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4 nukes and resistance question
Oct 27, 2004

I have a 2 part question. I am a resident and have a patient with these meds on admission: Stavudine, abacavir, didanosine, tenofovir and nelfinavir. Now my first question is if there's a rational to give 4 nukes...instead of adding an NNRTI. 2nd question: On admission this patient was taking 1250mg nelfinavir BID but another resident wrote the order for 650mg po BID which was detected by a pharmacist only 8 days later. Of course this underdosing is causing me to be concern about resistance (and us being "responsible" for it) How fast can these occur? Is there a general rule or pattern for underdosing vs resistance? Is there some data/resources that you could recommend me to read on this issue to help me understand that not so clear issue of resistance. Any insight on this would be greatly appreciated Thank you

Response from Dr. Sherer

My hope is that you called the patient's physician when he entered the hospital, in addition to sending this email, as that physician is the only person who can answer your question specifically. There may be reasons for this choice that I am unaware of. If you did not, that's an error of the same magnitude as the mistaken dose.

In general, there is little evidence that four drugs are superior to three in first ART regimens (note that I don't know whether this was a first or later regimen, or whether it resulted from 'intensification' of a first regimen.) More specifically, there was no difference in a short term study of Trizivir plus efavirenz compared to Combivir plus efavirenz; further studies are still in progress. You are right to be concerned about underdosing, even for a singly dose, let alone 8 days. This is particularly true for nelfinavir, which is vulnerable to a single amino acid mutation causing resistance (the D30N or the L90M).

From Mark Dybul's studies at the NIH we learned that in an individual with excellent viral suppression (eg < 50 copies), viral replication does not resume fully for about 7 days after cessation of therapy. I can't comment on your patient, as I don't know if he had been controlled at his last patient visit or when he entered the hospital -only his primary HIV physician would know that.

The last reason to call that physician is not only to get an answer to these questions, but to build a relationship with an HIV clinician that might allow for further education in the future.

The best single reference on drug resistance is at the IAS-USA website,, i.e. the updated guidelines on resistance - 2003.

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