1. Glycerol Monolaurate Microbicide Protection against Repeat High-Dose SIV Vaginal Challenge.
- Author
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Haase AT, Rakasz E, Schultz-Darken N, Nephew K, Weisgrau KL, Reilly CS, Li Q, Southern PJ, Rothenberger M, Peterson ML, and Schlievert PM
- Subjects
- Animals, Female, HIV Infections drug therapy, HIV Infections prevention & control, HIV Infections virology, HIV-1 drug effects, Humans, Macaca mulatta, Mucous Membrane virology, Simian Acquired Immunodeficiency Syndrome virology, South Africa, Vagina, Anti-Infective Agents pharmacology, Anti-Retroviral Agents pharmacology, Laurates pharmacology, Monoglycerides pharmacology, Simian Acquired Immunodeficiency Syndrome drug therapy, Simian Acquired Immunodeficiency Syndrome prevention & control, Simian Immunodeficiency Virus drug effects
- 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.
- Published
- 2015
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