RESUMEN
OBJECTIVE: To evaluate lymphocyte reconstitution after protease inhibitor therapy in children with human immunodeficiency virus (HIV) infection. STUDY DESIGN: Forty-four HIV-infected children receiving ritonavir monotherapy followed by the addition of zidovudine and didanosine were evaluated during a phase I/II clinical trial. The cohort had a median age of 6.8 years and advanced disease (57% Centers for Disease Control and Prevention stage C, 73% immune stage 3) and was naive to protease inhibitor therapy. RESULTS: After 4 weeks of therapy, there was a significant increase in CD4(+) and CD8(+) T cells. CD4(+) T cells continued to increase, whereas CD8(+) T cells returned to baseline by 24 weeks. Unexpectedly, there was a significant increase in B cells. Changes in CD4(+) T-cell subsets revealed an initial increase in CD4(+) CD45RO T cells followed by a sustained increase in CD4(+) CD45RA T cells. Children <6 years of age had the highest increase in all lymphocyte populations. Significant improvement in CD4(+) T-cell counts was observed even in those children whose viral burden returned to pre-therapy levels. CONCLUSIONS: Early increases in lymphocytes after ritonavir therapy are a result of recirculation, as shown by increases in B cells and CD4(+) CD45RO and CD8(+) T cells. Children exhibited a high potential to reconstitute CD4(+) CD45RA T cells even with advanced disease and incomplete viral suppression.
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Fármacos Anti-VIH/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/inmunología , Inhibidores de la Proteasa del VIH/uso terapéutico , Ritonavir/uso terapéutico , Adolescente , Relación CD4-CD8 , Linfocitos T CD4-Positivos , Linfocitos T CD8-positivos , Niño , Preescolar , Didanosina/uso terapéutico , Quimioterapia Combinada , Humanos , Inmunofenotipificación , Lactante , Antígenos Comunes de Leucocito , Subgrupos Linfocitarios , Carga Viral , Zidovudina/uso terapéuticoRESUMEN
BACKGROUND: Children with human immunodeficiency virus (HIV) infection have an increased susceptibility to severe and unusual infections, malignancies, and disorders characterized by abnormal lymphoproliferation (e.g., lymphoid interstitial pneumonitis). We report a novel disease entity associated with pediatric HIV infection that is characterized by massive enlargement of the thymus as a result of lymphoid hyperplasia and multicystic changes. METHODS: Eight patients with HIV infection and cystic enlargement of the thymus are subject of this report. The status of their HIV disease and its clinical and radiologic manifestations at the time of diagnosis of the mediastinal mass are described. Tissue specimens were obtained from six patients and examined by microscopy and immunohistochemistry. The specimens were also evaluated for the evidence of HIV and Epstein-Barr virus by in situ hybridization. RESULTS: Patients were between 2.1 and 12.1 years of age, with CD4+ cell counts between 102 and 733 cells/mm3. In all eight cases an anterior mediastinal mass was discovered incidentally on radiography of the chest, and computed tomography of the chest revealed a multicystic appearance. Histologic examination demonstrated distortion of the thymic architecture by focal cystic changes, lymphoid follicular hyperplasia, diffuse plasmacytosis, and multinucleated giant cells. In situ hybridization revealed HIV particles on the surface of follicular dendritic cells. Further, results of in situ hybridization for EBV were positive in lymphoid cells from biopsy samples of four patients. The patients were followed between 8 months and 4.8 years. In five patients the mass either decreased in size or resolved completely. CONCLUSIONS: We describe a series of children with HIV infection and multilocular thymic cysts. We hypothesize that aberrant immunoregulation in these HIV-infected children leads to follicular hyperplasia and multicystic changes in the thymus, causing massive enlargement. EBV infection might also contribute to the pathogenesis of this process. Because none of our patients had symptoms from the mass, and there was no evidence of malignancy in the examined biopsy samples, it seems prudent to manage such children with careful follow-up examinations.
Asunto(s)
Infecciones Oportunistas Relacionadas con el SIDA/patología , Quiste Mediastínico/patología , Infecciones Oportunistas Relacionadas con el SIDA/diagnóstico por imagen , Recuento de Linfocito CD4 , Niño , Preescolar , ADN Viral/genética , Células Dendríticas/patología , Células Dendríticas/virología , Susceptibilidad a Enfermedades , Femenino , Estudios de Seguimiento , Células Gigantes/patología , VIH/genética , VIH/aislamiento & purificación , Infecciones por Herpesviridae/patología , Herpesvirus Humano 4/genética , Herpesvirus Humano 4/aislamiento & purificación , Humanos , Hiperplasia , Inmunohistoquímica , Hibridación in Situ , Tejido Linfoide/diagnóstico por imagen , Tejido Linfoide/patología , Tejido Linfoide/virología , Trastornos Linfoproliferativos/patología , Masculino , Quiste Mediastínico/diagnóstico por imagen , Quiste Mediastínico/virología , Células Plasmáticas/patología , Radiografía Torácica , Timo/diagnóstico por imagen , Timo/patología , Timo/virología , Tomografía Computarizada por Rayos X , Infecciones Tumorales por Virus/patologíaRESUMEN
OBJECTIVE: To determine whether zidovudine, administered to reduce vertical transmission of human immunodeficiency virus type 1 (HIV-1), impacts the level of maternal viral DNA within the lymphocytes of infected pregnant women. STUDY DESIGN: A prospective, nonrandomized study of 42 HIV-1 infected pregnant women. Nineteen women received zidovudine therapy to reduce HIV-1 perinatal transmission, and 23 were untreated. HIV-1 DNA was determined by polymerase chain reaction amplification of lymphocyte DNA from maternal blood samples obtained at the time of delivery. Treated and untreated, transmitting and nontransmitting groups were compared for clinical, virologic, and immunologic parameters with at test or a Fisher Exact Test, and for copies of HIV-1 DNA per 10(6) CD4+ T cells with a Mann-Whitney rank sum test. RESULTS: Untreated pregnant women who transmitted HIV-1 to their infants had tower CD4+ T-cell counts and a greater degree of immune complex dissociated p24 antigenemia than did the untreated nontransmitting group (p < 0.01) but did not differ significantly with respect to age, race, or mode of delivery. The level of HIV-1 proviral DNA within lymphocytes was significantly greater in the untreated transmitting group than in the nontransmitting mothers (p = 0.003). Zidovudine treatment resulted in a 78% decrease in maternal transmission (p = 0.017). However, there was not a significant difference in DNA copy numbers in CD4+ T cells in the treated compared with the untreated groups. CONCLUSION: Zidovudine reduces HIV-1 maternal transmission independent of its effect on the level of the maternal peripheral blood proviral load.