SBIR-STTR Award

According to recent estimates ~33 million people are living with HIV, with 96% residing in the developing world. While antiretroviral therapy is effective and increasingly available, the standard of care requires periodic monitoring of patients' viral load to individualize treatment and to control the emergence and spread of drug- resistant strains of HIV. Currently, viral-load is most commonly assessed with quantitative PCR-based or branched chain DNA assays, which require expensive equipment, infrastructure, and skilled technicians, which are not readily available in resource-limited settings. As a result, man HIV patients are not subjected to the recommended periodic, viral load testing. AC Diagnostics (ACD), in collaboration with University of Pennsylvania (UPenn), will develop inexpensive, automated, fully-integrated, point of care devices for molecular-based detection and quantification of HIV-1 in blood. The core of the technology is a novel, multifunctional, isothermal enzymatic amplification reactor for nucleic acid detection that utilizes a membrane capture scaffold to isolate nucleic acids from complex samples without prior purification and without a need for elution, thereby greatly simplifying flow control and enabling molecular diagnostic devices that are just slightly more complicated than dipsticks and, yet, have nearly comparable performance of benchtop equipment. Our preliminary experiments indicate that the proposed device can detect as few as 10 HIV copies per sample (i.e., less than 100 copies/ml of blood) in less than 60 minutes. Competing technologies currently under development utilize expensive and complex processors and may be unaffordable in many regions of the world. Phase I will provide proof of concept and target clade B and clade C HIV-1 subtypes. By appropriate selection of primers and without any modifications in hardware, the device can be modified to detect other clades according to the region of use. The proposed technology will also enable early detection of HIV-1 during the highly contagious pre- seroconversion acute-stage of infection to facilitate early treatment and minimize the spread of the disease (which is particularly important with increasing emphasize on "test-and-treat" and "treatment-as-prevention" concepts). Yet another important application is the diagnosis of infection in babies born to HIV-infected mothers since persistent maternal antibody makes traditional testing impossible. Such babies are typically started on therapy without testing, resulting in overtreatment of the majority to save the few infected. Our technology can help prevent unneeded exposure and expense. Although the proposed technology is particularly needed in developing countries, it is anticipated that both the instrumented (quantitative) and qualitative devices will also have market niche in the developed world, especially in places located far from major medical centers; in settings when "real-time" decisions based on viral load measures may be beneficial, and would likely improve efficiency, patients' convenience, adherence to drug therapy, and enable more timely, treatment decisions. Our devices can also be used for home testing to provide early detection.

Public Health Relevance Statement:


Public Health Relevance:
The proposed STTR effort will lead to a new generation of point-of-care (POC), molecular (nucleic acid)-based diagnostic devices that will enable the monitoring of the viral load of HIV in patients undergoing therapy and screening for HIV infection in individuals at risk during the seroconversion period and in babies born to AIDS- infected mothers when antibody tests are ineffective. The proposed device will foster improved healthcare both in resource-poor settings and in developed countries.

NIH Spending Category:
Bioengineering; Biotechnology; Genetics; Human Genome; Infectious Diseases; Prevention

Project Terms:
Acquired Immunodeficiency Syndrome; Acute; Adherence (attribute); Antibodies; antiretroviral therapy; assay development; base; Biological Assay; Blood; Blood specimen; Buffers; Cellular Phone; Characteristics; Clinical; Collaborations; Communicable Diseases; Complex; cost; design; Detection; Developed Countries; Developing Countries; Development; Devices; Diagnosis; Diagnostic; Diagnostic Reagent Kits; Diagnostic tests; Disease; DNA; Drug resistance; Early Diagnosis; Early treatment; Encapsulated; Equipment; Evaluation; experience; Fluorescence; Food Safety; Fostering; Funding; Future; Generations; Healthcare; HIV; HIV-1; Home environment; Immobilization; improved; Individual; Infection; instrument; laboratory facility; Lead; Life; man; Marketing; Maternal antibody; Measures; Mediating; Medical center; Membrane; Microfluidics; Modification; Molecular; Monitor; Mothers; Newborn Infant; novel; nucleic acid detection; nucleic acid purification; Nucleic Acids; operation; Partner in relationship; pathogen; Patient Monitoring; Patients; Pennsylvania; Performance; Pharmaceutical Preparations; Pharmacotherapy; Phase; Plants; Plastics; point of care; Preparation; prevent; Prevention; Process; product development; public health relevance; Reagent; Research; Research Infrastructure; research study; resistant strain; Resources; Reverse Transcription; Risk; RNA; Sampling; scaffold; screening; Sensitivity and Specificity; Small Business Technology Transfer Research; solid state; Southern Africa; Specimen; Staging; standard of care; success; System; Technology; Test Result; Testing; Time; Transportation; United States National Institutes of Health; Universities; Validation; viral detection; Viral Load result; viral RNA; Virus; Virus Diseases; Whole Blood