Minimally-instrumented home HIV detection and care linkage system Project Summary/Abstract: According to recent estimates, ~37 million adults and 3.4 million children live with HIV. High sensitivity diagnostic tests for HIV are needed to reduce the spread and burden of the disease and allow detection during the seroconversion window to enable ?test and treat? and modify behavior. There is also a great need for inexpensive, home / point of care viral load tests for HIV patients undergoing therapy to individualize treatment, control the emergence and spread of drug-resistant strains of HIV, and monitor adherence. To address these needs, an interdisciplinary team of scientists from Penn Engineering, Penn Center for Aids Research (CFAR), and Centers of Disease Control and Prevention (CDC) is proposing a system consisting of an inexpensive disposable diagnostic cassette and inexpensive reusable processor. Our cassette will carry out all unit operations from sample introduction, including plasma separation from whole blood, to multi- plex enzymatic amplification, facilitating co-detection and quantification of HIV-1 clade B, Hepatitis B (HBV), Hepatitis C (HCV), and beta Globin (positive control) with detection limit of 10 targets in a sample (e.g., 350 copies/mL when whole blood sample volume is 100L) and of HIV-1 Group M (subtype- independent) in under 40 minutes. The cassette stores all reagents refrigeration-free with a shelf-life exceeding 12 months. Our cassette mates with a simple battery-powered processor that provides temperature-control, actuation, and an interface for a smartphone. The smartphone instructs the user in operating the device; controls device operation, monitors and analyzes enzymatic amplification processes; reports test results to the patient, to the medical team and public health officials (in compliance with prevailing laws); and provides counseling. Our system carries out all the necessary unit operations from sample introduction to test results. At the conclusion of this effort, we will have developed a remarkable system for home/point-of-care molecular detection of HIV-1 and co-infections with minimal instrumentation. Our system will be able to detect HIV during seroconversion to encourage individuals to start therapy early and modify transmission behavior; monitor viral rebound to detect development of drug- resistance and non-adherence, and enable personalized therapy with novel long-acting agents such as broadly neutralizing antibody infusions likely to emerge over the next decade; and detect infection in infants born to HIV?infected mothers (particularly in the developing world). As such, this system has the potential to allow rapid detection of viremia and rapid intervention to prevent HIV transmission to the uninfected and reduce the complications of HIV in those infected. More broadly, our system will enable individuals to assume responsibility for their own care.
The proposed effort will result in a new generation of home / point-of-care molecular (nucleic acid) - based diagnostic devices to monitor viral load of HIV in patients undergoing therapy and high-sensitivity screening for HIV infection in individuals at risk, including during the seroconversion period, as well as newborns of AIDS- infected mothers when antibody tests are ineffective. The proposed device will foster improved healthcare both in developed countries and in resource-limited settings. The technology platform is adaptable for the detection of other infectious diseases and amenable to multiplexing and detection of co-infections that are common in AIDS patients.