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HIV Drug ResistanceHIV Drug Resistance
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Feb 2, 2008

i just realized that i forgot to take my ATRIPLA last night before falling asleep - i simply passed out and even slept throught the alarm that i have set to remind me about my atripla nightly.

i'm at work right now so i won't be able to take my next dose until tonight, having skipped a dose for a full 24 hours - HOW DANGEROUS is this? I'm suddenly petrified that i've put myself at immense risk. i've only been on atripla for a month now & prior to starting my cd4 was at 450 & vl about 15k. the reason i started atripla in the first place was to treat my hbv.

please enlighten me on exactly what might happen.


Response from Dr. Sherer

It sounds as though you know something about my answer: Your best course with ART, especially in the first critical months on treatment, is to take every dose as prescribed. Even minor lapses like this one can lead to the development of drug resistance.

Having said that, it is remarkable how frequently this type of lapse in adherence occurs in people on the NNRTIs, such as Sustiva or Atripla (efavirenz), or Viramune (nevirapine) WITHOUT the development of resistance. It is remarkable because the genetic vulnerability of the NNRTIs, in which a single amino acid substitution can render the virus completely resistance to the first generation NNRTIs, might suggest that it would happen easily and more frequently than it does.

You should talk to your doctor ASAP about the lapse and arrange to see him or her sooner than usual, in order to repeat your viral load and look for evidence of viremia. If your viral load is elevated >1,000 copies/ml, your doctor can order a genotype resistance test to see if drug resistance has already occured.

If that is the case, you still have several alternative regimens left that can still completely suppress the virus and elevate your CD4 cells for prolonged periods of time, i.e. years or more, just as Atripla can.

Fortunately, your high CD4 cell count and low viral load at the start of ART lower your risk of breakthrough viremia. Even with only one month of ART, you may have already achieved a viral load below the level of detection, or at least one log below your baseline, i.e. at or below a viral load of 1,500. It would be reasonable to think that the other active drugs in the regimen, i.e. tenofovir and emtricitabine, which also have a long half life like efavirenz in the blood, as well as the remaining circulating efavirenz, may have combined to control viral replication during the 24 hours when you missed the dose.

But I can't reassure you that no trouble has occured, because there is a low risk that it did. Only time will tell when you and your doctor check your viral load and CD4 cell count.

In future, take some steps with your doctor to prevent this type of lapse, and to mitigate the effect when lapses do occur - because your and your doctor surely know that neither of you are perfect. For example, keep an extra supply of your medication in a safe place at work, or in the glove compartment of your car, or in a safe compartment in your backpack or valise, so that you can promptly take the dose if your discover or realize in the morning that you forgot to take your evening dose the night before. In that way, you will reduce the period of time when you are risk for sub-optimal blood levels of drug from 24 hours to 12 hours or less.

Finally, living with HIV is a long haul. You will do better if you maintain a calm demeanor as best you can and appreciate that there is nothing to be 'petrified' about at this early stage. You have some time to get this right, and there are three or more good regimens that you can turn to before you start to run out of treatment options. It is true that there will be disadvantages to second and third options; for example, they will not be as simple or convenient as Atripla. Rather than one pill once daily, they may require 2-5 pills one or twice per day. They will have a different side effect profile, and you may not react as well, or as poorly, as you have reacted to date with Atripla. But what quality of life will you have if you are petrified easily and often while on ART?

You and your doctor can achieve excellent adherence that will lead to durable suppression of the virus and durable good health, e.g. for 5-7 years or more. Take the lesson from this episode, and respect the discipline that the virus is imposing on your life. Respect it...but leave the petrified status behind. You're in this for the long haul, so just do all you can to avoid a repeat of this episode, and take it easy.

China's breakthrough on HIV drug resistance?
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