data reported for South American populations. This strongly supports screening for the presence of HLA-B*57:01 in abacavir treatment of HIV-1 in our country.

HIV mother-to-child transmission: a complex genetic puzzle tackled by Brazil and Argentina research teams.

Human immunodeficiency virus (HIV) mother-to-child transmission is a complex event, depending upon environmental factors and is affected by host genetic factors from mother and child, as well as viral genetic elements. The integration of multiple parameters (CD4 cell count, virus load, HIV subtype, and host genetic markers) could account for the susceptibility to HIV infection, a multifactorial trait. The goal of this manuscript is to analyze the immunogenetic factors associated to HIV mother-to-child transmission, trying to unravel the genetic puzzle of HIV mother-to-child transmission and considering the experience in this topic of two research groups from Brazil and Argentina.

Detrimental effects of mannose-binding lectin (MBL2) promoter genotype XA/XA on HIV-1 vertical transmission and AIDS progression.

BACKGROUND: The literature on the involvement of mannose-binding lectin (MBL) in human immunodeficiency virus (HIV) transmission and acquired immunodeficiency syndrome (AIDS) is conflicting. Polymorphisms in the MBL2 gene reduce the level of protein and alter its structure. Thus, we investigated whether MBL2 alleles and plasma concentrations of MBL are associated with perinatal HIV transmission and disease progression. METHODS: Frequencies of MBL2 allelic variants (B, C, D, and X) were estimated among 345 HIV-exposed children and 147 blood donors. AIDS-free time was evaluated for different MBL2 genotypes and MBL plasma levels. The median duration of follow-up was 96.5 months. RESULTS: In the Argentinean population, gene frequencies of MBL2 variants were 18%, 15%, and 3% for the X, B, and D alleles, respectively, with no identified C allele. The haplotype XA/XA was associated with an 8-fold risk of acquiring HIV-1 (P= .054; odds ratio [OR], 8.11 [95% confidence interval {CI}, 0.96-67.86]) and almost a 3-fold risk of progression to pediatric AIDS (P= .026; OR, 2.81 [95% CI, 1.14-7.47]). We also found an independent positive correlation between the rate of AIDS progression and MBL plasma concentration (P= .008; OR, 1.28 [95% CI, 1.07-1.55]). CONCLUSIONS: Our results demonstrate that homozygosity for the MBL2 promoter genotype XA/XA is an important genetic determinant of HIV-1 acquisition through vertical transmission and the pathogenesis of pediatric HIV/AIDS, via a mechanism that remains to be established.

Characterization of Bordetella bronchiseptica strains using phenotypic and genotypic markers.

Thirty-five strains of Bordetella bronchiseptica, recovered primarily from pigs, rabbits, dogs, cats and humans, were characterized by phenotypic and genotypic markers. Biochemical typing only showed variation in the ability to reduce nitrate to nitrite. OMP profiles from virulent strains showed variations in the region of 85-95kDa, which lead us to describe five OMP-types alpha, beta, gamma, delta and epsilon. Genotypic markers included the presence of IS1001, and polymorphisms in the flagellin gene (flaA) and pertussis toxin (PT) promoter region. The IS1001 was detected in 16 isolates (2 from humans and 10 from pigs) but was absent in rabbit isolates. The restriction profiles of the flaA gene allowed us to differentiate the strains into types A-C. The PT types were characterized by an RFLP assay and could be typed through patterns III-V. There was no apparent association between the flaA or PT types and the origin of the isolates. Eleven groups of isolates were identified on the basis of specific combinations of the analyzed markers. The combination of phenotypic and genotypic tests used could be useful in characterizing isolates and differentiating between certain clonal types of B. bronchiseptica.

HIV-1 genetic diversity in Argentina and early diagnosis of perinatal infection

HIV-1 diagnosis of perinatally exposed children is usually performed by molecular biology-based methods, allowing the direct detection of the virus. Thus, HIV-1 genomic variability within and across strains plays a major role in relation to the sensitivity of these tests, often leading to misdiagnosis. We describe the performance of an in-house multiplex nested PCR (nPCR) for early detection of HIV-1 infection in perinatally exposed children born in Argentina, where the percentage of diverse BF recombinants is as high as 80%. After evaluation of 1316 HIV-1 perinatally exposed children collected over a 7-year period, the specificity and sensitivity of the diagnostic nPCR was of 100% and 99.2% respectively, with only two false negative cases indicating a good performance of the diagnostic nPCR in the Argentine pediatric cohort. In search of unusual HIV-1 subtypes among 22 HIV-1 infected cases presenting partial or complete HIV-1 gene amplification failure, we performed phylogenetic and recombination analysis of a vpu-env fragment in addition to gag and env Heteroduplex Mobility Assay screening. The most unusual findings included two subtypes A and a novel BC recombinant, while the majority of the strains were a variety of different BF recombinants. These results indicate the presence of novel and heterogeneous genotypes in our country and the need of continuous viral surveillance not only for diagnostic test optimization but also for the eventual implementation of a successful vaccine.

HIV-1 genetic diversity in Argentina and early diagnosis of perinatal infection

HIV-1 diagnosis of perinatally exposed children is usually performed by molecular biology-based methods, allowing the direct detection of the virus. Thus, HIV-1 genomic variability within and across strains plays a major role in relation to the sensitivity of these tests, often leading to misdiagnosis. We describe the performance of an in-house multiplex nested PCR (nPCR) for early detection of HIV-1 infection in perinatally exposed children born in Argentina, where the percentage of diverse BF recombinants is as high as 80%. After evaluation of 1316 HIV-1 perinatally exposed children collected over a 7-year period, the specificity and sensitivity of the diagnostic nPCR was of 100% and 99.2% respectively, with only two false negative cases indicating a good performance of the diagnostic nPCR in the Argentine pediatric cohort. In search of unusual HIV-1 subtypes among 22 HIV-1 infected cases presenting partial or complete HIV-1 gene amplification failure, we performed phylogenetic and recombination analysis of a vpu-env fragment in addition to gag and env Heteroduplex Mobility Assay screening. The most unusual findings included two subtypes A and a novel BC recombinant, while the majority of the strains were a variety of different BF recombinants. These results indicate the presence of novel and heterogeneous genotypes in our country and the need of continuous viral surveillance not only for diagnostic test optimization but also for the eventual implementation of a successful vaccine.(AU)

HIV-1 genetic diversity in Argentina and early diagnosis of perinatal infection

HIV-1 diagnosis of perinatally exposed children is usually performed by molecular biology-based methods, allowing the direct detection of the virus. Thus, HIV-1 genomic variability within and across strains plays a major role in relation to the sensitivity of these tests, often leading to misdiagnosis. We describe the performance of an in-house multiplex nested PCR (nPCR) for early detection of HIV-1 infection in perinatally exposed children born in Argentina, where the percentage of diverse BF recombinants is as high as 80%. After evaluation of 1316 HIV-1 perinatally exposed children collected over a 7-year period, the specificity and sensitivity of the diagnostic nPCR was of 100% and 99.2% respectively, with only two false negative cases indicating a good performance of the diagnostic nPCR in the Argentine pediatric cohort. In search of unusual HIV-1 subtypes among 22 HIV-1 infected cases presenting partial or complete HIV-1 gene amplification failure, we performed phylogenetic and recombination analysis of a vpu-env fragment in addition to gag and env Heteroduplex Mobility Assay screening. The most unusual findings included two subtypes A and a novel BC recombinant, while the majority of the strains were a variety of different BF recombinants. These results indicate the presence of novel and heterogeneous genotypes in our country and the need of continuous viral surveillance not only for diagnostic test optimization but also for the eventual implementation of a successful vaccine.(AU)

Tratamiento antirretroviral de alta eficacia en pediatría: nuestra experiencia / Highly active antiretroviral therapy in children: our experience

El tratamiento antirretroviral de alta eficacia (TAAE) modificó la morbilidad y mortalidad de la infección HIV. Con el objetivo de determinar el efecto del TAAE en la evolucón clínica, virológica e inmunológica y los factores que inciden en dicha respuesta, se realizó este estudio. Métodos: estudio prospectivo, incluyó 228 niños con infección HIV con TAAE desde 01/1998 a 12/2003 seguidos en el hospital. Se calcularon las tasas de incidenica (TI) por 100 pacientes/año de eventos incluídos en las categorías clínicas del CDC y se analizó el efecto sobre la respuesta al TAAE de la edad al inicio del tratamiento, presencia de SIDA, carga viral y % de CD4 basales. A través de las curvas de Kaplan Meir se determinó el efecto de los predictores sobre la ocurrencia de eventos. Resultados: la mediana de edad al inicio del TAAE fue 53 meses, 62% presentaban SIDA. La TI de eventos categoría B pre-TAAE fue de 28,6 por 100 pacientes/año mientras que post-TAAE fue de 20 por 100 pacientes-año (p<0.0001). La TI de eventos C pre -TAAE fue 11.6 por 100 pacientes/año y posterior fue de 1.9 por 100 pacientes/año(p<0.0001). La respuesta de CD4 a los 6 meses fue el predictor más potente de reducción de eventos B y C. La tasa de mortalidad fue de 6% a los 60 meses de TAAE. Conclusiónes: El TAAE se asoció con una marcada reducción de la morbilidad de la infección HIV. Dicha respuesta clínica estuvo asociada a la disminución de la carga viral y la restauración de la función inmunológica.

Human T lymphotropic virus types I and II proviral sequences in Argentinian blood donors with indeterminate Western blot patterns.

Human T-cell lymphotropic virus (HTLV) seroindeterminate blood donors have been reported worldwide including Argentina. To investigate the significance of HTLV-I/II seroindeterminate Western blot (WB) patterns, we conducted an 8-year cross-sectional study. Of 86,238 Argentinian blood donors, 146 sera were reactive by screening tests. The WB results indicated that 20% were HTLV-I reactive, 8% HTLV-II reactive, 61% indeterminate, and 11% negative. The overall seroprevalence was 0.034% for HTLV-I, 0.014% for HTLV-II, and 0.103% for indeterminate. In 57 reactive specimens, HTLV-I/II provirus could be examined by type specific PCR for tax, pol, and env regions. When at least two gene fragments were amplified HTLV-I/II infection was considered confirmed. PCR results confirmed all WB seropositive samples for HTLV-I (n = 15), and HTLV-II (n = 7), and the only WB negative case was also PCR negative, showing a complete concordance between PCR and WB. However, of 34 WB seroindeterminate sera studied by PCR, in 5 was proviral DNA amplified. According to our criteria PCR confirmed one to be HTLV-I, and one HTLV-II, 3 remained indeterminate since only tax sequences were amplified. Among WB indeterminate samples tested by PCR, most of their serological profile showed reactivity to gag codified proteins but lacked env reactivities (70%). One sample with a WB gag pattern showed proviral tax sequences, but of the four samples with reactivity to env proteins GD21 (n = 3) or rgp46II (n = 1) PCR results indicated that one was HTLV-I, one was HTLV-II, and two were indeterminate (only tax sequences). In conclusion, the majority of HTLV-seroindeterminate WB donors exhibited a gag indeterminate profile lacking HTLV provirus, and were thus considered uninfected. However, seroreactivity to env proteins, in particular to GD21, may indicate infection and a follow-up study of each seroreactive blood donor should be considered.

Distribution of CCR5-Delta 32 and CCR2-64I alleles in an Argentine Amerindian population.

In order to evaluate the frequency distributions of CCR5-Delta 32 and CCR2-64I polymorphisms in an Amerindian population, we tested a total of 42 Chiriguanos individuals that are aboriginal inhabitants of the north west of Argentina. Only one carried the CCR5-Delta 32 allele (0.0238), while 17 out of 35 carried the CCR2-64I mutation, including one homozygous for the mutated allele (0.2571). Although the cohort studied is considered highly endogamic, the HLA genotyping revealed that 8 out of 42 subjects had a gene flow from Caucasian populations. The only heterozygous CCR5+/Delta 32 found and three heterozygous CCR2+/64I belonged to the admix group. In conclusion, the protective deletion CCR5-Delta 32 is practically absent in Chiriguanos whereas the CCR2-64I allele is highly frequent.