ABSTRACT The global HIV epidemic has profoundly impacted public health. HIV affects tens of millions of people worldwide, including over a million in the United States. While antiretroviral therapy (ART) allows individuals to suppress the virus and live normal lives, it is expensive, has side effects, and requires lifelong adherence. The need for a cure has led to the development of new therapeutic strategies. However, large-scale clinical testing is hindered by the low virus concentration in blood during ART and the lack of sensitive, cost-effective point-of-care (POC) tests for measuring small changes in viral load on a regular basis. There is an urgent need for a test that can quantitatively differentiate between individuals maintaining suppression after stopping ART and those experiencing viral rebound, so as to enable quick detection of rebounds and re-initiation of therapy. The goal of the project proposed here is to develop a POC-compatible quantitative test for accurate viral load monitoring that could support large-scale clinical trials of HIV cure strategies. Our approach uses digital loop- mediated isothermal amplification (dLAMP), which has been shown to provide precise viral load measurements on raw, unpurified samples. Such capabilities make dLAMP well suited for POC settings. Our collaborative network, composed of engineers, clinical experts, and researchers, will collaborate to create a groundbreaking diagnostic platform that addresses major limitations in HIV testing and accelerates progress towards an HIV cure. By leveraging the combined expertise and resources, we will develop a cost-effective microfluidic consumable test and reusable assay instrument. Ultimately, this tool will improve HIV management and eradication efforts. This project will be led by Fluid Discovery, whose mission is to commercialize point-of-care pathogen diagnostics based on digital LAMP technology. Through the support of Professor Adam Abate, who will also guide development of the technology, the company will collaborate with UCSF and the Gladstone Institute investigators. These include Dr. Charles Chiu (Director of the CLIA-certified Pathogen Testing Lab) and Dr. Melania Ott (Director of Virology at the Gladstone Institute), who will support the validation process. Additionally, the project will involve collaborations with Dr. Steven Deeks (Director of the Delaney AIDS Research Enterprise to Find a Cure, which oversees and invests in clinical trials of new therapies) and Dr. Michael Busch (Director at Vitalant Research Institute). The project will utilize authentic biospecimens from the SCOPE and RAVEN trials. Working with Fluid Discovery, this team will apply the technology to demonstrate its utility for HIV load monitoring.

NARRATIVE This project will develop a point-of-care (POC) test for accurate HIV viral load monitoring, addressing a major unmet need in large-scale clinical trials of HIV cure strategies and general point-of-care quantitative diagnostics. By leveraging digital LAMP technology and an interdisciplinary team of experts, this grant will create a groundbreaking diagnostic platform to accelerate progress towards an HIV cure.