Hello, Thanks to all involved in providing this useful forum. My question concerns possible next steps. I tested positive in 1995, started treatment in 2001 (taking it faithfully). Today the genotype test indicate my virus is resistant to all NNRTI and NRTI medications. My doctor proposes my next treatment be Fuzeon, Kaletra and (fos)Amprenavir. My concern is twofold; first the twice daily shots will put additional constraints in my life so is there another treatment as effective and less intrusive, and second is this the time to be taking Fuzeon or should I be holding it off for later. Or am I already at the end of the line?

Thanks and best regards - Tom

Your doctor has information that is essential to the answer to this question, so I will provide some thoughts for you and him or her to consider. One key peice of information that you ommitted is your current CD4 cell count and viral load, and the rapidity of the fall of the CD4 cell count, which might give an indication of the urgency of this change.

It is unusual to be 100% resistant to all NRTIs at once, especially after taking a single regimen since 2001. There may be some agents, such as ABC, TDF, or DDI, which retain partial activity, and hence might offer some value in the next regimen. Obtaining a phenotype test would be useful, if that has not been done, to supplement the results of the genotype test.

NNRTI resistance is usually complete, once it occurs, and it is unlikely that any further use of these agents is possible.

I would agree with your doctor that a dual PI regimen is appropriate. I would be concerned about the combination proposed, as the pharmacokinetic interaction between them is complex, and the optimum dose has not been worked out. Kaletra and Invirase(saquinavir) would be a reasonable alternative, and the pK is more clearly worked out.

The timing of Fuzeon (enfuvirtide) is complex. A dual PI, as above, with a partially active NRTI (if available) might allow for you to postpone enfurvitide and the injections until the next regimen.

Another new PI is available by compassionate access, i.e. tipranavir, which requires 200mg twice daily of ritonavir for boosting, and has complex drug interactions, particularly with the PIs. It has good activity against virus resistant to all current PIs, so it may offer one pillar of the next (3d) regimen, if and when its needed, and could accompany enfurvitide.

As above, these suggestions should be put in context with all of the information that I lack with your doctor.