Blocking of cell-free and cell-associated HIV-1 transmission through human cervix organ culture with UC781.
OBJECTIVE
To determine the efficacy of UC781 in preventing HIV-1 transmission through cervical tissue.


METHODS
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 microM 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 microM UC781 for 20 min, or 10 microM 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 microM 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 microM 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.
Zussman
Ariela
A
R. Ben-Ari Institute of Clinical Immunology & AIDS Center, Kaplan Medical Center, Hebrew Uuniversity Hadassah Medical School, Rehovot, Israel.
Lara
Liliana
L
Lara
Humberto H
HH
Bentwich
Zvi
Z
Borkow
Gadi
G
D000813:Anilides / Q000494:pharmacology*; D019380:Anti-HIV Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D002584:Cervix Uteri / Q000187:drug effects / Q000473:pathology / Q000821:virology*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005663:Furans / Q000494:pharmacology*; D005782:Gels; D015658:HIV Infections / Q000517:prevention & control* / Q000635:transmission; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D009924:Organ Culture Techniques; D012661:Semen / Q000821:virology; D013854:Thioamides; D013997:Time Factors
D000813:Anilides; D019380:Anti-HIV Agents; D005663:Furans; D005782:Gels; D013854:Thioamides; C100668:UC-781