Protection of Rhesus Macaques from Vaginal Infection by Vaginally Delivered Maraviroc, an Inhibitor of HIV-1 Entry via the CCR5 Co-Receptor.
Summary of "Protection of Rhesus Macaques from Vaginal Infection by Vaginally Delivered Maraviroc, an Inhibitor of HIV-1 Entry via the CCR5 Co-Receptor."
An effective vaginal microbicide could reduce human immunodeficiency virus type 1 (HIV-1) transmission to women. Among microbicide candidates in clinical development is Maraviroc (MVC), a small-molecule drug that binds the CCR5 co-receptor and impedes HIV-1 entry into cells. Delivered systemically, MVC reduces viral load in HIV-1-infected individuals, but its ability to prevent transmission is untested. We have now evaluated MVC as a vaginal microbicide with use of a stringent model that involves challenge of rhesus macaques with a high-dose of a CCR5-using virus, SHIV-162P3. Gel-formulated, prescription-grade MVC provided dose-dependent protection, half-maximally at 0.5 mM (0.25 mg/mL). The duration of protection was transient; the longer the delay between MVC application and virus challenge, the less protection (half life of approximately 4 h). As expected, MVC neither protected against challenge with a CXCR4-using virus, SHIV-KU1, nor exacerbated postinfection viremia. These findings validate MVC development as a vaginal microbicide for women and should guide clinical programs.
Affiliation
Tulane National Primate Research Center, Covington, Louisiana, and 2Department of Microbiology and Immunology, Weill Medical College of Cornell University, New York, New York.
Journal Details
This article was published in the following journal.
Name: The Journal of infectious diseases
ISSN: 1537-6613
Pages:
Links
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/20629537
- DOI: http://dx.doi.org/10.1086/655661
Medical and Biotech [MESH] Definitions
Cross Protection
Protection conferred on a host by inoculation with one strain or component of a microorganism that prevents infection when later challenged with a similar strain. Most commonly the microorganism is a virus.
Marburg Virus Disease
An RNA virus infection of rhesus, vervet, and squirrel monkeys transmissible to man.
Vaginal Smears
Collection of pooled secretions of the posterior vaginal fornix for cytologic examination.
Episiotomy
An incision of the posterior vaginal wall and a portion of the pudenda which enlarges the vaginal introitus to facilitate delivery and prevent lacerations.
Allergy And Immunology
A medical specialty concerned with the hypersensitivity of the individual to foreign substances and protection from the resultant infection or disorder.
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