The following are the specific aims and hypotheses of the projects: 1. To determine the extent of suppression of early HIV infection achieved by antiviral chemotherapy compared to combined antiviral chemotherapy and immunotherapy with ultralow-dose interleukin-2 (IL-2). Hypotheses: a. Early antiretroviral therapy will eliminate the unintegrated proviral resevoir and slow the establishment of the integrated, potentially infectious latent reservoir HIV in PBMC and lymph nodes. b. IL-2 immunotherapy will augment and prolong HIV-specific CTL. c. The magnitude of viral load (plasma RNA, integrated DNA, and unintegrated DNA) correlates with the fitness (replicative capacity) and drug resistance of the early HIV isolate. d. Suppression of HIV replication, and disease prigression, will correlate with establishment of in vitro resistance of PBMC to endogenous and exogenous virus growth. 2. To evaluate the extent of immune system damage that occurs in early HIV infection, and the effect on antiviral combination chemotherapy alone vs. combined antiviral chemotherapy plus ultralow-dose IL-2 on immune system recovery. Hypotheses: a. Acute Hiv infection leads to depletion of memory cell and development of """"""""holes"""""""" in the T cell repertoire. b. IL-12 production is defective even in early HIV infection, and this defect is mediated by a complement-CD46 interaction similar to that seem in measles infection. c. IL-2 reduces the extent of damage and accelerates immune system recovery. 3. To establish a repository of specimens of plasma, serum, peripheral blood and lymph node mononuclear cells, and HIV-1 isolates that can be used for additional studies of HIV pathogenesis.
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