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To Blip Or Not To Blip Update
Feb 1, 2003

Hi Dr. Cohen, I'm writing to update you as requested following my question you answered on January 14th.

I finally got my VL results after waiting 12 days for LabCor to process the sample (ridiculous). It came back undetectable (below 50). My CD-4 was stable from 1400 to 1410. My doctor and I spoke today and we think the previous 449 may have been a "bad lab." It could have also been a blip but I've never seen one like that. I've only had a blip in the week following a Remunue injection and I've been off that for over a year now. We also went back and checked my previous geno-types for mutations and I was correct that I do have the 215/AZT and 184/3TC mutations along the 30 on Nelfinavir that I referred to in my previous question. I spoke with him regarding your concerns about the 215 creating resistance to AZT, Abacavir and to some extent Viread and that possibly I should intensify my regimen. After some research and consultation on resistance we found that while 215 certainly does indicate resistance to AZT, Abacavir and even to some extent Viread and while 184 of course causes resistance to 3TC, when 215 and 184 are seen together without further mutations in the NRTI group, the resistance is actually reversed and causes increased efficacy of all three drugs. I was told if you have to have mutations, 215 and 184 were the two to have and addtionally 181 on Viramune with the 215 and 184. It was brought to my attention that Trizivir alone would not have held my virus in check for three years if that were not the case because all three drugs in the combination would have reduced efficacy with the mutations listed above. They also brought up viral fitness and stated that 215 and 184 together without the presence of further NRTI mutations actually hampers viral fitness. I'm kind of torn on this theory because very few publications have printed information on combinations of mutations and viral fitness. Any ideas? I've decided that since the VL came back undetectabe, I'll just monitor it closely and if it rears it's ugly head again, I'll take the hint and get further resistance testing (geno and virtual pheno)and change the regimen. What do you think? If it pops out again I'll write you for ideas of new regimens. By the way, I wanted to say, "thank you." Even though you are far away, you've only been an e-mail away for me. Your expert advice, comfort and humor have made things much easier for me since my diagnosis in May of 1997. Your work and your humanity are both greatly appreciated!

Response from Dr. Cohen

Thanks for your kind words... amazing power of this e- technology stuff I agree... you could be as you noted either 5 miles from me here in Boston, or 5000 miles in Eastern Europe... and it all works out the same.

So - as for your summary on the interactions of mutations. I would agree that the mutation at position 184V is a important consideration - as it clearly does alter HIV to become more sensitive to some drugs including AZT when it is there - and can even override the impact of the mutation at position 215 which causes some resistance to the meds you are on. But it is also fair to state that while we can make general statements about these mutations, there are still factors that alter the sensitivity of HIV to these meds in ways we cannot always predict. Meaning that some would have your two mutations and not stay well controlled on Trizivir while others would remain well controlled as you are. There are viral mutations in other positions that we don't factor in that alter the impact of these mutations. And there are fitness issues. And finally there are immune system issues - sometimes the immune system is contributing to this control we see. So while we might not recommend Trizivir to someone with the mutation pattern you have, it is mainly because we don't know enough to account for these other factors - and we know there are combinations with a higher likelihood of success. But if it is working - and your years of suppression is certainly a definition of working - then it only underlines how muc there is still to learn.

So - keep going, stay well. Don't fret the blips. And write back with whatever else you need... and maybe someday in addition to all the good that this e-connecting gives us, we'll figure out a way to stop the incessant onslaught of email advertising lower mortgage rates and bigger "body parts" all guaranteed...



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