HIV is a major global epidemic that requires sophisticated clinical management. While there have been remarkable efforts to develop new strategies for detecting and treating HIV, it has been challenging to translate them into resource-limited settings. Significant research efforts have been recently devoted to developing point-of-care (POC) diagnostics that can monitor HIV viral load with high sensitivity by leveraging micro- and nano-scale technologies. These POC devices can be applied to monitoring antiretroviral therapy, early infant detection of HIV during mother-to-child transmission, and identification of latent HIV reservoirs. In this review, we discuss current challenges in HIV diagnosis and therapy in resource-limited settings and present emerging technologies that aim to solve these challenges using novel micro- and nanoscale solutions.