DRUG CLASSES USED IN FORMULATION DESIGN AND DEVELOPMENT OF HIV PREVENTION MICROBICIDES

Topical microbicides have proved to be an important tool for prevention of HIV transmission in women of reproductive age. Large populations studies including CAPRISA 004, VOICE, DREAM and FACTS001 proved 50-60% efficacy could be achieved with good adherence. These studies have shown the success of microbicides to be largely dependent of patient adherence, partner consent, multiple dosing requirement, aesthetic feel and retention in the cervicovaginal mucosa. To improve efficacy and adherence to microbicides, long-acting formulations are now more actively designed and considered in product development. Formulation design has evolved to provide low cost, scalable, discreet and easy to use multipurpose prevention technologies that provide protection against multiple sexual reproductive health issues. Active pharmaceutical ingredients used for microbicides have also evolved from small molecules and first-generation surfactants to large molecules including antimicrobial peptides and neutralising antibodies with broad spectrum efficacy and reduced viral resistance. The ability of novel molecules to inhibit and disrupt multiple sites in the HIV life cycle have shown potential to increase microbicide efficacy from the preclinical and clinical research work done. Good safety profile, sustained drug release and localized effect have been achieved. Controlled drug delivery greatly improves outcomes in HIV prevention but clinical data on safety and efficacy in pregnancy are still lagging. As more innovative intravaginal delivery systems and active molecules are designed the science on their interaction in vaginal microenvironment and microbiome has also led to areas and opportunity for research to improve therapeutic outcomes and drug development for microbicides.