Blocking of cell-free and cell-associated HIV-1 transmission through human cervix organ culture with UC781

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Abstract
Objective: To determine the efficacy of UC781 in preventing HIV-1 transmission through cervical tissue. Design: Use of human cervical tissue organ culture, in which the cervix is in the upper chamber of a transwell and transmission of infective virus is quantified in the lower chamber. Methods: Five-millimeter pieces of cervical tissues are exposed to UC781. After thorough removal of the drug, the tissues are exposed to high doses of cell-free or cell-associated HIV-1. Transmission of HIV-1 through the cervix is measured by determining infection of target cells in the lower chamber. Results: Exposure of cervix to 0.5 μM UC781 for 30 min, followed by extensive washing away of the residual drug, resulted in 95% reduction of subsequent viral transmission. Exposure of the cervix to 1 μM UC781 for 20 min, or 10 μM UC781 for 2 min, resulted in neutralization of T- and M-tropic HIV-1 isolates of various clades, and prevention of cell-associated HIV-1 transmission. Moreover, a 20 min incubation with 10 μM UC781 abolished HIV-1 transmission through the cervix for 48 h after drug pretreatment. Importantly, UC781 was not toxic, even when the cervical tissues were exposed to 20 μM UC781 for 24 h. UC781 was effective against transmission of both cell-free and cell-associated HIV-1 also when formulated into a non-spermicidal (Replen) or spermicidal (BufferGel) gel. Conclusions: Exposure of the cervix to UC781 results in blocking of subsequent HIV-1 transmission with no toxicity. Therefore, UC781 is an excellent candidate microbiocide.