—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.
A TALE OF TWO TESTS 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.
WHAT’S YOUR (GENO)TYPE? 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.
PHENO KNOW-HOW 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.
THE FINE PRINT 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.)
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WIMP OR WARRIOR? 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.
