RESUMO
The relationship among CCR5 genotype, cytomegalovirus infection, and disease progression and death was studied among 159 human immunodeficiency virus (HIV)-infected patients with hemophilia. One patient (0.6%) had the CCR5Delta32/CCR5Delta32 genotype (which occurs in approximately 2% of the Scandinavian population) and a rapid disease course. His HIV V3 region contained genotypic features attributable to X4 virus and resembled functionally verified X4 virus and virus from patients treated with a CD4 cell-stimulating drug, tucaresol. Age-related differences in disease progression rate and survival time were seen for CCR5/CCR5 patients. Surprisingly, no protective effect of the CCR5/CCR5Delta32 genotype on disease progression or survival was seen for children but was evident for adults. Age group-related immunologic differences might explain this variation, and transmission route and/or viral phenotype variation within donor virus may be related to the limited protection of the CCR5Delta32/CCR5Delta32 genotype. Sequence comparisons indicate that X4 virus can be selected in vivo due to either absence of CCR5 receptors or relative increase of CXCR4 receptors.
Assuntos
Predisposição Genética para Doença/genética , Infecções por HIV/complicações , Infecções por HIV/genética , HIV/classificação , Hemofilia A/complicações , Hemofilia B/complicações , Receptores CCR5/genética , Adolescente , Adulto , Envelhecimento/genética , Envelhecimento/fisiologia , Sequência de Aminoácidos , Contagem de Linfócito CD4 , Estudos de Coortes , Infecções por Citomegalovirus/complicações , Infecções por Citomegalovirus/genética , Progressão da Doença , Feminino , Genótipo , HIV/isolamento & purificação , HIV/fisiologia , Infecções por HIV/epidemiologia , Infecções por HIV/virologia , Hemofilia A/genética , Hemofilia B/genética , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Receptores CCR5/química , Fatores de Risco , Taxa de SobrevidaRESUMO
INTRODUCTION: Beta-thalassemia major occurs with increasing frequency among Danish children as a result of immigration. The aim of the study was to estimate the occurrence of beta-thalassemia major in Denmark, analyse the treatment and organ functions, and identify areas for an improved treatment strategy. MATERIAL AND METHODS: During 1998-99 all Danish pediatric departments were contacted for identification of children aged 0-18 years with beta-thalassemia major. Blood transfusions and chelation therapy were registered, and for Eastern Denmark clinical, endocrine, cardiac, and serologic parameters were performed. RESULTS: Twenty-six children had beta-thalassemia major. Out of these, 20 received blood transfusions, and 17 patients were chelated. Eight patients were not chelated owing to previous bone marrow transplantation, treatment with hydroxyurea or ferritin < 2000 micrograms/l and young age. One patient had died. The body height was between 1.5 and -5.4 SDS (median -1.7) and the sitting height was -0.6 to -5.6 SDS (median -2.3). The bone age was delayed 1-5 years (median -2.5) in six out of ten examined patients, and puberty delayed in four out of five. A dilated left ventricle was documented in one out of eight patients examined. All patients were HIV and hepatitis C negative. For 75% of the children, the parents were related. DISCUSSION: Children and adolescents with beta-thalassemia major in Denmark experience major heterogenicity with regard to treatment and late effects. An earlier and more effective iron chelation therapy together with improved patient support may reduce growth disturbances and endocrine and cardiac late effects.
