Hi Dr. Daar,

Thank you in advance for your time and energy for this site! I am a long term surviver, (21 years) and very drug experienced. I have reached another cross roads in my HIV journey. I have just completed the tests to see if I am R5 tropic for the Pfizer drug Maraviroc. Huge shock....I am. The challenge is they also did a PhenoSense Assay and I have major mutations in all classes of drugs. My current regimen is Epivir, Viread and t-20. I was also on Sustiva until December 05 but had to stop because of major CNS side effects. This combination is just over a year old. Viral load has risen to 420,000, CD-4 has dropped to 150. The only time I have ever been undetectable was 4 months into this last regimen. I would appreciate your oppinion on whether I should risk going into the Maraviroc study at this point with a "not so great" optimized background therapy and ruin my chances of really benefiting from this drug now or in the future. Or is it better to play around with some salvage therapies and wait for some other drugs that are in the pipeline to put together a stronger combo. I was with my Dr. today and I told him my gut was to wait. He agreed, however, said that it is a very difficult call. I have had no CD-4 cell before and stayed relatively healthy. Let me know what you think! Thanks again!

I will start by making some general comments and then specifics regarding your situation. Anytime someone is "failing" their antiretroviral treatment it is worth defining whether that is because their viral load has rebounded, because their immune system is getting weaker (declining CD4 cells) or that they are developing symptoms of HIV disease, such as opportunistic infections. For people with many treatment options without significant drug resistance the goal should be complete viral suppression (undetectable viral load). For those with significant resistance, the goal should be to maintain CD4 cells and to remain healthy while minimizing side effects from the antiretroviral drugs and preserving the drug or drugs that are active until a regimen can be put together that is likely to achieve full viral suppression.

It appears, from what you have written that you are not ill and that if your CD4 cells remain stable would allow you to maintain good health while on PCP prophylaxis for some time. As you have done, it is important to sit down with your provider and review your treatment history and most recent drug resistance data to determine the likelihood that you could create a regimen that would include at least two very active drugs, for which the CCR5 inhibitor might be one. Based upon what you have written, it sounds like you are likely to be resistant to NNRTIs and probably T-20 if you have been on these with persistently detectable viral loads. The usual strategy for those who are highly experienced, as you appear to be, is to assess whether one of the new/newer protease inhibitors (PIs) may be an option to use with a new drug, such as the CCR5 inhibitor. Information is available to assist your provider in predicting the likelihood that you would respond to tipranavir. In contrast, at this time less data is available to make such an assessment for response to darunavir (TMC114), the latter being available by expanded access. It is based upon this type of assessment and the nature of the clinical trial you are looking into as to what you would do next. The long and short of it is, if you and your provider agree that you can not be confident that you will be able to start at least two highly active agents at this time then you should take advantage of the fact that you are clinically stable and be monitored closely while awaiting more data and the availability of new drugs.

Thank you for your question and best of luck. Eric