New viral fitness test helps determine regimens
New viral fitness test helps determine regimens
Test is offered along with resistance testing
The enigma of failing antiretroviral regimens and rising viral load in patients who are not progressing to AIDS now has an explanation and a tool that will help clinicians determine which patients will experience this phenomenon. It appears that at the same time HIV mutates and becomes resistant to antiretrovirals in some patients, the virus also has a reduced ability to replicate.
"This is something completely different from the resistance of the virus," says Nick Hellmann, MD, vice president of clinical research for ViroLogic Inc. in South San Francisco, CA. "We have some data already presented and some upcoming data that suggest when you have a virus that can’t replicate as well, it is associated with a better outcome as far as CD4 cell counts are concerned," he says. "The CD4 cell counts don’t decline as rapidly as they would if you had a wild-type virus that was not mutated."
This apparent silver lining in drug resistance now can be accurately measured in patients who require resistance testing. ViroLogic, which has developed the PhenoSense tests for phenotypic resistance testing, now has launched a replication capacity (RC) test that will give clinicians an indication of the viral fitness of drug-resistant HIV.
"Each patient has a unique strain of virus, and wild-type virus means it has no classically defined resistance mutations," Hellmann says. "You find there’s a broad range of replication capacities in those viruses, which can go as high as 200% compared with the reference virus we use, and as low as 10% of the reference virus."
ViroLogic’s RC test uses 100% as the median of wild type viruses for comparison, he says. Below that the virus has diminished ability to replicate and over that median, the virus can replicate more effectively than wild-type HIV. "When we perform our assay, we developed things called resistance test specters, a molecular copy of HIV that we insert in protease and reverse transcriptase virus. We run a parallel test with the assay, using the patient’s virus and then reference viruses, as well, and that gives us a constant point of comparison across viruses."
In ViroLogic’s studies, the variability in the reference test has been less than 0.2 logs. All of the RC testing is done within ViroLogic’s lab because the process is complex and would not be easy to put into a kit for other labs to reproduce, Hellmann says. "We are considering licensing out the test to other labs, but the decision to do that will rest on the quality of the lab that will perform the testing. We have agreements with all of the major national and regional labs around the country."
Since ViroLogic already provides both phenotypic and genotypic resistance testing, clinicians may send a sample to be simultaneously tested for drug resistance and for replication capacity. There is a two-week turnaround on test results.
This type of information would be especially useful clinically in instances in which a patient has been on a variety of therapies and is failing those regimens, he says. "The physician is in a quandary about what to do with the patient, whether he should evaluate the patient and switch therapy or continue therapy on the patient or stop therapy altogether. That’s a scenario where looking at replication capacity or the fitness of the virus may be helpful because if the physician finds out that the patient’s virus is unfit and there are no treatment options left to the patient, then the patient might do better to stay on the current therapy and not change."
Recent data show that this strategy would lead to slower disease progression. However, if the RC test shows the opposite, that the virus has a high replication capacity, then the physician would want to switch the patient to some new treatment to make the virus less fit and to slow down the pace of disease progression, Hellmann says.
ViroLogic will continue to improve the RC test, working toward a second-generation fitness test that would be able to identify which drugs in a treatment regimen contribute to poor viral fitness, he says. "Eventually, we would like to get to the point of helping the physician select which is the best drug from a therapy standpoint and from a fitness standpoint, as well," Hellmann says. "At this point in time, we can measure that, but we haven’t done enough testing to validate that type of drug-fitness testing, and we need to do more work before we can find the best strategy."
[Editor’s note: For more information about replication capacity testing, call (800) Pheno-AID.]
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