RESUMO
Thirty-five children with symptomatic human immunodeficiency virus infection were enrolled in a 12-week, three-center phase I study of intravenous and oral zidovudine therapy. At enrollment the children ranged in age from 5 months to 13 years, with a median age of 3 1/2 years. Twenty-one children (60%) had acquired immunodeficiency syndrome and 14 (40%) had the related complex; 20 children had less than 0.5 10(9) CD4+ lymphocytes per liter (less than 500 cells/mm3) at entry. Zidovudine was administered in one of three escalating dose regimens. One or two months of intravenous treatment with zidovudine every 6 hours was followed by orally administered drug on the same schedule; zidovudine was infused at 80, 120, or 160 mg/m2/dose, and the oral dose was one and one-half times the intravenous dosage. Adverse events were similar to those observed in adults. Neutropenia (absolute neutrophil count less than 0.75 10(9)/L (750 cells/mm3] occurred in nine patients. The median neutrophil count fell from 2.50 10(9)/L at entry to 1.72 10(9)/L at the end of the study. Anemia requiring transfusion occurred in seven 10(9)/L at the end of the study. Anemia requiring transfusion occurred in seven patients; the median hemoglobin level among nontransfused patients decreased from an entry value of 108 to 105 gm/L (10.8 to 10.5 gm/dl). Dosage adjustments were made in 15 patients, in 12 because of anemia or neutropenia. No patients required permanent discontinuation of zidovudine because of toxic effects. Positive effects included a faster-than-anticipated rate of weight gain, decreased hepatosplenomegaly, and lowering of the total IgG and IgM concentrations toward more normal values. Zidovudine appears to be safe and to have manageable toxic effects in children.
Assuntos
Complexo Relacionado com a AIDS/tratamento farmacológico , Síndrome da Imunodeficiência Adquirida/tratamento farmacológico , Infecções por HIV/tratamento farmacológico , Zidovudina/uso terapêutico , Complexo Relacionado com a AIDS/sangue , Complexo Relacionado com a AIDS/imunologia , Síndrome da Imunodeficiência Adquirida/sangue , Síndrome da Imunodeficiência Adquirida/imunologia , Administração Oral , Adolescente , Criança , Pré-Escolar , Avaliação de Medicamentos , Tolerância a Medicamentos , Seguimentos , Infecções por HIV/sangue , Infecções por HIV/imunologia , Humanos , Lactente , Infusões Intravenosas , Estudos Multicêntricos como Assunto , Segurança , Zidovudina/administração & dosagem , Zidovudina/efeitos adversosRESUMO
Neutralizing antibodies (NAs) against four isolates of human immunodeficiency virus type 1 (HIV-1) were assayed in HIV-1 antibody positive sera from the United States, Haiti, Zimbabwe, and Zaire. Overall, there were NAs detected in 95, 81, 60, and 73% of sera with reciprocal geometric mean titers (GMTs) of 626, 23, 10, and 20, respectively, against HIV-1MN, HIV-1IIIB, HIV-1RF, and HIV-1Z3. Sera from North America had significantly higher NA titers against HIV-1MN. In each country, the highest antibody titers observed were against the MN strain. Otherwise, sera from the U.S. neutralized most strongly HIV-1IIIB, sera from Zaire neutralized most strongly HIV-1Z3, and sera from Zimbabwe had equal titers against all three viruses. The differences between countries were reflected in analyses of NA titers of subgroups classified on the basis of clinical status, indicating that the differences were not likely to be related to differences in clinical status of the patients being tested. Some of this antigenic variation is reflective of known genetic diversity, while some is not. The results suggest that undefined preserved and variable regions containing neutralization epitope(s) exist. These data do not indicate a need to define antigenic subtypes of HIV-1 at present. The existence of conserved neutralization epitope(s) may indicate the potential for broad immunogenicity of appropriately selected vaccine antigens.
Assuntos
Anticorpos Anti-HIV/imunologia , HIV-1/imunologia , Complexo Relacionado com a AIDS/imunologia , Síndrome da Imunodeficiência Adquirida/imunologia , Análise de Variância , República Democrática do Congo , Feminino , Haiti , Humanos , Masculino , Testes de Neutralização , Gravidez , Estados Unidos , ZimbábueRESUMO
Human immunodeficiency virus type 1 (HIV-1) core antigen was assayed in the plasma of children at risk for infection with HIV to determine its usefulness in the diagnosis of infection and to correlate it with the clinical stage of disease. Antigen was detected in the plasma of all children less than 15 months of age with acquired immunodeficiency syndrome (AIDS). Two thirds of children with AIDS-related illnesses and half of children with asymptomatic infection had antigen. Although 53% of plasma specimens originating from HIV-infected children younger than 6 months of age contained antigen, only 25% of plasma specimens from children younger than 6 months who had no symptoms and none of the 10 specimens from HIV-infected newborn infants contained antigen. Half of the specimens containing core antigen also contained anticore antibody. Quantitative mean antigen levels were more likely to be elevated in children with AIDS (516 pg/ml) than in children with AIDS-related illnesses (295 pg/ml) or in those who had no symptoms (70 pg/ml). Antigen levels tended to increase over time in children with advancing clinical illness, but they tended to decrease over time after a diagnosis of AIDS was made. Antigen was detected in the plasma of 4 of 14 children without symptoms who subsequently reverted to an HIV seronegative state. We conclude that the detection of core antigen occurs with high frequency in children, even young infants, with symptomatic HIV infection. Plasma core antigen was less frequent in children without symptoms and was not detected in 10 infected children when they were tested at birth.
Assuntos
Síndrome da Imunodeficiência Adquirida/diagnóstico , Antígenos HIV/análise , HIV-1/imunologia , Proteínas do Core Viral/imunologia , Complexo Relacionado com a AIDS/diagnóstico , Complexo Relacionado com a AIDS/imunologia , Síndrome da Imunodeficiência Adquirida/imunologia , Ensaio de Imunoadsorção Enzimática , Soropositividade para HIV/imunologia , Humanos , Lactente , Recém-NascidoRESUMO
In order to investigate the IgG HIV-1 antibodies reactivity to structural components of the virus, 85 sera from infected Brazilians, comprising the total spectrum of HIV infection, were analysed by Western blot assay. The sera were confirmed as being positive to HIV with enzyme linked immuno assay (ELISA) and indirect immunofluorescence (IIF). Although the sera from patients reacted less intensively to the gag polypeptide of 55 KDa, no distinctive antigen reaction patterns were observed between sera patients with different clinical forms. Because of the higher frequency of reactivity to the gag p24 in AIDS patients, the patterns of anti-HIV IgG responses are similar to those observed in their African counterparts.
Assuntos
Síndrome da Imunodeficiência Adquirida/imunologia , Anticorpos Anti-Idiotípicos/análise , HIV-1/imunologia , Imunoglobulina G/análise , Complexo Relacionado com a AIDS/imunologia , Western Blotting , Infecções por HIV/imunologia , Soropositividade para HIV , HumanosRESUMO
Alteraçöes imunológicas na Síndrome de Imunodeficiência Adquirida em pacientes do Rio de Janeiro, Brasil. O perfil imunológico de 15 pacientes com Síndrome de Imunodeficiência Adquirida (AIDS) e 11 com Síndrome de Linfadenipatia Crônica, foram estudados. Os pacientes com AIDS mostraram reduzida percentagem de linfócitos T (CD3) totais e T auxiliares (CD4), aumento relativo no número de linfócito T-supressores (CD8) e uma marcante inversäo na relaçäo T-auxiliares/supressores (CD4/CD8). A resposta linfoproliferativa para PHA, ConA, PPD e PWN, estava diminuída. Foi também observado hipergamaglobulinemia e níveis aumentados de complexos imunes circulantes. Os pacientes com Síndrome de Linfadenopatia Crônica também mostraram importantes alteraçöes imunológicas, mas näo täo intensas como nos de AIDS. Estes dados säo similares aos observados nos Estados Unidos e na Europa (U)
Assuntos
Adolescente , Adulto , Pessoa de Meia-Idade , Humanos , Masculino , Feminino , Complexo Relacionado com a AIDS/imunologia , Síndrome da Imunodeficiência Adquirida/imunologia , Brasil , Imunoglobulinas/análise , Linfócitos T Auxiliares-Indutores/análiseRESUMO
The immunological profile of acquired immunodeficiency syndrome (AIDS) and chronic lymphadenopathy syndrome (CLAS) in 15 and 11 Brazilian patients, respectively, was studied. The AIDS patients showed reduced percentage of total T (CD3) and T-helper-inducer (CD4) lymphocytes, relative increase in numbers of T-suppressor-cytotoxic (CD8) cells and a marked inversion of T-helper-inducer/suppressor-cytotoxic (CD4/CD8) ratio. Lymphoproliferative responses to PHA, ConA, PPD and PWM were diminished. Hypergammaglobulinemia and high levels of circulating immune complexes were also found. The CLAS patients also showed important immunological alterations, but not so intense as those with AIDS. These data seems to be similar to those observed in other parts of the world.
Assuntos
Complexo Relacionado com a AIDS/imunologia , Síndrome da Imunodeficiência Adquirida/imunologia , Adolescente , Adulto , Complexo Antígeno-Anticorpo/análise , Brasil , Feminino , Homossexualidade , Humanos , Imunoglobulinas/análise , Masculino , Pessoa de Meia-Idade , Comportamento Sexual , Linfócitos T/análise , Linfócitos T Auxiliares-Indutores/análiseRESUMO
The present study evaluates the in vitro cellular immunity response in cases of suspected Acquired Immunodeficiency Syndrome (AIDS). The immunological features of 111 patients were correlated with those from eleven healthy controls. Patients were divided into three groups: RISK, LAS/ARC and AIDS, using CDC criteria. The AIDS showed leucopenia, lymphopenia, diminished number of T and B lymphocytes, normal number of thermostable E-rosette forming cells (TE), decreased helper-inducer T cell, elevated suppressor-cytotoxic T cell, reversed helper T cell/suppressor T cell ratio and depressed proliferative response using mitogens like phytohemagglutinin (PHA), concanavalin-A (Con-A), pokeweed mitogen (PWM) and purified protein derivative antigen (PPD). These findings confirm a severe deficiency in cellular immunity and permit to establish an immune cellular profile, characteristic of the AIDS patients.
Assuntos
Síndrome da Imunodeficiência Adquirida/imunologia , Complexo Relacionado com a AIDS/imunologia , Adulto , Humanos , Técnicas In Vitro , Contagem de Leucócitos , Leucócitos/classificação , Ativação Linfocitária/efeitos dos fármacos , Linfócitos/classificação , Masculino , Pessoa de Meia-IdadeAssuntos
Adulto , Pessoa de Meia-Idade , Humanos , Masculino , Feminino , Complexo Relacionado com a AIDS/imunologia , Técnicas In Vitro , Síndrome da Imunodeficiência Adquirida/imunologia , Contagem de Leucócitos , Leucócitos/classificação , Ativação Linfocitária/efeitos dos fármacos , Linfócitos/classificação , Mitógenos/farmacologiaRESUMO
Serologic reactivity against EBV-infected lines was assayed in patients with AIDS (n = 4) or the AIDS related complex (AIDS-RC) (n = 46) residing in Argentina. Anti-VCA serology was comparable to that of controls. However sera from AIDS and AIDS-RC could induce antibody dependent cell mediated cytotoxicity (ADCC) to EBV-infected cell lines (P3HRIK and Raji). ADCC activity could be recovered in the high molecular weight fractions of AIDS and AIDS-RC sera. ADCC was observed in sera with high levels of PEG precipitable material (PEG-pp) but was unrelated to the presence of complement-fixing immune complexes (Clq-F) or to anti-VCA titers. Fc receptor (FcR) bridging between target cells FcR and effector cells FcR may play a role in the outcome of total ADCC.