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The HIV-1 epidemic remains unchecked despite existing technology; vaccines and microbicides in development may help reverse the epidemic. Reverse transcriptase inhibitors (RTIs) formulated in gels tenofovir (TFV) and IVRs (dapivirine) are under clinical development. While TFV or similar products may prove successful for HIV-1, alternatives to RTIs may provide additional benefits, e.g., broader STI prevention. Biopharmaceutical agents under development as microbicides include cyanovirin, RANTES analogues, commensals, and Mabs. Cost of manufacturing biopharmaceuticals has been reduced and they can be formulated into tablets, films, and IVRs for vaginal delivery. Nanotechnology offers a novel approach to formulate microbicides potentially leading to uniform epithelial delivery. Delivery through vaginal mucus may be possible by controlling nanoparticle size and surface characteristics. Combining prevention modalities may be the most effective means of preventing STI transmission, importantly, codelivery of microbicides and vaccines has demonstrated. Finally, the safety of microbicide preparations and excipients commonly used can be assessed using a mouse/HSV-2 susceptibility model. Screening of new microbicide candidates and formulation excipients may avoid past issues of enhancing HIV-1 transmission. This article forms part of a special supplement covering several presentations on novel microbicide formulations from the symposium on “Recent Trends in Microbicide Formulations” held on 25 and 26 January 2010, Arlington, VA.Abbreviations: RTIs: reverse transcriptase inhibitors; IVRs: intravaginal rings; HIV-1: human immunodeficiency virus-1; IUD: intrauterine device; STI: sexually transmitted infection; SRH: sexual and areproductive health; MPT: multipurpose technology; ARV: antiretroviral therapy; Mabs: human monoclonal antibodies; EVAc: poly (ethylene-co-vinyl acetate); PLGApoly(lactide-co-glycolic acid); PSA: poly(sebacic acid), poly(lactic acid); MPPs: mucus-penetrating nanoparticles; PEG: polyethylene glycol; FITC: fluorescein isothiocyanate; N9: nonoxynol-9; HSV-2: human simplex virus type 2; CHX: chlorhexidine; ID50: 50% inhibitory dose; APIs: active pharmaceutical ingredients; SDS: sodium docecylsulfate; EDTA: ethylenediaminetetraacetic acid; GML: glycerol monolaurate; PrEP: pre-exposure prophylaxis; RTIsreproductive tract infections; TFV: tenofovir; HEChydroxethylcellulose; NHP: non-human primate.