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Title

Semen enhances HIV infectivity and impairs the antiviral efficacy of microbicides

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Organization

 

Journal Name

Sci Transl Med

Publication Date

11/1/2014

PubMed Search

http://www.ncbi.nlm.nih.gov/pubmed/?term=25391483

Link to full-text

 

PMID

25391483

Abstract

‚ÄčTopically applied microbicides potently inhibit HIV in vitro but have largely failed to exert protective effects in clinical trials. One possible reason for this discrepancy is that the preclinical testing of microbicides does not faithfully reflect the conditions of HIV sexual transmission. We report that candidate microbicides that target HIV components show greatly reduced antiviral efficacy in the presence of semen, the main vector for HIV transmission. This diminished antiviral activity was dependent on the ability of amyloid fibrils in semen to enhance the infectivity of HIV. Thus, the anti-HIV efficacy of microbicides determined in the absence of semen greatly underestimated the drug concentrations needed to block semen-exposed virus. One notable exception was maraviroc. This HIV entry inhibitor targets the host cell CCR5 co-receptor and was highly active against both untreated and semen-exposed HIV. These data help to explain why microbicides have failed to protect against HIV in clinical trials and suggest that antiviral compounds targeting host factors hold promise for further development. These findings also suggest that the in vitro efficacy of candidate microbicides should be determined in the presence of semen to identify the best candidates for the prevention of HIV sexual transmission.

Keywords

 

Topic

Adherence; Behavior

Attachments

Created at 11/24/2014 10:44 AM by Davis, Gregory P
Last modified at 11/24/2014 10:44 AM by Davis, Gregory P