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Go for undetectable at any cost?
Jul 10, 2007

I've been positive for 22 years. Until two years ago, I was bothered only by minor symptoms, even though my CD4 count was below 200 for most of those 22 years. Two years ago, intense diarrhea struck and I was hospitalized with wasting syndrome, requiring intravenous nutrition for one year. My viral load was around 90,000 and t-cells remained below 50. Tests showed I had resistance to ALL approved HIV meds. What finally stopped the diarrhea and weight-loss was going on the new drugs MK-0518 and TMC-125. Here is my concern: Although my VL dropped to around 150 just two weeks after I started the new drugs (Hooray!!), should I still be trying to get it to below 50? My VL has been tested three times over the past 9 weeks I've been on this regimen. 170, 110, 143 were the exact results. Of course, I'm happy about this, but because I'm not "undetectable", how aggressive should my doctor be about trying new and different drugs? Shouldn't that be weighed against not using up any future potential drugs? For example, should I go for Maraviroc now (or add Atazanavir, etc.) and try to knock the VL down to below 50? Or should I be content that the number is below, say, 400, and keep some new developing drugs IN RESERVE in case my virus breaks through and I need them? Can us salvage patients use up our potential arsenal too quickly? Should I be satisfied with my "below 200" results and not risk eventually becoming resistant to these brand new classes of drugs? Or am I at risk now anyway because I'm not at totally undetectable levels? Thanks for helping.

Response from Dr. Sherer

I will make some observations that may be useful to you, but I will caution you that this website is not a very good way in which to answer your complex question, because invariably there will be important information that I lack that would be helpful in answering your question. For that reason, I urge you to take these observations to your doctor and talk to him or her about them.

I will refer you also to the most recent version of the HHS Guidelines, which have an extensively revised section on the management of people living with HIV who are heavily treatment experienced with resistance mutations, as you are. The URL is http:://AIDSinfo.nih.gov/. What is new in this section is that the new goal for the treatment of such individuals is to fully suppress the virus to below the level of detection (if possible) and to elevate the CD4 cell count. In the past, the guidelines offered a different goal, i.e. to maintain the CD4 cell count (i.e. prevent further decline) and to maintain low level viremia, rather than achieve full suppression.

The reason for this change, as your case illustrates pretty dramatically, is the availability of new, third line medications that have been shown to acheive potent viral suppression below the level of detection in 50% or more of people who are heavily treatment experienced. These medications include tipranavir and darunavir (new FDA approved protease inhibitors that are active against virus with resistance to earlier PIs); TMC-125 (a second generation NNRTI, also known as etravirine, that is available by expanded access); reltegravir, the first integrase inhibitor that is available by expanded access; and miraviroc, the new oral entry inhibitor (actually a CCR5 entry protein inhibitor) that is available by expanded access.

However, having said all of that, it still may not be possible to achieve viral load reduction to <50 copies in all cases, and maintaining ongoing low level viremia, as in your case, may be the best that can be achieved. Particularly if this is accompanied by rising or level CD4 cell counts and clinical improvement, then this would represent a desirable outcome. Low level viremia does carry an increased risk of ongoing drug resistance, but that may be unavoidable.

So, in sum: You and your doctor can reasonably have the goal of achieving viral loads below detection, i.e. < 50 cop/ml. There may be additional steps that you can take with this regimen, or with intensification, to achieve that threshold. And even if this cannot be achieved, good outcomes are associated with regimens that lead to rising or stable CD4 cell counts and low level viremia.

As above, talk to your doctor about all of these issues. guidelines


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