Is HIV drug resistance a limiting factor in the development of anti-HIV NNRTI and NRTI-based vaginal microbicide strategies?

Antiviral drugs that act at specific sites within the HIV life cycle have important rationale for development as anti-HIV microbicides. However, to be effective, such drugs must act by directly interfering with viral enzymatic function and eliminate the ability of HIV to mediate infection. Compounds that are developed as microbicides must have high potency, and should ideally not be well absorbed from the vaginal cavity in order to minimize any potential problems of drug resistance. Such compounds should also be active over long periods of time and should be able to be combined with other active agents, in order to promote the concept of synergy, such as that which has been demonstrated in HIV therapeutic studies.