HIV is the cause of a chronic, incurable infection in 37 million people worldwide in 2014. This thesis investigates how the immune system detects HIV and how in turn HIV avoids detection by the immune system. The understanding of the viral evasion mechanisms that prevent immune detection (“Hide and Seek”) is important to successfully develop future vaccines and cure strategies for HIV. Primate lentiviruses belong to the retrovirus family and include the human immunodeficiency viruses (HIV-1 and HIV-2) and simian immunodeficiency viruses (SIV). HIV infects cells of the immune system, including subsets of T cells and dendritic cells (DC). Upon cell entry, the detection of the virus by cellular pattern recognition receptors triggers an intracellular cascade of innate antiviral defense mechanisms. In DCs, these mechanisms include the secretion of interferon α and the induction of cellular restriction factors, among these members of the APOBEC3 family that inhibit viral replication. As demonstrated in Paper III, low doses of interferon α protected DCs from HIV-1 infection and limited viral spread from DCs to T cells by inducing an increase in APOBEC3G, F and A expression. DCs are professional antigen presenting cells that present antigen to cells of the innate and adaptive immune system. Invariant natural killer T cells (iNKT) cells are innate T cells that recognize endogenous and exogenous lipid antigens presented by CD1d. Activated iNKT cells regulate the immune response by producing cytokines that recruit and activate innate and adaptive immune cells. Previous studies have shown that the HIV-1 accessory proteins Vpu and Nef interfere with CD1d cell surface expression in infected DCs, thus inhibiting the effective activation of iNKT cells. The results of Paper II demonstrated that infected DCs respond to HIV-1 infection by increasing CD1d surface levels and enhanced presentation of the endogenous lipid GlcCer. This enabled iNKT cell activation by HIV-infected DCs. However, HIV-1 counteracts iNKT cell activation by ...