Microbicides: chemistry, structure, and strategy.
OBJECTIVE
To highlight promising areas of research and preview future generations of microbicides, this review will focus on reports that described new cellular or viral targets, drug substances, or strategies that are specifically intended for topical microbicides. Those reports that dealt with the design, discovery, and synthesis of anti-HIV agents for use in oral or parenteral formulations, while important for the microbicide field, are beyond the scope of this review.


RESULTS
Drug substances intended for topical microbicides are becoming increasingly target specific and, structurally, more complex. New production methods might reduce the cost of microbicides that contain these complex molecules. Genetically engineered probiotic vaginal bacteria express an even wider range of antiviral compounds, perhaps resulting in uninterrupted, coitally independent protection. Combination microbicides that contain two or more drug substances frequently act synergistically. The discovery of new cellular targets such as syndecan-3 might lead to more effective microbicides.


CONCLUSIONS
Future generations of microbicides will likely contain one or more complex or highly specific drug substances, resulting in safer and more effective products. Since compliance issues continue to confound HIV and herpes simplex virus trials, efforts to bring practical, coitally independent microbicides to developing countries will become a top priority.
Population Council, HIV/AIDS Program, New York, New York 10065-6307, USA. tzydowsky@popcouncil.org
Thomas M
TM
Zydowsky