The development of highly selective anticancer drugs that can discriminate between tumor cells and normal cells is the most important goal of current oncology research. The potential use of ligand-conjugated liposome-encapsulated drugs to target tumor cells and vasculature is very promising. Peptides that specifically bind to tumor targets can be coupled to the PEG terminus of sterically stabilized liposomes and subsequently precisely deliver chemotherapeutic agents to tumor cells or blood vessels. Peptide-mediated liposomes that target vasculature are a new generation of chemotherapy delivery systems with superior pharmacokinetics, controlled biodistribution, efficacy, and safety profiles. Elevation of Intact and Proteolytic Fragments of Acute Phase Proteins Constitutes the Earliest Systemic Antiviral Response in HIV-1 Infection The earliest immune responses activated in acute human immunodeficiency virus type 1 infection (AHI) exert a critical influence on subsequent virus spread or containment. During this time frame, components of the innate immune system such as macrophages and DCs, NK cells, β-defensins, complement and other anti-microbial factors, which have all been implicated in modulating HIV infection, may play particularly important roles. A proteomics-based screen was performed on a cohort from whom samples were available at time points prior to the earliest positive HIV detection. The ability of selected factors found to be elevated in the plasma during AHI to inhibit HIV-1 replication was analyzed using in vitro PBMC and DC infection models. Analysis of unique plasma donor panels spanning the eclipse and viral expansion phases revealed very early alterations in plasma proteins in AHI. Induction of acute phase protein serum amyloid A (A-SAA) occurred as early as 5–7 days prior to the first detection of plasma viral RNA, considerably prior to any elevation in systemic cytokine levels. Furthermore, a proteolytic fragment of alpha–1-antitrypsin (AAT), termed virus inhibitory peptide (VIRIP), was observed in plasma coincident with viremia. Both A-SAA and VIRIP have anti-viral activity in vitro and quantitation of their plasma levels indicated that circulating concentrations are likely to be within the range of their inhibitory activity. Our results provide evidence for a first wave of host anti-viral defense occurring in the eclipse phase of AHI prior to systemic activation of other immune responses. Insights gained into the mechanism of action of acute-phase reactants and other innate molecules against HIV and how they are induced could be exploited for the future development of more efficient prophylactic vaccine strategies. Although human immunodeficiency virus type 1 (HIV-1) induces a chronic infection ultimately culminating in the development of an acquired immunodeficiency syndrome, it is now recognized that critical damage to the host immune system is mediated during the acute phase of infection, when an exponential burst of viral replication takes place, associated with massive depletion of the central memory CD4 + T cell pool [1, 2] . Prophylactic strategies to combat HIV-1 infection thus need to modulate events in the earliest stages of infection leading up to and impacting on this acute viral burst -which prompts an urgent need to understand the virus-host interactions occurring during this ''window of opportunity''.