Microbicides - How they work

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Given that HIV has to cross this epithelial layer in order to mount an infection, there are various strategies that can be used to stop the virus crossing the epithelium or to stop it binding some of its target immune cells. These strategies are illustrated in the diagram below and are described underneath.


Modified and reprinted by permission from Nature Reviews Microbiology www.nature.com/reviews/micro (Vol 1 Oct, pp.25-34) copyright (2003) Macmillan Magazines Ltd.


Physical barriers
These formulations provide a physical barrier at the epithelium which could be of a gel or cream nature which provides lubrication to guard against physical damage or abrasion of the epithelial cells.

Maintaining the natural flora
The vagina has its own set of resident microorganisms which help to keep the vagina healthy. These microorganisms tend to keep the pH of the vagina low and this low pH is actually virucidal i.e. it will kill off viruses. Hence maintaining natural microorganisms in the vagina will help in keeping the vagina in a virus free state.

Preventing sexually transmitted infections (STI's)
The presence of STI's is associated with damage to the vaginal epithelium such as ulceration and inflammation. This damage can increase the risk of HIV infection. Hence preventing STI's can decrease the chances of HIV transmission.

Viral disruption
The HIV virus may be able to be disrupted by drugs in the vagina such that it doesn't get the chance to cross the epithelium. These drugs may for example damage the outer layers of the virus such that the virus can't function properly. However, it is crucial that these drugs don't damage the epithelial cells as this could lead to an increased risk of infection.

Stopping viral fusion to target cells
HIV binds to certain receptors (mainly CD4) and co-receptors on host cells to initiate the infection process. Drugs can be designed to block for example, the proteins on the surface of the HIV virus that bind the receptor, or the receptor itself could be blocked so that there is nowhere for the virus to bind.

Stopping the virus replicating itself
Once the HIV virus has bound and fused with a target host cell it then uses the host cell to replicate itself i.e. make more copies of itself. Drugs can be designed to interrupt this process so that the virus can't be replicated. Drugs of this nature are the most common anti HIV therapy today and can delay the onset of HIV and AIDS symptoms for long periods of time. However, although they stop the virus replicating they don't stop the virus infecting or remove it from the host completely.

Stopping the virus binding other immune cells
In addition to binding target cells that have CD4 on their surface, HIV will also bind to the surface of other immune cells such as dendritic cells. Just as for HIV binding to CD4 target cells, drugs can be designed to stop the binding of HIV to these other types of immune cells as well.