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Sustiva causing resistance to other nNRTIs
Feb 13, 2003

Sustiva (efavirenz)-Induced Mutation in Subtype C HIV May Confer Multi-NNRTI Resistance

A mutation at codon 106 in HIV-1 clade C viruses that occurs after exposure to efavirenz appears to result in high-level resistance to other non-nucleotide reverse transcriptase inhibitors (NNRTIs), according to a report published in the January 3rd issue of AIDS.

Dr. Bluma Brenner, from McGill University AIDS Centre in Montreal, and colleagues genotyped 440 B and 84 non-B HIV-1 clinical isolates. The non-B isolates included 39 clade C variants.

In 94 of cases, the clade C viruses carried the natural GTG polymorphism at codon 106, which can allow the valine-to-methionine mutation to arise at this location under drug selection pressure. In contrast, the B isolates "overwhelmingly" expressed the GTA sequence at codon 106.

In tissue culture, the V106M mutation occurred when clade C viruses from treatment-nave patients were exposed to efavirenz, but not to nevirapine or delavirdine.

Once present, the codon 106 mutation was found to cause high-level resistance to all NNRTIs, the authors note. Testing with recombinant viruses containing the mutation confirmed this finding.

The V106M mutation "may be a signature mutation in clade C patients treated with efavirenz and may have the potential to confer high-level multi-NNRTI resistance," the researchers conclude. "Physicians should be aware of the...mutation and its potential impact on virological responsiveness," they add.

01/29/03

I know this may seem self-explanatory..but do you know how extensive and how many people this can/will affect? The reason I am asking is because Sustiva has been shown to be highly effective in all it's trial studies, and this seems to very much so spoil a lot of that.I've included a web link address that i got this from (another great website) And I wrote and asked you becasue I myself attended CU boulder years ago (off the subject)thanks Doctor Young.

http://hivandhepatitis.com/recent/nnrtis/012903h.html

Response from Dr. Young

Thanks for pointing out the research.

So far, this does not seem like a very common issue-- however, a different mutation at codon 103 is commonly found among persons with clade B HIV (the US, Western Europe flavor)- this mutation usually causes high level resistance to all NNRTIs.

Go Buffs. -BY



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