The objectives of this project are to develop a commercial single well HIV-1 Limiting Antigen Avidity EIA, developed in Phase I as a research tool, and establish its suitability for identifying recent HIV-1 infections on both a population an on an individual clinical basis as an aid to early intervention in acute infections. Such methods are needed for accurate measures of the incidence of new HIV infections to enable monitoring of the epidemic in populations, optimal targeting of public health resources and assessment of intervention effectiveness. In addition, identification of persons recently infected is important a these persons are typically hyper-infectious and at greater risk of transmitting the disease to partners. The scientific literature estimates that nearly half of all infections are transmitted frm partners who themselves are recent infections. Such high risk individuals should be aggressively identified treated, counseled and contact-traced to immediately reduce the risk of further transmission. In Phase I, the assay was developed for Research Use Only for liquid plasma and serum specimens and is being evaluated by the our collaborator, the CDC Global AIDS Program Laboratory Branch and other investigators around the world for its ability to measure HIV incidence in populations. In Phase II, the assay validation will be expanded and completed for conformation to consensus standards, including expanded testing by CDC, Consortium for Evaluation of Performance of HIV Incidence Assays (CEPHIA) and others seeking new and improved incidence assays. The assay will be further adapted to expand use to dried blood spot specimens (DBS) using proprietary formulations and approaches similar to those used for our current DBS products and evaluated along a similar path. DBS specimens are widely used in many developing countries preferentially, and sometimes exclusively, over liquid blood specimens and will expand access to this assay worldwide. In addition, an individual (diagnostic) use application will be developed, evaluated and validated. Application to individual use and management of care requires an FDA approved product in the U.S. In addition to a series of non-clinical laboratory studies to evaluate such parameters as the assay performance, accuracy, robustness and reproducibility, and to accurately assess recency window periods, extensive testing will be done with panels of well characterized specimens of established recency and compared to other incidence assays by CDC, CEPHIA and in-house and commercial panels. This data will be used to extend validation of population incidence application, support third party clinical trials of prospectively collected clinical specimens from high risk longitudinal cohorts and culminate in an FDA application for approval for individual clinical use. The project is of additional significance to the U.S. Public Health, as the CDC currently manages a national HIV/AIDS surveillance system that is the nation's source for timely information used to track the epidemic in the U.S. The CDC uses HIV recency data from that system to make estimates of HIV incidence and track the epidemic in the U.S., and is seeking to obtain more accurate data through the use of potentially improved assays.
This project will expand the applicability of and fully develop a commercially viable assay for an HIV antibody avidity assay (the Sedia HIV-1 LAg-Avidity EIA) and establish its superiority over current methods for identifying recent HIV-1 infections. Identification of recent infections enables 1) measurement of new HIV-1 infections in a population to monitor the epidemic spread and 2) diagnosis of new HIV-1 infection in individuals allowing the identification and targeting of hyper-infectious early cases who are at greatest risk of transmitting HIV to sexual partners. The assay will be used to generate improved estimates of HIV incidence in the U.S. and internationally, as well as to improve public health efforts and optimize use of limited resources by targeting treatment, follow-up and contact tracing of individuals at highest risk of HIV transmission.