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discordant responder
Nov 22, 2007

I have a long history of treatment -20 years - and I have some level of resistance to most drugs. In 1998, I spent a year in a failing clinical trial regimen that had Sustiva and abacavir as the backbone; my viral loads during this year were around 600,000/ml. In 1999, I switched to saquinavir/r + zerit + epivir and somehow went undetectable for a month and then settled into low level viremia (1000/ml)and CD4 counts in the 300-400 range. In 2004 I switched to Lexiva/r + truvada + fuzeon due to lipodystrophy. Again, I went undetectable for about 3 months and settled back into my low level viremia with about 350 CD4+ T-cells. I am worried that staying on lexiva with low level viremia will induce resistance to prezista, and I am thinking about switching to prezista, etravirine, isentress and staying on truvada. My fear is that I will use up these new drugs and get resistance to them. What do you think about this combination? I have mixed feelings about trying for undetectable, because it has never worked. I have even thought about going back to saquinavir/r + truvada + fuzeon to preserve my Prezista option - if I still have it. I had a genotype done 4 weeks ago, but I have not seen it, and I am am skeptical about a genotype derived from low level viremia. My health, except for HARS, is good.

Response from Dr. Daar

Thank you for your posting.

This is an excellent question and raises many important issues. As you probably know it is difficult to formally address your specific question without having a great deal more information about you, your treatment history and recent and past drug resistance tests. But I certainly can provide some general responses that I hope will help you discuss this further with your expert HIV provider.

Needless to say the most important thing is to make sure that you have been able to take your medications consistently. Without this changing regimens further would likely set you up for failure and limit treatment options for the future. Assuming this has not been a problem you can move on to consider what treatment options exist.

Based upon your treatment history I suspect you have considerable resistance to the NRTIs and PIs. If you have been on NNRTIs in the past I would also expect resistance to this class. The fact that you have been on fuzeon (T-20) in the past with detectable viremia I would expect that you are probably resistant to this drug as well. Therefore, the next step is to use this information, along with resistance data to determine which drugs are likely to still be fully or partially active against your virus. Often one of these options will be a PI, such as one of the newer ones like darunavir (prezista) or tipranavir (aptivus). The resistance testing may provide some guidance as to which if either of these is likely to be the best option. If you have been on NNRTIs in the past the new drug in this class that is currently available by expanded access, TMC125 (etravirine) may remain active. Again, resistance test results from the past or now may provide some insight as to whether this drug is likely to be active against your virus. If you have never been on an integrase inhibitor before it is assumed that raltegravir (isentress) should be an active drug. The important thing is that it be combined with at least one if not two other very active drugs in order to enhance the likelihood of viral suppression and avoid the risk of developing resistance to this new class. The other drug that might be active for you is maraviroc, a ccr5 antagonist. You will not know this without getting a tropism assay to determine whether your virus uses the other receptor (CXCR4), in which case this new class of drugs is less likely to be of use.

Only after going through the above exercise with your provider will you be able to make an informed decision regarding what to do next. If you have 2 or 3 fully active drugs to use now I would suggest you strongly consider making the move now. My concern is that by remaining on your current regimen you may limit the activity of drugs such as PIs (darunavir or tipranavir) for the future and these may be very important agents to use in conjunction with some of the newer drugs such as raltegravir, maraviroc and etravirine.

I hope these general comments help you work with your provider.

Eric


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