Predictors of Immunologic Long-term Non-Progression in Children with HIV

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DESCRIPTION (provided by applicant): This proposed study will evaluate the activation and other surface markers of T and B lymphocytes, natural killer cells and monocytes in children who are enrolled in the PREDICT Study (CIPRA 1U19AI53741-01A1, An open label, randomized study to compare antiretroviral therapy initiation (ART) when CD4+ is between 15- 24% to ART initiation when CD4+ falls below 15% in children with HIV infection and moderate immune suppression). Measurements of the following markers will be performed by flow cytometry in 300 children at baseline and yearly for 3 years: CDS, CD4, CDS, CD19, CD16/56, CD4/45RA/62L, CD8/45RA/62L, CD4/DR/38, CD8/DR/38, CD3/4/45RO, CD3/4-/45RO, CD14/16/DR and CD14/16/163 The primary objectives and hypotheses are to 1) Determine if children randomized to deferred antiretroviral therapy who survive at 8 years and longer without CD4 falling below 15% display an early unique expression of activation or other markers on their peripheral blood mononuclear cells. Hypothesis: Low or high values of activated and other T cell subset distributions such as low activated cytotoxic T cells (CD8+DR+CD38+) and high naive T cells (CD45+RA+62L+) predicts those children who will not need antiretroviral therapy to keep their CD4+ T cell percentages above 15%. 2) Determine if children with neurodevelopment impairment display an early unique expression of activation or other markers on their peripheral blood mononuclear cells Hypothesis: High activated cytotoxic T cells (CD8+DR+CD38+), activated monocytes (CD14+CD16+DR+) and perivascular macrophages (CD14+CD16+CD163+) predict those children with neurodevelopment impairment. This study complements two collaborative research funded by NIH including the NIAID-funded CIPRA grant for the main when to start study and supplemental grants for the neurodevelopment sub-study from both NICHD and NIMH. This study is relevant to public health because it will provide knowledge on whether certain cells in the blood can predict children who will have worsening of HIV disease or neurodevelopment. This will be important in deciding when to treat children with antiretroviral therapy.