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Glycerol Monolaurate Microbicide Protection against Repeat High-Dose SIV Vaginal Challenge
Journal article   Open access   Peer reviewed

Glycerol Monolaurate Microbicide Protection against Repeat High-Dose SIV Vaginal Challenge

Ashley T Haase, Eva Rakasz, Nancy Schultz-Darken, Karla Nephew, Kimberly L Weisgrau, Cavan S Reilly, Qingsheng Li, Peter J Southern, Meghan Rothenberger, Marnie L Peterson, …
PloS one, Vol.10(6), pp.e0129465-e0129465
2015
DOI: 10.1371/journal.pone.0129465
PMCID: PMC4461171
PMID: 26057743
url
https://doi.org/10.1371/journal.pone.0129465View
Published (Version of record) Open Access

Abstract

Measures to prevent sexual mucosal transmission are critically needed, particularly to prevent transmission to young women at high risk in the microepidemics in South Africa that disproportionally contribute to the continued pandemic. To that end, microbicides containing anti-retroviral (ARV) agents have been shown to prevent transmission, but with efficacy limited both by adherence and pre-existing innate immune and inflammatory conditions in the female reproductive tract (FRT). Glycerol monolaurate (GML) has been proposed as a microbicide component to enhance efficacy by blocking these transmission-facilitating innate immune response to vaginal exposure. We show here in an especially rigorous test of protection in the SIV-rhesus macaque model of HIV-1 transmission to women, that GML used daily and before vaginal challenge protects against repeat high doses of SIV by criteria that include virological and immunological assays to detect occult infection. We also provide evidence for indirect mechanisms of action in GML-mediated protection. Developing a sustained formulation for GML delivery could contribute an independent, complementary protective component to an ARV-containing microbicide.
South Africa HIV Infections - prevention & control Mucous Membrane - virology HIV-1 - drug effects Anti-Infective Agents - pharmacology HIV Infections - virology Humans Anti-Retroviral Agents - pharmacology Vagina Macaca mulatta Monoglycerides - pharmacology Simian Acquired Immunodeficiency Syndrome - prevention & control Simian Acquired Immunodeficiency Syndrome - virology Animals Simian Acquired Immunodeficiency Syndrome - drug therapy Female HIV Infections - drug therapy Laurates - pharmacology Simian Immunodeficiency Virus - drug effects

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