HIV remains a dangerous and prevalent disease globally contributing to millions of infections and deaths per year and tens of billions of dollars in healthcare costs. Pre-Exposure Prophylaxis (PrEP) is 99% effective at preventing HIV infection if taken daily, but its impact on reducing HIV burden is limited by poor adherence. PrEP is recommended by the Centers for Disease Control (CDC) in populations at a high risk of HIV infection, which include men who have sex with men, intravenous drug users, and people with a HIV positive partner. Similarly, antiretroviral therapy, used to treat HIV, can be effective and suppress viral load when following the dosing schedule. Due to poor adherence, not only are patients inappropriately treated, the chance of developing resistant strains is increased. Drug adherence monitoring is well known to improve drug compliance, but there are no commercial products for rapid long-term adherence monitoring of PrEP and ART. Hence, there is a critical unmet need for a tool that will allow physicians to monitor adherence to PrEP and ART in patients. To be acceptable to patients and feasible in the physician workflow, this adherence test needs to be minimally-invasive, painless, inexpensive, easy to administer and provide rapid, accurate results. Of note, an existing SBIR grant is funding the development at UrSure of a POC test for the metabolite Tenofovir (TFV). The TFV test measures recent adherence (when was the most recent dose taken over the last 7 days) while this application proposes developing a test to measure Tenofovir Diphosphate which is a measure of long-term adherence (average number of doses taken over the last 6 weeks). The overall goal of this project is to develop a point-of-care (POC) test that will measure long-term adherence with PrEP and ART. The POC test will be based on existing literature that measures intracellular TFV-DP using a laboratory-based mass spectrometry. The POC assay will be faster (minutes to get a result) and can be used during a clinic visit to measure PrEP and ART adherence and, if appropriate, counsel patients on how to improve their compliance. There is also evidence that TFV-DP level is a reliable indicator of viral suppression, and prediction of future viremia or seroconversion, offering provider valuable information and improving clinical efficacy. The aims of this project are to: 1) optimize and screen for the top 3 monoclonal antibodies, 3) establish basic performance and architecture of an LFIA test strip, 4) optimize the performance of the POC device and produce a verification lot, and 5) Scale-up assay procedures, and produce pilot lots to ensure lot-to-lot reproducibility. The final deliverables of this Direct to Phase II project will be mAbs with high sensitivity/specificity, a validated Lateral Flow Immunoassay TFV-DP blood POC test for long-term tenofovir adherence, and 3 pilot lots to ensure lot-to-lot reproducibility. Successful completion of this project will leave us in a position to start FDA validation studies and put together our pre-market 501k for FDA approval.
Public Health Relevance Statement: PROJECT NARRATIVE Tenofovir-based regimens can prevent new HIV infections and treat HIV effectively, but eligible people at high risk for HIV exposure and HIV-positive patients have 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 blood test to monitor long-term tenofovir use. Test results will be used during clinic visits to encourage and increase drug adherence in order to prevent new HIV infections and treat HIV-positive patients more effectively.
Project Terms: Address; Adherence; Affinity; AIDS prevention; antiretroviral therapy; Architecture; base; Bedside Testings; Biological Assay; Blood; Blood specimen; Blood Tests; Centers for Disease Control and Prevention (U.S.); Cessation of life; Clinic Visits; Clinical; clinical efficacy; compliance behavior; Contracts; cost; Counseling; cross reactivity; Dangerousness; Data; Development; Devices; Diagnostic tests; Diphosphates; Disease; Documentation; Dose; Ensure; Enzyme-Linked Immunosorbent Assay; Evaluation; Exposure to; Funding; Future; Generations; Goals; Grant; Health; Health Benefit; Health Care Costs; high risk; HIV; HIV Infections; HIV Seropositivity; Immunoassay; immunogenic; improved; Individual; Industry Standard; Infection; infection risk; insight; instrumentation; International; intravenous drug user; Laboratories; Lateral; Liquid Chromatography; Literature; Manufacturer Name; Mass Spectrum Analysis; Measures; medication compliance; men who have sex with men; minimally invasive; Monitor; Monoclonal Antibodies; novel; Outcome; Painless; Patients; Performance; Pharmaceutical Preparations; Phase; Physicians; pilot lot production; point of care; Population; Positioning Attribute; pre-exposure prophylaxis; prevent; Prevention; Procedures; Production; programs; Prophylactic treatment; prototype; Provider; Public Health; Quality Control; Regimen; Reproducibility; Research; resistant strain; Resources; Risk; scale up; Schedule; Sensitivity and Specificity; seroconversion; Small Business Innovation Research Grant; Specificity; success; tandem mass spectrometry; Technology; Technology Transfer; Tenofovir; Test Result; Testing; therapy adherence; Time; tool; Treatment Protocols; Urine; user-friendly; validation studies; Viral; Viral Load result; Viremia; Visit; Whole Blood
