PROJECT
Nonclinical Laboratory Studies: PC-815
(Carraguard + MIV-150) 

Laboratory scientists at the Population Council's Center for Biomedical Research are developing several second-generation formulations based on the Council's lead first-generation microbicide candidate, Carraguard^®.

PC-815 is a combination microbicide containing Carraguard and MIV-150 (an NNRTI or non-nucleoside reverse transcriptase inhibitor, which binds to reverse transcriptase enzymes that in turn prevents the cell from producing new virus).

Carraguard’s safety and activity against sexually transmitted infections has already been extensively proven (see Nonclinical Laboratory Studies: Carraguard project page). MIV-150 was originally being developed in a joint venture by Medivir AB (Huddinge, Sweden) and Chiron Corporation (Emeryville, CA) (Medivir/Chiron) as an anti-HIV therapeutic. In nonclinical tests conducted by Medivir/Chiron, MIV-150 has shown significantly increased activity against HIV-1 primary isolates, mutants, and strains of HIV-1 resistant to other anti-HIV drugs. An extensive pharmacology and toxicology profile prove that MIV-150 is nontoxic in vitro and in vivo but demonstrated poor bioavailability when taken orally. However, this property makes it ideal for use in a microbicide because it diminishes the chances that MIV-150 will cause systemic side effects.

Pharmacological testing conducted in vitro has indicated that PC-815’s activity against HIV is significantly higher than the activity of Carraguard alone. Because MIV-150 and Carraguard have different mechanisms of action against HIV when formulated into PC-815, there is an additive effect in activity. MIV-150’s anti-HIV activity is not affected by the presence of seminal fluid or vaginal secretions. Carraguard’s activity is not affected by the addition of the MIV-150 compound.

Quality tests have shown that PC-815’s chemical components are stable and do not interact, causing degradation. Impurity and microbiological analysis has verified the absence of any form of contamination within the formulation, and a study has proven the effectiveness of the formulation’s preservative. Currently, two-year stability studies are in progress.

Toxicological testing has established that PC-815 is not toxic to vaginal cells in vitro and vaginal epithelial cells in rabbits. Additional testing is under way, which will indicate its effect on the vaginal epithelia of rabbits and rats following longer duration of exposure and increased frequency of dosing.

* Carraguard® is the Population Council's U.S. trademark for pharmaceutical preparations, namely microbicides, for use in preventing infection.

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Population Council researcher

Melissa Robbiani

Non-Council collaborators

Ethox International, Sterilization Technical Services Life Sciences Division

National Food Laboratory

TherImmune (Gene Logic)

Toxikon

Donors

Swedish International Development Cooperation Agency

Swedish Ministry of Foreign Affairs

US Agency for International Development

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Related Projects

• Nonclinical Laboratory Studies: Carraguard
• Nonclinical Laboratory Studies: PC-710
• PC-815 Clinical Studies

Contact: microbicide@popcouncil.org

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