Microbicide actions

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.

However, if the virus has already entered host cells, or has entered the host through virus-infected cells, specific antiretroviral therapy, targeting one of the replication steps between entry and proviral incorporation could be necessary.(Microbicide drug candidates to prevent HIV infections: Jan Balzarini, Lut Van Damme)

Potential mechanisms of action for microbicide compounds
Microbicides that act as a lubricant coat the epithelial surface, which might reduce the risk of trauma and provide a physical barrier against viral infection. Prevention (or treatment) of other STDs can reduce the risk of HIV transmission by reducing the risk of epithelial inflammation and ulceration. In the vagina, maintaining the normal flora, and therefore maintaining the vaginal pH at virucidal levels (pH less than 4.5), could also reduce the risk of transmission.

Once the virus has crossed the epithelial barrier, potential microbicidal strategies include targeting HIV uptake by dendritic cells, targeting HIV adsorption and fusion, and targeting reverse transcriptase and integration into the host cell genome. (From Shattock RJ, Moore JP. Inhibiting sexual transmission of HIV-1 infection. Nature Rev Microbiol 2003;1:25-34).

Systemic absorption and drug resistance
Absorption of microbicides used intravaginally or intrarectally may result in systemic side effects or viral drug resistance or both. The development of viral drug resistance should be avoided as much as possible.