The overall goal of this SBIR project is to develop a point-of-care (POC) plasma test to measure adherence to dolutegravir (DTG), a drug that virally suppresses HIV if taken adherently (over 95% of daily doses taken). HIV is a dangerous and prevalent disease globally, contributing to millions of infections and deaths per year and billions of dollars in healthcare costs. HIV can be virally suppressed and those afflicted can lead relatively normal lives if the prescribed medications are taken daily, but adherence with the recommended dosing regimen is relatively poor. Monitoring of drug adherence is well known to improve drug compliance, but there are no POC commercial products for adherence monitoring of Dolutegravir. Hence, there is a critical unmet need for a rapid noninvasive inexpensive POC test to monitor recent DTG adherence. UrSure Inc. is an adherence company that develops tests to measure adherence with medication regimens, and has previously established an adherence test for the antiretroviral drug Tenofovir, which is taken as Pre- Exposure Prophylaxis (PrEP and Antiretroviral Therapy (ART). We developed and validated a semi- quantitative liquid chromatography-tandem mass spectrometry (LCMS/MS) urine assay with high sensitivity/ specificity for tenofovir (TFV, one of the component drugs of PrEP) in urine. The objectives of this Phase I project are to produce a novel DTG analog, use it to produce a novel mAb able to detect the drug, and validate mAb stability on nitrocellulose for LFIA development. UrSure has relationships in place with LFIA experts and organizations with deep experience in LFIA assay development, validation and assay kit production.
The Specific Aims are to: 1) To synthesize and characterize one DTG analog. This derivative will be conjugated to be used as immunogens for antibody production and conjugated to BSA to be used for ELISA development; 2) Develop and select 5 monoclonal antibody (mAb) candidates able to detect DTG based on ELISA performance using plasma samples from healthy patient samples spiked with varying concentrations of metabolite; 3) Demonstrate proof of principle by showing that the mAb is stable on nitrocellulose in the presence of metabolite-spiked buffer samples and we can generate a curve that spans the critical clinical cutoff of 200 ng/mL. The final deliverables of this Phase I project will be the novel DTG analog (immunogen), novel anti-DTG mouse mAb, and validation that the mAB is stable for future LFIA development. Successful completion of this Phase I project will result in the materials needed to produce the LFIA for the UrSure POC Dolutegravir adherence test in an anticipated future Phase II project.
Dolutegravir (DTG) in combination with other antiviral medications is used in the treatment of HIV. This course of treatment is highly effective; however, the regimen consists of daily pill ingestion, and patients struggle with adherence, which, combined with the high cost of HIV, makes this disease costly to payors around the world. Successful completion of this research program will result in a rapid point-of-care plasma test to monitor Dolutegravir use, which will be used during clinic visits to encourage and increase drug adherence. Increased adherence to DTG will lead to better viral load suppression for HIV infected patients, saving lives and costs both through treatment and the prevention of future infections and development of resistance.
