Labwork : Resistance Testing - by Staff

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Resistance Testing

by Staff

—EXPERTS CALL IT: “HIV genotype”
—IT TELLS YOU: Which, if any, mutations (changes in shape) your virus has that may decrease a drug’s power
—TAKE IT: Upon diagnosis or before starting meds. When on a regimen but your viral load increases. When on a new regimen but your viral load doesn’t drop.
—RESULTS IN: 2–4 weeks

M. Lo Talks: Michelle’s April 2002 genotype test showed only one major mutation: the non-nuke knockout K103N. “I was in shock,” says the lucky long-termer. “I felt relieved because I still have a lot of options to play around with.”

Drug resistance—the bane of HIVers’ existence—occurs when the virus mutates and therefore escapes partial or complete control of a drug or class of drugs.

See, even when drugs have lowered your viral load to undetectable (below 50 copies), there may be a tiny amount of replication taking place. As it copies itself, the virus often makes mistakes. Some of these mutated strains of HIV sneak past the meds. With enough mutations accumulated—or even just one heavyweight that can KO all of a drug’s strength in one round— the virus muscles past your combo and “breaks through.”

Resistance testing tells you what mutations your HIV has developed and which drugs it may have become resistant to. This is important even if you’ve never taken HIV meds—drug-resistant strains of the virus are present in about one in seven treatment-naive U.S. HIVers.

If you have resistance, it may be time for a regimen change. Each HIVer’s profile is different, and a little resistance may not be all bad, so talk with your doc about the best strategy for you. You also want to keep resistance in mind when choosing a new combo, since different drugs cause different mutations. Some meds are more likely to cause one of the mutations that can singlehandedly make you resistant to a whole class of drugs; others may cause mutations that need to be present in bigger numbers before they can gang up on meds. Ask your doc what your Plan B options are likely to be if the combo you’re looking at stops working.

Two blood tests measure drug resistance: the genotype and the phenotype. The geno identifies which med-meddling mutations your virus is brewing. The pheno tells you how “susceptible” (or vulnerable) your HIV is likely to be to each drug.

You need a viral load of at least 500 to 1,000 for either test to work. And both should be taken while you’re still on your meds—once you go off, your HIV reverts back to its natural, or “wild type,” form making resistance more difficult to detect.

Genotypic tests “read” your HIV for specific mutations that may cause resistance to certain drugs. Mutations go by license-plate-looking names like Michelle’s “K103N,” which knocks out all of the NNRTIs (the non-nukes).

The upside of the genotypic test is that it’s cheaper and faster than the phenotype. The downside is that it doesn’t directly measure resistance, just mutations that are likely to cause resistance. Plus genotypes are wide open to interpretations, right and wrong. In January 2003, Elmhurst Hospital Center in Queens, NY, surveyed 100 self-described “experts” who did genotypic testing. Only 53 percent of the respondents were able to correctly match classes of HIV drugs with their associated mutations.

To directly measure the amount of resistance you have to a certain drug, you need a phenotype test. Here’s how it works: A lab tech puts samples of your virus in test tubes, each containing a different HIV drug. They count the number of copies your HIV makes in each tube. The technician  repeats the process using lab-standard, nonmutated samples of HIV.

The tech then calculates your resistance by performing a few measurements and calculations.

First, they look at your “IC50”—how much of a drug it takes to cut your HIV’s replication by 50 percent. Then they compare your IC50 with the IC50 of the lab’s plain old, unmutated virus. This comparison is measured in “folds.” If it takes 10 times more drug to suppress your HIV than it does the lab’s, you’re said to be “10-fold” less susceptible to that particular drug.

Finally, every lab defines a “cutoff”—how much resistance is likely to cause drug  failure—for each HIV med. The tech uses this cutoff to determine how well your virus may respond to a drug. For example, it takes 18 times more Sustiva to suppress Michelle’s HIV than it does the lab’s. This is well past the lab’s cutoff, so she has “reduced susceptibility” to the NNRTIs listed in her report.

Because phenotypes cost about $750 to $1,110 a pop, some docs make do with just the genotype. But like Marvin and Tammy said, it takes two—to get the clearest picture of resistance, that is. Phenotypic testing is vital for HIVers with few treatment options; a partially effective combo is likely a keeper.

Most major insurers cover a phenotype if your doctor orders it. (A combined geno/pheno by Monogram Biosciences, the only company that offers it, may save dollars.)

                                  *                      *                         *

How to tell if your HIV is fit or flabby

Being mistakes, many mutations make faulty—or less “fit”—versions of the original virus. Your HIV may have learned how to duck the drugs, but in the process it may also have become too weak to do battle against your immune system. How can you tell if mutations are making your HIV more wimp than warrior? By taking a viral fitness test!

The test measures your HIV’s “replicative capacity”— its ability to make copies of itself. If your virus is resistant but unfit, doc may decide to keep you on a combo that otherwise may seem to be “failing.”

At present, this test is commercially available only through Monogram Biosciences. The good news: It’s free when doc orders a phenotype or combined geno and pheno test.

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