PROJECT SUMMARY/ABSTRACT The development of a low cost, point of care diagnostic device or kit in a ?rapid test? or ?self test? format would be highly beneficial to the global effort to diagnose, manage and treat HIV. We are proposing to evaluate the scientific finding that HIV proteins are present in urine associated with extracellular vesicles, also commonly referred to as exosomes. The development of one or more diagnostic tests designed to detect and measure extracellular vesicle-associated HIV proteins in urine is the ultimate goal. Because viral proteins are detected, and not HIV-specific antibodies, this type of diagnostic assay will be useful for detecting infection, including during the acute phase prior to the development of antibodies, monitoring disease status under antiretroviral therapy and discriminating between infection and vaccination. Products can be developed and ultimately produced using technologies and materials that are standard to the industry and assay formats can be produced as standard EIA kits or as single patient lateral flow devices, similar to home pregnancy tests. Preliminary data are limited but they clearly demonstrate that HIV proteins can be readily detected in the urine of HIV patients. The findings are novel, patent protected in all major potential markets and manufacturing countries. The intellectual property is available to NewMark Diagnostics LLC through an exclusive option license agreement. For the proposed research we will critically evaluate the working hypothesis that viral load in HIV+ patients, measured in plasma, is positively correlated with our ability to detect extracellular vesicle-associated HIV proteins in urine. To accomplish this, we will first determine the plasma viral load using blood samples provided by HIV+ volunteers using an FDA-approved PCR-based test. A research level extracellular vesicle capture EIA will then be used to measure the concentration of multiple HIV proteins in urine samples obtained from the same HIV+ volunteers. We will determine preliminary ?assay cut-off values? as an estimate of the EIA sensitivity using multiple statistical analyses including Receiver Operator Characteristic Curves. The evaluation of the basic scientific discovery in this manner is a crucial first step towards the potential future development of a new type of rapid diagnostic test for HIV that can be used globally and in numerous settings.

R41MH122980

2019-09-12

2021-09-11