Prophylactic contraceptives for HIV/AIDS

Abstract

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.

Lack of adverse effects on fertility of female cd‐1 mice exposed to repetitive intravaginal gel–microemulsion formulation of a dual‐function anti‐HIV agent: aryl phosphate derivative of bromo‐methoxy‐zidovudine (compound WHI‐07)

“…1 The emergence of AIDS as a disease spread through sexual intercourse has prompted the search for new, effective, safe and female-controlled vaginal microbicides for curbing mucosal and perinatal viral transmission. 2 Microbicides would provide protection by inactivating viruses or preventing viruses from replicating either in semen or the infected host cells that line the vaginal wall.…”

Influence of long-term stability conditions on microbicidal nucleoside prodrug (WHI-07)-loaded gel-microemulsion

“…[3][4][5][6] Consequently, the development of safe, efficacious vaginal microbicides capable preventing the transmission of HIV-1 from infected leukocytes via semen is of paramount importance in the fight against the spread of sexually transmitted AIDS. [7][8][9] WHI-07 (5-bromo-6-methoxy-5,6-dihydro-3′-azidothymidine-5′-(p-bromophenyl)-methoxyalaninyl phosphate), a novel aryl phosphate derivative of zidovudine (ZDV) is an anti-HIV-1 prodrug with in vivo microbicidal and contraceptive properties. [10][11][12][13][14] WHI-07 was rationally designed to bypass the kinase activation step, especially in thymidine kinase deficient or lacking monocytes/macrophages, the main carriers of HIV-1 in semen and female genital tract secretions.…”

Conceival, a novel noncontraceptive vaginal vehicle for lipophilic microbicides

“…7 The emergence of HIV/AIDS as a disease spread through sexual intercourse, combined with growing public awareness about the problems associated with other viral sexually transmitted infections (STIs), has prompted the search for new, cost-effective, and safe vaginal microbicides for curbing transmucosal viral transmission. 8,9 Microbicides would provide protection by inactivating viruses or preventing viruses from replicating either in semen or the infected host cells that line the vaginal wall. Microbicides that are currently being investigated are directed mainly at preventing pregnancy as well as protection against STIs.…”