IVD Technology Magazine | IVDT Article Index
Originally published January, 1997
IVD Technology News
CDC, FDA, and manufacturers work together to improve identification
of group O HIV
Manufacturers of HIV-1 tests and federal scientists are working earnestly to expand the sensitivity of test kits to include group O HIV-1. Currently marketed assays to detect infection with HIV-1 are optimized to detect group M viruses, and their track record has been less than stellar when it comes to detecting viruses of group O, which is associated with a relatively small population in central Africa (Lancet, 344:1333 1334, 1994).
The antibody response elicited by group O strains can slip through the screening process of current commercial enzyme immunoassays because in them this form of the virus is "weakly reactive," notes Patrick Sullivan, DVM, PhD, an epidemiologist who has been working on surveillance of "O" infections at the Centers for Disease Control and Prevention in Atlanta. This situation was thought to be "exceedingly rare," however, because fewer than 100 cases of group O HIV infection had been reported worldwide, and none had been recognized in the United States.
But then group O was found in a patient whose test results had been negative for HIV. With the help of CDC researchers, the Los Angeles County Department of Health identified a group O strain in a woman with symptoms of AIDS but a history of negative HIV testing (MMWR, 45:561565, 1996). Since then, another case has been found in another area of the country. "Now we are in a mode of systematic surveillance; however, the conclusion--that this is very rare--is still the same," stresses Sullivan.
But not so rare that in some regions of the country--Southern California, for example--the health departments aren't sending out some warnings. The Los Angeles County Department of Health has mailed letters to primary-care physicians across the region urging them to consider double-checking patients who have symptoms suggestive of HIV infection but negative test results, and naming group O as a possible culprit.
This increased concern has fueled stepped-up efforts to refine HIV test kits, and manufacturers have had a willing partner in the process: the federal government. "CDC and FDA are collecting sera from persons infected with group O HIV for use in evaluating reconfigured test kits," affirms Sullivan. The substance is so scarce that CDC and the agency have collaborated closely to collect the material, and are working together with business to expedite evaluation of the reconfigured kits. FDA has given the effort top priority.
The news of group O has cast a shadow over the AIDS research community at a time when cautious optimism seemed justified. Last summer the international AIDS conference in Vancouver unveiled findings showing that a powerful cocktail of antiviral drugs could prolong life, even largely eradicate the virus. It seemed that the elusive virus had met its match in emerging biotechnology, and that demand for HIV assays would increase.
The widely read Annals of Internal Medicine followed up with a study that demonstrated the efficacy of rapid HIV testing. Accompanying the article was a glowing editorial, which stated that the assay may have the potential for improving clinical outcomes, thanks in part to early detection (Ann Intern Med, 125: 509, 1996).
Now some in the field are privately wondering if health-care providers or companies could be held liable for undiagnosed cases. Could infected individuals claim that an IVD test's failure to detect the group O virus meant delayed access to drugs that could have staunched the infection if caught earlier? Ordinarily, says Michael D. Roth, a Los Angeles attorney who formerly chaired the Medicine and Law Committee of the American Bar Association, a case in which a lab test result is a "negative when it should be a positive should generally be an easy one for a plaintiff to win in court."
But, in the case of group O, there is a question of whether there is any liability. The courts haven't clearly defined where standard of care begins or ends in areas of evolving technology. A case can rest largely on whether changing a test truly constitutes an innovation or is merely a correction of an original oversight, Roth says. If a judge or jury concludes the latter, damages can be sought. And some in public health are openly concerned about the impact of the current efforts to improve HIV test kits.
"CDC has a way to identify group O that most commercial labs don't have," notes Paul Simon, MD, the Los Angeles County epidemiologist who helped uncover the index case of group O. Combining the methods presents a formidable technical challenge, Simon points out. Current testing picks up the overwhelming majority of HIV. Whatever the new test is, "you just don't want it to be something that compromises the ability to detect these more common strains," he warns. --Anne Scheck
