Author(s): Shelley N. Facente 1,*, Teri Dowling 1, Eric Vittinghoff 2, Deanna L. Sykes 3, Grant N. Colfax 1
In June of 2004, the OraQuick ADVANCE ® Rapid HIV-1/2 Antibody Test (OraSure Technologies, Inc., Bethehem, PA) was approved as a CLIA-waived rapid HIV test for use with oral mucosal transudate (oral fluid) specimens in addition to whole blood. In February of 2005, this test first became available for point-of-care HIV antibody testing in publicly-funded HIV testing sites in San Francisco. Because California regulations required phlebotomy certification before performing a fingerstick or blood draw (California Code of Regulations 17§1034; California Business and Professions Code §1240-1246.5), most community-based testing sites in San Francisco were prevented from performing rapid HIV tests using whole blood specimens, and therefore the advent of an oral fluid option led to a swift, significant increase in rapid testing in public HIV test sites (Facente, presented at HIV Diagnostics: New Developments and Challenges; Orlando, FL, 2005).
United States regulations currently require that all reactive rapid HIV tests be considered "preliminary positive" and confirmed in a high-complexity laboratory via Western blot (WB) or indirect immunofluoresence assay (IFA). In cases where the WB or IFA is negative or indeterminate, the results are considered "discordant" and follow up testing is indicated. This follow up testing is needed to determine whether the original reactive result was a false positive or if the patient has HIV infection but is in early seroconversion, causing the tests used for confirmation - some with lower sensitivity - to fail to detect antibodies. From 2003 through early 2006 in San Francisco, all patients with discordant results were asked to submit blood specimens after one month for follow up testing according to the above protocol. This was done regularly with all patients who were successfully contacted one month after the initial result disclosure. In February of 2006, with the agreement of the California Department of Public Health, Office of AIDS and Centers for Disease Control and Prevention, San Francisco began using a new algorithm that included the use of Nucleic Acid Amplification Testing (NAAT) to resolve most discordant tests from the first visit (Dowling and Facente, presented at XVI International AIDS Conference; Toronto, Canada, 2006). From this point forward, follow up testing was not regularly done if an oral fluid rapid HIV test was reactive but blood drawn that same day yielded non-reactive results for another OraQuick rapid test, an EIA, an IFA and/or WB, and NAAT.
According to the manufacturer, the OraQuick ADVANCE ® has a specificity of 99.8% (95% Confidence Interval (CI) 99.60%-99.89%) when used with oral fluid. However, clusters of excess false positive results have been well documented-, including in San Francisco. To date, these false positive clusters have remained unexplained, with issues such as test kit lot defect, storage or testing area temperature, and operator error being generally ruled out as causes.
In April - July 2008, we noticed a cluster of false positive test results in San Francisco which occurred with kits close to their...