Several fundamental virologic issues represent important hurdles for the development of effective prevention and treatment strategies for pediatric HIV infection. Questions include: (1) Are certain viral phenotypes or genotypes more likely to be transmitted from an infected mother to her infant? (2) Does viral load during pregnancy correlate with maternal-fetal transmission? (3) What are the optimal methods to quantitate virologic load in infants and children to monitor disease progression and antiretroviral therapy? (4) What is the role of antiretroviral resistance in drug failure and disease progression? The research proposed will develop dependable, standardized and biologically meaningful assays of virus replication to assess disease risk and effective interventions.
The Specific Aims of the research are: (1) To identify and validate phenotypic and genotypic markers correlating with disease progression and antiviral resistance. For these studies maternal-infant transmission will be correlated with phenotypic properties including syncytia induction, growth rate and cell tropism. The genotypes associated with these phenotypic variations will also be correlated with HIV transmission. (2) To quantitate HIV virus load by optimization of assays of infectivity and viral DNA and RNA. These methods will be applied for quantitation of specific components of the peripheral blood including plasma, CD4+ lymphocytes, monocyte/macrophages and dendritic cells, and correlated with the development of viral resistance. (3) Develop improved methodologies to screen for antiretroviral resistance by phenotypic and genotypic assays, and apply these assays to children receiving treatment as part of ACTG protocols. The research proposed will identify virologic markers for monitoring HIV infection of pregnant women and children, and will provide new approaches to treatment and prevention of HIV infection.
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