For 10 years I have been on nucs only - the rationale being that my t-cells were always stable and my viral load was not high enough for a genotype or phenotype. My doctor never liked this 4 nuc combo, but he inherited me with this drug combination. When the more sensitive genotype became available, my doctor and I decided to take a genotype. It revealed the unfortunate mutation called killer-69 insertion. My doctor explained that all current nucs were not effective w/ this mutation and that I would need to switch to the other two classes - to which I am not resistent at all. He says the only real benefit I am getting from the current regiman is supression of the wild-type virus in my body and that that was not good enough...that I was just growing more mutant virus in my body. (is this right?)

I currently have between 220 and 320 t-cells and between 500 and 2000 copies - this has been the same for 10 years - with the t-cell results coming in the 200s more lately..

I know I need to switch - but I am afraid. I have not developed any lipodystrophy or fat redistribution w/ all these nucs for 10 years...and I, like everyone, don't want it.

What do you feel is the best treatment option for someone in my situation - limited to non-nucs and protease w/ my counts.

I need a good synergistic combo that will 1) last a long time w/o going resistant 2) have least amount of side effects.

I am worried about blowing the non-nuc class as I have heard this is very easy to do. It worries me to take Sustiva because my doctor says if I develop a mutation tot his one - then the other two drugs in this case are gone too!

I am 33 years old.

Am I stating things that are true? Will my available treatments keep me healthy for a long time??

Thank you for your posting. While it is true that you have resistance to the NRTI (nuc) class, it does appear that you still have other options. In particular you should be fully susceptible to protease inhibitors (PIs). In general providers are reluctant to add a single drug (or in this case probably a PI boosted by low dose ritonavir). Consequently, conventional wisdom would be to add two active drugs which would require using the PI with a NNRTI or T-20.

Alternatively, one could make the case that you are stable on your current regimen and already resistant to all NRTIs so have little more to lose by staying on these drugs as long as your T cells are maintained. However, with your T-cells mostly less than 320 it probably is a reasonable time to seriously consider a change. If you did decide to modify your therapy you almost certainly would use a boosted PI. This could be given with a NNRTI. However, one could argue that it might be worth a trial of adding a potent boosted PI to your current regimen. It may be that this will be enough to get your viral load from 500-2000 copies/mL to <50 copies/mL. This strategy may not be terribly conventional but with drugs like Lopinavir/ritonavir (Kaletra) you are unlikely to develop drug resistance quickly and will have the luxury of time over the next few months to see if your viral load goes to undetectable levels. If so, great. If not, you regroup and probably are no worse off. The key is to be followed closely so that if viral suppression to undetectable levels is not achieved you regroup earlier than later so that PI resistance is not given a chance to develop.

Clearly there are several options that you need to discuss with your provider. The most important thing is that whatever you do next, you must be monitored closely. I think you should do great and if you stay on your next regimen should remain suppressed for many years.

Best, Eric