Future prospects and perspectives on microbicides.

This special issue of Current HIV Research emphasizes two uncontestable facts: (i) HIV prevention is an essential public health and moral imperative and (ii) microbicides (AKA: “topical PrEP”), as one mode to address this need, have arrived as contenders in the fight. While the chapters here detail the increasing numbers of agents which may potentially contribute to a combination prevention approach (essential), they also highlight critical advances in the fields of understanding HIV transmission [1], selection of optimal combinations of drugs for pre-exposure prophylaxis and formulation science. The articles also serve to remind us all how far and how fast this field of HIV prevention has grown. The successes in recent, large-scale, complex prevention trials with geopolitical, cultural, gender and behavior diversity have demonstrated significant reductions of new HIV infections, a dramatic achievement by dedicated teams, institutions and participating study populations [2,3]. And, as with any successful venture, the same successes have opened new controversies and challenges. The future plans, development and application are as strategically important now as before, with no appreciable decrease in the ~7000 new infections daily around the world. This is where “efficacy” will be translated into “effectiveness”. This field’s charge is to provide more options to analyze and address these needs as the first preventives are rolled-out into more public use, which will included HIV-positive and HIV-unknown populations as will as multiple-infected individuals. The charges for future innovation and improvement are becoming clearer. The degree of success in recent trials would have benefitted from more accurate, behaviorally-transparent metrics of adherence, if they existed, enabling more confident subset analyses and, perhaps, earlier, focused roll-out of approved agents. This single feature would have assisted more in larger public health goals of determining how generalizable trial results might be and for which more-at-risk populations. Having improved confidence on which study sub-groups actually took the drug in prescribed fashion would help distinguish a ~40% versus ~90% protection trial result and is critical. But having to wrestle with these issues is, in itself, a huge advance in HIV prevention. Proof of concept has now been achieved. That a topically-applied or an orally-delivered anti-HIV medication can significantly reduce acquisition of new HIV infection in real-world populations is no longer debated. How to do it better, safer, cheaper, provide options for application independent of coitus (surreptitious, if needed), user-driven, stable, acceptable and accessible are now more tangible and real challenges. From this point, the call to safely implement effective preventives in HIV-positive/HIV-status unknown, younger adolescent, pregnant and other subpopulations and to bridge HIV prevention with contraception and other STI preventions will emerge as key factors as prevention science advances. The following topics identify some important, focused areas for future development of HIV preventives. The topical PrEP (microbicide) field has, for the past 2–3 decades been exemplary in cross-disciplinary, complementary, collaborative research efforts. Many, including the very proactive advocacy groups, have been at the table on all levels helping focus on acceptability, actual-use preferences, potential product roll-out, political and financial feasibility, community educational and marketing aspects that bring these research/science-based advances into daily, health-promoting practice.