The Body Covers: The 47th Interscience Conference on Antimicrobial Agents and Chemotherapy
ICAAC 2007 Study Summaries: An Interview With Claudia Martorell, M.D.
September 20, 2007
My name is Dr. Claudia Martorell. I am an infectious disease specialist. I work at the Research Institute; I am the director of research. This is the clinical presentation of hypersensitivity reaction to abacavir by HLA-B*5701 status. Abacavir [ABC, Ziagen] is one of the HIV medications that we give to patients. It is a very potent and safe medication, overall. But it has one particular side effect, and it is very rare, but if it happens, it may kill people. The name of that potential side effect is hypersensitivity reaction. It is known by fever, rash, gastrointestinal symptoms, respiratory symptoms, and constitutional symptoms -- which means muscle pain, fatigue, among others.
If people have two or three of those symptoms [while taking abacavir], that is what we call a hypersensitivity reaction. So, what SHAPE, which was presented at IAS1 [The 4th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention in Sydney, Australia, which took place in July 2007) this past month or so, presented was, the sensitivity and specificity of the HLA-B*5701 marker among blacks and whites. The HLA-B85701 is a genetic marker that, if people have it, i.e., if people are HLA-B*5701-positive, then they have a predisposition to develop these hypersensitivity reaction.
That is very important because, now, in our DNA area, and in this HIV area, if we can have a marker that tells us that we have a gene that tells us that a person is predisposed to have this side effect, it is better to do the blood test. We know this person has this gene, this marker; this drug then is not for this person.
On the other hand, if this person does not have that marker, the drug is perfect for that person -- and it is safe. This drug [abacavir] is so potent. It's so safe overall that, with a simple test -- a simple blood test -- we can provide even more safety for our patients. So that's the basis of this SHAPE trial.
Based on SHAPE, we were determining this hypersensitivity reaction -- sometimes it is difficult to diagnose. For instance, a hypersensitivity reaction can be confused with Bactrim allergies. It can be confused with Sustiva [EFV, efavirenz, Stocrin] rashes. It can be confused with nevirapine [NVP, Viramune] rashes. So sometimes a doctor or a healthcare provider might diagnose hypersensitivity reaction in a person because it is a clinical diagnosis in the past and a person might not have had hypersensitivity reaction. Once a person has a diagnosis of hypersensitivity reaction, you are not supposed to rechallenge, or give the medication again.
So, with this blood test we can now confirm whether the person has it [hypersensitivity reaction] or not from the beginning at screening, before we give the medication.
This particular study that we are presenting at ICAAC2 tells us by HLA-B*5701 what are the clinical symptoms that a person has if they really had hypersensitivity reaction. Based on that, the results are that the person that has HLA-B*5701 positivity has three clinical symptoms, and two of them are more common than in people who do not have hypersensitivity reaction -- and these are fever and constitutional symptoms. Usually, people with hypersensitivity reaction with HLA-B*5701 will develop these symptoms within the first 21 days. No one will develop those symptoms after 42 days. The sensitivity of the test of the HLA-B*5701 is 100%. So those are basically the results.
But once we start giving people the genetic test to see if they have HLA, if they do test positive, then they won't take abacavir, ever. Right?
If someone has an HLA-B*5701-positive blood test, that person should not, or must not, get abacavir. Because there is a probability of developing hypersensitivity reaction. On the other hand, if the person has a negative blood test for HLA-B*5701, then it is safe to give abacavir, because there is a negative predictive value of 100%. It is very specific.
So, if this is related to the SHAPE study then isn't it true that African-Americans experience hypersensitivity reaction less commonly than caucasians?
Yes. There were five total African-Americans that had a positive HLA-B*5701 test with confirmed patch testing. So there is a significant number of African-Americans that participated, but only five had both an HLA-B*5701-positive test with a patch that confirmed that they really had a reaction.
It's thus very unusual among people who are African American and Hispanic?
Well, in Hispanics, there is always a combination of genes. Hispanics are a mix of a little bit of everything. It is also less common. But the message should be the same, even in the African-American population. Because in African Americans who had the HLA-B*5701 positivity, they did develop hypersensitivity reaction. That should be the message. Anyone who has the HLA-B*5701, even if they are African American, Hispanic or white; they should not take the medicine [abacavir].
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