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Review
. 2012 Aug;20(8):369-75.
doi: 10.1016/j.tim.2012.05.005. Epub 2012 Jun 15.

Microbicides: still a long road to success

Christophe Vanpouille  1 , Anush Arakelyan, Leonid Margolis
Affiliations
Review

Microbicides: still a long road to success

Christophe Vanpouille et al. Trends Microbiol. 2012 Aug.

Abstract

The development of efficient microbicides, the topically applied compounds that protect uninfected individuals from acquiring HIV-1, is a promising strategy to contain HIV-1 epidemics. Such microbicides should of course possess anti-HIV-1 activity, but they should also act against other genital pathogens, which facilitate HIV-1 transmission. The new trend in microbicide strategy is to use drugs currently used in HIV-1 therapy. The success of this strategy is mixed so far and is impaired by our limited knowledge of the basic mechanisms of HIV-1 transmission as well as by the inadequacy of the systems in which microbicides are tested in preclinical studies.

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Figures

Figure 1
Figure 1. Use of human cervico-vaginal tissue ex vivo as a microbicide testing platform
Upper panel: Human tissue explants cultured ex vivo serve as a model for HIV-1 transmission. Briefly, human cervico-vaginal tissues obtained from surgery are dissected into tissue blocks, which are cultured at the liquid-air interface. Transmissions of HIV-1 and HIV-1 copathogens are simulated by applying viral suspensions in seminal fluid. This model simulates some of the in vivo mechanisms by which HIV-1 penetrates cervico-vaginal mucosa and infects cell targets. Lower panel: A human cervico-vaginal tissue system complemented with seminal fluid is used as a platform to test microbicides. Microbicides may prevent HIV-1 transmission by inactivating pathogens, preventing viral entry, and suppressing HIV-1 infection of target cells.
Figure 2
Figure 2. Dual targeted drugs as potential microbicides
HIV-1 infection is associated with infection by copathogens that in turn may facilitate HIV-1 replication and/or transmission. Well-known specific antivirals used in therapy against particular viruses may target viruses other than the ones against which they were originally designed. Acyclovir, originally designed to suppress herpes simplex virus type 2 (HSV-2) (red arrow), suppresses HIV-1 as well. Tenofovir, originally designed against HIV-1 (red arrow), has anti-HSV-2 activity. Tenofovir also has activity against hepatitis B virus (HBV) (dotted arrow).
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