Repetitive exposures with simian/human immunodeficiency viruses: Strategy to study HIV pre-clinical interventions in non-human primates

Caryn N. Kim, Debra R. Adams, Sheila Bashirian, Sal Butera, Thomas M. Folks, Ron A. Otten

    Research output: Contribution to journalArticle

    30 Scopus citations

    Abstract

    Background: Non-human primate models for human immunodeficiency virus (HIV) infection represent a valuable pre-clinical tool to evaluate interventions (e.g., topical microbicides, vaccines, and chemoprophylaxis) designed to prevent transmission or slow disease progression after infection. Standard transmission models use a single-dose exposure with high, non-physiologic levels of virus to approach 100% infection rates of control animals. These single-exposure models do not represent the circumstances of mucosal HIV transmission in humans and may result in misleading data with regard to intervention efficacy. Therefore, we have developed a repetitive mucosal exposure model using doses of virus that better reflects human exposures. Methods: The virus used for these evaluations was simian-human immunodeficiency virus [SHIVSF162P3 (R5-using, subtype B HIV-1 envelope)] and the virus dose used (approximately 105 -106 viral particle equivalents or approximately 10 tissue culture infectious doses per exposure) approximates viral loads observed in the semen during acute HIV-1 infection. Using the repeated mucosal exposure approach, we have evaluated a candidate vaginal microbicide (cellulose acetate phthalate, CAP) given 15 minutes prior to each weekly virus exposure. Pig-tailed macaques were exposed weekly by vaginal inoculations with and without microbicide until systemic viral RNA was detected. Results: Groups of naïve control monkeys were infected after an average of three to four exposures for the vaginal route of inoculation. Data from the first application of this monkey model to evaluate the topical microbicide CAP suggested that protection from SHIV infection was possible with three of four CAP-treated monkeys remaining uninfected after 12 exposures (P = 0.015). CAP efficacy was markedly improved from 66% in a previous single-dose virus exposure study to 92% in this repeated exposure system. Conclusion: Our experience with using repetitive virus exposures to study topical microbicides and the findings to date from this study provides a basis to refine monkey models to more closely resemble human exposure during HIV transmission. This model may be highly relevant to pre-clinical evaluation for a variety of therapeutic interventions which is discussed here.

    Original languageEnglish (US)
    Pages (from-to)210-216
    Number of pages7
    JournalJournal of medical primatology
    Volume35
    Issue number4-5
    DOIs
    StatePublished - Aug 1 2006

    Keywords

    • HIV interventions
    • HIV transmission
    • Macaques
    • SHIV

    ASJC Scopus subject areas

    • Animal Science and Zoology
    • veterinary(all)

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