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The formulated microbicide RC-101 was safe and antivirally active following intravaginal application in pigtailed macaques

Cole, AM and Patton, DL and Rohan, LC and Cole, AL and Cosgrove-Sweeney, Y and Rogers, NA and Ratner, D and Sassi, AB and Lackman-Smith, C and Tarwater, P and Ramratnam, B and Ruchala, P and Lehrer, RI and Waring, AJ and Gupta, P (2010) The formulated microbicide RC-101 was safe and antivirally active following intravaginal application in pigtailed macaques. PLoS ONE, 5 (11).

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Background: RC-101 is a congener of the antiretroviral peptide retrocyclin, which we and others have reported is active against clinical HIV-1 isolates from all major clades, does not hemagglutinate, and is non-toxic and non-inflammatory in cervicovaginal cell culture. Herein, film-formulated RC-101 was assessed for its antiviral activity in vitro, safety in vivo, retention in the cervix and vagina, and ability to remain active against HIV-1 and SHIV after intravaginal application in macaques. Methodology/Principal Findings: RC-101 was formulated as a quick-dissolving film (2000 μg/film), retained complete activity in vitro as compared to unformulated peptide, and was applied intravaginally in six pigtailed macaques daily for four days. At one and four days following the final application, the presence of RC-101 was assessed in peripheral blood, cervicovaginal lavage, cytobrushed cervicovaginal cells, and biopsied cervical and vaginal tissues by quantitative western blots. One day following the last film application, cervical biopsies from RC-101-exposed and placebo-controlled macaques were collected and were subjected to challenge with RT-SHIV in an ex vivo organ culture model. RC-101 peptide was detected primarily in the cytobrush and biopsied cervical and vaginal tissues, with little to no peptide detected in lavage samples, suggesting that the peptide was associated with the cervicovaginal epithelia. RC-101 remained in the tissues and cytobrush samples up to four days post-application, yet was not detected in any sera or plasma samples. RC-101, extracted from cytobrushes obtained one day post-application, remained active against HIV-1 BaL. Importantly, cervical biopsies from RC-101-treated animals reduced RT-SHIV replication in ex vivo organ culture as compared to placebo-treated animals. Conclusions/Significance:Formulated RC-101 was stable in vivo and was retained in the mucosa. The presence of antivirally active RC-101 after five days in vivo suggests that RC-101 would be an important molecule to develop further as a topical microbicide to prevent HIV-1 transmission. © 2010 Cole et al.


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Item Type: Article
Status: Published
CreatorsEmailPitt UsernameORCID
Cole, AM
Patton, DL
Rohan, LCrohanl@pitt.eduROHANL
Cole, AL
Cosgrove-Sweeney, Y
Rogers, NA
Ratner, Ddampf@pitt.eduDAMPF
Sassi, AB
Lackman-Smith, C
Tarwater, P
Ramratnam, B
Ruchala, P
Lehrer, RI
Waring, AJ
Gupta, Ppgupta1@pitt.eduPGUPTA1
ContributionContributors NameEmailPitt UsernameORCID
Date: 9 December 2010
Date Type: Publication
Journal or Publication Title: PLoS ONE
Volume: 5
Number: 11
DOI or Unique Handle: 10.1371/journal.pone.0015111
Schools and Programs: School of Public Health > Infectious Diseases and Microbiology
Refereed: Yes
MeSH Headings: Administration, Intravaginal; Animals; Antiviral Agents--administration & dosage; Antiviral Agents--pharmacology; Cervix Uteri--drug effects; Cervix Uteri--virology; Colposcopy; Dose-Response Relationship, Drug; Female; HIV-1--drug effects; HIV-1--growth & development; HeLa Cells; Humans; Macaca nemestrina; Peptides--administration & dosage; Peptides--pharmacology; Simian Acquired Immunodeficiency Syndrome--prevention & control; Simian Acquired Immunodeficiency Syndrome--virology; Simian immunodeficiency virus--drug effects; Simian immunodeficiency virus--growth & development; Time Factors; Vagina--drug effects; Vagina--virology
Other ID: NLM PMC2993972
PubMed Central ID: PMC2993972
PubMed ID: 21124745
Date Deposited: 22 Aug 2012 21:53
Last Modified: 02 Feb 2019 16:56


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