In Project 1 we propose to identify and recruit 30 persons per year with acute (within < 30 days) HIV-1 infection and 60 persons per year with recent (within 31-90 days) HIV-1 infection into a series of therapeutic clinical trials that will provide potent antiretroviral therapies directed at suppressing HIV-1 replication to levels below the limit of detection with ultrasensitive assays. These trials will serve as the background in which to conduct intensive immunologic and virologic investigation as outlined in Projects 2-5 of this Program Project, and to evaluate the longer-term immunologic, virologic, and clinical outcomes of potent therapy administered in the setting of early HIV-1 infection. A collaborative infrastructure of clinical sites has been established to identify and recruit subjects into the proposed clinical trials. This infrastructure is comprised of two sites in the U.S.: 1) the University of Colorado Health Sciences Center (UCHSC)Adult AIDS Clinical Trials Unit (AACTU) and the Denver Public Health and Hospitals (DPH) Unit, both in Denver; 2) the AIDS Research Consortium of Atlanta (ARCA) in Atlanta, Georgia; and two sites in resource-limited settings outside the U.S.: 3) Hospital Universitario Prof. Edgard Santos - Universidade Federal da Bahia (HUPES-UFBA) and the Center for Research and Education on AIDS (CREAIDS) in Salvador, Bahia, Brazil, and 4) University of Zimbabwe School of Medicine in Harare, Zimbabwe. Investigator-initiated clinical trials of potent antiretroviral therapies will initially focus on initiation of potent, well-tolerated, and convenient regimens that will facilitate complete and durable suppression of HIV-1 replication in plasma. Subsets of subjects who remain fully suppressed in these initial studies after 26-52 weeks of potent therapies will then be recruited to participate in studies of therapeutic immunization, using vaccines selected on the basis of strong immune responses, in particular CTL responses, observed in Phase I studies underway by investigators of this Program Project. Immunization strategies will be coupled with potent antiretroviral therapies and will then be followed by planned periods of treatment interruption to evaluate the ability of these strategies to augment control of viral replication in the absence of antiretroviral therapy. Data from this research will also contribute to long-term follow-up studies of the NIH/NIAID Acute Infection and Early Disease Research Program.