Abstract We propose to develop an advanced rapid point of care diagnostic for HIV. This approach will leverage a novel D4 diagnostic assay platform: The D4 is so named because of the chain of events that occur upon addition of blood: (1) Dispense blood onto chip; (2) Dissolution of “soluble” detection reagent spots (3) Diffusion of coated virion across a surface and binding to specific capture Ab spots; (4) Detection of binding with fluorescence imaging. We will enhance HIV virion capture using a lectin, Griffithsin, which can bind to the glycan shield of HIV virions spikes and induce exposure of CD4 binding sites which can be captured by antibodies. Individual virions can be captured, labelled and imaged using next generation cell phone based microscopy. This diagnostic test enables not only rapid “window independent” diagnosis independent of patient antibodies, but also potentially for routine viral load monitoring.