BEAT AIDS

Q. Why is the reported increase in false positives when using the oral fluid HIV test in NYC important?

A. Even though the New York City Department of Health and Mental Hygiene (NYC DOHMH) experience is cause for further investigation, it is important to keep in mind that the oral fluid tests have always performed above the Food and Drug Administration’s (FDA) specificity threshold and, monitored appropriately, continue to play an important role in HIV testing.

The reported increase in false-positive results from a specific HIV test is important for many reasons. From a patient’s standpoint, receiving a false-positive HIV test result can create anxiety over one’s health and mistrust of the medical system. From a provider’s standpoint, a pattern of false-positive test results from a specific test may cause a loss of confidence in the test and can negatively impact the relationship between the provider and the patient, as well as incur additional costs due to repeat testing. From CDC’s standpoint, occasional increases in false-positive test results can keep people from knowing their HIV infection status and prevent behavior changes which could reduce the transmission of HIV infection.

Q. What is CDC doing about the increase in New York City?

A. CDC is:

• Assessing ongoing efforts aimed at establishing the cause of the increases in false-positives from this test.

• Encouraging all jurisdictions and organizations that use rapid HIV tests to report to the manufacturer and to CDC any patterns or clusters of false positive (or false negative) results.

• Encouraging all organizations that conduct oral fluid rapid HIV tests to link to their state health departments so that any irregularities in results will quickly be documented.

• Recommending that all providers clearly tell patients the strengths and weaknesses of oral fluid rapid HIV tests.

• Ensuring that all sister governmental agencies and key external stakeholders are aware of this situation.

Q. Does CDC still recommend oral fluid rapid HIV tests?

A. At this time, CDC believes that oral fluid rapid HIV tests, managed appropriately, continue to play an important role in HIV testing. CDC recognizes that ease of use and patient acceptance of oral fluid rapid tests have lowered or eliminated barriers that previously may have kept people from getting an HIV test. It is also important to keep in mind that the oral fluid tests have always performed above the FDA’s specificity threshold.

NYC data suggest repeating the rapid test on whole blood after a reactive oral fluid HIV test can effectively reduce the number of false positive results. However, CDC recommends that FDA-approved blood or serum testing be used whenever possible, as these tests produce fewer false positives and false negatives. CDC’s HIV testing recommendations for adults, adolescents, and pregnant women state that any positive test results – including oral fluid – must receive confirmatory testing before a diagnosis of HIV is given.

Q. Are there explanations for why these false-positive results occurred?

A. At this time, the cause of the increases in the numbers of false-positives has not been determined. NYC DOHMH reported that no consistent relationship was detected between false-positive results and test kit handling, storage conditions, lot numbers, clinic sites, test operators, or patient characteristics. To understand fully the cause of these episodic false-positive test results, CDC plans to initiate a case-control study, with acceptance by the NYC DOHMH, to be performed in jurisdictions that perform large numbers of HIV tests and where false-positive test results have been reported.

Q. How significant is the problem reported by NYC DOHMH?

A. From March 2005, when NYC DOHMH, began using oral fluid rapid testing, through May 2008, 0.27% of the 160,174 oral fluid rapid HIV test results were confirmed false-positive.

In the first 7 months after oral fluid testing was introduced, 35 (0.16%) of 21,722 tests proved to be false-positive, consistent with the 99.8% specificity claim in the manufacturer’s package insert. In October 2005 and November 2005, false positives increased to 0.27% and 0.97%, respectively – both below the manufacturer’s specificity. This phenomenon did not persist when fingerstick whole blood replaced oral fluid testing during 3 weeks in December 2005.

In late 2007, another, larger increase in false-positive oral fluid rapid test results was noted. Between November 2007 through April 2008, between 23 and 54 false-positive oral fluid rapid tests occurred monthly (specificity, 98.88%-99.49%) – representing nearly half of reactive oral fluid tests in the STD clinics. In May 2008, the increase in false-positive tests subsided: 5 of the 4749 oral fluid tests were found to be false positive (specificity 99.89%).

Despite these episodic elevated levels of false-positive results, the oral fluid test has always performed within FDA regulations, which calls for a minimum threshold of 98.0% specificity.

Q. Why has NYC DOHMH discontinued the use of oral fluid rapid tests in its STD clinics, but continues to use them in other venues?

A. Because of the way the NYC DOHMH is structured, the STD clinics are separate from other types of clinics. The false-positive results were reported only in STD clinics; therefore, the decision to stop oral fluid rapid HIV tests was limited to those clinics.

Q. Have other jurisdictions reported increased numbers of false-positive results from these tests?

A. CDC is investigating reports to see whether this phenomenon is occurring in other jurisdictions. This MMWR article is limited to New York City’s experience. However, previous reports of elevated levels of false-positive results with oral fluid tests have been reported and investigated (MMWR: Supplemental Testing for Confirmation of Reactive Oral Fluid Rapid HIV Antibody Tests).

CDC is investigating reports to see whether this phenomenon is currently occurring in other jurisdictions. CDC is also encouraging others to let CDC and the manufacturer know if they are seeing an increase in the level of false-positive test results with the use of oral fluid rapid HIV tests at their testing sites.