This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Pediatric HIV infection represents a health disparity. Prenatal and postnatal treatment have been remarkably effective in lowering the risk of vertical transmission in developed countries. Yet this mode of transmission remains an important health issue in many developing countries and among minority populations with limited access to high quality health care. The relative lack of studies of HIV/AIDS in children exacerbates this problem. Among vertically infected children, some progress rapidly (within four years) to AIDS, while others maintain control of the infection and do not develop AIDS for more than eight years. Many factors may account for this different clinical presentation, including genetic variation in the virus. In adult infection, deficiencies in viral nef and LTR sequences have been linked to several cases of long-term nonprogression. We will use an innovative and complementary approach of studying the viral sequences that account for rapid infection as compared to the normal or slower rate, to identify the viral elements responsible for development of AIDS in pediatric patients. We have four target sequences: tat exon 1, tat exon 2, nef, and LTR. These sequences will be compared in two groups of Puerto Rican HIV-1-infected children (Group 1 = HIV/AIDS;Group 2 = HIV/no AIDS). The same sequences will be compared longitudinally (for thirty months at six-month intervals) in each participant in this pilot study. Our hypothesis is that viral gene expression levels (determined by LTR and Tat) and viral sequences of Nef and Tat will comprise important determinants of disease progression rate in HIV infection. This successful completion of the specific aims of this pilot proposal will address our medium-term goal to generate data for publication and for use in design of a study involving a larger population of Puerto Rican children to more firmly establish the roles of these viral components in disease progression. This work will address our long-range goal of advancing our understanding of the mechanisms employed by the virus to propagate infection and cause disease. It is expected that such information will prove of clinical benefit as a prognostic factor in pediatric HIV infection. Further, it may result in the development of therapeutic alternatives to the current antiretroviral drugs. This is particularly important as resistance to antiretrovirals develops and in light of the lack of physical facilities and economic support for these expensive interventions in the developing world.
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