Semen suppresses antiviral activities of microbicides against HIV

 

Microbicides have been considered as a controller of sexual transmission of HIV in vitro. However, many microbicides showed poor performances in clinical trials. This result may be due to different conditions of HIV sexual transmission between in vitro and in vivo. Zirafi et al. reported that microbicides, which can target HIV components, showed ineffective in the presence of semen. The article was published on Science Translation Medicine, recently.

 

The efficiencies of several candidate microbicides were examined in TZM-bl reporter cells with or without semen. Those microbicides includes antiviral drugs targeting HIV outside host cells, such as polyanions and neutralizing antibodies, and antiviral drugs targeting intracellular HIV, such as tenofovir disoproxil fumarate, nevirapine, and elvitegravir. In the present of semen, the effects of all those antiviral therapeutics decreased dramatically. To investigate the underlying mechanism, researchers examined the role of amyloid in semen under the same experimental conditions, and  found the similar results compared with those obtained in the present of semen. Together with the result that semen lacking amyloid did not enhance HIV infection, researchers demonstrate amyloid is a key component for the process of reduced antiviral efficacy by semen. Above all, these findings suggest that in order to identify the best candidates, the effective of microbicides should be examined in the present of semen.

 

Reference:
Sci Transl Med. 2014 Nov 12;6(262):262ra157.

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S1742	Nevirapine (NSC 641530)	Nevirapine (NSC 641530,NVP) is a non-nucleoside reverse transcriptase inhibitor (NNRTI) used to treat HIV-1 infection and AIDS.
S1400	Tenofovir Disoproxil Fumarate	Tenofovir Disoproxil Fumarate belongs to a class of antiretroviral drugs, it inhibits the activity of HIV reverse transcriptase by competing with the natural substrate deoxyadenosine 5’-triphosphate and, after incorporation into DNA, by DNA chain termination.
S2001	Elvitegravir	Elvitegravir is an HIV integrase inhibitor for HIV-1 IIIB, HIV-2 EHO and HIV-2 ROD with IC50 of 0.7 nM, 2.8 nM and 1.4 nM in cell-free assays, respectively.

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Reverse Transcriptase