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Journal of Virology, October 2009, p. 10358-10365, Vol. 83, No. 20
0022-538X/09/$08.00+0     doi:10.1128/JVI.01073-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Complete Protection from Repeated Vaginal Simian-Human Immunodeficiency Virus Exposures in Macaques by a Topical Gel Containing Tenofovir Alone or with Emtricitabine{triangledown}

Urvi M. Parikh,1 Charles Dobard,1 Sunita Sharma,1 Mian-er Cong,1 Hongwei Jia,1 Amy Martin,1 Chou-Pong Pau,1 Debra L. Hanson,2 Patricia Guenthner,1 James Smith,1 Ellen Kersh,1 J. Gerardo Garcia-Lerma,1 Francis J. Novembre,3 Ron Otten,1 Thomas Folks,4 and Walid Heneine1*

Laboratory Branch,1 Quantitative Sciences and Data Management Branch, Division of HIV/AIDS Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia,2 Yerkes Primate Center, Emory University, Atlanta, Georgia,3 Southwest Foundation for Biomedical Research, San Antonio, Texas4

Received 26 May 2009/ Accepted 29 July 2009

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.

* Corresponding author. Mailing address: Laboratory Branch, Division of HIV/AIDS Prevention, Centers for Disease Control and Prevention, 1600 Clifton Road, Atlanta, GA 30329. Phone: (404) 639-0218. Fax: (404) 639-1174. E-mail: wmh2{at}cdc.gov

{triangledown} Published ahead of print on 5 August 2009.

Journal of Virology, October 2009, p. 10358-10365, Vol. 83, No. 20
0022-538X/09/$08.00+0     doi:10.1128/JVI.01073-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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