Q&A HIV screening tool: New HIV combo assay identifies infection earlier than standard test
New HIV combo assay identifies infection earlier than standard test
It could help prevent infections
Peter Leone, MD, a professor of Medicine at the University of North Carolina in Chapel Hill and the medical director of the North Carolina HIV and STD Prevention and Care Program, has studied the ARCHITECT HIV Combo Assay, a new HIV test that identifies infection sooner than the standard antibody HIV test.
Leone answered AIDS Alert's questions about this new assay in this question-and-answer interview:
AIDS Alert: According to findings presented about the Abbott ARCHITECT HIV Combo assay at the July, 2009, American Association for Clinical Chemistry annual meeting, the HIV test can detect HIV virus up to nine days earlier than antibody-only tests. Would you please describe how this assay works differently from the current HIV screening tools.
Leone: This assay is different from the current HIV tests that are approved. The tests that are routinely used for diagnostic purposes are looking for antibodies. The current third generation ELISA [Enzyme-linked immunosorbent assay] now look at IgG and IgM antibodies specifically against HIV. The ARCHITECT, a fourth generation assay, does two things: it looks for antibodies but it also looks for the P24 protein produced by HIV very early in infection, which is what it allows us to make the diagnosis of HIV infection among people who haven't had time to produce antibodies under current tests. That's a significant step forward. It turns out that a significant number of folks who are tested for HIV are antibody-negative, but are infected with HIV. That very early phase of acute HIV is a time of active viral replication. People usually have hundreds of thousands to several million copies per mL, and they have very high loads in general secretions.
They're infected, but the standard test won't pick them up. We estimate the number of folks with HIV infection who might be in this acute window in any given time might be 3% to 20-25%. In North Carolina, we know that three to four% of HIV-infected individuals who come in for HIV testing at all of our publicly-funded testing sites are antibody negative, but have HIV in their bloodstream.
In San Francisco, at their STD clinic the people who are HIV positive and antibody-negative will be around 10%. In New York City, where they're doing screening for this early phase of HIV, between 15 to 20% of people who are antibody negative have HIV in the bloodstream.
AIDS Alert: And when do you expect it to be approved by the Food and Drug Administration (FDA)?
Leone: It's been submitted to the FDA and has been in use already in Australia and Europe for years. The CDC [Centers for Disease Control and Prevention] has been pushing for the assay to be made available. I have every reason to be hopeful that this test will become commercially available in 2010. Then we'll have to educate clinicians about why this is an important tool.
AIDS Alert: What do you believe will be the chief impact of the new assay when it's available commercially in the U.S.?
What we're realizing now is we have folks who are coming in for testing who we would have missed without the ARCHITECT. You could say finding 3% is small, but in San Francisco, it's an additional 10 to 15%. Even detecting just 3% of HIV infections earlier is important because they're detected while in the acute phase of HIV, which is the most infectious stage of HIV. People in the acute phase of HIV infection are 10 to 100 times more infectious than they are later on, and this group may contribute to 15 to 50% of all transmissions. So we have a very small window period that is four to eight weeks, and it's right after someone gets infected.
There is no HIV test that will close the window to zero days after infection. Right now the antibody tests find infection from four to eight weeks, and with the new test we're looking at reducing that window to two to four weeks. This new test approaches the results we find for individual RNA tests.
The incubation period for HIV is around one week to two weeks. If someone is exposed to the virus and becomes infected, it's in the body those first couple of weeks, and we can't detect it with the standard antibody screening tests. Within 7-14 days after infection, the person will get a burst of viremia, and the virus will spread through their bloodstream. From 85 to 90 percent of people will experience an acute retroviral syndrome at this stage. They'll have nonspecific symptoms, and they might be antibody negative, but HIV RNA positive. So if a clinician suspects an acute HIV infection, but orders an ELISA, the patient's infection might not be identified.
So it's very important to have the right tool.
There is one qualitative RNA test that has been approved for diagnostic purposes, but it's expensive, and it has a higher rate of false positives as a screening tool.
The beauty of this new test is it allows us to do HIV testing when we have only a suspicion of acute HIV, or we can use it to screen people and shorten that window period of identifying infection even more. In populations with higher HIV incidence, this test will fit in well.
For example, we know men-who-have-sex-with-men (MSM) populations continue to have ongoing HIV transmission, so testing services that target MSM populations could be an important screening tool. MSM populations often present early for testing. In Seattle, the average time in their STD clinic for men to come in for repeat testing is six months. Anytime you catch someone within an acute phase of HIV, you catch someone who is actively transmitting the virus.
In North Carolina, where we have an acute HIV testing program, about 50 percent of HIV cases come out of the STD clinics, so we think those would be another place that could use this test.
AIDS Alert: How does Abbott's HIV combo test compare with the RNA test?
Leone: One study from San Francisco, Mark Pandori's study, showed that the Abbott test picked up 80 to 85 percent of individuals who are RNA positive and antibody negative. It doesn't get everyone, but it's 80 to 85 percent. And it will be cheaper than an individual RNA test. Cost is a critical question Abbott is going have to decide. I'm a public health person, and pricing will be the real issue here. The individual RNA test costs $150-$200. The standard antibody test costs $2.50 -$3, but this doesn't include lab time. The rapid HIV test ranges from $8-$15. So what we would have to see for this test is for it to approach the cost or be cheaper than the rapid HIV test, which would make it less than $15. It would be a very attractive alternative.
Another advantage of this test is its turnaround time. It can be used almost like a rapid test. You draw blood and get it to where the test can be done. With a continuous operation, the test can be finished in one to two hours. Large clinics and hospital settings might be able to give this test a relatively quick turnaround.
AIDS Alert: The Centers for Disease Control and Prevention (CDC) has been pushing for early HIV detection for several years now, but national numbers still reflect a major problem with people being diagnosed late. How do you believe or hope this new tool might address or resolve this problem? For example, would this test be a more effective tool for hospital emergency rooms to use in universal screening?
Leone: It could be used as a primary test or as a back-up test. It makes more sense to use it as a primary test in those individuals with recent high risk exposure or who have symptoms that make you concerned they have acute HIV infection. We published an article in JAIDS in June looking at our acute HIV infected population in North Carolina. Bill Miller is the first author. And we were able to figure out that we could reduce HIV testing to 50 percent of the population, who'd be identified through visits to STD clinics and through prenatal testing because we don't want to miss HIV in pregnancy. I can see a couple of things happening: someone could come into the ER, saying he's had a recent high-risk exposure, and you'd use this test. Or, in certain settings, we'd just say that we'd use this test for all screening, period. These would be in areas with high incidence of HIV, and we know where those areas are in the United States. So if you put this test in place it becomes a primary test.
We think in North Carolina this has been a helpful tool in preventing transmission within networks. The problem with standard antibody testing, in looking at HIV transmission networks, is that you identify someone who may have been infected 6, 7 years ago. Their behavior or partners identified at the time of diagnosis may have little or no relationship to the sexual/social networks and behavior at the time they were initially infected. We think we can identify acute HIV infection, which has the added benefit of stopping transmission. It doesn't solve the problem we have of folks who don't know their HIV status and who aren't being tested at all, but it's an important piece.
AIDS Alert: Has use of the assay changed any HIV testing and surveillance practices in Europe where it was launched in 2004? If so, how?
Leone: In Great Britain, the test is recommended for use as a primary HIV test. There is recognition in Great Britain that we don't want to miss people when they come to be tested.
It's funny when we talk with folks from other places they say they've been using this test for a while now. They can give you anecdotal information about people the test identified as HIV positive who would have been missed otherwise.
Peter Leone, MD, a professor of Medicine at the University of North Carolina in Chapel Hill and the medical director of the North Carolina HIV and STD Prevention and Care Program, has studied the ARCHITECT HIV Combo Assay, a new HIV test that identifies infection sooner than the standard antibody HIV test.Subscribe Now for Access
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