The purpose of this Funding Opportunity Announcement (FOA) is to encourage Small Business Innovation Research (SBIR) grant applications from Small Business Concerns (SBCs) that focus on the development of sensitive and quantitative assays, methods, or imaging techniques, including the development or novel applications of imaging agents or probes that can be applied to the measurement of residual HIV reservoirs in HIV-positive individuals, who are on effective antiretroviral therapy. Such technologies are required to have commercial potential. NIH is especially interested in next-generation tools and methods that can quantitate replication-competent virus or integrated provirus or distinguish HIV-infected cells in situ. The new tools proposed in the application should provide substantially increased sensitivity, reproducibility, spatiotemporal resolution, and/or scalability, as compared to existing methodologies and be able to characterize the replicative capacity of HIV-infected cells and tissues. These novel technologies will aid in obtaining a fine-grained and dynamic view of the persistent HIV reservoir. In addition, NIH is interested in quantitative methods and analytical tools to assess the viral load, either replication competent or integrated provirus, in a reproducible manner so as to monitor the dynamic changes in persistent infection.