Etravirine-based highly active antiretroviral therapy in HIV-1-infected paediatric patients.

BACKGROUND: We evaluated the efficacy, safety and tolerability of etravirine in paediatric patients vertically infected with HIV-1. METHODS: A multicentre retrospective study of 23 multidrug-resistant paediatric patients (five children and 18 adolescents) enrolled in the study from 1 September 2007 to 28 February 2010 was carried out. We performed a longitudinal analysis of immunological, virological and clinical data. RESULTS: The median age of the patients was 14.2 years [interquartile range (IQR) 12.5-15.8 years]. At baseline, the median HIV-1 RNA was 29 000 (4.5 log(10) ) HIV-1 RNA copies/mL (range 4300-83 000 copies/mL), the median CD4 T-cell count was 445 cells/µL (range 221-655 cells/µL) and the median CD4 percentage was 19.6% (IQR 13.0-31.0). Remarkably, 16 of 23 patients (70%) harboured one or more etravirine-associated resistance mutations. The backbone regimen included at least two fully active drugs in 91% of patients. After etravirine-based therapy, 20 patients (87%) achieved HIV-1 RNA<400 copies/mL and 18 of 23 (78%) achieved HIV-1 RNA<50 copies/mL: three (13%) within the first month, seven (30%) within the first 4 months, and six (26%) between the 5th and 8th months. CD4 T-cell recovery was observed in 19 patients (83%). The median follow-up time was 48.4 weeks (IQR 35.7-63.4 weeks); four patients (17%) were exposed to etravirine for >120 weeks. Three mild/short-term and two moderate skin rashes were observed in the adolescents. Laboratory abnormalities included hypercholesterolaemia (11 of 23 patients), hypertriglyceridaemia (eight of 23 patients), and reduced high-density lipoprotein cholesterol (10 of 23 patients). Adherence was complete in seven patients (30%). No patients showed complete resistance to etravirine after follow-up. However, three of 21 patients (14%) who initially showed intermediate resistance interrupted etravirine treatment because of virological failure. CONCLUSIONS: We observed a sustained antiviral response and improved immunological parameters in multidrug-resistant paediatric patients, most of whom had received etravirine as part of salvage regimens with at least two fully active drugs.

Trastornos neuropsiquiátricos asociados a estreptococo / Neuropsychiatric disorders associated with streptococci: a case report

Los trastornos neuropsiquiátricos compulsivos son frecuentes en la infancia, siendo el más común el síndrome de Gilles de la Tourette. Recientemente ha sido descrito el síndrome PANDAS (pediatric autoimmune neuropsychiatric disorders associated with streptococci), de etiología incierta, pero asociado a infección reciente por estreptococo del grupo A (SGA). Niño de 3 años y 9 meses que inició bruscamente, tras un episodio de faringitis, un cuadro de tics consistentes en inclinación de la cabeza y elevación del hombro, junto con muecas faciales, coprolalia y posteriormente compulsiones como golpear objetos de manera compulsiva. Se realizó estudio bioquímico completo, incluyendo cobre y ceruloplasmina (normales), antiestreptolisina O y anti-DNAsa, que resultaron elevadas, y se realizó cultivo faríngeo, que fue positivo para SGA. Fue inicialmente tratado con ácido valproico, aunque su mejoría posterior coincidió con el tratamiento durante 10 días con penicilina. A los 3 meses, los valores de antiestreptolisina O (ASLO) disminuyeron, y en su seguimiento a los 6 meses se comprobó una mejoría mantenida, incluso tras la suspensión del ácido valproico. Se solicitaron estudios de inmunohistoquímica. El síndrome PANDAS fue descrito en 1998 en niños que presentaban: a) trastornos obsesivo-compulsivos y/o trastorno de tics; b) curso episódico con exacerbaciones bruscas; c) alteraciones neurológicas (movimientos coreiformes), y d) relación temporal entre infección por SGA y exacerbación de los síntomas. La etiología se discute actualmente, se postula la existencia de reacciones cruzadas entre antígenos del SGA y proteínas presentes en los ganglios de la base, encontrándose cierta evidencia serológica a favor de varios antígenos proteicos implicados (B8/17 y otros). Está recomendado tratar con penicilina en cada exacerbación en la que se demuestre SGA, e incluso utilizar tratamientos más agresivos (inmunoglobulina intravenosa o plasmaféresis) en caso de tics graves y discapacitantes. Creemos que es un caso interesante de posible síndrome PANDAS, y sería el primero descrito en España

Compulsive neuropsychiatric disorders are common in children and the most frequent is Gilles de la Tourette syndrome. Recently, a new disease has been described: the PANDAS syndrome (pediatric autoimmune neuropsychiatric disorders associated with streptococci). The etiology of this syndrome is uncertain but it has been associated with recent group A streptococcal infection (GAS). After an episode of pharyngitis, a boy aged 3 years and 9 months showed abrupt onset of a variety of neurobehavioral problems such as tics (consisting of elevation of the head and ipsilateral shoulder, winking, and grimaces) and compulsions (such as repeatedly hitting objects). A complete biochemical study was performed, including Cu and ceruloplasmin (which had normal values), antistreptolysin O (ASLO) and anti-DNAse (showing elevated values). Pharyngeal culture revealed GAS. The child was initially treated with valproic acid, but his subsequent improvement coincided with penicillin treatment for 10 days. Three months afterwards, ASLO values were reduced and at the 6-month follow-up the improvement was maintained even after suspension of valproic acid. Immunohistochemical studies were requested. PANDAS syndrome was first described in 1998 in a group of children who presented 1) obsessive compulsive disorders and/or tics, 2) episodic course with abrupt exacerbations, 3) abnormal results of neurologic examination (choreiform movements), and 4) temporal relation between GAS infection and onset of symptoms. The etiology of this syndrome is unclear, and it has been postulated that certain streptococcal antigens trigger antibodies which, through a process of molecular mimicry, cross-react with epitopes on the basal ganglia of susceptible hosts, such as the B8/17 antigen, among others. Current recommendations include penicillin treatment of each exacerbation with positive throat culture, and more aggressive therapies (intravenous immunoglobulin or plasmapheresis) when symptoms are severe. We believe that the case presented herein is a probable PANDAS syndrome, which would be the first case described in Spain