Smartphone-based diagnostic for HIV self-testing

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SUMMARY ABSTRACT The 90-90-90 Target endorsed by UNAIDS, proposes diagnosing 90% of people infected with HIV worldwide, engaging 90% of them on effective antiretroviral treatment, and ensuring that 90% of those treated achieve sustained viral load suppression by 2020. The United States is woefully unprepared to reach this target; only 30% of HIV infected individuals in the U.S. currently achieve viral load suppression. Clearly, a paradigm shift in viral load testing will be required to accomplish this goal. This proposal aims to create a quantitative, handheld, viral load self-test that can be used by patients themselves to support their management of this chronic condition and that delivers relevant clinical insights to remote healthcare providers. Building on our preliminary work, the objective of the R61 phase is to combine isothermal loop- mediated nucleic acid amplification (LAMP) with a highly sensitive and label-free readout method called particle diffusometry for quantification of HIV viral load in a hand held platform with minimal process steps. Specific milestones include: 1) optimization of LAMP assays to ensure the lowest possible limit of detection, 2) optimization of a microfluidic test chip for minimal sample prep, 3) algorithm development and testing to obtain real-time viral detection. Assessment of usability and stakeholder needs with our partners at Moi University (Moi) in Eldoret, Kenya, and Indiana University School of Medicine (IUSM) in Indianapolis, Indiana will ensure that the handheld platform and HIV test will be readily adopted by stakeholders. At the conclusion of the R61 phase we will have a platform that is ready for implementation testing. The objective of the R33 phase is to develop a proof-of-concept device that is validated in small manufacturing runs and fully assessed against clinical performance metrics in plasma and whole blood. The handheld platform and test chips will be evaluated for process control reproducibility and an initial pilot clinical study will be performed with banked or prospectively collected samples from HIV patients at IUSM and Moy University. The outcome of this R33 Phase will be a highly characterized, sensitive, quantitative handheld HIV viral load detection platform that performs robustly with real clinical samples and is ready for scale up. Completion of these objectives will position us for FDA pre-submission and regulatory approval, rapid scale up, and implementation of a highly accurate HIV viral load self-test in the U.S. and East Africa. By enabling patients to monitor their HIV viral load while remaining connected to healthcare provider support, we will help to reduce barriers to treatment compliance and ultimately increase the number of patients with sustained viral load suppression as called for by the UNAIDS 90-90-90 targets.