Rapid Testing Stalled
An article in The Los Angeles Times recently reported that seven babies in the region had acquired HIV at birth. The children had been infected at varying times during the past few years but had not been identified sooner because California does not routinely test newborns for HIV. Not surprisingly, most cases of transmission involved women who had declined to be tested for HIV during their pregnancies or had not received prenatal care. Dr. Jonathan Fielding, Los Angeles County's director of public health confirmed that, "Those most at risk of not receiving prenatal care -- including HIV tests -- include women who are drug addicts, incarcerated, homeless, non-English speakers, undocumented immigrants, uninsured or teenagers."
It's known that transmission of HIV to infants is largely preventable with either a course of AZT as a part of prenatal care or with a single dose of nevirapine administered prior to or during labor. Even a single nevirapine dose to the baby if given within 24 hours of birth may prevent infection from taking hold. Antiretroviral therapy can reduce the newborn infection rate from as much as 50 percent to less than 8 percent (what happens next is a different problem: See "HIV and Breast Feeding" in this issue). In parts of the world with high HIV prevalence and limited resources for prenatal care and testing, some have proposed offering nevirapine to every mother as she enters labor since the drug is cheaper than the test. But in areas with low rates of HIV incidence, knowing the HIV test result prior to delivery is essential to identify everyone who can be helped by treatment.
In Los Angeles, at least one of the HIV-positive infants was not treated because test results were not received in time to alert the medical staff. With conventional tests, a lag of up to four days between the time blood is drawn to when the results are known leaves the door open for preventable infections to slip through. Dr. Andrea Kovacs, chief of the Los Angeles County-USC Medical Center's program for HIV-positive women, children and adolescents was quoted in The Times article as saying rapid testing could have provided results within an hour. "We would have treated the baby if we knew the mom was HIV-positive."
Rapid tests for HIV perform the same job that standard laboratory-based HIV tests do -- but faster. Currently, before a definite diagnosis of HIV infection can be given, an initial positive result with either the rapid or conventional test must be confirmed with another type of laboratory-based HIV test called the "Western Blot." But in situations when labor has already begun and there is no time for laboratory confirmation, a positive rapid test result may justify offering the mother and child nevirapine treatment. The convenience of rapid testing, however, does not preclude the need for pre-test informed consent and post-test counseling.
There are more than a dozen rapid HIV tests on the market throughout the world and simple one-step tests are the norm in regions without expensive laboratory resources. But in a strange twist on the usual story of the Haves and Have Nots, no easy-to-use rapid HIV tests have been approved by the FDA for use at the point of care in U.S. hospitals, clinics and testing centers. The single one-hour test that has been approved still depends on laboratory processing and expert interpretation.
The potential demand for a rapid HIV test in the United States is huge. Rapid tests cost no more than conventional tests and the FDA has recently indicated that confirmation of a positive rapid result with another type of rapid test may be an acceptable substitute for confirmation by Western Blot. (See "Rapid New World" for how this problem is handled elsewhere in the world.) Providers of HIV counseling, testing and referral services are also anxiously waiting for point-of-care rapid testing. Statistics show that up to a third of people who have a sample taken for conventional testing never return to get their results. Point of care testing promises to be far more cost effective than conventional testing because fewer tests will be wasted on no-shows. In addition, prevention experts are eager to find ways to reach those most at risk for slipping through the cracks of existing counseling and testing services that require follow-up appointments.
So why are rapid HIV tests that are available in Japan, France and Thailand unobtainable in the U.S.? The answer seems to be because the big companies that make the conventional tests don't want the competition. And because of a complicated web of patents and intellectual property agreements, these corporations have the clout to keep rapid testing out of the established $200 million per year U.S. market for laboratory-based tests.
According to a recent article in The Wall Street Journal, the problem stems not from testing for HIV-1, the most common HIV infection in the world, but with patents that cover testing for HIV-2, an AIDS-causing virus most prevalent in West Africa. Although HIV-2 infections have been reported in areas with large immigrant populations such as New York, overall, infections with the "other" HIV are rare in the U.S. When a test for HIV-2 became available in 1990, the Centers for Disease Control, the federal agency responsible for the safety of the national blood supply, recommended that HIV blood-screening tests should be able to detect both types of HIV. Although the FDA requires that blood-screening tests check for HIV-2, the agency does not ask the same of tests used to diagnose HIV in individuals. Yet producers of HIV diagnostic assays have voluntarily adopted the standard that an HIV test should be able to test for all forms of HIV prevalent in the world.
The patent for the HIV-1 test is controlled by the U.S. National Institutes of Health (NIH). The NIH has freely issued permission to use the patent in exchange for modest royalty payments which are shared with the French Institut Pasteur, a co-discoverer of HIV-1. Several years after the first test for HIV-1 became available, researchers at the Institut Pasteur learned that HIV-2 could also cause disease and that the existing HIV test could not reliably detect it. The Institut Pasteur received a comprehensive U.S. patent for HIV-2, which was then licensed to a spin-off, for-profit corporation. In a complicated series of business transactions, effective control of the U.S. patent was subsequently traded among the big-three makers of conventional diagnostics, including Abbott Laboratories, the largest supplier of HIV tests. The result: anyone who wants to market an HIV test that detects both HIV-1 and HIV-2 in the U.S. needs the permission of Abbott and the others.
Several makers of rapid assays that detect both HIVs have tested the waters for U.S. approval. Most have received positive signals about their chances. Yet in every case, failure to come to terms over the HIV-2 patent has sunk efforts to bring these tests to market. According to The Wall Street Journal, one company, Universal Healthwatch, attempted to license HIV-2 but was stonewalled by the patent holder. The company, afraid to risk a lawsuit over an alternative method for detecting HIV-2 and unwilling to offer a product that only tested for HIV-1, abandoned the campaign. Until recently, a rapid test called OraQuick that had been successfully used by the CDC on an experimental basis seemed poised for FDA approval. When the company realized it would not be able to obtain a license to use the HIV-2 patent in the U.S., it tried a different tack. Abbott was approached about distributing OraQuick under their license for HIV-2, yet the diagnostic giant would not agree to guarantee minimum yearly sales of the test. According to The Journal, the OraQuick executives feared that Abbott was only interested in obtaining the rights to their product as a ploy to keep it off the market.
In 1999 ownership of the HIV-2 patent with all of its encumbrances passed to Bio-Rad Laboratories, a California corporation. Bio-Rad claims that it has since entered into HIV-2 licensing agreements with numerous companies, yet suggests that, when it comes to the U.S. market, its hands are tied by the inherited obligations to Abbott and the others. In a letter to GMHC, David Schwartz, president of Bio-Rad said, "We evaluate each request on a case-by-case basis and enter into licensing agreements based on a variety of criteria, some of which we are obligated to maintain as a result of our acquisition of... the HIV-2 patent."
The frustration over the deadlock is evident in a statement quoted by The Journal from Bernard Branson, who heads the CDC's HIV diagnostics program. "I'd call it restraint of trade. It's a travesty to stand by and allow these tests to languish." Reportedly, the CDC has asked the Justice Department to investigate if BioRad and its partners have violated antitrust laws.
Faced with this stalemate and with clamor from the prevention community for rapid testing, the FDA last year finally gave a clear signal that diagnostic products that tested for HIV-1 alone would receive a favorable review as long as trial data demonstrated performance comparable to lab-based assays. Reportedly, this has unlocked the gates and several rapid test makers have submitted applications to the agency. It's possible that an approval could be seen later this year. As for HIV-2, the patent expires in 2010.
This article was provided by Gay Men's Health Crisis. It is a part of the publication GMHC Treatment Issues. Visit GMHC's website to find out more about their activities, publications and services.