Response from Dr. Sherer
The hardest question for treatment experienced patients with many resistance mutations like you is, when should a change of medications be made with the very latest drugs, and on the basis of what criteria?
The answers often differ from one patient to the next, depending on the details of their treatment history and response, their experience with side effects and toxicities, the results of their resistance tests over time, and the remaining ART options available to them. Often there are other important considerations as well, such as concomittant hepatitis B or C, or other chronic medical conditions and medications.
A few general points can be made. This is a better era for patients in your position, for two important reasons. First, there are new drugs on the market, such as tipranavir, and also available now via expanded access, such as TMC-114, that have shown activity against viruses that are resistant to all current PIs. There are also many promising drugs that target new points in the virus life cycle, such as Fuzeon (also know as enfurvitide or T-20).
Whenever such a change in regimen is made, its clear that the best outcomes will result from a regimen that has at least one new class of drugs (if possible) and as many active drugs as possible.
Note also that there is NO clear benefit to using the above new PIs, i.e. tipranavir or TMC-114, if your current virus has good susceptibility to one or more of the current PIs, such as LPV/r (Kaletra). So its a good thing that these drugs are still available to you some time in future (if necessary).
Finally, the goals of treatment are different for patients in your position, in that some viremia may be unavoidable, and the best outcome that may be achieved with CD4 cells is to prevent further decline (rather than continuing CD4 cell elevation).
I don't have enough information to comment on your specific regimen, or the likelihood that it will last for one or more years. I would take these comments to your doctor and talk to him or her about your concerns and questions regarding your specific regimen.
I would say that the fact that your CD4 cells are above 200, and your viral load is below 10,000 are favorable signs, and if they have been this way for some time, that also is favorable.
If you have had phenotype resistance tests as well as genotype tests, you might ask your doctor about the 'replicative capacity' of the virus, which is a laboratory measure of the virus' ability to replicate in the presence of various drugs. It gives your physician a rough measure of the 'fitness' of the virus, which ART can influence and impair.
I would note, however, that you have two active PIs still available to you now, i.e. tipranavir and TMC-114. As you are taking T-20 already, there would not be a member of that new class, i.e. the entry inhibitors, available to you at present. It's not possible to predict exactly when the next generation of entry inhibitors might be available on the market, but there are some clinical trials of these drugs that are enrolling patients now. You can ask your doctor about these, and also call the trial hotline for sites, 1-800-TRIALS-A.
There are also promising NRTIs and NNRTIs in development that are active against most resistant virus, and, as your doctor suggests, they may be available as early as 2007, but there is no way to predict these events.
For example, we were all disappointed when two recent promising candidates for new entry inhibitors were dropped from clinical development - one for liver toxicity and the other for lack of clinical efficacy. A third candidate remains in clinical trials, and other new drugs and targets are also in early development.
As above, please review these thoughts with your doctor, as he or she has much more information on your specific situation.
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