WHI-07 [5-bromo-6-methoxy-5,6-dihydro-3'-
azidothymidine-5'-(p-bromophenyl)-methoxy alaninyl
phosphate] is a novel dual-function aryl
phosphate derivative of
zidovudine with potent anti-human immunodeficiency virus (HIV) and spermicidal activities.
WHI-07 was active against the feline immunodeficiency virus (FIV). This study evaluated whether topical application of
WHI-07 as a single agent and in combination with an organometallic
vanadium complex,
vanadocene dithiocarbamate (VDDTC), via a nontoxic gel microemulsion can block vaginal as well as rectal transmission of
feline AIDS (
FAIDS) by chronically FIV-infected feline T cells in the natural host model. Genital transmission of FIV was monitored in recipient cats by the appearance of
viral antibodies to FIV Gag
proteins and by virus isolation of blood leukocytes as measured by FIV
reverse transcriptase activity and FIV-specific PCR. Microbicidal activity was considered effective when the treated cats did not show evidence of FIV
infection for up to 18 weeks postchallenge. An aggregate analysis of 46 specific-pathogen-free cats revealed that a single dose of the infected cell inoculum efficiently transmitted FIV
infection when delivered into the vagina (100%) or rectum (66%). Pretreatment of the vagina or rectum with 2%
WHI-07 alone or in combination with 0.25% VDDTC significantly (P = 0.004) protected cats from genital transmission by the highly infectious inoculum (7 million FIV(Bangston)-infected feline T cells). Collectively, using the vaginal and rectal transmucosal model for
FAIDS, our studies demonstrated that
WHI-07 either alone or in combination with a vanadocene has clinical potential for the development of a dual-function anti-HIV
microbicide for sexually active women.