Preclinical evaluation of the HIV-1 fusion inhibitor L'644 as a potential candidate microbicide.

Abstract:

:Topical blockade of the gp41 fusogenic protein of HIV-1 is one possible strategy by which microbicides could prevent HIV transmission, working early against infection, by inhibiting viral entry into host cells. In this study, we examined the potential of gp41 fusion inhibitors (FIs) as candidate anti-HIV microbicides. Preclinical evaluation of four FIs, C34, T20, T1249, and L'644, was performed using cellular and ex vivo genital and colorectal tissue explant models. Increased and sustained activity was detected for L'644, a cholesterol-derivatized version of C34, relative to the other FIs. The higher potency of L'644 was further increased with sustained exposure of cells or tissue to the compound. The activity of L'644 was not affected by biological fluids, and the compound was still active when tissue explants were treated after viral exposure. L'644 was also more active than other FIs against a viral escape mutant resistant to reverse transcriptase inhibitors (RTIs), demonstrating the potential of L'644 to be included as part of a multiactive antiretroviral (ARV) combination-based microbicide. These data support the further development of L'644 for microbicide application.

authors

Harman S,Herrera C,Armanasco N,Nuttall J,Shattock RJ

doi

10.1128/AAC.06108-11

subject

Has Abstract

pub_date

2012-05-01 00:00:00

pages

2347-56

issue

5

eissn

0066-4804

issn

1098-6596

pii

AAC.06108-11

journal_volume

56

pub_type

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