In vitro selection and characterization of human immunodeficiency virus type 2 with decreased susceptibility to lopinavir.

Published

Journal Article

Lopinavir (LPV)-ritonavir has demonstrated durable antiviral activity in human immunodeficiency virus type 1 (HIV-1)-infected antiretroviral-naïve and protease inhibitor (PI)-experienced patients. However, information on LPV activity against HIV-2 and the patterns of mutations in HIV-2 in response to selection by LPV is limited. The activity of LPV against three strains of HIV-2 was assessed and compared to activity against a reference HIV-1 strain. LPV 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 10-fold-reduced susceptibility was observed with the third HIV-2 strain, HIV-2(CDC310319). Passage of HIV-2(MS) with increasing concentrations of LPV selected mutations V47A and D17N in the HIV-2 protease gene. The introduction of both 17N and 47A either individually or together into HIV-2(ROD) molecular infectious clones showed that the single V47A substitution in HIV-2 resulted in a substantial reduction in susceptibility to LPV. In contrast, this mutant retained wild-type susceptibility to other PIs and appeared to be hypersusceptible to atazanavir and saquinavir.

Full Text

Duke Authors

Cited Authors

  • Masse, S; Lu, X; Dekhtyar, T; Lu, L; Koev, G; Gao, F; Mo, H; Kempf, D; Bernstein, B; Hanna, GJ; Molla, A

Published Date

  • September 2007

Published In

Volume / Issue

  • 51 / 9

Start / End Page

  • 3075 - 3080

PubMed ID

  • 17576848

Pubmed Central ID

  • 17576848

International Standard Serial Number (ISSN)

  • 0066-4804

Digital Object Identifier (DOI)

  • 10.1128/AAC.00146-07

Language

  • eng

Conference Location

  • United States