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Revista de SIDA e investigación clínica

In vitro and In vivo Resistance to Human Immuno Deficiency Virus Type 1 Entry Inhibitors

Abstract

Yosuke Maeda, Kazuhisa Yoshimura, Fusako Miyamoto, Eiichi Kodama, Shigeyoshi Harada, Yuzhe Yuan, Shinji Harada and Keisuke Yusa

Viral entry is one of the most important targets for the efficient treatment of Human immunodeficiency virus type 1 (HIV-1)-infected patients. The entry process consists of multiple molecular steps: attachment of viral gp120 to CD4, interaction of gp120 with CCR5 or CXCR4 co-receptors, and gp41-mediated fusion of the viral and cellular membranes. Understanding the sequential steps of the entry process has enabled the production of various antiviral drugs to block each of these steps. Currently, the CCR5 inhibitor, maraviroc, and the fusion inhibitor, enfuvirtide, are clinically available. However, the emergence of HIV-1 strains resistant to entry inhibitors, as commonly observed for other classes of antiviral agents, is a serious problem. In this review, we describe a variety of entry inhibitors targeting different steps of viral entry and escape variants that are generated in vitro and in vivo.

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