Abstract
To investigate the immunological and virological factors that may lead to different patterns of disease progression characteristic of HIV-1-infected children, two HIV-1-infected siblings, a slow and a fast progressor, were followed prospectively before the onset of highly active antiretroviral therapy. Viral coreceptor usage, including the use of CCR5/CXCR4 chimeric receptors, macrophage tropism, and sensitivity to the CC-chemokine RANTES, has been studied. An autologous and heterologous neutralizing antibody response has been documented using peripheral blood mononuclear cells- and GHOST(3) cell line-based assays. Viral evolution was investigated by env C2-V3 region sequence analysis. Although both siblings were infected with HIV-1 of the R5 phenotype, their viruses showed important biological differences. In the fast progressor there was a higher RANTES sensitivity of the early virus, an increased trend to change the mode of CCR5 receptor use, and a larger genetic evolution. Both children developed an autologous neutralizing antibody response starting from the second year with evidence of the continuous emergence of resistant variants. A marked viral genetic and phenotypic evolution was documented in the fast progressor sibling, which is accompanied by a high viral RANTES sensitivity and persistent neutralizing antibodies.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Adolescent
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Antiretroviral Therapy, Highly Active
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CD4 Lymphocyte Count
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Chemokine CCL5 / metabolism*
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Child
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Disease Progression
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Evolution, Molecular
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Genotype
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HIV Antibodies / blood*
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HIV Infections / drug therapy
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HIV Infections / physiopathology*
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HIV Infections / virology*
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HIV-1 / genetics
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HIV-1 / immunology
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HIV-1 / isolation & purification
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HIV-1 / physiology*
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Humans
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Molecular Sequence Data
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Neutralization Tests
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Phenotype
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Receptors, Chemokine / metabolism
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Receptors, HIV / metabolism*
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Siblings
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Viral Load
Substances
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Chemokine CCL5
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HIV Antibodies
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Receptors, Chemokine
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Receptors, HIV
Associated data
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GENBANK/EF657890
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GENBANK/EF657891
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GENBANK/EF657892
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GENBANK/EF657893
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GENBANK/EF657894
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