title: Preclinical studies of alkylureas as anti-HIV-1 contraceptive.
abstract: The HIV-1 epidemic continues to spread at a rate of over 15, 000 new cases daily. HIV-1 transmission through heterosexual contact became the dominant risk for women globally. About half of the over 40 million HIV-1 infected individuals worldwide are now women. The lack of empowerment of women is the fundamental cause for the rampant spread of HIV-1 in women. Topical microbicides applied intravaginally offer an option for female-initiated HIV-1 prevention. There is an urgent need to develop microbicides with and without contraceptive qualities to also address socio-cultural settings where the woman's status is linked to fertility. A safe and efficacious anti-HIV-1 vaginal formulation is not yet available though a large number of candidates are in preclinical or clinical studies. Presently marketed topical microbicides are by and large toxic and damage the vaginal mucosa with frequent use. The microbicidal system of alkylureas evaluated here lends itself to contraceptive and non-contraceptive anti- HIV-1 formulations. Alkylureas are agents that irreversibly disrupt free and intracellular HIV-1, have a wide margin of safety and are spermicidal above their virucidal concentration without any mucosal toxicity. Butylurea, the lead compound is also effective against other sexually transmitted diseases (STDs) while sparing the normal vaginal flora. Alkylureas with longer alkyl chains still have to be explored and may have a greater selective microbicidality.
authors.affiliation: Department of Pediatrics, Albert Einstein College of Medicine and Montefiore Hospital Medical Center, 1525 Blondell Avenue, Bronx, NY 10461, USA. rubinste@aecom.yu.edu
authors.forename: Arye
authors.initials: A
authors.lastname: Rubinstein
mesh_terms: D000282:Administration, Intravaginal; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000138:chemical synthesis / Q000494:pharmacology* / Q000633:toxicity; D015197:Carcinogenicity Tests; D003271:Contraceptive Agents, Female / Q000008:administration & dosage / Q000138:chemical synthesis / Q000494:pharmacology* / Q000633:toxicity; D005260:Female; D015658:HIV Infections / Q000517:prevention & control*; D006801:Humans; D008297:Male; D014508:Urea / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology* / Q000633:toxicity
chemical_list: D019380:Anti-HIV Agents; D003271:Contraceptive Agents, Female; D014508:Urea; C006865:butylurea