Efficacy of HIV antiviral polyanionic carbosilane dendrimer G2-S16 in the presence of semen

Abstract

The development of a safe and effective microbicide to prevent the sexual transmission of human immunodeficiency virus (HIV)-1 is urgently needed. Unfortunately, the majority of microbicides, such as poly(L-lysine)-dendrimers, anionic polymers, or antiretrovirals, have proved inactive or even increased the risk of HIV infection in clinical trials, most probably due to the fact that these compounds failed to prevent semen-exposed HIV infection. We showed that G2-S16 dendrimer exerts anti-HIV-1 activity at an early stage of viral replication, blocking the gp120/CD4/CCR5 interaction and providing a barrier to infection for long periods, confirming its multifactorial and nonspecific ability. Previously, we demonstrated that topical administration of G2-S16 prevents HIV transmission in humanized BLT mice without irritation or vaginal lesions. Here, we demonstrated that G2-S16 is active against mock- and semen-exposed HIV-1 and could be a promising microbicide against HIV infection.

Keywords:

• G2-S16
• dendrimer
• HIV-1
• SEVI
• microbicide
• antiretrovirals

Acknowledgments

This work has been partially funded by the RD12/0017/0037 project as part of the Acción Estratégica en Salud, Plan Nacional de Investigación Científica, Desarrollo e Innovación Tecnológica 2008–2011 and cofinanced by Instituto de Salud Carlos III (Subdirección General de Evaluación) and Fondo Europeo de Desarrollo Regional, RETIC PT13/0010/0028, Fondo de Investigacion Sanitaria (grant number PI13/02016), CTQ2011-23245 (MIMECO), Comunidad de Madrid (grant numbers S-2010/BMD-2351 and S-2010/BMD-2332), CYTED 214RT0482. CIBER-BBN is an initiative funded by the VI National R&D&i Plan 2008–2011, IniciativaIngenio 2010, the Consolider Program, and CIBER Actions and financed by the Instituto de Salud Carlos III with assistance from the European Regional Development Fund.

Disclosure

The authors report no conflicts of interest in this work.