|
|
|
|
||
|
Abstract INTRODUCTION: The microbicide, Carraguard®, which contains carrageenan as the active ingredient, is currently in Phase 3 clinical trials. Laboratory studies indicate that Carraguard or carrageenan is effective in preventing infection by HIV-1 and herpes simplex type 2 (HSV-2) in vitro, SIV in monkeys, and in mice preventing HPV-induced transformation, HSV-2 infection, and Neisseria gonorrhoeae infection. Clinical trials show that the formulation is safe and acceptable in humans. Carrageenan, as well as several other sulfated polymers, has been shown to be active in blocking HIV infection of lymphoma cells by T-tropic viruses in vitro. However, there is concern and controversy over whether sulfated polymers will be as effective in blocking M-tropic Clade C viruses of Southern Africa. In order to render Carraguard more effective against Clade C viruses, Carraguard was re-formulated to include the non-nucleoside reverse transcriptase inhibitor (NNRTI), MIV-150. Previous studies have demonstrated that MIV-150 is highly efficacious in blocking infection by various HIV-1 strains including those resistant to other NNRTIs and protease inhibitors. In addition, previous in vitro studies demonstrated that resistance to MIV-150 develops slowly. Previous animal and human studies have shown that MIV-150 is nontoxic, and although the compound is well tolerated, it has poor systemic absorption via oral intake. METHODS: Peripheral blood mononuclear cells and a reverse transcriptase assay were used to assay the activity of Carraguard and PC-815 against 12 clinical Clade C isolates obtained from the NIH AIDS Research and Reference Reagent Program. Centriprep YM-30 filtration columns were used to assay activity against free virus. RESULTS: Evidence indicates that PC-815 is more efficacious in blocking Clade C clinical isolates of HIV-1 in vitro than Carraguard or MIV-150 alone. On average PC-815 is an order of magnitude more effective against the viruses assayed than Carraguard. In addition, MIV-150 can inactivate free virus and is active against HIV-2. Results also indicate that seminal fluid had no effect on the activity of PC-815. CONCLUSION: MIV-150 is especially suitable for a microbicide because resistance to this NNRTI develops slowly, and it is poorly absorbed. As PC-815 is active against free virus, HIV-2, and Clade C viruses it is likely to be a more efficacious microbicide than Carraguard. Poster Session
This page updated |
