re: stubborn numbers follow up
Aug 17, 2006
Hi Dr Young,
Thanks so much for your previous response: it was really helpful and friendly, I really appreciated it! Im the stubborn numbers patient from a couple of weeks back. I took the post/response to my doctor and he agreed that a genotype/phenotype resistance test was a good move. If you dont mind, the results came back today Id really value your thoughts sorry to be a bit involved but thought it might be easier for you to comment if you know the proper results. I only sort of understand what these mean, but here goes
List of mutations detected: M41L, E44D, A62V, K70R, F77L, F116Y, M184V, Q151M, T215Y/F, L10F/I, D30N, M46L, A71V/T, V32I, L90M.
Fold change: AZT=21, FTC=12, lamivudine=>max, d4T=2.1, Nelfinavir=15, lopinavir/ritonavir=39.
Unfortunately my doctor tells me that this means I am therefore resistant to all of my current meds, and will probably be partially resistant or sensitive to most of the other NRTIs and PIs. Though he says there are a couple of options:
2) Try an NNRTI-based regimen. Sustiva+fuzeon+tenofovir.
Which would you recommend of these two? Or is there anything else? Do you think I have the option to wait until one of the new classes of drugs (CCR5 co-receptor inhibitors or integrase inhibitors right?) comes into use?
However, there are a couple of issues: tipranavir, and certainly darunavir, though theoretically available, are difficult to gain access to here. Also, since I have had significant toxicity issues in the past (liver related) PIs might be a problem? This is also why my doctor is concerned about a viramune-based regimen. Also, my doctor does say that my resistance indicates that I may have sensitivity to tipranavir already, due to cross-resistance. Incidentally, my CD4 is now 159 (11%), viral load 305,000. Is it possible I just have an aggressive form of HIV? Or does this not happen? Im a bit worried about all this should I be? Or is this an easy fix?
Sorry for a lot of questions I know youre really busy. It all just seems to be a bit complicated! Thanks for your advice. It has been invaluable; if you have any suggestions, Id certainly love to hear them!
Response from Dr. Young
Thank you for your follow up question and comments.
I'm happy to hear that your doctor got the geno/pheno tests. You do indeed have a complex pattern of genotypic drug resistance and cross resistance. It's in these circumstances that having both resistances tests adds a degree of confidence in regimen selection.
I often like to use the Stanford University HIV Drug Resistance Database as a way of checking the genotypic predictions rendered by the commercial lab. If you input your genotypic data into this, you'll find a sobering prediction of resistance to essentially all nucleosides, with the possible exception of tenofovir; with regard to the PIs, intermediate to high level resistance to many PIs, with the exception of tipranavir, which is listed as low level resistance.
These genotypic predictors are in line with your HIV phenotype; here it would be useful to know what the fold-changes (FC) were to the medications that your doctor has proposed- clearly there's high level resistance to AZT, d4T, FTC and 3TC, nelfinavir and lopinavir/ritonavir; as such, these wouldn't be my choices. It's much more important to know what the FC was to tipranavir and darunavir (TMC114), since these new PIs could be essential to the next regimen.
Based on what I can interpret, option #1 would be a reasonable one for you. I have a couple of patients on this regimen; they've had great responses with (finally) undetectable HIV viral loads. T20 (Fuzeon) hasn't been too much of an issue for them, either.
I'd need a little of additional information before concluding about #2. You've not commented on whether you've previously been on a NNRTI regimen; if so, it's unlikely that you'd benefit from the use of efavirenz (Sustiva, Stocrin) in the next one (this affects option #2).
The last set of options to discuss is the use of investigational (not yet FDA approved) medications. In this area, the CCR5 inhibitor, maraviroc is closest to expanded access; there are a integrase inhibitors availabe (but only in clinical trials) from Merck and Gilead. Using these medications comes with some uncertainty about long-term safety and drug interactions, but could be essential to getting your viral load suppressed.
The key thing here is to try to get at least two potent drugs in your next regimen. Failing to do so might jeopardize getting resistance to T20 (Fuzeon) or other drugs in your regimen.
I hope this helps. Write back to let us know what you decide and how you're doing. BY
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