This application will bring forward novel topical microbicide products that will be formulated using pH andthermo sensitive gels and intravaginal rings. To ensure that these products in their formulations are safe andeffective, the Explant Core will evaluate them for toxicity to cervcial explant tissues and efficacy against HIV-1 infection. Over years 1 through 3, 10 gels and 10 ring formulations (20 total) will be evaluated yearly. Fourcombination products (e.g. two product candidates in gels or one product in a gel and one product in a ring)will be evaluated in year 2 and 3. The unique aspects of this Core will be studying the timing issues ofproduct application and whether the proudct(s) is effective if used several hours prior to HIV-1 exposure totest for coital independance. The products that are the least toxic and most effective will be further refined fordevelopment. Over years 4 and 5, this refined evaluation will include use of product in the cervical explantcultures in the presence of seminal plasma. Because seminal plasma will influence the infectivity of HIV-1, itis necessary to include these studies. To ensure that the products that are being developed are safe, theExplant Core in conjunction with the Virology Core will evaluate cervicovaginal lavages obtained fromwomen using the placebo formulations of gels to measure innate immune factors and intrinsic anti-microbialactivity. The work provided by this Core will serve Projects 1 (Novel Delivery Systems) and 2 (MicrobicidePerformance Analysis). The findings from this Core will be used by Project 3 to ensure only those productsare the safest are used in women. Collectively, this Core will evaluate new product formulations for safetyand efficacy against HIV-1 using a state-of-the-art cervical explant culture system. The findings from thisCore will help to quickly evaluate new products to move the microbicide product pipeline forward.Relevance: Microbicides are being developed to prevent the spread of HIV-1. The Explant Core will providethe investigators of this application information regarding microbicide safety and the ability to protect againstHIV-1 infection using human tissue that would normally be discarded after surgery. The human tissue usedby these scientists provide us the best bridge between the laboratory and the clinic to study microbicides.
Showing the most recent 10 out of 25 publications
