The overall objectives of the proposed research are to elucidate the roles of Human Immunodeficiency virus and the Herpes family of viruses in the genesis of oral disease in HIV+infected hemophiliac children.
The specific aims of the proposal are: 1.) To adapt newly developed polymerase chain reaction (PCR) methodologies to the detection of virus shedding and infections in the oral cavity; 2.)To measure longitudinally HIV (replication competent and defective genomes) and Herpesvirus shedding and infections in the oral cavity of HIV+ and HIV- hemophiliac children using PCR techniques; 3.)To measure longitudinally the development of oral disease in the HIV+ and HIV- hemophiliac children by clinical examination; and 4.)To correlate the patterns of virus shedding and infections in the oral cavities of these children with the extent to which they are immunosuppressed, and with the development of specific oral diseases. The first specific aim will be accomplished by determining specific PCR reaction conditions and oligonucleotide primers that can be used to reliably amplify portions of the HIV and Herpes virus genomes present in DNA mixtures prepared from oral mouth rinses. The second specific aims will be achieved by applying the adapted PCR techniques to measure the extent to which infection and shedding of these viruses occurs in the oral cavities of the HIV+ and HIV- children during the 5 year course of these studies. The third specific aim will be accomplished by clinical determination of the oral health of these children at 5 month intervals during regular dental care. The fourth specific aim will be effected by correlating the data obtained with respect to oral virus shedding with measures of immune function and of oral health. These studies will generate the first longitudinal data for any population with respect to oral infection and shedding of all 7 human Herpes viruses using the extremely sensitive PCR techniques. The experiments will also generate a permanent record of the genesis and temporal stability of defective HIV viruses in a unique and not to be replenished population of children. This data may provide us with new insights into the immunosuppressive effects of specific HIV virus species and into the processes of Herpes virus induced oral pathologies. The studies will also continuously generate extremely detailed profiles of the enrolled children with respect to HIV and Herpes virus viremia that may be of direct value to the children and their physicians in monitoring their treatments.
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