Microbicides can act in various ways. Microbicides can be nonspecific, moderately specific or highly (exclusively) specific to HIV. The nonspecific and moderately specific agents are often active against a variety of sexually transmitted microorganisms (e.g., chlamydia and herpesvirus) and may have a contraceptive effect. The HIV-specific agents interact directly with one or several steps of the infection or replication cycle of HIV.
Nonspecific microbicides
The nonspecific microbicides consist of buffering agents and of detergents or surfactants that include nonionic, anionic or cationic compounds. The detergents destroy the viral envelope by solubilizing membrane proteins. However, this nonspecific mechanism of action may also disrupt the cell membranes of the vaginal and cervical epithelium and cause erosions and lesions, leading to an increased risk of HIV infection.
Moderately specific microbicides
Moderately specific microbicides mainly comprise macromolecular linear anionic polymers. Linear polyanions are active against HIV, HSV and in some cases demonstrate inhibitory activity against human papillomavirus (HPV), Neisseria gonorrhoeae and Chlamydia trachomatis. They block viral entry into cells through electrostatic interactions with the viral envelope proteins and, in some cases, host cell receptors. The lack of potency of linear polyanions for HIV and the ability of semen to further abrogate anti-HIV activity, may in part explain the lack of in vivo efficacy of these microbicides. In addition, adherence to product use and transmission via anal receptive sex, which would not be prevented by a vaginally applied microbicide, are other considerations.
Highly specific anti-HIV agents
HIV-specific microbicides should preferentially block the viral infection cycle before the viral genome gets
incorporated in the target cells as proviral DNA.
Targeting viral entry seems the most promising method, preventing virus particles from entering its susceptible cells and, as shown or expected for most entry inhibitors, also preventing transmission of the virus from virus-infected cells to uninfected cells or transmission of dendritic cell-captured virus to lymphoid cells, or both.
