Prevalent polymorphisms in wild-type HIV-1 integrase are unlikely to engender drug resistance to dolutegravir (S/GSK1349572).

Cindy Vavro, Samiul Hasan, Heather Madsen, Joseph Horton, Felix DeAnda, Louise Martin-Carpenter, Akihiko Sato, Robert Cuffe, Shuguang Chen, Mark Underwood, Garrett Nichols

Antimicrobial agents and chemotherapy 2013 Mar

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The majority of HIV-1 integrase amino acid sites are highly conserved, suggesting that most are necessary to carry out the critical structural and functional roles of integrase. We analyzed the 34 most variable sites in integrase (>10% variability) and showed that prevalent polymorphic amino acids at these positions did not affect susceptibility to the integrase inhibitor dolutegravir (S/GSK1349572), as demonstrated both in vitro (in site-directed mutagenesis studies) and in vivo (in a phase IIa study of dolutegravir monotherapy in HIV-infected individuals). Ongoing clinical trials will provide additional data on the virologic activity of dolutegravir across subject viruses with and without prevalent polymorphic substitutions.

Citation

Cindy Vavro, Samiul Hasan, Heather Madsen, Joseph Horton, Felix DeAnda, Louise Martin-Carpenter, Akihiko Sato, Robert Cuffe, Shuguang Chen, Mark Underwood, Garrett Nichols. Prevalent polymorphisms in wild-type HIV-1 integrase are unlikely to engender drug resistance to dolutegravir (S/GSK1349572). Antimicrobial agents and chemotherapy. 2013 Mar;57(3):1379-84