30 Next to the standardization element, this NIH GU mucosal immunology working group will study number and functional phenotypes of cells obtained from selleck compound non-invasive specimens with brushes and see if they are equivalent to those isolated from biopsies. This will then inform the field to what extent endocervical

sampling is representative for the local cellular immunology. Good results have been obtained in measuring total cell number and their phenotype but it remains to be seen if cell yield is sufficiently high enough to follow antigen-specific responses to an HIV vaccine. Ulcerative and non-ulcerative pathogens that infect the vagina have been shown to affect the local immunity.31,32 The presence of these pathogens may confound the relationship between an experimental medication

or vaccine and the local immune response. Therefore it is important to test for sexually transmitted infections such as C. trachomatis, N. gonorrhea, T. vaginalis, Human papilloma virus selleck as well as shedding for HSV. In addition, serum samples should be taken to test for active syphilis, HIV and HSV. Menstrual cycle phase have been shown to be a powerful determinant for levels of cytokines and numbers of immune cells.24,33 Serum or urine samples for endogenous hormones should be collected and menstrual phase applied to the analysis of results. Finally, vitamin D is an important immune modulator, can be tested in serum and considered as a confounder.34 Planning a sampling strategy for a clinical trial requires balancing of study objectives and endpoints, participant acceptability, available infrastructure and study budget. Extra samples may be needed to account for local confounding factors

as mentioned above, other vaginal infections (yeast, bacterial vaginosis) and to perform diagnostic tests (Amsel versus Nugent, InPouch versus wet mount) for the participant. The use of antiretroviral drugs for the prevention of heterosexual transmission introduced concerns about the development of HIV drug resistance and has heightened the interest in product PK/PD. As a result cervical, endocervical and uterine biopsies are now more commonly collected in Phase I safety studies. Figure 2 selleck screening library proposes a basic set of samples to study mucosal immunology and confounding factors without additional biopsies. The figure incorporates sampling methods, volumes of samples, markers, storage issues and volumes for assays. The sampling strategy is specific to each individual trial, since each trial has its own objectives and endpoints. Nevertheless, we believe that it is feasible and desirable to establish standardized sampling methods in conjunction with standardized assays, so that results are comparable between trials.