Jan 17, 2007
Hi, Carol. In May 2007 I will have completed a 96 week maraviroc study, and all I can say is that this drug is miraculous. But have you heard any buzz about developing a resistance to it? I don't get a lot of info from the study's administrating clinic.
I've been positive for 15 years. I've developed a resistance to every anti-viral on the market including (most likely they tell me) Fuzeon even though I have a near perfect adherence to my drug regimen. Due to those wretched injection side effects, I was allowed to discontinue Fuzeon 9 months ago.
I'm a little worried. About 6 months after starting the study my VL dropped to 551, but in the past year it has inched back up to near 5,000.
Many thanks, RLT
Response from Ms. Salisbury
Hi RLT, I am unaware of current resistance data on maraviroc. There is a resistance expert on this web site and I recommend we ask him this question. His name is Renslow Sherer. I will post your question to him. I am anxious to hear his response also. Carol
Response from Dr. Sherer
Maraviroc is one of several CCR5 inhibitors, and the mechanisms and implications of resistance are as yet poorly understood. I urge the patient to discuss this good question with the study investigator, and to understand that the change in his or her viral load may well be related to resistance in other members of the regimen, rather than maraviroc, or to other factors.
One recent study analyzed the mechanism of resistance of small molecule CCR5 inhibitors in the test tube (in vitro). It appears that drug-resistant viruses have acquired the ability to utilize CCR5 in its inhibitor-bound form.
This story is further complicated by wide variations in the type of assays that currently can be used to detect resistance, and standardization of the assays is needed to help sort this out.
In addition, it appears that this class of drug behaves differently than simple competitive resistance mutations, in which an increasing concentration of virus with resistant mutants will lead to a corresponding increase in viral load and an increased IC50, i.e. the amount of drug needed to inhibit 50% of the virus. With CCR5 inhibitors, the IC50 does not change in the presence of resistance mutations, rather there is a reduction in the percent of maximal concentration with no change in the IC50.
That may mean little or nothing to our questioner, but it poses a new obstacle to clinicians, who have to interpret these tests, in that the very definition of resistance is somewhat different for this class of drugs.
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