Results of drug resistance for HCV in http://hcv.geno2pheno.org comes up with fold change/resistance factor. What significance have these fold changes?
Hello Nadeem,
The fold change or resistance factor is the increase in curative dosage (for treatment and in vivo models) or EC50 value (when done with a pathogen in culture) of a specific pathogen strain, compared to the 'normal/drug sensitive' control.
A practical example: if a patient would normally be cured by a standard dose of, say, 150 mg of a drug, but you find that this particular patient does not respond to the treatment and you need an increased dose of 750 mg instead to effect a cure, the fold-increase is of course 5. Similarly, if a culture of malaria parasites, Plasmodium falciparum is normally sensitive to chloroquine at 20 microgram per ml as EC50, and you are testing in parallel a strain isolated from a patient that did not respond to chloroquine and find that the dose-response curve has shifted to a new EC50 value of 200 microgram per ml, the resistance factor is 10. The EC50 value, by the way, is the value (concentration) at which the growth or viability of the pathogen culture is inhibited by 50% (Effective Concentration 50%). The resistance factor is an important indicator as to how severe the resistance phenotype is. If it is low, a cure may still be possible by increasing the dosage or treatment schedule. A high resistance factor probably means the treatment is no longer effective, at least for the strain or patient in question. It is important to understand that treatment failure with a specific drug does not necessarily indicate drug resistance. Drug resistance is defined as the pathogen becoming less sensitive to the drug, almost always through a genetic change. But a treatment can fail because a lot of other factors as well, for instance:
1. the patient is too severely ill already
2. the patient is immunocompromised and the drug relies in part on the immune system
3. The administration was faulty or the patient did not take the medication as recommended
4. The drug quality was sub-standard. Perhaps the storage of the drug was inappropriate, or the drug was old. There instance of deliberate falsification of drugs, especially in developing countries. Generic drugs are cheaper but not always of the necessary quality.
5. Simply, many treatments cure only a percentage of patients; there is a statistical distribution
Hope this is of use.
Harry de Koning
Hello Nadeem,
The fold change or resistance factor is the increase in curative dosage (for treatment and in vivo models) or EC50 value (when done with a pathogen in culture) of a specific pathogen strain, compared to the 'normal/drug sensitive' control.
A practical example: if a patient would normally be cured by a standard dose of, say, 150 mg of a drug, but you find that this particular patient does not respond to the treatment and you need an increased dose of 750 mg instead to effect a cure, the fold-increase is of course 5. Similarly, if a culture of malaria parasites, Plasmodium falciparum is normally sensitive to chloroquine at 20 microgram per ml as EC50, and you are testing in parallel a strain isolated from a patient that did not respond to chloroquine and find that the dose-response curve has shifted to a new EC50 value of 200 microgram per ml, the resistance factor is 10. The EC50 value, by the way, is the value (concentration) at which the growth or viability of the pathogen culture is inhibited by 50% (Effective Concentration 50%). The resistance factor is an important indicator as to how severe the resistance phenotype is. If it is low, a cure may still be possible by increasing the dosage or treatment schedule. A high resistance factor probably means the treatment is no longer effective, at least for the strain or patient in question. It is important to understand that treatment failure with a specific drug does not necessarily indicate drug resistance. Drug resistance is defined as the pathogen becoming less sensitive to the drug, almost always through a genetic change. But a treatment can fail because a lot of other factors as well, for instance:
1. the patient is too severely ill already
2. the patient is immunocompromised and the drug relies in part on the immune system
3. The administration was faulty or the patient did not take the medication as recommended
4. The drug quality was sub-standard. Perhaps the storage of the drug was inappropriate, or the drug was old. There instance of deliberate falsification of drugs, especially in developing countries. Generic drugs are cheaper but not always of the necessary quality.
5. Simply, many treatments cure only a percentage of patients; there is a statistical distribution
Hope this is of use.
Harry de Koning
Thanks Harry,
You reduce my ambiguity related to the fold change in Resistance. Morr informative words.
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