If you are thinking about obtaining TMC 125 (Etravirine, a new non nucleoside yet to be approved) via Tibotec’s expanded access program (EAP) and you have developed resistance to non nucleosides in the past (Sustiva, Viramune, Rescriptor), be aware that it is very difficult to know if TMC 125 will work for your virus since the mutations that predict its efficacy may not be present in your genotype. Non nucleoside old mutations are “archived” and may not show up in your current genotype or phenotype tests. In fact, many people with past non nucleoside resistance show complete sensitivity to non-nucleosides years after developing resistance and not using that drug class. Doctors sometimes try to search old charts to see if they can pull out old genotype test results from a time when the patient was on non-nucleosides and failing. In many instances, that information is not found. We are also learning that TMC 125 specific mutations were not included in genotype tests years ago, so looking for old patient charts may be a moot subject.
We know from studies so far that TMC 125 is not effective in people with previously accumulated and extensive NNRTI resistance, but it can still work in those with more limited mutations.
My suggestion is that if you are going to start TMC 125, make sure that you are not gambling about assuming drug sensitivity, so NEVER start it with only one fully active agent but TWO. This will ensure that you have enough of an active background for viral suppression and sustained response in case that you may not have sensitivity to TMC 125.
Possible combinations :
No resistance to Prezista but resistance to Fuzeon: Darunavir (Prezista) + TMC 125 + Raltegravir (Merck integrase available via expanded access as of Aug 2007) + nukes (approved agents + two EAPs)
If you have resistance to Prezista and Fuzeon and have an R5 tropic virus: Maraviroc+ TMC 125+ Raltegravir + nukes (approved agents + two EAPs)
If you do not have resistance to Fuzeon or Prezista: Fuzeon + TMC 125 + Prezista + nukes ( all approved agents + one EAP)
If you have resistance to Prezista but not Fuzeon: Fuzeon + TMC 125 + raltegravir (approved agents plus two EAPs)
If you do not have a R5 only tropic virus and have resistance to Fuzeon and Prezista: TMC 125 + raltegravir + ???…you may want to wait
If you have resistance to Prezista, Fuzeon, and have a R5 tropic virus: TMC 125 + Maraviroc +raltegravir
A lot of these combinations have not been fully researched. So far, we have some knowledge of interaction data between these agents and the only contraindication that I have seen is TMC 125 + Tipranavir (Aptivus)
Message: a new agent may not be an active agent, so be cautious and combine agents in such a way that you do not take too many chances. Make sure that you have a doctor who knows the data on these agents, potential interactions, and how to deal with lacking resistance information.