The goal of this Phase II SBIR project is to develop a point-of-care (POC) test to measure patient adherence with Pre-exposure Prophylaxis (PrEP) as a prevention against HIV infection in people known to be at risk of HIV exposure. HIV contributes to millions of infections and deaths per year and tens of billions of dollars in healthcare costs around the world. PrEP is recommended by the Centers for Disease Control and World Health Organization in people at high risk for HIV exposure. It is 99% effective at preventing HIV infection if taken daily, but its impact on reducing HIV burden is limited by poor adherence. Monitoring actual drug use by patients improves drug adherence, but there is no commercial test for PrEP. The UrSure rapid TFV POC test will measure PrEP adherence based on the UrSure laboratory-based mass spectrometry urine test for tenofovir (TFV), which is a component of both PrEP and Truvada. The POC test will be noninvasive, painless, rapid (minutes to get a result) and inexpensive. It can be used during a clinic visit to measure PrEP adherence and, if appropriate, counsel patients on how to improve compliance. Since Truvada is a common first-line therapy for confirmed HIV infection, this test also will measure adherence in known HIV-positive patients who do not have access to frequent viral load testing. Phase I of this project demonstrated the feasibility of this approach. A novel TFV derivative was synthesized and used to produce polyclonal antibodies that are specific and sensitive for TFV. A prototype ELISA was developed and validated with urine samples confirmed as positive or negative for TFV, for use in evaluating the POC test. A urine sample bank with known TFV results was established. The objective of this Phase II project is to advance development of the UrSure TFV POC test toward commercialization.
The Aims are to: 1) produce up to three monoclonal antibodies with sensitivity and specificity >95% for TFV in urine; 2) use those monoclonal antibodies to develop a Lateral Flow Immunoassay (LFIA) strip; 3) integrate that strip with a self-contained assay cassette and optimize its performance; 4) verify the performance of the LFIA and prepare it for manufacture; and 5) transfer the LFIA prototype to a contract manufacturer and produce validation lots. UrSure has relationships in place with LFIA experts and organizations with deep experience in LFIA assay development, validation and assay kit production. The final deliverables of this Phase II project will be monoclonal antibodies sensitive and specific for TFV in urine, a locked prototype of a LFIA for rapid detection of TFV in urine, and a lot of 1,000 UrSure TFV POC tests with at least 85% sensitivity and specificity for urine samples positive and negative for TFV. Successful completion of this Phase II project will result in a prototype suitable for initiating the FDA regulatory process. A Class 2 de novo classification is expected and will support commercialization of the POC test.
Pre-exposure prophylaxis and HIV treatment with drugs such as tenofovir can prevent new HIV infections and end the HIV epidemic. However, eligible people at high risk for HIV exposure have a very low success rate in adhering to the recommended drug regimen. Successful completion of this research program will result in a rapid, non-invasive point-of-care urine test to monitor tenofovir use. Test results will be used during clinic visits to encourage and increase drug adherence in order to prevent new HIV infections.