HIV This Week

Female genital tract secretions and semen impact the development of microbicides for the prevention of HIV and other sexually transmitted infections

Herold BC, Mesquita PM, Madan RP, Keller MJ. Am J Reprod Immunol. 2011; 65:325-333

Pharmacologic strategies for the prevention of HIV include vaccines, post-exposure prophylaxis with antiretroviral therapy, and topical microbicides. Vaginal microbicides have the potential to augment innate defenses in the genital tract but may also disrupt endogenous protection and increase HIV acquisition risk, as observed in clinical trials of nonoxynol-9. The initially disappointing results of microbicide clinical trials stimulated the development of more sensitive and comprehensive pre-clinical safety studies, which include dual-chamber culture systems to model the epithelial barrier and post-coital studies to evaluate the effects of semen and sexual intercourse on microbicide efficacy. This review discusses the key factors that contribute to a healthy female genital tract environment, the impact of semen on mucosal defense, and how our understanding of these mediators informs the development of effective vaginal microbicides.

Abstract

Editors’ note: This article provides strong justification for conducting pharmacokinetic and pharmacodynamic studies for microbicide candidates using post-coital samples rather than ordinary cervicovaginal secretions. The female genital tract has several natural host defences that semen counteracts. It neutralises the protective acidic pH of vaginal fluid, stimulates inflammatory cytokines, and causes white cells and Langerhans cells to come into the path of HIV. More directly, semen contains prostatic acid phosphatise which forms fibrils that capture HIV and help their attachment to target cells. Semen may also interfere with defensins, SLPI (secretory leukocyte protease inhibitor), and other antimicrobial proteins found in cervicovaginal secretions. Clearly, when we are trying to measure the effects of a microbicide candidate on the multilayered squamous epithelial barrier of the vagina we have to include semen. Predictive safety assays such as those described in this article are helping us understand why microbicide candidates such as non-oxynol 9 and cellulose sulfate increased risk of HIV acquisition. We need to better understand mucosal immunity and the role of semen in order to find ways to increase women’s natural defenses. In the meantime, reading this article brings the reader right back to square one—if there is any possibility of HIV or genital herpes, use a condom if you are not trying to get pregnant!