Prophylactic contraceptives for HIV/AIDS.
The current pandemic of sexually transmitted human immunodeficiency virus (HIV) infection--the causative agent of acquired immunodeficiency syndrome (AIDS), has created an urgent need for a new type of contraceptive: one that is both a spermicide and a microbicide. Because most women at risk for HIV infection are of reproductive age (15-44 years), effective use of dual-function contraceptives is important to prevent HIV transmission and unintended pregnancies. In the absence of an effective prophylactic anti-HIV therapy or vaccine, new emphasis has been placed on the development of intravaginal microbicidal agents capable of reducing the transmission of HIV. Topical microbicidal spermicides would ideally provide a female-controlled method of self-protection against HIV as well as preventing pregnancy. However, several microbicides that are undergoing preclinical and human clinical trials contain detergent-type ingredients. The detergent-type spermicide, nonoxynol-9, the only recommended microbicide for protection against sexual transmission of HIV has been shown to cause lesions in vaginal and cervical epithelia leaving women more vulnerable to HIV infection. Therefore, a major challenge in microbicide research has been to design mechanism-based microbicides that are highly effective against pregnancy and HIV transmission while lacking detergent-type effects on epithelial cells and normal vaginal flora. We present an overview of current microbicide research and report on the identification and preclinical development of novel non-detergent spermicidal nucleoside and non-nucleoside inhibitors aimed at decreasing pregnancy and preventing sexual transmission of HIV.
Uckun
F M
FM
Department of Virology, Hughes Institute, St Paul, Minnesota 55113, USA. faith_uckun@mercury.ih.org
D'Cruz
O J
OJ
D000818:Animals; D019380:Anti-HIV Agents / Q000494:pharmacology; D017280:Condoms; D003267:Contraception / Q000379:methods*; D004341:Drug Evaluation; D004353:Drug Evaluation, Preclinical; D005260:Female; D006678:HIV / Q000187:drug effects; D015658:HIV Infections / Q000517:prevention & control*; D000882:Haplorhini; D006801:Humans; D007509:Irritants / Q000009:adverse effects; D008297:Male; D009092:Mucous Membrane / Q000187:drug effects; D012309:Risk-Taking; D012725:Sexual Behavior; D016097:Simian Acquired Immunodeficiency Syndrome / Q000517:prevention & control; D013089:Spermatocidal Agents / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013501:Surface-Active Agents / Q000494:pharmacology; D014621:Vagina / Q000187:drug effects
D019380:Anti-HIV Agents; D007509:Irritants; D013089:Spermatocidal Agents; D013501:Surface-Active Agents