Carrageenan/MIV-150 (PC-815), a Combination Microbicide

Abstract

Theoretically, PC-815 is likely to be a more efficacious microbicide than Carraguard.

The Nonnucleoside Reverse Transcriptase Inhibitor MIV-150 in Carrageenan Gel Prevents Rectal Transmission of Simian/Human Immunodeficiency Virus Infection in Macaques

“…We have previously demonstrated that MIV-150 possesses strong antiviral and potentially virucidal properties, which are not affected by the presence of seminal fluid, and blocks transmission of both R5-and X4-tropic HIV isolates at nanomolar concentrations in vitro (12,50). In our first tests of MIV-150-carrageenan gels, we showed that 500 M MIV-150 in carrageenan was 10 times more active against clinical HIV isolates in vitro than carrageenan alone (12).…”

“…While Carraguard, a 3% carrageenan gel, was found not to be effective in significantly reducing the number of HIV infections in the treatment arm compared to placebo in a phase 3 clinical trial (45), it was shown to be safe and acceptable by the women who used it in the trial (45) as well as by participants in other studies (27,28,33,35,41,54). Carrageenan-based gels also have favorable rheological properties (12,50), rendering them promising candidates for delivering potent antiviral agents.…”

“…MIV-150 was developed by Medivir AB (Huddinge, Sweden) as an oral antiretroviral drug but was discontinued because of poor systemic absorption and rapid systemic clearance (12). Although these properties rendered MIV-150 a poor candidate for oral therapy, they are not problematic for a topical microbicide that is applied at the site of virus exposure and may need only to be absorbed locally to be effective.…”

A Review of Current Intravaginal Drug Delivery Approaches Employed for the Prophylaxis of HIV/AIDS and Prevention of Sexually Transmitted Infections

“…There appears to be no effect on sperm motility (84)(85)(86). (85,87). Pre-clinical tests of MIV-150 have shown a significant increase of activity against HIV-1 primary isolates with no toxic effects.…”

The Future of HIV Prevention: Prospects for an Effective Anti-HIV Microbicide

“…However, the mechanism of this cell-free inhibition has yet to be determined, and its relevance in vivo is unknown [41]. NNRTI compounds currently in development as microbicides include dapivirine (TMC120), MIV-150, UC 781, and S-DABO [27,42,43].…”