Collinearity of protease mutations in HIV-1 samples with high-level protease inhibitor class resistance

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Collinearity of protease mutations in HIV-1 samples with high-level protease inhibitor class resistance

OBJECTIVES To determine whether pan-protease inhibitor (PI)-resistant virus populations are composed predominantly of viruses with resistance to all PIs or of diverse virus populations with resistance to different subsets of PIs. METHODS We performed deep sequencing of plasma virus samples from nine patients with high-level genotypic and/or phenotypic resistance to all licensed PIs. The nine ...

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HIV-1 protease mutations and protease inhibitor cross-resistance.

The effects of many protease inhibitor (PI)-selected mutations on the susceptibility to individual PIs are unknown. We analyzed in vitro susceptibility test results on 2,725 HIV-1 protease isolates. More than 2,400 isolates had been tested for susceptibility to fosamprenavir, indinavir, nelfinavir, and saquinavir; 2,130 isolates had been tested for susceptibility to lopinavir; 1,644 isolates ha...

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An Update on HIV-1 Protease Inhibitor Resistance

Protease inhibitors (PIs) were initially introduced in the mid-1990s and when used in combination with nucleoside reverse transcriptase inhibitors (NRTI), ushered in the era of highly active antiretroviral therapy (HAART). These agents dramatically altered the treatment of HIV infection, enabling suppression of viral replication to undetectable levels and significantly impacting disease progres...

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Drug Resistance Mutations Alter Dynamics of Inhibitor-Bound HIV-1 Protease

Under the selective pressure of therapy, HIV-1 protease mutants resistant to inhibitors evolve to confer drug resistance. Such mutations can impact both the dynamics and structures of the bound and unbound forms of the enzyme. Flap+ is a multidrug-resistant variant of HIV-1 protease with a combination of primary and secondary resistance mutations (L10I, G48V, I54V, V82A) and a strikingly altere...

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Unique Flap Conformation in an HIV-1 Protease with High-Level Darunavir Resistance

Darunavir (DRV) is one of the most powerful protease inhibitors (PIs) for treating human immunodeficiency virus type-1 (HIV-1) infection and presents a high genetic barrier to the generation of resistant viruses. However, DRV-resistant HIV-1 infrequently emerges from viruses exhibiting resistance to other protease inhibitors. To address this resistance, researchers have gathered genetic informa...

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ژورنال

عنوان ژورنال: Journal of Antimicrobial Chemotherapy

سال: 2012

ISSN: 1460-2091,0305-7453

DOI: 10.1093/jac/dks409