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Antimicrob Agents Chemother. 2013 Mar;57(3):1379-84. doi: 10.1128/AAC.01791-12. Epub 2013 Jan 7.

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

Author information

1
GlaxoSmithKline, Research Triangle Park, NC, USA. cindy.l.vavro@gsk.com

Abstract

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.

PMID:
23295935
PMCID:
PMC3591886
DOI:
10.1128/AAC.01791-12
[Indexed for MEDLINE]
Free PMC Article

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