Stampidine is a potential nonspermicidal broad-spectrum anti-human immunodeficiency virus microbicide.

Objective: Stampidine (2,'3'-didehydro-3'-deoxythymidine-5'-(p-bromophenyl methoxy alaninyl phosphate) is a novel aryl phosphate derivative of stavudine/d4T with broad-spectrum anti-HIV activity in vitro and in vivo. This study investigated the potential utility of stampidine as a nonspermicidal microbicide.

Design: Prospective, controlled study.

Setting: Center for Advanced Preclinical Sciences and Reproductive Biology Department.

Patient(s): Seven sperm donors.

Animal(s): Fifty-two sexually mature, female and twenty-four male New Zealand white rabbits.

Intervention(s): Human semen and genital tract epithelial cells were exposed to stampidine (up to 1 mM). Ovulated does in subgroups of 12 were artificially inseminated with rabbit semen pretreated with stampidine (1 mM) or vehicle. Does in subgroups of four and three, respectively, were exposed intravaginally to a gel or a thermoreversible ovule formulation with and without 0.5%, 1.0%, or 2.0% stampidine (9 to 36 mM) for 14 days.

Main Outcome Measure(s): Effect of stampidine on human sperm motility, kinematics, penetration through cervical mucus, and epithelial cell viability. Reproductive parameters on gestation day 8. Vaginal tissues were histologically scored 24 hours after dosing.

Result(s): Exposure of human sperm to stampidine even at a concentration 10(6)-times higher than its in vitro anti-HIV-1 activity (50% inhibitory concentration = 1 nM) had no adverse effect on sperm motility, kinematics, cervical mucus penetrability, or the viability of vaginal and endocervical epithelial cells. Reproductive indices of pregnancy rate, embryo implantation, and preimplantation losses were not affected by pretreatment of rabbit semen with stampidine. Gel formulations of 0.5% to 2.0% stampidine (9 to 36 mM) lacked mucosal toxicity.

Conclusion(s): The broad-spectrum anti-HIV agent stampidine had no adverse effect on sperm functions, was not cytotoxic, and did not induce mucosal toxicity. Stampidine has clinical potential as a prophylactic microbicide without contraceptive activity.