IMMUNOLOGY AND EARLY DIAGNOSIS OF HIV-1 INFECTION IN THE NEONATE

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The current armamentarium of compounds available for the treatment of HIV-1 disease is dominated by chain terminators like zidovudine (ZDV) which have been shown to be potent inhibitors of de novo infection of susceptible cells in vitro, but with no demonstrable activity against chronically infected cells. Therefore, to maximize the therapeutic efficacy of these compounds, treatment should be initiated as soon as possible after infection and before the establishment of a large reservoir of infected cells. With most groups at risk for HIV-1 infection, this is not practical. However, infants born to HIV-1 seropositive mothers present a unique opportunity for early therapeutic intervention since their time of exposure is well defined (ie in utero or during birth). However, newborns also present a formidable obstacle to early diagnosis since serologic assessment of true antibody status is complicated by the presence of maternal antibody. Therefore, alternate strategies aimed at early diagnosis of HIV-1 infection in the newborn must be developed. The overall goal of this project is to combine currently available immunologic and virologic technologies into an assessment panel which will provide definitive evidence of HIV-1 infection at the earliest possible timepoints. Virologic determinations will be assessed by viral culture of fresh lymphocytes, direct p24 antigen capture of 'plasma or serum, and detection of viral DNA by the polymerase chain reaction. Serologic evaluations will include HIV-1 IgM Western blot and peptide specific antibody responses. HIV-1 specific cellular reactivity, changes in the lymphocyte subpopulations and blastogenic responses to various stimuli will be evaluated. The effects of HIV-1 infection on the production of various cytokines will also be assessed.