A topical vaginal microbicide preventing the HIV virus from establishing an infection through the female genital tract could be live saving for young women and other women at risk. With the recent evidence from the Caprisa004 trial showing a 39% reduction in HIV incidence among those using 1% tenofovir gel,7,8 we urgently need to strengthen and broaden the vaginal HIV prevention research by designing and developing more user-friendly formulations (such as vaginal rings) and more effective products, including the design of new chemicals that are not used for the treatment of HIV, thereby limiting the spread

of resistance to drugs that are part of critical combination treatments. Researchers from the Europrise consortium, representing see more 14 projects funded by the European Commission, are now developing combined antiretroviral vaginal gel products, mucosal vaccines, and vaginal ring devices. Each of these new products will need to prove that they are safe and

efficacious through development pathway steps. Safety trials should BVD-523 mw be designed with the utmost care and specifically assess products for maintenance of healthy vaginal ecology and local mucosal immunity. Similarly, oral pre-exposure prophylaxis (PrEP) or an HIV vaccine, applied intramuscularly, nasally, subcutaneously or through any route should not negatively affect the local vaginal milieu. Of equal importance is the assessment of the presence or absence of protective humoral and cellular immunity in response to a vaccine whatever

the route of application. The cellular immunity (HIV-specific CD8 +  T cells) induced by the MRKAd5 HIV-1 gag/pol/nef vaccine in the Step trial did not provide protection from HIV. In this trial, an opportunity Telomerase was missed to evaluate the local mucosal immune responses to gain insight in the vaccine’s failure.9,10 The best way to assess safety and immune responses to products is by sampling the vaginal milieu; studying the local immune system before, during and after use of the products. A proven, well-documented and standardized sampling strategy will provide high quality data to be able to assess both safety and local immune response. The focus of this review is to critically assess the methods used for vaginal sampling in the context of clinical trials for vaginal products, and to highlight areas that need further exploration. At present, a wide range of clinical methods for sampling is used and new methods are being explored.