Evolution of the human immunodeficiency virus type 2 envelope in the first years of infection is associated with the dynamics of the neutralizing antibody response.

BACKGROUND: Differently from HIV-1, HIV-2 disease progression usually takes decades without antiretroviral therapy and the majority of HIV-2 infected individuals survive as elite controllers with normal CD4⁺ T cell counts and low or undetectable plasma viral load. Neutralizing antibodies (Nabs) are thought to play a central role in HIV-2 evolution and pathogenesis. However, the dynamic of the Nab response and resulting HIV-2 escape during acute infection and their impact in HIV-2 evolution and disease progression remain largely unknown. Our objective was to characterize the Nab response and the molecular and phenotypic evolution of HIV-2 in association with Nab escape in the first years of infection in two children infected at birth. RESULTS: CD4⁺ T cells decreased from about 50% to below 30% in both children in the first five years of infection and the infecting R5 viruses were replaced by X4 viruses within the same period. With antiretroviral therapy, viral load in child 1 decreased to undetectable levels and CD4+ T cells recovered to normal levels, which have been sustained at least until the age of 12. In contrast, viral load increased in child 2 and she progressed to AIDS and death at age 9. Beginning in the first year of life, child 1 raised high titers of antibodies that neutralized primary R5 isolates more effectively than X4 isolates, both autologous and heterologous. Child 2 raised a weak X4-specific Nab response that decreased sharply as disease progressed. Rate of evolution, nucleotide and amino acid diversity, and positive selection, were significantly higher in the envelope of child 1 compared to child 2. Rates of R5-to-X4 tropism switch, of V1 and V3 sequence diversification, and of convergence of V3 to a ß-hairpin structure were related with rate of escape from the neutralizing antibodies. CONCLUSION: Our data suggests that the molecular and phenotypic evolution of the human immunodeficiency virus type 2 envelope are related with the dynamics of the neutralizing antibody response providing further support for a model in which Nabs play an important role in HIV-2 pathogenesis.

Envelope-specific antibody response in HIV-2 infection: C2V3C3-specific IgG response is associated with disease progression.

OBJECTIVE: To examine the unspecific and envelope-specific IgA and IgG responses in acute and chronic HIV-2 infection. METHODS: Twenty-eight chronically infected adults and two children with perinatal infection were studied. Total plasma concentrations of IgA and IgG were determined by nephelometry. IgA and IgG reactivity against the immunodominant region in gp36 and the C2V3C3 region in gp125 was tested with the enzyme-linked immunosorbent assay (ELISA)-HIV-2 assay. Clonal sequences of the C2V3C3 env region were obtained for most patients. RESULTS: Total plasma IgG concentration, but not IgA, was significantly higher than normal in HIV-2 patients and correlated inversely with CD4 T-cell counts. Seroconversion to gp36 occurred during the first year of life in both infants. The infant with rapid disease progression did not elicit C2V3C3-specific antibodies. Most chronically infected patients produced plasma IgG1, IgG3 and IgA antibodies against gp36 and C2V3C3. Lack of C2V3C3-specific IgG response in two patients was associated with a major antigenic change in the V3 region. In longitudinal analysis, there was a significant inverse association between the C2V3C3-specific IgG antibody response and the number of CD4 T cells. CONCLUSION: HIV-2 promotes an early, strong and broad gp36 and C2V3C3-specific IgG and IgA response. Increase in the IgG response against the envelope C2V3C3 region is associated with increased loss of CD4 T cells in chronically infected patients. These results provide further support for the immune protective role of the C2V3C3 envelope region during HIV-2 infection and have direct implications for HIV-2 diagnosis, clinical management and pathogenesis.

[Kikuchi-Fujimoto disease]. / Doença de Kikuchi-Fujimoto.

Kikuchi and Fujimoto's disease, also known as histiocytic necrotizing lymphadenopathy, is a rare and benign disorder of the lymph nodes of young adults. The etiology of this disease is unknown, an autoimmune mechanism has been suggested, although some cases of association with several viruses has been described. We report a pediatric case of Kikuchi and Fujimoto's disease in a 14 years old girl with persistent fever, enlarged cervical lymph node and weight loss. A diagnosis of Kikuchi and Fujimoto's disease was made by cervical lymph node histology. We present a case of Kikuchi and Fujimoto disease that benefited significantly from steroids.

Clinical and laboratory effects of hydroxyurea in children and adolescents with sickle cell anemia: a Portuguese hospital study.

Our aim was to assess the efficacy and safety of hydroxyurea (HU) in children with severe forms of sickle cell anemia followed in a Portuguese hospital. We carried out an open-label uncontrolled prospective study, which included children with severe forms of sickle cell anemia. Hydroxyurea was started at 15 mg/kg/day and increased to a maximum dose of 25 mg/kg/day. Patients were monitored to assess compliance, clinical and hematological response and toxicity. Nine children and adolescents, five girls and four boys, with a median age of 13 years (range 8 to 16) were enrolled in the study during a period of 24 months. All patients completed at least 15 months of therapy. Hb F was significantly increased, from a mean of 7.0 +/- 3.9% to 13.7 +/- 5.3% (p = 0.028). Clinically, all patients responded significantly with a reduction of 80% in the number of vaso-occlusive crises (VOC), 69% in hospital admissions, 76% in hospitalization days and 67% in transfusion requirements, without significant toxicity. We concluded that, in our population, HU proved to be effective in increasing Hb F levels, and in decreasing hospitalizations for VOC and transfusion requirements with no major side effects. Long-term clinical follow-up is important to certify benefit maintenance.

Evaluation of the clinical sensitivities of three viral load assays with plasma samples from a pediatric population predominantly infected with human immunodeficiency virus type 1 subtype G and BG recombinant forms.

The viral load assays AMPLICOR HIV-1 Monitor Test 1.5, Nuclisens HIV-1 QT, and Quantiplex HIV RNA 3.0 (bDNA) were evaluated for their abilities to quantify human immunodeficiency virus type 1 (HIV-1) RNA in 64 plasma samples from 21 children infected in Portugal. The children were infected with HIV-1 subtypes A1, B, F1, G, and BG recombinant virus. AMPLICOR v1.5 and Quantiplex v3.0 detected all samples, and there was a good correlation of results between the two kits. Thirty-eight specimens containing HIV-1 subtype B, G, or recombinant BG, could not be detected by Nuclisens HIV-1 QT. We also evaluated the new Retina HIV-1 assay on 21 samples that were HIV-1 positive; Retina HIV-1 failed to detect 5 of 11 subtype G specimens. AMPLICOR v1.5 and Quantiplex v3.0 assays may be used for HIV-1 RNA quantification in Portugal, whereas an improvement in sensitivity for subtype G and recombinant BG is required for Nuclisens HIV-1 QT and Retina HIV-1.