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Resistance, falling blood counts, and current options
Feb 19, 2007

I have a long history of HIV, and when treatment drugs first came available, I was a proponent of the options these could provide (life vs death and hit hard, hit early). I was part of an Indinavir/D4T/3TC trial in 1995 and have generally remained in good health with reasonable blood counts. I am, however, not aware of ever having a non detectable viral load, and in recent years my v/l has been in the range of 40,000 to 80,000. Of course I am now showing resistance to all current classes of drugs. My current combination is Efavirenz, Lopinavir and Amprenavir, however this appears to be failing and I am concerned about further degeneration before the new drugs are available here in Australia. Over the past 12 months my CD4s counts have been as follows: March 2006 - 450, 15%; July 2006 390, 13%, Oct 2006 330, 10%, Jan 2007 288, 9%. My prescribing clinician, who also supervises trials I am and have been on (currently on the control arm of the Esprit interluken II trial) continues to try to encourage me to move to T20, or to wait until the Integase, NNRTI, and CCR2 drugs come available. In Australia, current advice is that this could take up to another year, and I currently don't qualify for any Special Access Scheme. I view T20 as an absolute last resort due to the lifestyle requirements associated with it. In my view, now is the time for me to take action, but I'm currently inhibited by the 200 CD4 count that serves as a threshold to access. I would prefer to not degenerate into the danger zone of less than 200, and am aware how difficult it can be to reinstate CD4 counts, no matter how good the drug. Do I wait for drug availabity and probably sustain further damage to my immune system, do I change my life to accommodate T20, or are there other options my clinician seems reluctant to consider, such as either recycling older drugs or trying some other available drugs to hold me over until the new ones are available?

With thanks Mark

Response from Dr. Sherer

I would advise waiting while you and your doctor repeat your CD4 cell count and viral load and genotype and phenotype test, and compare this genotype to the last one to see what resistance price you are paying, if any, for the delay.

First, my standard caveat with the most complex cases like yours: It's very likely that I lack some important information in your case to make informed choices. Only your doctor has all the necessary information, like specific results of resistance tests, prior treatment regimens and your responses, side effects, etc. So take my suggestions with a large grain of salt, and review them with your doctor.

As you suggest, you have had a gradual decline in your CD4 cell count, so I think you are getting near to a point when you and your doctor may want to change the regimen. My hope is that an additional new drug - one or more - become available to you to pair with enfurvitide when you start your new regimen. You will clearly have a superior response, and a greater benefit from starting enfurvitide, if you have one or more active drug to pair it with.

I would like to see the current genotype and phenotype to best select the next NRTI combination, e.g. Truvada, or Epzicom, or DDI/3TC. There may be a role for a recycled NRTI combination in a shorter time frame as well, as you suggest, and the phenotype offers useful additional information on this issue in addition to the genotype.

I would also want those tests to judge the merits of darunavir vs. tipranavir for you, if and when they become available, as well as other PI alternatives.

As you suggest, there are several new drugs that will be available in the US by compassionate access in 2007 that you would benefit from, and they may be available in Australia in the next 1-2 years. These include: etravirine, the new second generation NNRTI for those resistant to efavirenz; miraviroc, the new oral entry inhibitor; and MK-0518, the new integrase inhibitor. It will be helpful for you and your doctor to watch these drugs and their manufacturers carefully to look for a means of gaining access to them.

I hope these thoughts are useful. I think the decision of when to make this type of change is among the most difficult in HIV medicine, and I urge you to talk to your doctor about your concerns and these suggestions.

Inmune reconstitution syndrome
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