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Antimicrob. Agents Chemother. doi:10.1128/AAC.00146-07
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

In vitro selection and characterization of human immunodeficiency virus type 2 (HIV-2) with decreased susceptibility to lopinavir

Antiviral Research, Global Pharmaceutical Research and Development, Abbott Park, IL, USA; Duke University Medical Center, Durham, NC, USA

^* To whom correspondence should be addressed. Email: Sherie.masse{at}abbott.com.

	Abstract

Lopinavir/ritonavir has demonstrated durable antiviral activity in HIV-1 infected antiretroviral-naïve and protease inhibitor (PI)-experienced patients. However, information on lopinavir activity against HIV-2 and the patterns of mutations in HIV-2 in response to selection by lopinavir is limited. The activity of lopinavir against three strains of HIV-2 was assessed and compared to activity against a reference HIV-1 strain. Lopinavir demonstrated activity similar to that observed against HIV-1 in two HIV-2 strains (HIV-2_MS and HIV-2_CBL-23) tested. On the other hand, approximately tenfold reduced susceptibility was observed with the third HIV-2 strain, HIV-2_CDC310319. Passage of HIV-2_MS with increasing concentrations of lopinavir selected mutations V47A and D17N in the HIV-2 protease gene. Introduction of both 17N and 47A either individually or together into HIV-2_ROD molecular infectious clones showed that the single substitution V47A in HIV-2 resulted in substantial reduction in susceptibility to LPV. In contrast, this mutant retained wild-type susceptibility to other PIs and appeared hypersusceptible to atazanavir and saquinavir.

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