What is the minimum Crix. blood concentration for lasting efficiency?
Nov 27, 2000
First of all, thank you for your so hard work in anwering all the questions. I have read your forum every week since 1997. Until today I have always found the answer to any question I had in the "read answered questions" list, and I never had to ask one special for me. Nevertheless I cannot find any information about what follows either on this forum or in other parts of your website and links. Here are the facts:
1. I have been on Crixivan (1,200mg twice a day) + Combivir (300mg/150mg twice a day) since october 1998. Since then my VL has always been undetectable (&;lt;50 copies). That is why I decided to stay in the twice a day group of Crixivan takers although the recomendation had been issued for everyone to go back to a thrice a day uptake. My CD4 count rose from an initial 260 (Ocober 1998) to a maximum 460 (October 1999) and slowly but steadilly decreased afterwards, until September 2000 when it reached 300.
2. My doc advised a Cixivan dosing in the blood. The results were: "C max:" = 12,173ng/ml (1 hour after taking it) et "C min" = 61ng/ml (12 hours after). He said the "C Min" was too low and we decided to try to boost the Crix by adding Norvir. I was also happy with that because it allowed me to take my meds with no consideration of meal time and with a bit more flexibility on hours.
The new regimen is: Crix (600mg twice a day, that is half the previous dose), Combivir (300mg/150mg twice a day, same dose as before) and Norvir (100 mg twice a day).
3. After one month on this new regimen my VL is still undetectable and my CD 4 count has risen again to 464. The new concentrations of Crix in the blood are "C max" = 5,107ng/ml (3 hours after taking it) which sounds logical to me as I take half as much Crix as before, and "C min" = 1,126ng/l (12 hours after) which sounds far better as compared to 61 ng/l with the previous regimen (additionally the Norvir concentrations are "C max" = 2,008ng/ml and "C min" = 487 ng/ml).
So here are my questions:
1/ can you tell me if there are "official" numbers (range) for the minimum "C min" necessary for the Crix. to remain efficient all day long (is 1,126 ng/ml enough?) and does a "C max" level at 5,107 ng/ml seem enough to you (I am a bit worried about this dramatic reduction in the Crixivan quantity I take, I have never read in any publication that it could be reduced to less than 800 mg twice a day even with Norvir boosting)
2/ Is there any reason or scientific explanation (even only as hypothesis) why a regimen could be evaluated as losing efficiency because of a decrease in the CD4 count although the viral load remains constantly undetectable (in such a case how could the virus dammage the CD4s if it is not active?).
Thank you for your reply, I am sure the question about the "efficient" concentration numbers will be of interest to a lot of people As I told you before, this information is really hard to find and it never appears in any of the various "how to read your results" information sheets I know.
Finally I hope you will excuse my so poor English (I am French).
Response from Dr. Pavia
Votre Anglais et tellement mieux que mon Français.
These are very, very good questions and I think we are beginning to enter an era where we can actually use drug levels effectively. We are not really there yet, and there are no really clear answers to your question about what is an ideal level. The best way to determine the ideal level would be a combination of knowing what blood level would mean that the level in all tissues remains higher than that for non-resistant ("wild-type") virus and for some resistant virus, and knowing from studies what levels are linked with long term success in patients. We don't have perfect answers to either of these.
The most commonly used regimen for crixivan and norvir is crixivan 800 mg with norvir 100 mg twice daily. I am not sure I have seen the combination you are on studied. There is at least one study that suggests that failure on crixivan is associated with Cmin (or trough) levels of less than 0.1 mg/L (100 ng/mL, unless I did my math wrong). That may still represent much too small a margin of safety, since virus with only 2 or 3 mutations may be resistant at that level. So, your higher Cmin levels are very reassuring. Your peak level is lower than what is usually seen with the 800/100 regimen. However, I don't know if that matters since the best data we have suggests that for crixivan the Cmin and the AUC (area under the curve) are better predictors of response than the peak level (Cmax).
There is no real precedent that explains why your CD4 count fell with an undetectable viral load, but now is climbing. I take it as a positive sign that is increasing, but it is an unusual pattern. Still, unusual things happen every day in HIV medicine. I would discuss the regimen, and decide whether the more studied 800/100 might make sense for you. Remember to keep drinking fluids (or rather keep drinking water in addition to wine), since you can definitely get kidney stones on the augemnted crixivan levels
Good luck, and thanks for the excellent question
Andrew T. Pavia, M.D.
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