By Renee DiIulio

OraQuick Rapid HIV-1/2 Antibody Test is expected to increase patient testing and improve care.

With a cure and vaccine remaining elusive, prevention is still the best method by which to avoid contracting the human immunodeficiency virus (HIV). Once an HIV diagnosis is given, there are drugs that can potentially prevent transmission to a fetus, halt infection of exposed health care workers, and postpone the onset of the more serious acquired immune deficiency syndrome (AIDS). Yet, according to the Centers for Disease Control and Prevention (CDC) in Atlanta, 31% of patients who test positive at CDC-funded HIV-testing sites do not return for their results and therefore neither discover their status nor begin treatment.

A number of factors may contribute to this decision, not the least of which is the delay between the test specimen being taken and the results being given, a period that traditionally took up to 2 weeks. The OraQuick Rapid HIV-1/2 Antibody Test, manufactured by OraSure Technologies Inc in Bethlehem, Pa, has been hailed by various governmental bodies and medical experts as a tool that can help eliminate this problematic situation. First available abroad, the Food and Drug Administration (FDA) has gradually expanded its clearance in the United States, most recently granting approval and a CLIA (Clinical Laboratory Improvements Amendments of 1988) waiver for use with oral fluids, a move expected to increase the number of patients willing to be tested.

A Growing Problem
The number of people living with HIV has continued to grow since it was first discovered to be the cause of AIDS in the 1980s. In the United States, the CDC estimates that there are 850,000 to 950,000 residents with HIV, and that one person in four is unaware of his infection. This means that 180,000 to 280,000 people do not know they have HIV. Of the 40,000 new infections per year that have occurred over the past decade, two thirds were unaware of their status. In addition to increased infection rates, those who do not know they are infected increase their chances of developing AIDS; the CDC reports that 41% find out they have HIV less than 1 year before an AIDS diagnosis. Earlier diagnosis can therefore decrease the incidence of infection and the onset of AIDS as patients often change risky behaviors and begin treatment.

The Quicker, the Better
Unfortunately, early diagnosis has been hindered by fear and inconvenience. Patients who overcome fear of a positive result or blood draw, may not be able to show similar courage to return for the actual result a week or two later. Because the illness does not express immediate symptoms, others may deem the results unnecessary. And still others may not be able to work around life’s complications and find the time, money, or transportation to return to the place of testing.

Ron Spair, executive VP and CFO, OraSure Technologies Inc

“Rapid testing takes any issues off the table,” says Ron Spair, executive vice president and chief financial officer of OraSure. “The patient stays while the test is run and receives counseling. If the result is positive, they are immediately notified of treatment options and safe behaviors.”

Additional advantages are seen in emergency rooms and obstetrics. OraSure quotes statistics from the American Foundation for AIDS Research (AmFAR)in New York. They report nearly 20% of all pregnant women are not aware of their HIV status at the time of delivery. “With a rapid test, physicians can immediately determine a mother’s HIV status when she presents for birth and immediately administer antiretroviral therapy, substantially reducing the chance that the infants will become infected with HIV. This happens quite frequently in Africa,” says Spair.

One Stripe if No, Two if Yes
The test has been approved for use with oral fluid, plasma, and whole blood and requires as little as a drop of a finger-stick or venipuncture specimen. The sample is transferred to a collection loop, which is inserted into a premeasured solution along with the test device. A reusable stand holds the device at the correct angle to ensure accurate test results.

Using lateral-flow technology similar to that of a pregnancy test, the sample flows up a nitrocellular strip, traversing the HIV-1- and HIV-2-specific antigen stripe. If antibodies are present in the blood or oral fluid sample, the stripe marked with a “T” for test reacts, turning a reddish-purple color, within 20 minutes. The test should not be read before 20 minutes or after 40. The control stripe, marked with a “C”, should appear in any case to determine that the test worked properly.

Thus, a nonreactive or negative result will show only one line, that of the control, while a reactive or preliminary positive result will display two lines. All reactive results must be confirmed, typically with a Western blot.

The OraQuick device can be stored at room temperature and requires no specialized equipment. Because it includes an internal control, there is no need to run external control specimens, though it is recommended that a positive and negative external control be run on each new lot. Spair also notes that the nature of the test allows laboratory technologists to perform exams as specimens come in, rather than waiting to batch them in lots.

Accuracy is another benefit. Results of a double-blinded multicenter clinical study using finger-stick and venipuncture whole blood specimens showed the overall sensitivity and specificity of the OraQuick Rapid HIV-1 Antibody test to be 99.6% and 100%, respectively.

Typical Limitations
According to the CDC, the test’s limitations are similar to those of other HIV-antibody tests and include:

1) False-positive results: Although the clinical trial produced no false-positive results, the CDC expects that as the test becomes widely used in outreach settings, “a very small number of people who are not infected will have reactive test results.” Therefore, a preliminary positive result should be confirmed with additional testing.

2) False-negative results: The CDC claims that “a small number of people who are infected … will have negative test results.”

3) Delayed detection of exposure: Because it can take up to 3 months for an exposed individual to develop the HIV-1 and/or -2 antibodies, those who are tested within that period may not be reactive and will require testing after the 3-month time period.

4) Follow-up testing: A confirmation test is required for all reactive results.

Government Approved
Because of these limitations and the nature of the disease, counseling is required for all patients being examined and is an FDA condition for use of all HIV tests. Subsequently, there are no imminent plans to make the OraQuick test available for over-the-counter use. However, Spair does not rule out such a possibility “much further down the road.”

Currently, the FDA has approved use of the OraQuick Rapid HIV-1/2 Antibody Test for testing of HIV-1 and HIV-2 antibodies on plasma, venipuncture whole blood, finger-stick whole blood, and oral fluid samples. CLIA waivers have been granted for these uses as well.

CLIA established less rigorous federal controls for all laboratory testing to ensure the accuracy, reliability, and timeliness of test results regardless of where the test is performed. As a result, the test is approved for use in more than 180,000 sites, including laboratories associated with HIV counseling and testing sites, STD clinics, community health centers, drug treatment centers, hospitals, physician offices, managed care organizations, and prisons.

In the summer of 2003, the CDC contracted with OraSure to purchase 250,000 of the OraQuick Rapid HIV-1 Antibody Tests for distribution to state health departments and CBO grantees as part of its four-step HIV prevention strategy, known as Advancing HIV Prevention (AHP).

Currently, OraSure is in negotiations with the Substance Abuse and Mental Health Services Administration to become the sole source provider of rapid HIV tests. “If approved, the organization will procure several hundred thousand units of the test for use in drug treatment centers. Because of the high risks associated with intravenous drug use, testing for HIV is one of the agency’s priorities,” says Spair.

Expanded Use, Improved Care
Spair says that in addition to government agencies, the company’s sales and marketing program addresses multiple channels. The company sells directly to public health and community-based organizations, hospitals, clients such as Abbott Laboratories, and other international partners.

The device has been available outside the United States for some time, having first begun development in the mid to late 1990s under the management of Epitope, a company that was merged into OraSure in September 2000. In addition to perfecting the technology, the company was also challenged by obtaining the proper licenses, which included a patent for lateral-flow technology, the HIV-1 antigen from the National Institutes of Health, and the HIV-2 patents from Bio-Rad Laboratories in Hercules, Calif.

Since the product’s debut, the FDA has been expanding its clearance, from investigational use by the CDC in March 2001 to use for HIV-1 antibody on finger-stick blood specimens in November 2002 to this year’s approval for use in HIV-2 antibody detection and testing with oral fluids.

Spair notes that OraSure offers both laboratory-based and point-of-care tests but has carved a particular niche in those that utilize oral fluid specimens.

HHS Secretary Tommy G. Thompson says, “Before the approval of this rapid test in November 2002, many people being tested for HIV in public clinics did not return for the results of standard tests. Where the rapid test is available, those tested get their results within minutes. This oral test provides another important option for people who might be afraid of a blood test. It will improve care for these people and improve public health as well.”

Renee DiIulio is a contributing writer for Clinical Lab Products.