Complete protection from repeated vaginal simian-human immunodeficiency virus exposures in macaques by a topical gel containing tenofovir alone or with emtricitabine

Urvi M. Parikh, Charles Dobard, Sunita Sharma, Mian Er Cong, Hongwei Jia, Amy Martin, Chou Pong Pau, Debra L. Hanson, Patricia Guenthner, James Smith, Ellen Kersh, J. Gerardo Garcia-Lerma, Francis J. Novembre, Ron Otten, Thomas Folks, Walid Heneine

    Research output: Contribution to journalArticlepeer-review

    166 Scopus citations

    Abstract

    New-generation gels that deliver potent antiretroviral drugs against human immunodeficiency virus type 1 have renewed hopes for topical prophylaxis as a prevention strategy. Previous preclinical research with monkey models suggested that high concentrations and drug combinations are needed for high efficacy. We evaluated two long-acting reverse transcriptase inhibitors, tenofovir (TFV) and emtricitabine (FTC), by using a twice-weekly repeat challenge macaque model and showed that a preexposure vaginal application of gel with 1% TFV alone or in combination with 5% FTC fully protected macaques from a total of 20 exposures to simian-human immunodeficiency virus SF162p3. FTC and TFV were detected in plasma 30 min after vaginal application, suggesting rapid absorption. FTC was detected more frequently than TFV and showed higher levels, reflecting the fivefold-higher concentration of this drug than of TFV. Two of 12 repeatedly exposed but protected macaques showed limited T-cell priming, which did not induce resistance to infection when macaques were rechallenged. Thus, single drugs with durable antiviral activity can provide highly effective topical prophylaxis and overcome the need for noncoital use or for drug combinations which are more complex and costly to formulate and approve.

    Original languageEnglish (US)
    Pages (from-to)10358-10365
    Number of pages8
    JournalJournal of virology
    Volume83
    Issue number20
    DOIs
    StatePublished - Oct 2009

    ASJC Scopus subject areas

    • Microbiology
    • Immunology
    • Insect Science
    • Virology

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