INTERLEUKIN-2 (IL-2) THERAPY WITH ANTIRETROVIRAL THERAPY

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. 1. To determine the extent of suppression of early HIV infection achieved by highly active antiretroviral therapy (HAART) compared to combined HAART and immunotherapy with ultralow-dose interleukin-2 (IL-2). Hypotheses: a. Early HAART will eliminate the unintegrated proviral reservoir 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 progression, 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 of HAART alone vs. combined HAART plus ultralow-dose IL-2 on immune system recovery. Hypotheses: a. Acute HIV infection leads to depletion of memory cells 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 seen 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. METHODOLOGY: This is a prospective, observational, and interventional study of people who have been acutely infected with HIV (< 2 month) or recently (2 - 12 months). It is anticipated that 30-50 recent HIV-1 seroconverters per year will be recruited for the study, including 10-15 who have been acutely infected, ranging in age from > 13 years, approximately 70% male, 25% non-Hispanic whites and 75% African-American, in Baltimore, Maryland. Participants may elect to receive or not receive highly active antiretroviral therapy (HAART). Participants who do not receive HAART will serve as a comparison group for those who do receive HAART. The effect of HAART on immune system integrity will be studied, as well as the effect of HAART on the recovery of immune system integrity as a function of the duration of infection at the time when HAART is started, using a variety of laboratory techniques including flow cytometry, lymphocyte proliferative assays, viral isolation, and quantitation of viral reservoirs.