HIV is a virus that establishes latency, and has developed multiple strategies to inhibit death by apoptosis of infected cellapoptosis of infected cells under a variety of circumstances.  The expression of select HIV proteins, such as Vpr, Nef and Tat, alter the transcriptional profile of some cell types to produce endogenous apoptosis inhibitory proteins. For example, in vitro, Tat induces cellular FLICE inhibitory protein (cFLIP) expression in T cells. Vpr increases Bcl2 and decreases Bax in the Jurkat T cell line, and there is increased X-linked inhibitor of apoptosis (XIAP) expression in latently infected cell line models. Both Tat-treated monocytes and primary CD4 T cells from HIV-infected patients develop tumor necrosis factor (TNF)-related apoptosis inhibitory protein (TRAIL) resistance. We have identified a potential inhibitor of this pathway, which in theory could lead to preferential death of HIV-infected CD4+ T cells. This inhibitor (TRAIL splice variant, or TRAIL) which preferentially binds TRAIL receptor (R)2 and prevents pro-apoptotic TRAIL from signaling.