SBIR-STTR Award

Rapid Test for Recent HIV Infection and Incidence Panels for Assay Evaluation Project Summary Accurate estimates of HIV incidence are required for monitoring the epidemic, for targeting resources, and for evaluating the effectiveness of various interventions. Yet the assays that underlie these estimates are widely understood to be flawed. Among the flaws are (1) the lack of consistent recency detection across HIV subtypes, (2) inconsistent availability of commercial test methods that have been modified to discriminate recent from long-standing infection, (3) difficulties to date in adapting incidence methods to test formats usable in resource-poor settings, and (4) lack of incidence panels (plasma samples from individuals with closely estimated infection dates) in sufficient volume for evaluation of multiple candidate assays. In this project, we propose to transform serological HIV incidence testing from the current ELISA methodology to a reliable lateral flow rapid test format with good coverage of all HIV subtypes and a low false recency rate. The rapid test will be stable, multi-colored, fast, simple to use, and applicable to populations where varyin HIV subtypes are dominant. We also plan development of pedigreed incidence plasma panels for evaluation of this new test method; panels will be made commercially available worldwide. These products will be based on three key assets: a new highly sensitive rapid test technology based on a novel colorimetric detection system, which allows for analysis of antibody titer and avidity within a single cassette, to be applied for the first time to an incidence test for HIV; a ew HIV antigen (rIDR-M) which combines immunodominant sequences corresponding to all major subtypes; and a proven, IRB-approved protocol for identifying, recruiting, and retaining recently HIV infected individuals for blood collections to form incidence panels. The new colorimetric detection technology for rapid test yields bright, high-contrast, multicolor bands on a membrane. The sensitivity of this method far exceeds that of conventional colloidal gold or similar labels used in lateral flow rapid tests, as well as exceeding the sensitivity of comparable ELISA assays. The new rapid test method will be based on avidity and has been demonstrated to distinguish between incident and prevalent samples. The incidence panels to be generated concurrently will provide the essential tool with which to characterize the performance of the rapid test as well as other candidate incidence methods. In Phase I, we expect to complete development and validation of a prototype rapid test and establish six incidence serum panels. Additional panels, including multiple clades, will be collected in Phase II to support final development and characterization of a commercial version of the rapid HIV incidence test.

Public Health Relevance:
Rapid Test for Recent HIV Infection and Incidence Panels for Assay Evaluation Project Narrative SeraCare and Immunetics propose jointly to develop a new, rapid HIV incidence test for discrimination of recent vs. past infections by all HIV subtypes worldwide. Incidence/prevalence panels of well-characterized plasma from recently HIV infected individuals will be collected for use in qualifying this assay and will be made available commercially to other investigators and test developers. Development of a rapid and reliable test for recent HIV infection is a critical public health need for accurate determination of HIV incidence and will allow epidemiologists and researchers to understand whether HIV infection is increasing, decreasing, or staying level within a given population, greatly advancing the monitoring of interventions to reduce the spread of HIV worldwide.

Public Health Relevance Statement:
Rapid Test for Recent HIV Infection and Incidence Panels for Assay Evaluation

NIH Spending Category:
Clinical Research; HIV/AIDS

Project Terms:
Achievement; Aliquot; Anti-Retroviral Agents; Antibodies; Antigens; Avidity; base; Biological Assay; Blood; Cells; Clinic; Collaborations; Collection; Color; Communicable Diseases; Detection; Development; Development Plans; Diagnostic; Discrimination (Psychology); Dissociation; Effectiveness; Enzyme-Linked Immunosorbent Assay; Epidemic; Evaluation; Gold Colloid; HIV; HIV Antibodies; HIV Antigens; HIV Envelope Protein gp41; HIV Infections; Human immunodeficiency virus test; Incidence; Individual; Infection; innovation; Institutional Review Boards; Intervention; Label; Laboratories; Lateral; M cell; Marketing; Membrane; Methodology; Methods; Monitor; next generation; novel; Participant; Peptides; Performance; performance tests; Phase; Plasma; Plasma Cells; Policies; Population; Population Heterogeneity; Population Surveillance; Prevalence; Procedures; Process; Protocols documentation; prototype; public health medicine (field); Recruitment Activity; Research Infrastructure; Research Personnel; Resources; RNA; Sampling; Sensitivity and Specificity; Series; Serological; Serum; System; Technology; Testing; Time; tool; Validation; Work

Rapid Test for Recent HIV Infection and Incidence Panels for Assay Evaluation Project Summary Accurate estimates of HIV incidence are required for monitoring the epidemic, for targeting resources, and for evaluating the effectiveness of various interventions. Yet the assays that underlie these estimates are widely understood to be flawed. Among the flaws are (1) the lack of consistent recency detection across HIV subtypes, (2) inconsistent availability of commercial test methods that have been modified to discriminate recent from long-standing infection, (3) difficulties to date in adapting incidence methods to test formats usable in resource-poor settings, and (4) lack of incidence panels (plasma samples from individuals with closely estimated infection dates) in sufficient volume for evaluation of multiple candidate assays. In this project, we propose to transform serological HIV incidence testing from the current ELISA methodology to a reliable lateral flow rapid test format with good coverage of all HIV subtypes and a low false recency rate. The rapid test will be stable, multi-colored, fast, simple to use, and applicable to populations where varyin HIV subtypes are dominant. We also plan development of pedigreed incidence plasma panels for evaluation of this new test method; panels will be made commercially available worldwide. These products will be based on three key assets: a new highly sensitive rapid test technology based on a novel colorimetric detection system, which allows for analysis of antibody titer and avidity within a single cassette, to be applied for the first time to an incidence test for HIV; a ew HIV antigen (rIDR-M) which combines immunodominant sequences corresponding to all major subtypes; and a proven, IRB-approved protocol for identifying, recruiting, and retaining recently HIV infected individuals for blood collections to form incidence panels. The new colorimetric detection technology for rapid test yields bright, high-contrast, multicolor bands on a membrane. The sensitivity of this method far exceeds that of conventional colloidal gold or similar labels used in lateral flow rapid tests, as well as exceeding the sensitivity of comparable ELISA assays. The new rapid test method will be based on avidity and has been demonstrated to distinguish between incident and prevalent samples. The incidence panels to be generated concurrently will provide the essential tool with which to characterize the performance of the rapid test as well as other candidate incidence methods. In Phase I, we expect to complete development and validation of a prototype rapid test and establish six incidence serum panels. Additional panels, including multiple clades, will be collected in Phase II to support final development and characterization of a commercial version of the rapid HIV incidence test.

Public Health Relevance Statement:


Public Health Relevance:
Rapid Test for Recent HIV Infection and Incidence Panels for Assay Evaluation Project Narrative SeraCare and Immunetics propose jointly to develop a new, rapid HIV incidence test for discrimination of recent vs. past infections by all HIV subtypes worldwide. Incidence/prevalence panels of well-characterized plasma from recently HIV infected individuals will be collected for use in qualifying this assay and will be made available commercially to other investigators and test developers. Development of a rapid and reliable test for recent HIV infection is a critical public health need for accurate determination of HIV incidence and will allow epidemiologists and researchers to understand whether HIV infection is increasing, decreasing, or staying level within a given population, greatly advancing the monitoring of interventions to reduce the spread of HIV worldwide.

NIH Spending Category:
HIV/AIDS; Infectious Diseases

Project Terms:
Achievement; Aliquot; Anti-Retroviral Agents; Antibodies; Antigens; Avidity; base; Biological Assay; Blood; Cells; Clinic; Collaborations; Collection; Color; Communicable Diseases; Detection; Development; Development Plans; Diagnostic; Discrimination (Psychology); Dissociation; Effectiveness; Enzyme-Linked Immunosorbent Assay; Epidemic; Epidemiologist; Evaluation; Gold Colloid; HIV; HIV Antibodies; HIV Antigens; HIV Envelope Protein gp41; HIV Infections; Human immunodeficiency virus test; Incidence; Individual; Infection; innovation; Institutional Review Boards; Intervention; Label; Laboratories; Lateral; M cell; Marketing; Membrane; Methodology; Methods; Monitor; next generation; novel; Participant; Peptides; Performance; performance tests; Phase; Plasma; Plasma Cells; Policies; Population; Population Heterogeneity; Population Surveillance; Prevalence; Procedures; Process; Protocols documentation; prototype; public health medicine (field); public health relevance; Qualifying; Recruitment Activity; Research Infrastructure; Research Personnel; Resources; RNA; Sampling; Sensitivity and Specificity; Series; Serological; Serum; System; Technology; Testing; Time; tool; Validation; Work