OraQuick Gets FDA Approval for Rapid Diagnosis of HIV-1

ROCKVILLE, Maryland—A quick HIV-1 diagnostic test with high specificity and sensitivity has received conditional approval by the US Food and Drug Administration (FDA) for use in detecting antibodies to the most common form of the virus found in the United States.

In approving the OraQuick Rapid HIV-1 Antibody Test (OraSure Technologies), the agency restricted its sales to the nearly 40,000 labs approved by the FDA under CLIA, the Clinical Laboratory Improvements Amendments of 1988. The FDA also specifically stated that the antibody test is not approved for use to screen blood or tissue donors.

OraQuick is classified by the FDA as a test of moderate complexity. CLIA requires that new diagnostic tests be categorized as either moderate or high complexity and their administration restricted to CLIA-certified laboratory technicians or medical staff at CLIA-approved laboratories. However, OraSure could seek a waiver for use of the test under less stringent conditions, and Health and Human Services Secretary Tommy G. Thompson pleaded with the company to do so.

"If the FDA finds that the company’s data proves that the OraQuick test is both easy and safe to use, it can get a CLIA waiver. Then the test could be given in many more health care settings, perhaps even administered by social workers in HIV counseling centers," Mr. Thompson said in announcing the FDA’s approval. "But the process can’t begin until OraSure applies for the waiver, so I ask them to please apply now!" The company agreed readily. "We absolutely plan to submit for a CLIA waiver," said OraSure spokesman William E. Bruckner.

HIV diagnosis in the United States currently involves screening with an enzyme immunoassay (EIA) and confirmation of repeatedly reactive EIAs with the Western blot test. Obtaining results from these testing procedures typically takes 2 days to 2 weeks.

The OraQuick test, however, is a single-use, qualitative immunoassay that can detect HIV-1 antibodies in finger-stick whole blood samples. A blood sample is mixed in a vial with a developing solution, and the test device, which resembles a dipstick, is inserted into it.

The test device contains synthetic peptides representing the HIV envelope. If the blood sample contains HIV-1 antibodies, their presence is revealed in as little at 20 minutes by two reddish-purple lines that appear in a small window on the test device. A positive result indicates a preliminary diagnosis of HIV infection that must be confirmed.

OraQuick’s results can be read in 20 to 60 minutes, and its labeling warns that reading the test before or after that time frame can yield erroneous results. The test kit requires no refrigeration and can be stored unopened at temperatures of 2° to 27° C.

Mr. Bruckner said that OraSure would begin shipping the test kits in late December 2002 or early January 2003. Under an agreement with OraSure, Abbott Laboratories will market the OraQuick test in the United States.

Clinical Trials

To support its approval application, OraSure submitted a series of clinical trials of OraQuick’s sensitivity and specificity. In a sensitivity study of 481 known HIV-1 positive individuals and 40 AIDS patients performed at eight clinical centers, the test detected antibodies in all of the AIDS patients and in all but two of the HIV-1 positive individuals.

A clinical trial of 625 previously unscreened, high-risk individuals at seven sites found that 20 were repeatedly reactive to a licensed EIA, and 17 of the 20 were positive by the Western blot test. OraQuick detected the 17 Western-blot-positive individuals, but not the false positives. On the basis of the combined results of the two trials, OraQuick has a calculated sensitivity of 99.6% (95% CI, 98.5% to 99.9%).

As for specificity, eight clinical trial sites assayed blood samples from 1,250 previously unscreened, low-risk individuals. Two were found to have HIV-1 antibodies and were removed from the specificity calculations. The remaining 1,248 samples gave nonreactive results using the OraQuick test. In addition, all of the 608 nonreactive individuals in the study of 625 high-risk persons described above also had nonreactive results with OraQuick. Combining the results for the two studies yielded a calculated specificity of 100% (95% CI, 99.7% to 100%).