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-naïve 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

AIDS 2003;17:F1-F5.