Labwork : We Shall Overcome - by Staff

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Back to home » HIV 101 » POZ Focus » Labwork

Table of Contents

 
Blood Simple

Resistance Testing

CD4 Count

Viral Load

CBC

Chem-Screen

Who's Got You Covered?

We Shall Overcome

In This Corner

Down At The Lab

 
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Sanctuary for Survivors (14 comments)

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It’s Time for Tenofovir 2.0 (8 comments)

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We Shall Overcome

by Staff

Drug resistance tests don’t just deliver bad news. They help you find a new treatment regimen. HIV specialist HOWARD GROSSMAN, MD, explains

Do you do many drug resistance tests?
We do them on treatment-experienced patients when we are contemplating a regimen switch—at the point when falling CD4s and rising viral load indicate that therapy is failing. But we also do them on treatment-naive patients, because there are plenty of people who were infected with resistant virus.

Do you use a genotype or a phenotype?
Both. I think that each test gives different information, and you use them differently. If somebody is very treatment experienced, their virus may have a whole series of genetic mutations, and from the genotype you get some idea of which drugs it’s resistant to. Then you look at the phenotype, and you may find, for example, that it’s 20-fold resistant to indinavir. In other words, the virus in that patient is 20 times less sensitive to that drug than is wild-type virus, or virus that has never been exposed to that antiviral drug. Well, it’s very possible that with ritonavir “boosting,” you can overcome that level of resistance. [A small dose of ritonavir  taken with indinavir boosts the latter drug, stabilizing levels in the blood and stopping the liver from metabolizing it too quickly.] So even though you see resistance in the test results, resistance isn’t an all-or-nothing thing. It’s a continuum. You can try to overcome it.

Do the tests give you different information over time?
What we’re actually doing in practice is a sort of serial phenotyping and genotyping, so that we can see the virus changing. I call it “banking” of the tests. Let’s say, for example, that somebody was on 3TC years ago and their virus has an M184V mutation. At this point they’ve been off 3TC for a long time, and you don’t see the mutation anymore when you do the test—but, in fact, it’s still there in “archived” virus—virus that exists in small numbers. And the minute you gave 3TC again it would come back out. If I’ve tested this patient before, I can look back at an old genotype I did a year and a half ago, when he or she was on a different regimen, and see the old mutations.

Overcoming resistance is a new approach. What does it really mean?
I have some patients who, when they get their resistance tests, have all black boxes—they’re resistant to every single drug. But then you have to look closer: With which ones, if you boost the drug levels, could you maybe overcome some resistance? Take Kaletra, for example, the ritonavir-boosted protease inhibitor. Kaletra has been shown to work in up to 50 percent of all patients who show a 40-fold resistance. So even if their HIV is 40-fold resistant—40 times more resistant than wild-type virus is—the drug might still have some benefit in about half those people. Now if I have someone who has other choices in this situation —other drugs to which their virus is sensitive—I’m not going to use Kaletra. But if they’re really experienced, and they’ve got less than 40-fold resistance, then I will try Kaletra—because I hope that at least 50 or 60 percent of them will respond.

You really have to be pretty skilled at interpreting that lab report.
It’s not cookbook science, that’s for sure.

Some studies have found that a good doctor, using a patient’s treatment history and viral load, can pick a treatment winner as often as a doc using a resistance test.
Maybe the first time you change your treatment regimen. But after someone has taken 10 drugs it’s very hard to guess from just their treatment history what they might respond to.

Do your patients really understand their resistance tests?
For the average person, it can get complicated, and you might depend a little more on your doctor’s interpretation. That’s OK. I try to give my patients some way to conceptualize this stuff—I put it in lay terms. They may not understand everything, but if they keep asking questions, they find a way to get it. And that really helps empower people and get them more involved in their care—which, in the end, is the key.  —Tom Beer



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