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UCSD Study Finds that Nucleic Acid Testing Increases HIV Detection Yield

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By Ben Butkus

Amplification-based nucleic acid testing increases HIV detection yield by more than 20 percent over rapid antibody-detection methods, according to research published this week by scientists from the University of California, San Diego.

The study adds to a growing body of evidence that nucleic acid testing can help diagnose HIV in patients in its earliest stages, which in turn could lead to more effective treatment and transmission prevention.

If nucleic acid-based HIV testing were to become more commonplace, it could be a boon for Gen-Probe and Novartis Diagnostics, which offer the only approved NAT for qualitative HIV diagnosis in the US; as well as for other companies developing similar tests, Sheldon Morris, lead author on the study, told PCR Insider this week.

"There is a market for it, but it needs to be high volume," said Morris, an assistant clinical professor at UCSD's Antiviral Research Center. "But we're not even at a stage where there is really any sort of widespread use throughout a state.

Morris and colleagues' research was published this week in the Annals of Internal Medicine. In their study, the researchers tested 3,151 patients who sought HIV testing in community-based clinics in the San Diego area.

Patients were first tested with a rapid saliva test from OraSure Technologies. If the result was positive, a counselor informed the patient and blood was obtained for an immunofluorescence-based confirmation test, viral load testing, and enzyme-linked immunoassay.

If the result was negative, blood was obtained for nucleic acid testing at the American Red Cross using the Procleix Ultrio HIV-1/HCV assay, manufactured by Gen-Probe and marketed by Novartis' Chiron.

The Procleix Ultrio test has been approved by the US Food and Drug Administration for qualitative detection of HIV-1 and HCV RNA from volunteer donors of whole blood and blood components.

Gen-Probe also manufactures the FDA-approved Aptima HIV-1 RNA qualitative assay for use in aiding diagnosis of HIV-1 infection, including acute or primary infection, directly from blood serum. According to the FDA website, Gen-Probe's test is the only one approved for such use.

If the nucleic acid test was positive, confirmatory testing was performed using Roche Molecular Systems' Cobas Amplicor HIV-1 quantitative test for viral load monitoring. A number of other companies also manufacture FDA-approved tests for viral load monitoring in plasma and blood donor screening, including BioMérieux, Siemens, Celera Diagnostics, BioLife Plasma Services, and Abbott, according to the FDA website.

Compared to these tests, however, Gen-Probe's qualitative HIV test "has a little more sensitivity," Morris said. "We actually picked up people who, on their reflex, had undetectable viral loads, but they were positive on our screening test and they did turn out to be positive. So it did seem to be that the qualitative test was more sensitive."

Of 3,151 persons tested in the UCSD study, 79 had newly diagnosed cases of HIV. Sixty-four of those patients had positive results from rapid HIV antibody testing; while 15 has positive results only by nucleic acid testing. Therefore, nucleic acid testing increased HIV detection yield by 23 percent.

Using an automated, anonymous data transfer system, the researchers also investigated whether patients were willing to access their NAT results via phone or computer. They found that of the 3,070 clients who had negative results after both antibody and nucleic acid testing, 2,105, or 69 percent, retrieved their results via computer or voicemail. Those who tested positive were contacted directly by testing center staff members.

The researchers concluded that NAT programs that include automated systems for result reporting can increase case yield, and might help decrease the HIV incidence rate by identifying people with acute infections who would otherwise be missed through routine screening.

"One of the big pushes in HIV prevention is what has been coined the "test and treat" strategy, where people get tested and get into treatment as early as possible, because we know if they go on treatment and their viral load is suppressed, their chances of transmission are significantly reduced," Morris told PCR Insider.

If such a strategy is widely implemented, "testing is probably going to want to still find people earlier and earlier, because those people in that window of time may be in their most infectious stage," Morris said.

Antibody-based testing is still, for the most part, the status quo among testing centers in the US, according to Morris. Nucleic acid testing is routinely used to screen blood donors for acute HIV infection; however, the cost of nucleic acid testing has been a roadblock to widespread, routine diagnostic applications.

The UCSD work is the latest in a growing body of evidence that routine nucleic acid testing may help diagnose HIV earlier and thus control its transmission.

One landmark study published in 2005 and cited in the UCSD paper involved testing more than 109,000 individuals at 110 state-funded testing and counseling sites in North Carolina.

That study compared enzyme immunoassay and Western blot testing with nucleic acid-based testing using BioMérieux's NucliSens HIV-1 quantitative assay for viral load monitoring in plasma.

Using an automated specimen-pooling method that produced a single sample with blood from 90 different patients, the researchers similarly found that nucleic acid testing could reveal HIV infections that standard testing could not, and earlier. However, the study also concluded that despite the pooling effort, adding nucleic acid testing translated to an additional $3.63 per person tested and about $17,000 per HIV infection.

The main reason for the spike in costs is that "for the whole state of North Carolina they were [testing] people who were quite low-risk – so there were a lot of places where people got tested," Morris said.

In contrast, in the UCSD study, more than half of the participants and more than 90 percent of positive cases were identified as men who have sex with men. The cost of finding additional HIV cases in the UCSD study was about $10,000 per case, about $7,000 less than in the North Carolina study, underscoring the particular applicability of nucleic acid testing to higher-risk populations.

"We were somewhat more targeted," Morris said. "Among people that are actually seeking HIV testing, particularly in our side of the world, we had a lot of men who had sex with men, and that's our main risk group."

Morris concluded that his group's study, along with others, does support the idea of increased use of nucleic acid testing for HIV diagnosis.

"I think there is broad support among us testers, the people who are running these programs, that this is something we should try and do," he said. "There is a little speed bump in the cost-constraining times we're in right now, where there has been a cut in funding for any testing, never mind expanding it to new methodology."

But in the long run, he added, "I think we'll benefit from companies developing these tests. I'm guessing Gen-Probe has a jump on this, but if they had competition and you could bring down price, that would make it even more feasible."

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