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Missed doses
Oct 3, 2008

Dear Doctor,

I'm on treatment (Darunavir+ritonavir+truvada+raltegravir)since october '07 and I'm undetectable since december '07. I've never forgotten to take my meds but yesterday night I forgot to take them. In the morning I took the pills as normal (including truvada which is just to be taken at night). I'm worried to have developed resistance to some of the meds I'm taking.

Sam

Response from Dr. Sherer

First, you did the right thing to take the full dose as soon as you recognized the lapse.

A single missed dose is less likely to lead to drug resistance in people who, like you, have achieved an undetectable viral load, as compared to individuals who have recently started treatment and whose viral load is still 'on the way down'. This is true because, once undetectable, a few days (5-7) are required following the cessation of ART before active HIV replication takes place.

Boosted PIs (such as darunavir/ritonavir) are generally less susceptible to the development of drug resistance with missed doses than regimens based on the NNRTIs (such as efavirenz). However, whether this general truth applies to you depends on how many PI resistance mutations you had at the time you were started on this later stage regimen. The high genetic barrier to resistance for which the boosted PIs are well known is diminished by accumulated PI resistance mutations.

If you had many PI mutations when you began this regimen, then your susceptibility to resistance with missed doses would be dependent on raltegravir, which, while somewhat less susceptible to resistance than the NNRTIs, is not as robust as the boosted PIs. With raltegrative, one of three single mutations, with one or more additional mutations, is all that is needed for reduced susceptibility. Similarly, the ability of Truvada to suppress resistance depends on the number of NRTI resistance mutations, particularly the K65R and TAMs (thymidine analogue mutations).

The sum of this answer is that a single missed dose is unlikely to lead to drug resistance. However, I share your concern, and you would be well advised to do everything that you can to avoid such lapses in future. I urge you to talk to your doctor about your concerns and this response. You and he can monitor your viral load to answer this question.


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