RESUMEN
The 2015 Paediatric European Network for Treatment of AIDS (PENTA) guidelines provide practical recommendations on the management of HIV-1 infection in children in Europe and are an update to those published in 2009. Aims of treatment have progressed significantly over the last decade, moving far beyond limitation of short-term morbidity and mortality to optimizing health status for adult life and minimizing the impact of chronic HIV infection on immune system development and health in general. Additionally, there is a greater need for increased awareness and minimization of long-term drug toxicity. The main updates to the previous guidelines include: an increase in the number of indications for antiretroviral therapy (ART) at all ages (higher CD4 thresholds for consideration of ART initiation and additional clinical indications), revised guidance on first- and second-line ART recommendations, including more recently available drug classes, expanded guidance on management of coinfections (including tuberculosis, hepatitis B and hepatitis C) and additional emphasis on the needs of adolescents as they approach transition to adult services. There is a new section on the current ART 'pipeline' of drug development, a comprehensive summary table of currently recommended ART with dosing recommendations. Differences between PENTA and current US and World Health Organization guidelines are highlighted and explained
Asunto(s)
Humanos , Niño , Infecciones por VIH/diagnóstico , Infecciones por VIH/tratamiento farmacológico , Síndrome de Inmunodeficiencia Adquirida/diagnóstico , Síndrome de Inmunodeficiencia Adquirida/tratamiento farmacológico , Terapia Antirretroviral Altamente ActivaRESUMEN
Human immunodeficiency virus type 1 (HIV-1) isolates from children receiving long-term therapy with an alternating regimen of zidovudine and zalcitabine, or with didanosine monotherapy, were evaluated for resistance to zidovudine, zalcitabine, and didanosine, and for mutations known to be associated with zidovudine or didanosine resistance. HIV-1 from four of six patients receiving zidovudine with zalcitabine developed high-level resistance to zidovudine. A mutation in the HIV-1 reverse transcriptase that is highly associated with zidovudine resistance was identified in all four zidovudine-resistant posttherapy isolates. In contrast, none of the HIV-1 isolates from the seven patients receiving didanosine developed high-level resistance to this agent, despite the identification of a didanosine-associated mutation in six of these posttherapy isolates, although small decreases in sensitivity to didanosine were observed. These results indicate that nucleoside analog-associated mutations in HIV-1 occur frequently in children receiving long-term antiretroviral therapy and that alternating combination therapy does not prevent the development of resistance to zidovudine. They also suggest that there may be differences in the degree of resistance conferred by mutations that result from therapy with different nucleoside analogs. These findings underscore the need for studies to define the clinical importance of these mutations, and for treatment strategies to overcome the emergence of viral resistance in vivo.
Asunto(s)
Síndrome de Inmunodeficiencia Adquirida/tratamiento farmacológico , Didanosina/antagonistas & inhibidores , VIH-1/efectos de los fármacos , Zalcitabina/antagonistas & inhibidores , Zidovudina/antagonistas & inhibidores , Síndrome de Inmunodeficiencia Adquirida/microbiología , Niño , Preescolar , ADN Viral/genética , Didanosina/administración & dosificación , Farmacorresistencia Microbiana , Quimioterapia Combinada , VIH-1/genética , VIH-1/aislamiento & purificación , Humanos , Lactante , Pruebas de Sensibilidad Microbiana/métodos , Mutación , Reacción en Cadena de la Polimerasa/métodos , Factores de Tiempo , Zalcitabina/administración & dosificación , Zidovudina/administración & dosificaciónRESUMEN
More than 250 children treated at our institution on antiretroviral treatment protocols have been monitored with brain imaging studies. We documented the occurrence and progression of aneurysms of major cerebral arteries in two children with advanced human immunodeficiency virus infection. In both cases these lesions remained clinically silent initially, despite progression to marked dilation.
Asunto(s)
Infecciones por VIH/complicaciones , VIH-1 , Aneurisma Intracraneal/complicaciones , Encéfalo/patología , Angiografía Cerebral , Niño , Didanosina/uso terapéutico , Quimioterapia Combinada , Infecciones por VIH/tratamiento farmacológico , Humanos , Aneurisma Intracraneal/diagnóstico , Imagen por Resonancia Magnética , Masculino , Zidovudina/uso terapéuticoRESUMEN
We reviewed the 22 cases of Mycobacterium avium-intracellulare (MAI) infection that occurred among 196 human immunodeficiency virus-infected children seen at the National Cancer Institute Pediatric Branch from December 1986 through April 1991, and an additional 65 charts from children with cultures negative for MAI. All patients with proven MAI were receiving antiretroviral therapy with zidovudine, dideoxyinosine, or a combination of zidovudine and dideoxycytidine. All patients had disseminated MAI infection, except one adolescent who had only evidence of localized lymphadenitis. All cases of MAI but one were diagnosed before death. The overall incidence of MAI was 11% in our patients but increased to 24% in patients whose absolute CD4 cell counts were < 100 cells/mm3. Symptoms most commonly associated with MAI infection included recurrent fever (86% of patients), weight loss or failure to thrive (64%), neutropenia (55%), night sweats (32%), and abdominal pain (27%). Children infected with MAI had a mean CD4 percentage of 2% (range, 0% to 7%) and a mean absolute CD4 count of 12 cells/mm3 (range, 0 to 48 cells/mm3), significantly lower than in the remainder of the clinic population or the group of children with cultures negative for MAI. Of 20 patients with MAI infection who were tested, 10 had measurable p24 antigen with a mean value 939 pg/ml (range, 77 to 3270 pg/ml) compared with 19 of 59 patients without MAI infection in whom the mean positive value was 413 pg/ml. There was no difference in survival time between those children with documented MAI infection (median survival time, 45.5 weeks) and those with similarly low CD4 counts and cultures negative for MAI (median survival time, 50.4 weeks). Future improvements in therapeutic options may make screening of pediatric human immunodeficiency virus-infected patients with low CD4 counts a reasonable plan.
Asunto(s)
Infecciones Oportunistas Relacionadas con el SIDA/diagnóstico , Infección por Mycobacterium avium-intracellulare/diagnóstico , Factores de Edad , Antígenos CD4 , Niño , Preescolar , Femenino , Proteína p24 del Núcleo del VIH/análisis , Infecciones por VIH/inmunología , Infecciones por VIH/transmisión , Humanos , Recuento de Leucocitos , Subgrupos Linfocitarios , Masculino , Factores de RiesgoRESUMEN
Bone marrow suppression is the major dose-limiting toxic effect of zidovudine (azidothymidine; AZT) in children with human immunodeficiency virus infection. We evaluated the effect of subcutaneously administered granulocyte colony-stimulating factor (G-CSF) in pediatric patients whose absolute neutrophil count was less than 0.8 x 10(9)/L during AZT therapy despite dosage reductions to 120 mg/m2 every 6 hours. Nineteen patients between 6 months and 20 years of age were treated with AZT and G-CSF and monitored for 2 to 12 months. All had previously shown improvement while receiving AZT but had required dosage reduction or discontinuation. By using a sliding dosing schedule of G-CSF, we attempted to maintain the absolute neutrophil count between 1.5 and 5.0 x 10(9)/L. Administration of G-CSF resulted in a significant increase in the median leukocyte count (2.0 x 10(9)/L to 4.14 x 10(9)/L; p = 0.004), and the median absolute neutrophil count (1.02 x 10(9)/L to 2.96 x 10(9)/L; p = 0.0006). G-CSF was well tolerated, but mild thrombocytopenia developed in nine children. Administration of G-CSF and AZT was discontinued in two patients because of continuing neutropenia. With doses of G-CSF ranging from 1 to 20 micrograms/kg per day, 17 of 19 patients were able to tolerate AZT at a dose of 120 to 180 mg/m2 every 6 hours. We conclude that G-CSF therapy enables patients who have had AZT-related neutropenia to receive therapeutic doses of AZT.
Asunto(s)
Factor Estimulante de Colonias de Granulocitos/administración & dosificación , Infecciones por VIH/terapia , Zidovudina/administración & dosificación , Adolescente , Niño , Preescolar , Quimioterapia Combinada , Femenino , Factor Estimulante de Colonias de Granulocitos/efectos adversos , Infecciones por VIH/sangre , Humanos , Lactante , Recuento de Leucocitos , Masculino , Neutrófilos , Proyectos Piloto , Recuento de Plaquetas , Zidovudina/efectos adversosRESUMEN
To determine the safety and pharmacokinetics of recombinant soluble CD4 (sCD4) administered by continuous intravenous infusion to children with symptomatic human immunodeficiency virus type 1 infection, we conducted a phase I study at the National Cancer Institute. Three dose levels of sCD4 were evaluated: 100, 300, and 1000 micrograms/kg per day. After an initial 12 weeks of treatment with sCD4 alone, dideoxyinosine at a dose of 90 mg/m2 every 8 hours was added and subjects were observed for an additional 12 weeks. Combination therapy was continued in patients in whom it was well tolerated. In addition to toxicity and pharmacokinetic monitoring, surrogate markers of antiviral activity were evaluated. Eleven children were enrolled in the study. During the 12 weeks of treatment with sCD4 alone, and during subsequent sCD4 plus dideoxyinosine combination therapy, no significant toxic reaction attributable to sCD4 or dideoxyinosine was encountered. Low-level anti-CD4 antibodies developed in two patients. Steady-state sCD4 levels increased proportionately at higher doses. The CD4 cell counts and serum p24 antigen levels did not provide evidence of antiviral activity. We conclude that sCD4 was well tolerated at doses up to 1000 micrograms/kg per day when administered by continuous intravenous infusion; however, evidence of in vivo antiviral activity was not observed in this study.
Asunto(s)
Síndrome de Inmunodeficiencia Adquirida/tratamiento farmacológico , Antígenos CD4/uso terapéutico , Didanosina/uso terapéutico , Síndrome de Inmunodeficiencia Adquirida/inmunología , Adolescente , Antígenos Virales/sangre , Antígenos CD4/administración & dosificación , Linfocitos T CD4-Positivos , Niño , Preescolar , Didanosina/administración & dosificación , Didanosina/farmacocinética , Evaluación de Medicamentos , Quimioterapia Combinada , Femenino , Humanos , Lactante , Infusiones Intravenosas , Recuento de Leucocitos , Masculino , Proteínas Recombinantes/administración & dosificación , Proteínas Recombinantes/farmacocinética , Proteínas Recombinantes/uso terapéutico , Resultado del TratamientoRESUMEN
Ganciclovir and foscarnet are both effective for cytomegalovirus retinitis in patients with acquired immunodeficiency syndrome, but the benefits of either agent given alone are limited. A child infected with human immunodeficiency virus who had cytomegalovirus retinitis that progressed despite treatment with either agent alone received the combination of ganciclovir and foscarnet. This treatment resulted in a sustained clinical response.
Asunto(s)
Antivirales/administración & dosificación , Infecciones por Citomegalovirus/tratamiento farmacológico , Ganciclovir/administración & dosificación , Infecciones por VIH/complicaciones , Ácido Fosfonoacético/análogos & derivados , Retinitis/tratamiento farmacológico , Preescolar , Infecciones por Citomegalovirus/complicaciones , Quimioterapia Combinada , Femenino , Foscarnet , Humanos , Ácido Fosfonoacético/administración & dosificación , Retinitis/complicacionesAsunto(s)
Infecciones por VIH/complicaciones , Infecciones Oportunistas/prevención & control , Neumonía por Pneumocystis/prevención & control , Femenino , Humanos , Lactante , Infecciones Oportunistas/complicaciones , Neumonía por Pneumocystis/complicaciones , Combinación Trimetoprim y Sulfametoxazol/uso terapéuticoRESUMEN
OBJECTIVE: To determine whether a short course of 2',3'-dideoxycytidine (ddC) could provide safe antiretroviral activity in children with symptomatic human immunodeficiency virus infection and whether it could be used with azidothymidine (AZT, zidovudine). The goal was to maintain uninterrupted antiretroviral therapy while sparing AZT-related myelosuppression and ddC-related neuropathy. METHODS: In a pilot study, we evaluated four dosage levels of ddC--0.015, 0.02, 0.03, and 0.04 mg/kg, given orally every 6 hours--in 15 children between 6 months and 13 years of age with Centers for Disease Control P2 (i.e., symptomatic) human immunodeficiency virus infection. Thirteen patients had not had any prior antiretroviral therapy; two patients had received and benefited from AZT, but dose-limiting neutropenia had developed. At each dosage level, ddC was given for 8 consecutive weeks and then stopped. After a 30-day rest, a schedule of ddC for 1 week was followed by 3 weeks of AZT therapy (180 mg/m2 every 6 hours); this alternating schedule was repeated for as long as tolerated. Age-appropriate psychometric testing was performed before the start of ddC therapy and after 8 weeks. RESULTS: During the 8 weeks of therapy with ddC alone, no neutropenia or anemia was observed; 6 of 9 patients had decreases in p24 antigen levels, and 8 of 15 had an increased CD4 cell count. At the 0.04 mg/kg level, a rash developed in three patients; mild mouth sores developed in 9 of 15 patients. On the alternating ddC/AZT schedule, no neuropathy was observed. CONCLUSIONS: 2',3'-Dideoxycytidine has antiretroviral activity in some children and appears to be safe for short intervals. Longer courses of ddC at lower dosage levels, and schedules integrating ddC into combination regimens, deserve to be explored.
Asunto(s)
Síndrome de Inmunodeficiencia Adquirida/tratamiento farmacológico , Zalcitabina/administración & dosificación , Zidovudina/administración & dosificación , Síndrome de Inmunodeficiencia Adquirida/diagnóstico , Administración Oral , Adolescente , Factores de Edad , Antígenos CD/análisis , Antígenos CD4/análisis , Niño , Preescolar , Quimioterapia Combinada , Femenino , Humanos , Lactante , Masculino , Pruebas Neuropsicológicas , Factores de Tiempo , Zalcitabina/efectos adversos , Zalcitabina/farmacocinética , Zidovudina/efectos adversosRESUMEN
To assess whether neuroendocrine dysfunction is present in children with acquired immunodeficiency syndrome (AIDS) and growth failure, we evaluated the thyroid, adrenal, and growth hormone-insulin-like growth factor I (IGF-1) axes in nine children with AIDS and failure to thrive. Basal thyroid-stimulating hormone, free thyroxine, and triiodothyronine levels were normal in eight of the nine children and indicated primary hypothyroidism in one child; thyroxine levels were elevated in four and normal in five children. Thyroxine-binding globulin levels were elevated in all children. Serial measurements of thyroid-stimulating hormone, made hourly from 2 to 6 pm and from 10 pm to 2 am, revealed a flat diurnal rhythm of thyroid-stimulating hormone in six children, which may indicate early central hypothyroidism, and a normal nocturnal rise in the remaining three children. Basal plasma corticotropin and aldosterone levels were normal in all children, plasma renin levels were normal in three and elevated in six children, and cortisol levels were normal or elevated in all children. Corticotropin-stimulated cortisol levels exceeded 500 nmol/L (18 micrograms/dl) in all children except one, who was receiving treatment with ketoconazole. Thus adrenocortical function appeared to be grossly intact. The peak growth hormone responses to provocative testing was normal (greater than 7 ng/ml) in eight children and low in one child. The plasma level of insulin-like growth factor I was normal in eight of the nine children and low in one child. We conclude that growth failure in children with AIDS does not usually result from a recognized endocrine cause and that adrenal function is usually normal. However, endocrine deficiency may contribute to morbidity in some children with AIDS.