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When is it time to switch and what did I do?
Jul 19, 2001

Dear Dr.,

I was diagnosed with HIV (actually, AIDS, since my T-cells were so low, but I had not had any opportunistic infections at the time) about 1.5 years ago. My T-cells were at a low of 14 and my viral load 'off the charts'>500,000. My doctor put me on Sustiva, Epivir, and Zerit. My T-cells have been climbing nicely (200 at 4-6 months, 500 now) and my viral load has come down as well, however, never to undetectable levels (~200). It reached 200 at about 4-6 months, and remained there for a while. Since I was doing so well on the current medication, we decided not to switch at the time. However, recently my viral load has started to come back up, 400 5 months ago, 800 3months ago, and 3000 last month. My questions are: 1) Isn't it time to switch meds? My doctor still thinks it may a longer-duration blip! 2) If I insist on resistance testing, which one should I get, or BOTH? 3) Are there other combinations out there that are easy to take as the one I am on now? Twice a day and no food restrictions is prettty good. 4) Did I ruin this combo early for me? Although I was pretty good in 1.5 years, I have to confess I did miss the morning zerit/epivir 2 times early in my treatment, and have taken the meds a few hours after the 12-hour mark a few times. Does one have to be 100 complaint? If/When I switch, does I truly have to be a perfectionist about it? 5) I know it is possible for both the T-cells and viral load to go up. Why is this happening, and are the events related?

Thanks so much for your help. I am very nervous that my doctor is not as up to date on resistance and resistance testing as I would like him to be. Otherwise, he is great.

Response from Dr. Little

You have done your homework and raise many very important issues. I would agree, especially given the drugs that you are taking, that it is time NOW to consider a change. I think that drug resistance testing is exactly what I would recommend - since this is likely to tell you whether one or more of your current drugs need to be switched. Unfortunately, people can develop drug resistance to the drugs sustiva (efavirenz) and lamivudine (3TC) very rapidly during periods of incomplete viral suppression (that is, viral load not less than 500 or 50). So, in answer to your first question, yes, I would recommend drug resistance testing. As for which one - this depends mostly on which test your provider is more comfortable interpreting. Both are likely to give the same answer. Your test results at present, I would predict will be quite easy to interpret, but you may need additional tests in the future and then it is always nicer to have an older test to compare to. So, I think that either test is fine, I would pick the one your doctor is more comfortable with, realizing that the interpretation may get more complicated with time. Worth knowing that the genotype is generally less expensive that the phenotype, but the quality of the results (often reflected in the lab that runs the test) is what is the most important.

For question #3 - there are now several twice a day regimens taken with food- the difficulty is that all of the drug combinations MAY be associated with side effects and it is difficult to predict for each individual whether they will have mild or more significant problems. MOST patients that communicate readily with their physician about side effects and problems can receive enough help and support to get through the initial side effects and then tolerate the drugs fairly well long term.

For question #4 - I suspect that you do have some drug resistance at this point given your viral load response. The important thing is to find our whether you have resistance to sustiva, 3TC, or both. Unfortunately, these tests are all less good at identifying markers of d4T drug resistance. In answer to how compliant you need to be - the regimen you were started on probably requires some of the best compliance possible if one wishes to avoid the development of drug resistance. No one expects perfection of anyone taking antiretroviral drugs. We all suggest it as a goal, but realize that most people fall short. What becomes the biggest problem is not the occasional missed dose (2 missed morning doses in 1.5 years), but the regular missed dose (several morning doses each week) or inconsistent dosing on a regular basis (taking a twice daily group of meds 4-6 hours apart rather than 10-12 hours apart). I suspect based upon your history, that the regimen was not potent enough for you and/or you may have had some pre-existing drug resitance before you even started therapy (transmitted to you from the person you acquired HIV from).

Question #5 - yes, T cells typically lag about 8-12 weeks after viral load (sometimes longer) - so that if you fail a regimen based upon an increasing viral load, it often takes several more weeks to see the T cells start to dip back down.

I wish you the best of luck!

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Combivir/Sustiva Resistance

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