January 31, 2000
Several different questions are raised when considering how to choose new therapies after resistance. Is there a way to determine the drugs from which someone is likely to benefit before they start new drugs? Some people believe that we may already have tests available that could supply this information. The tests, referred to as "resistance tests," are of two distinct types -- genotypic or phenotypic. Genotype tests look at an individual's virus to determine "mutations" and to record where on the virus's genetic code these mutations occur. If mutations occur in the same place as mutations that are associated with resistance to a particular drug, then the virus is determined to be "resistant" to that specific drug. Phenotypic tests use an individual's virus to grow a new virus in test tubes and then record how much of a particular drug is required to suppress the virus's ability to reproduce. Based on this information, the test reports to which drugs an individual's virus is most likely not to respond. There is currently disagreement among providers about how useful these tests are when developing "salvage" therapies.
The presenter observed that many of the people on the study who were resistant to one or more of the nucleoside analog reverse transcriptase inhibitors (NRTI) were "hypersensitive" to drugs from the non-nucleoside reverse transcriptase inhibitor (NNRTI) class of drugs. Based on this observation, the researchers looked at a database of people who had similar NRTI resistance to see if they were also hypersensitive to the NNRTIs.
They determined that when you compared people with resistance to the NRTIs to those without this resistance, the people with resistance exhibited hypersensitivity to NNRTIs, while those without resistance did not. While the presenter was quick to point out that the study could not determine the clinical significance of this information, it does seem to suggest that some people may respond better to a salvage regimen that includes a NNRTI if they have a virus that is resistant to NRTIs.
Dr. Calvin Cohen presented a preliminary analysis of a study that asked providers to choose a therapy for people who had developed resistance to their first therapy, which included a protease inhibitor. The study participants where separated into similar groups -- with the first group's providers given the results of a phenotypic resistance test and the second group not having a phenotypic test performed.
The providers using the phenotypic test placed people on at least three active drugs 77% of the time. The providers who did not have phenotypic test, placed people on at least three active drugs 68% of the time. There was also a difference in how large of a median decline in viral load participants in each arm of this study experienced. The people who were not given a phenotypic test had a median viral load drop of .75 log. The people who received a phenotypic test had a median drop of 1.27 log.
It is important to note that this study did not provide the study doctors with "expert interpretation" of the phenotypic test, they simply provided them with the results and allowed them to reach their own conclusions. While this study does not guarantee people will have better results with "salvage therapy" if they use phenotypic testing, it does suggest that providers might benefit from the additional information provided by this type of resistance test.
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