Abstract
Topical agents, such as microbicides, that can protect against human immunodeficiency virus (HIV) transmission are urgently needed. Using a chimeric simian/human immunodeficiency virus (SHIV SF162), which is tropic for the chemokine receptor CCR5, we report that topical application of high doses of PSC-RANTES, an amino terminus-modified analog of the chemokine RANTES, provided potent protection against vaginal challenge in rhesus macaques. These experimental findings have potentially important implications for understanding vaginal transmission of HIV and the design of strategies for its prevention.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Administration, Intravaginal
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Animals
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Anti-HIV Agents / administration & dosage
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Anti-HIV Agents / therapeutic use*
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Anti-Infective Agents, Local / administration & dosage
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Anti-Infective Agents, Local / therapeutic use*
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Antibodies, Viral / blood
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CCR5 Receptor Antagonists*
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Chemokine CCL5 / administration & dosage
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Chemokine CCL5 / analogs & derivatives*
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Chemokine CCL5 / therapeutic use*
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Dose-Response Relationship, Drug
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Drug Evaluation, Preclinical
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Female
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HIV Infections / prevention & control*
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HIV Infections / transmission
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HIV-1 / drug effects
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Macaca mulatta
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Receptors, CCR5 / metabolism
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Simian Acquired Immunodeficiency Syndrome / prevention & control*
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Simian Acquired Immunodeficiency Syndrome / transmission
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Simian Immunodeficiency Virus / drug effects
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Simian Immunodeficiency Virus / immunology
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Vagina / virology*
Substances
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Anti-HIV Agents
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Anti-Infective Agents, Local
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Antibodies, Viral
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CCR5 Receptor Antagonists
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Chemokine CCL5
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RANTES, N(alpha)-(n-nonanoyl)-desSer(1)-(thioproline(2),cyclohexylglycine(3))-
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Receptors, CCR5