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HIV Drug ResistanceHIV Drug Resistance
           
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Dealing with Dwindling Options
Sep 19, 2004

Thanks for all of the advice you have been giving us. I've been on nearly all of the meds since 1987 (all three classes, but not entry inhibitors) and the virus has managed to eventually develop some resistance to all of them (i.e. detectable viral load) despite my perfect adherence. Most of the drugs have been added sequentially after theyve become available. Most recently, I added high dose Keletra and Saquinavir this winter to three NRTIs. Rather than decrease, viral load increased to 10,000 on these PI's in only three months. Fortunately my CD4 is still above 20% and Ive never experienced any illness or adverse drug side effects. But it seems I've run out of options for getting an undetectable viral load again.

I have two questions. Pending guidance from genotype/phenotype test results (which I have not yet received), will it be possible to kludge together an effectively suppressive regimen using one or two of the newer medications (i.e. Fuzeon and potentially Tipranavir, TMC 114 or TMC 125) that I have not yet taken? If not, what hard evidence exists to suggest that people like me can continue to take a cocktail of meds for an extended period of time (i.e. 3-5 years) and remain healthy despite incomplete viral suppression? This might help me to remain healthy and buy valuable time until more powerful new meds come along. Put another way - is there really any hard evidence that the virus becomes less pathogenic or less fit when it carries so many mutations under continuing and ongoing multi-class drug pressure?

Response from Mr. Kurtyka

1. "will it be possible to kludge together an effectively suppressive regimen using one or two of the newer medications (i.e. Fuzeon and potentially Tipranavir, TMC 114 or TMC 125) that I have not yet taken?"

Part of the answer to this question lies in the results of your resistance testing. Assuming you qualify for one or more of these studies, the addition of fuzeon with these investigational agents sounds like a decent plan.

2. "is there really any hard evidence that the virus becomes less pathogenic or less fit when it carries so many mutations under continuing and ongoing multi-class drug pressure?"

There is an evolving body of knowledge related to viral fitness and replication capacity. Heavily mutated, resistant virus is often significantly less fit than wild-type virus and is probably responsible for helping to maintain immunologic (CD4 count) and virologic (VL) control despite significant drug resistance. Studies are not showing that certain mutations are more likely to reduce viral fitness than others. So yes, it may be quite possible to stay on an ARV regimen an extended period of time (i.e. 3-5 years) and remain healthy despite incomplete viral suppression.

--dk


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