Defensins Defensins are the first family of cationic antimicrobial peptides to have been discovered in human cells [12,13]. died from HIV-related causes globally, and the cumulative death toll had risen to more than 35 million people [1]. Subsaharan Africa was the most affected region globally, accounting for over two-thirds of the people living with HIV as well as two-thirds of new HIV infections. In the same year, an estimated 1.2 million people were living with HIV in the U.S., and approximately an eighth of these individuals are estimated to be unaware of their infection status [2]. Over the decade from 2005 until 2014, the number of new HIV diagnoses in the USA had fallen 19%. Due to increased HIV testing, improved availability of antiretroviral therapy, and emerging antiretroviral prophylaxes, this suggests that there had been a tangible decline in p-Coumaric acid HIV infections during that time period. While the epidemic appears to be stabilizing in the USA, this perception has given rise to an increasing level of complacency in individuals who view HIV as a clinically manageable chronic condition. This recent, disturbing trend p-Coumaric acid is compounded by the fact that, with an increasing number of people receiving antiretroviral therapy, viral resistance to most of the available drugs is inevitable. In order to continue controlling the pandemic, there must be a constant influx of next-generation antiretrovirals coupled with other innovative strategies to combat HIV. The holy grail of HIV prevention would be an effective, long-term HIV vaccine, yet vaccine trials to date have shown little to no promise in the clinic [3]. In the absence of an available vaccine, the field has turned to various methods to prevent or limit the transmission of HIV. The most successful prevention strategy to date, termed Pre-Exposure Prophylaxes (PrEP), has utilized oral antiretrovirals to treat the uninfected partner of a serodiscordant couple prophylactically, to reduce the incidence of HIV transmission from the HIV infected partner [4]. It should also be noted that this and other oral PrEP studies have shown greater efficacy in treating the infected partner, underscoring the importance of limiting viral load in an infected individual to reduce the likelihood of sexual transmission to the uninfected partner. However, as with any antiretroviral therapy given to an infected individual, the likelihood of HIV acquiring resistance would remain high. Other promising prevention strategies studied over the past two p-Coumaric acid decades include topical microbicides, which are prophylaxes self-administered by an p-Coumaric acid uninfected individual to the cervix/vagina or anus/rectum to prevent or limit sexual or vertical (mother to newborn) transmission of HIV. This type of prevention therapy targets these highly HIV-susceptible mucosal environments, and has several potential benefits: (1) surreptitiously applying a gel, cream, film, or other slow-release method to provide long-lasting protection could empower individuals from societally vulnerable populations to take HIV prevention measures in their own hands; (2) the topical application of a microbicide is confined to surfaces of the body where sexual or vertical (mother to newborn) transmission of HIV is greatest, vastly reducing the amount of drug required as compared to systemic delivery; (3) targeting prevention measures to the uninfected partner should substantially reduce the likelihood of HIV resistance; and (4) formulations engineered to retain the antiretroviral drug in the mucosa and reduce systemic absorption could also reduce or delay the onset of viral resistance. As with HIV vaccines, an all-too-familiar lack of success has plagued the field of topical microbicides. While self-applied prophylaxes have the potential to target populations that are susceptible to acquiring HIV sexually or vertically, clinical trials have instead revealed that patient acceptability, psychosocial issues, and adherence to proper drug application regimens were more problematic than originally envisioned and likely contributed to failures in p-Coumaric acid the clinic [5]. Goserelin Acetate The rapid emergence of the new field of topical microbicides led to questionable early decisions to promote compounds, which were insufficiently vetted.