In vitro selection and characterization of human immunodeficiency virus type 2 with decreased susceptibility to lopinavir.
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.
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- Virus Replication
- RNA-Directed DNA Polymerase
- Pyrimidinones
- Phenotype
- Mutagenesis, Site-Directed
- Molecular Sequence Data
- Microbiology
- Lopinavir
- Humans
- HIV-2
Citation
Published In
DOI
ISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Virus Replication
- RNA-Directed DNA Polymerase
- Pyrimidinones
- Phenotype
- Mutagenesis, Site-Directed
- Molecular Sequence Data
- Microbiology
- Lopinavir
- Humans
- HIV-2