Nonclinical Laboratory Studies: PC-1005 Gel (Carrageenan with Added MIV-150 and Zinc Salts)
Council scientists are investigating microbicide gels containing carrageenan, MIV-150, and zinc salts that might block acquisition and transmission of HIV.
Laboratory scientists at the Population Council's Center for Biomedical Research (CBR) are developing water-based combination gels (two active agents) to block HIV infection in humans. The gels contain varying amounts of MIV-150 (an enzyme inhibitor that prevents infected cells from producing new virus) and zinc acetate (a broad-spectrum antiviral agent) in a base of carrageenan (a natural polymer isolated from seaweed).
Using an animal model of infection, the scientists have shown that PC-1005, a gel comprising carrageenan with 0.002% MIV-150 and 0.3% zinc acetate, completely blocks a modified form of HIV infection in monkeys for up to 24 hours after two weeks of daily gel application.
MIV-150 was originally developed as a potential HIV therapy by Medivir AB, which licensed the drug to the Council for development as a microbicide. In nonclinical tests conducted by Medivir and Chiron Corporation, and confirmed by Council scientists, MIV-150 has shown significant activity against HIV-1 primary isolates, mutants, and strains of HIV-1 that are resistant to other anti-HIV drugs. Extensive pharmacology and toxicology testing showed that MIV-150 is nontoxic in vitro and in vivo.
The scientists are now optimizing PC-1005 gels in terms of efficacy, safety, and stability. Once an optimized formulation is identified, the microbicide product development team will prepare clinical-grade material at CBR to support a Phase 1 clinical trial; clinical trials are studies performed with human subjects. Based on current progress, Phase 1 trials testing the MIV-150/zinc acetate gel versus the zinc acetate alone are projected to commence in early 2012.
A single dose of a MIV-150/zinc acetate gel provides 24 h of protection against vaginal simian human immunodeficiency virus reverse transcriptase infection, with more limited protection rectally 8-24 h after gel use (abstract) (HTML)
Kenney,Jessica; Singer,Rachel; Derby,Nina R.; Aravantinou,Meropi; Abraham,Ciby J.; Menon,Radhika; Seidor,Samantha; Zhang,Shimin; Gettie,Agegnehu; Blanchard,James; Piatak Jr.,Michael; Lifson,Jeffrey D.; Fernandez-Romero,Jose A.; Zydowsky,Thomas M.; Robbiani,Melissa
AIDS Research and Human Retroviruses 28(11): 1476-1484
Publication date: 2012
An intravaginal ring that releases the NNRTI MIV-150 reduces SHIV transmission in macaques (abstract) (HTML)
Singer,Rachel; Mawson,Paul; Derby,Nina R.; Rodriguez,Aixa; Kizima,Larisa; Menon,Radhika; Goldman,Daniel; Kenney,Jessica; Aravantinou,Meropi; Seidor,Samantha; Gettie,Agegnehu; Blanchard,James; Piatak Jr.,Michael; Lifson,Jeffrey D.; Fernandez-Romero,Jose A.; Robbiani,Melissa; Zydowsky,Thomas M.
Science Translational Medicine 4(150)
Publication date: 2012
An antiretroviral/zinc combination gel provides 24 hours of complete protection against vaginal SHIV infection in macaques (abstract) (PDF)
Kenney,Jessica; Aravantinou,Meropi; Singer,Rachel; Hsu,Mayla; Rodriguez,Aixa; Kizima,Larisa; Abraham,Ciby J.; Menon,Radhika; Seidor,Samantha; Chudolij,Anne; Gettie,Agegnehu; Blanchard,James; Lifson,Jeffrey D.; Piatak Jr.,Michael; Fernandez-Romero,Jose A.; Zydowsky,Thomas M.; Robbiani,Melissa
PLoS ONE 6(1): E15835-
Publication date: 2011
Location: United States
HIV and AIDS
Duration: 1/2004 - ongoing
Agegnehu Gettie (Aaron Diamond AIDS Research Center)
David Katz (Duke University)
James Blanchard (Tulane National Primate Research Center)
Jeffrey Lifson (National Cancer Institute)
Julian Bess (National Cancer Institute)
Michael Piatak (National Cancer Institute)
Morseth Consulting, LLC