HIV-CRISP for Same Visit Test and Switch Viral Load and Resistance Testing

About This Grant

Project Summary HIV drug resistance represents a growing and underappreciated threat to the U.S. HIV response. Although more than 1.2 million people are living with HIV in the U.S., only about 60% achieve durable viral suppression, and resistance is a major contributor to treatment failure and regimen switching. Current resistance testing relies on centralized, PCR and sequencing-based platforms that are expensive, slow, and available only at specialty laboratories, requiring multiple clinic visits and highly trained personnel. As a result, same- day, resistance-informed treatment decisions are rarely possible, even in major U.S. cities, and are essentially inaccessible in rural areas, mobile care units, and safety-net clinics serving areas where the epidemic is increasingly concentrated. These gaps most severely affect communities already carrying the highest burden of HIV incidence and treatment failure in the U.S. Without affordable, accessible, point-of-care (POC) resistance testing, the durability of ART and the success of the national Ending the HIV Epidemic initiative are at risk. Our project aims to develop HIV-CRISP to addresses this critical gap by developing a cost-effective, same- visit “test-and-switch” POC device that integrates CRISPR-based nucleic acid detection with a bioinspired microfluidic chip (CamoChip). This fully automated platform enables simultaneous detection of HIV viral load and drug resistance to four major ART classes (NRTIs, NNRTIs, INSTIs, and PIs) during a single clinic visit. By empowering providers to make immediate, resistance-informed treatment decisions, HIV-CRISP reduces delays in therapy initiation or modification and minimizes the risk of treatment failure. The project is structured around three specific aims: Specific Aim 1: optimize a PAMmer-assisted CRISPR system for accurate detection and profiling of HIV drug resistance mutations; Specific Aim 2: enhance CamoChip readout technology for rapid, multiplex POC testing; and Specific Aim 3: integrate these components into a user-informed POC device and validate its performance against standard methods with clinical samples. Each aim not only drives independent scientific advances but also converges on the development of a transformative POC diagnostic. HIV-CRISP represents an innovation in HIV diagnostics with broad public health significance. This platform supports wide access to high-quality HIV care in under-resourced settings across the U.S. and globally, while also providing a foundation adaptable to other infectious diseases and health conditions.