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What Really Happens if One Misses a Single/Multiple Dose?
Aug 31, 2010

Dear Dr.: thanks for helping all of us -- you're all God-sends. My question is what really happens if a single dose of retovirals are missed, say Atripla. (Don't worry, I never did this, and have never missed a single dose) Is such a short time of lapse really so terrible ... does the virus mutate THAT fast? What about ten doses? 24 just seems just too pat a metric. I imagine the level of the drug goes down to ineffectiveness pretty quickly, in a few hours. (How much is in the blood, typically, at 18 hrs post-dose?) How come the virus isn't mutating during that period?

I write this because I'm terrified that something could easily happen to the supply-line of the drugs. Some sort of social or natural disaster occurs, interrupting or cutting the supply line. Like Katrina or something like the LA riots. In the event of such a contingency, what shouls somebody do? Should people have a 30 day reserve supply or something as an "emergency backup"?????

I feel the drugs are like the air supply for a deep sea diver .... if something cuts off the supply, your soon in trouble. Please don't think I'm some kind of nutty neurotic-alarmist. Thank you very much!

Response from Dr. McGowan

Thanks for your question.

When a dose of HIV medication is missed, the blood level of the meds will drop...they are cleared by the liver and kidneys from the blood. Most meds will work only when the amount is above the level needed to kill the virus. Once the level drops below that amount the virus can grow. The most dangerous time is when the blood level is slowly decreasing but still present..that is the time that most pressure for resistance is placed on the virus. Anytime that you have virus growing in the presence of a low level of medicine, there is a chance for drug resistance to emerge. Every time the virus copies itself, it makes a mistake (or mutation) in its genetic code. Some of these random mistakes may pass on the ability of the "baby" virus to grow better in the presence of the meds and bit by bit, by adding mutations one by one, the virus can break through.

So...when can a single missed dose make a difference:

Even though most meds are indeed cleared very quickly and the time of exposure is brief, there are some such as nevirapine or efavirenz (which is part of Atripla) that are cleared slowly and can persist at low levels for days. This is particularly worrisome when the other drugs in the cocktail are cleared more quickly. When that happens it may leave a single medicine alone in the blood....the virus only has 1 med to overcome at a time that way.

The other risky time is when doses are missed at the beginning of therapy, before the virus is fully suppressed. That is when virus is growing...remember you never want a low level of medicine in the blood when virus is growing. After the viral load has been undetectable for months or years a single missed dose will be less worrisome because the virus doesn't "wake up" that quickly.

So, based on the above, several missed doses just gives more opportunity for mutations to build up. Given the opportunity and enough chance (unlike you or me) the virus will get lucky and hit the jackpot...it will come up with the right combination of mutations to lead to drug resistance if it is given enough opportunity.

Hope this helps, Joe



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